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FDA approved Orserdu (elacestrant) for postmenopausal women or adult men with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy.
On May 25, 2020, George Floyd said “I can’t breathe” more than 20 times before he suffocated on a street in Minneapolis. On Jan. 7, 2023, Tyre Nichols repeatedly screamed, “Mom, mom, mom” as he was beaten to death on a street in Memphis.
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Both were Black men. Both died at the hands of police officers wielding the power of life and death.
“This is like déjà vu all over again. That’s only two years ago,” said Robert Winn, director and Lipman Chair in Oncology at the Virginia Commonwealth University Massey Cancer Center, a professor of pulmonary disease and critical care medicine at the VCU School of Medicine, and the guest editor of The Cancer Letter during February, Black History Month.
“It’s a cultural problem. It’s some kind of bias. It’s a disrespect,” said Otis Brawley, Bloomberg Distinguished Professor of Oncology and Epidemiology at Johns Hopkins University, and co-editor of the Cancer History Project.
Both physicians have had life-threatening encounters with police—Brawley was thrown to the ground and held at gunpoint for standing in the garage of his own home; Winn was thrown to the ground and held at gunpoint for walking toward his own car.
“We both happen to be Black men. With the events in the last several weeks involving Tyre Nichols in Memphis, we thought we should have a chat, because both of us have in the past talked about our experiences with police, our experiences in society growing up,” Brawley said.
The Cancer Letter invited Winn and Brawley to discuss the structural biases and racism in law enforcement as well as in health care.
This conversation is also available as a video and podcast.
It’s important for physicians and public health professionals, as individuals in positions of power, to reflect on the problems in policing in America, and identify areas where these problems are also present in health care, Brawley and Winn said.
“Someone had said the other day, ‘The Tyre thing is very different than the thing from George Floyd, because, well, with George Floyd, the policemen that were doing that were predominantly white, and in this case, the policemen were all African American,’” Winn said.
For me, the only time I’ve had guns pulled out on me has been when I was encountering law enforcement. It wasn’t by a gang or anything like that.
Robert Winn
“And I essentially said that that is actually incorrect,” Winn said. “Policemen still see, even whether they’re Black, Asian, or white, based on the way sometimes that unit is taught or the culture of that unit, that they would treat an African American different than they would treat a white person for the same traffic stop violation. It’s a power dynamic.”
“And I worry about that power dynamic in medicine as well,” Brawley said.
Race is one dimension of that power dynamic.
“We have a medical system that is segregated by socioeconomics, and separate cannot be equal. Separate is not equal,” Brawley said.
Class is another dimension, albeit less talked about, Winn said.
“Class does not protect, whether it’s in law enforcement nor, actually, in medicine,” Winn said. “But I guarantee you this: if you’re Black and you’re poor, that becomes an issue.
“I hope that with Tyre’s death that one of the good things that could come out of this would be for us to take a pause and be all recommitted, as many of us were at the time that George Floyd actually was also murdered in front of all of our eyes.”
The conversation between Brawley and Winn follows:
Otis Brawley: Hello. I’m Otis Brawley, and I’m a medical oncologist. I’m here with my good friend Rob Winn, who is director of the Massey Cancer Center at Virginia Commonwealth University. And we are two major players in oncology. We both happen to be Black men.
With the events in the last several weeks involving Tyre Nichols in Memphis, TN, we thought we should have a chat, because both of us have in the past talked about our experiences with police, our experiences in society growing up.
I’ll start out by simply saying, I personally think that there is a problem in the United States with police and policing, and it’s a cultural problem. It has to do with biases and disrespect. We can talk about whether it’s biases and disrespect because of race or because of social positioning.
There is a problem in policing, and unfortunately, the police are not ready to deal with it.
Now, we are in medicine, and I think it’s a good time to actually think if some of these problems that we see in policing that actually do go into the rest of society, actually transcend into medicine. And that’s an area where we actually can do something about it and can be leaders in bringing about change.
So, Brother Winn, thank you for joining me in this conversation. It’s been two years since George Floyd, and now we’ve seen Tyre Nichols. And along the way, we’ve had Breonna Taylor and so many others who have been abused by police.
My first question for you is why do you think it’s important that we, as physicians and public health professionals, have an understanding of these issues in depth and think about them broadly?
Robert Winn: Dr. Brawley, I want to thank you for all that you have and continue to do, particularly in bringing light to these issues that really impact our communities and our patients.
I was thinking, as you were talking, about a line—and just for transparency’s sake, my brother just retired from the police force as a state trooper—I remember when we had been talking at some point it came up, the saying that “When you’re Black in America, there is no such thing as a routine traffic stop.”
That extends to when you are Black in America and you wind up going to an ER for certain problems; that many things that should be routine are not; that are really impacted by historical things that have happened long before us and continue to impact both, not only policing.
But I still think what we do in making sometimes unconscious, biased decisions about, for example, the lack of African Americans wanting to be on clinical trials.
I think that is a myth. I still think, to this day, that if you were to ask first and be able to communicate effectively, we’d have many more people from African American and many other communities, including rural communities, wanting to be on clinical trials.
So, I’ll start there by saying that it did make me think this weekend that 32 years after Rodney King, two years after George Floyd, that this is like déjà vu all over again, except for I think this time it may be a little different.
OB: Now, some of the folks who are listening to this or reading this may not be aware, but two years ago, you and I both wrote pieces for The Cancer Letter, talking about our negative experiences with the police throughout our years.
I, in particular, was an aide to the Surgeon General and a tenured researcher at the NIH, but I found myself face down in my driveway handcuffed for opening my garage door.
Yes. And then, when they saw that I had a military ID, one of the police—and by the way, one was Black, one was white—actually challenged my military ID’s validity, because they decided that I was too young to be the rank on my ID.
Some of these things get really, really stupid that the police do. And unfortunately, we see a lot of these things. And it’s some kind of bias. It’s a disrespect.
And it’s not all police. There’s three kinds of police. There’s the police who do this, the police who let it happen, and the police who are ignorant to the fact that it’s happening. I’m worried about that in medicine... We’ve recently had an article that medical students at a major university—I’ll tell you, it was the University of Virginia—thought that Black people don’t feel pain the way white people feel.
Black people do it, too. I hear about Black breast cancer as if it’s a proud thing among Black women. They’re talking about triple-negative disease. Last time I looked at it, 20% of Black women have it, and 12% of white women have it. Now, we’re going to claim it as Black breast cancer.
Help me out here. We’ve got to get away from some of these labels, and the bias, and we need to start respecting each other, and being concerned about each other.
RW: I absolutely couldn’t agree with you more. Going back to your first point, it was senseless. The use of appropriate policing is always in order.
In fact, my brother would say that the people who dislike that kind of bad policing are good police.
For me, the only time I’ve had guns pulled out on me has been when I was encountering law enforcement. It wasn’t by a gang or anything like that.
And Henry Louis Gates, remember, when [he was] trying to get into his own house? I only say that to say that class does not protect, whether it’s in law enforcement nor, actually, in medicine.
You and I have talked about that sometimes we have these feelings like African Americans do less well from things like multiple myeloma, until we actually have studies like the ones out of the University of Wisconsin-Madison, and others that are looking at multiple myeloma.
They actually show that if you give the appropriate access to care, it may not be-all-end-all, but it certainly reduces the disparities.
It’s not so much that biology is a major driver, but those things around the biology. I hope that not only will we grow as a society in being much more thoughtful around policing, but I also think that we will take this moment of Tyre’s death to figure out how many of us in the medical community said, or at least stated, that we wanted to be better; that we wanted to do things better after George Floyd’s death. That’s only two years ago.
The reality is, I hope that with Tyre’s death that one of the good things that could come out of this would be for us to take a pause and be all recommitted, as many of us were at the time that George Floyd was also murdered in front of all of our eyes.
And that extends to health care. I think many of us in the cancer world said, “How could we make access to care better? And how can we address these issues?”
Because sometimes, there’s the DWB—driving while Black—but I think that there’s also these same phenomena when we’re talking about our patients. That just simply being Black means that you, in some cases, say, “It’s our biology,” and don’t look at other issues that happen in the context of the ZNA, or the ZIP code-neighborhood association.
Other factors also play a role.
OB: You and I are great believers that the ZNA, or the ZIP code, is far more important than the DNA in many of these issues. And indeed, there are studies going back to the 1990s that show that equal treatment yields equal outcome amongst equal people, but there is not equal treatment.
Let me just go into my disease. Black men who have stage 3 prostate cancer are twice as likely to die as white men in the United States. When they’re treated in American College of Surgeons-certified hospitals that have a cancer program, they’re only one and a half times as likely to die.
When they’re treated in some of the premier hospitals in the United States, equal treatment yields equal outcomes. It’s Black and white one-to-one in terms of outcome.
And so, here we have in prostate cancer, clearly, a problem that a large number of Black men, actually some white men too, don’t get good treatment.
I suspect the same is true in breast cancer. I suspect the same is true in a myriad of cancers. I think the way to overcome implicit bias—and all of us have it—is to realize that these disparities exist, number one.
And two, try to do your best, to give your best care to every patient in front of you. Get back to basic principles. Who was it? Was it [Francis] Peabody who said, “The secret in caring for the patient is caring for the patient?”
RW: Is caring for the patient. Yes.
Otis, you bring up a good point. And you bring up a good point that I think is, as we started this conversation, the broad range of how we can address this issue. Number one, it turns out that just sensitivity training alone for policemen and “sensitivity” or diversity equity modules that get just taught about unconscious bias may not be enough.
What we really ought to get to is what you just said. And some of that can’t be policed, and some of that can’t be driven by law. Some of that’s going to have to be instilled in a culture, of medicine and hopefully, in policing, that every person does count, and that the truth of the matter is to see the person in front of you, not your image of what you think about them.
Now, someone had said the other day, “The Tyre thing is very different than the thing from George Floyd, because, well, with George Floyd, the policemen that were doing that were predominantly white, and in this case, the policemen were all African American.”
And I essentially said that that is actually incorrect. Policemen still see, even whether they’re Black, Asian, or white, based on the way sometimes that unit is taught or the culture of that unit, that they would treat an African American differently than they would treat a white person for the same traffic stop violation. It’s a power dynamic.
OB: And I worry about that power dynamic in medicine as well.
RW: Exactly. And these tags of Black men just come out, “they do worse from prostate cancer,” as if it’s a gospel truth, without understanding that it probably takes more data.
Or that we do worse in lung cancer. We have the data to show it, but the question is, what’s the why? And the why is not frequently as easy as “Well, because I’m Black.”
We usually are fascinated, and we push lots of dollars towards really getting down to the molecular and submolecular levels of science, and molecular therapies. We’re always asking the additional why question.
But it turns out, when it comes to issues around population health, health delivery, implementation sciences, sometimes we don’t have the same patience, and particularly when it comes to health systems—and they’re dealing with collecting data, using data in appropriate ways, and making sure that all people have the access to the same care, in the same manner—those are actually also important questions. I’m not sure that we do that as well as we could.
OB: I’m also concerned that in medicine we are letting the perception of biological differences amongst the races—keep in mind, I think race is a sociopolitical categorization.
Area of geographic origin, there’s some biological differences there, but when we started talking about area of geographic origin, when we talk about Black people or people of dark skin, there’s well over 100 of those in Africa.
When we talk about areas of geographic origin amongst Caucasians, there’s more than 600 of those that have been identified in Europe and Eurasia. So, I think race is just too big a thing, and it’s really sociopolitical.
But getting back to my original point, I think we worry too much about racial differences in biology and not the true racial issue, which is getting all people adequate care.
RW: Recognizing that structure matters. And as we get adequate care, we also have to account for the structures that are sometimes even creating and contributing to the disease.
I am so happy that what you just said is that when we now talk about ancestry and we talk about African Americans with ancestry, we don’t recognize that everyone has ancestry.
If you trace some of this back to ancestral markers as opposed to just Black—for example, I thought that the work from Lisa Newman and Melissa Davis were actually important about women.
African Americans who were considered African Americans with triple-negative breast cancer. What they said about having more Eastern African descent or ancestry as opposed to Western African ancestry, there was a difference in outcome.
I actually think that goes beyond just people who were “Black,” which is a social construct to fit everyone, whether you’re Asian, Latino, or Caucasian.
An awakening and an awareness of that idea will be helpful as we try to come up with new therapies as opposed to using the shorthand Black and using the shorthand white for everything.
As we progress, those tags hopefully will become relics of the past.
OB: I wanted to talk about this later on in this talk, but since you brought up two extraordinary scientists... I personally am very pleased with the young folks coming up and their absolutely amazing contributions in this area to help us understand it better.
I’m especially fond of Lisa because I’ve been able to watch her grow over the last 25 to 30 years.
But what do you think senior leaders in health care, Black and white, need to be doing in this area? And tell me a little about what you think about the next generation of health care. Then I’m going to go back to what I was originally going to talk to you about or ask you about.
RW: Thank you for asking that question. I think that I’m going to make a parallel to what’s happening in law enforcement to medicine.
The first is the reality that more diverse voices at the table do matter, and ultimately, understanding that you’re picking the best and the brightest to be able to fill the jobs matters.
I think in law enforcement, it’s becoming clearer that what happened in Memphis, and the speed in which it happened—of getting the information out, of being able to deal with things—in large part, was because there was a different type of leader at the helm.
I would say that when I think about Massey Cancer Center and I think about the next generation of leaders, having the first woman of color now be the cancer center director at University of New Mexico doesn’t guarantee, but allows for a different voice to be at the table and different perspectives.
Humility, caring about the patient, and awareness that we all have these prejudices—we need to overcome them. I think that’s the solution to giving good high-quality care
Otis Brawley
It doesn’t mean that, as I told someone as a cancer center director here at VCU Massey, that just because I’m an African American doesn’t mean that all I’m focused on is African Americans.
As if I were the governor of the state, I have multiple constituencies to be concerned about, including white rural, and people who are well off.
My number one goal is to make sure that anybody with cancer certainly benefits from having our cancer center. But I don’t want to pretend that I come in different than some of my colleagues—from not just being an African American, but from a class perspective—with also understanding some of the structural issues that are contributing to disease.
Maybe in a more nuanced way than others.
Having said that, I think our future is bright. You have folks like John Carpten. You have, like I said, Melissa Davis, Lisa Newman, Brian Rivers, Chanita Hughes-Halbert. There is a host of new and up-and-coming researchers in the basic science, translational, clinical, and data field.
And I’m feeling very comfortable that if you look at cancer center directors in 1971 and you now look at 2023, we have women, we have people from underrepresented groups.
And as a result of that, I think we’ve made over the last several years significant strides in progress in “normalizing” the concept that while people may look different on the outside, there are some core things that we all have to do to deliver the best, the highest care, and our research matters for all of them.
OB: Getting back to where I was going to go first, tell me what you think of this: I worry about people who mean well, but don’t understand the entire situation. We have people who are pro-life, but once the child is born, they don’t care about the child’s upbringing, and education, and grooming, and health care.
You might say, in so being pro-life, they should say they’re “pro-birth,” because they’re not really pro-life, because life is taking care of the person after they’re born.
We have people who are nowadays going to very resource-poor hospitals that take care of a lot of people who are from socioeconomically deprived backgrounds, and they’re pushing programs on these resource-poor programs to try to help poor people.
For example, I was director of the cancer center at Grady Hospital, which is an inner-city, county facility. It’s a safety net hospital. It’s common now for people to try to go and get places like Grady to do lung cancer screening.
Lung cancer screening is wonderful. It saves lives. It does have some drawbacks that we don’t talk about enough, but it does save lives.
I like to point out the study that shows that it works was done in 30 of the finest hospitals in the country. It showed that for every 5.4 lives you save, you kill one person; so, benefits and harms.
But if you go down to Grady, and you start doing lung cancer screening, you make the line for those four CT scanners at Grady longer. You actually create disparities and worsen the care of people who need that CT scanner by making the line longer.
And by the way, the current director of the cancer center at Grady constantly has folks saying, “Why aren’t you doing lung cancer screening?” I just told you why. That’s just one example. We have a medical system that is segregated by socioeconomics, and separate cannot be equal. Separate is not equal.
People who are poor who go to these resource-strapped hospitals and clinics do not get the same quality of care as people who go to the places that accept the private insurances. And I’ve been preaching, you can respond to that.
RW: Your point is well made. 85% of the people don’t wind up in NCI-designated cancer centers and academic centers. They’re being treated in the community setting.
And yet, these folks in the community setting frequently are under-resourced. As you just said, we’re layering on top what they should be doing without layering on additional resources for them to get the job done. Dr. Brawley, you know this.
We first met when I was in Chicago at University of Illinois where I had a dual role of being a cancer center director there. I was director of the University of Illinois Cancer Center, but I was also the associate vice president at that time of community-based practice, which is a fancy title.
I ran the network of Federally Qualified Health Centers, which came to be as part of the act on making sure in the 1960s that people had access to care, poor people in particular. There would be well-intentioned scientists who wanted to do studies within the FQHC settings.
When they would come in, well-meaning, well-intentioned, they would never-ever come with additional resources that wouldn’t disrupt my team.
Once I remember famously saying to someone, “I love your research. I’m sure it’s going to be of value, but the reality is the number one job of my team in this FQHC, at this site is to see patients that are, by the way, lined up in the hallway to be seen. If they’re not seen here, then they wind up in the emergency room. So, if you want to do research, what additional resources are you going to bring to the table so that you don’t disrupt?”
I would actually say the same thing is true with most of our community hospitals. The ACCC is doing a wonderful job in shedding light that there are community hospitals that have resources, but there are other community hospitals that do not. We are fooling ourselves that we’re giving the same care. It’s not even separate and equal. It’s separate and unequal in most cases.
And we have to do a better job from policy perspectives on how the academic centers can partner better, how there will be better policies, how we can get more resources that are used appropriately to do those things that we know can help.
But until we bring resources to the table, I think it’s unrealistic to have our community hospitals be mini, if you will, NCI-designated cancer centers. It just will not work.
OB: We’ve covered a couple of issues here, Dr. Winn. There’s a bunch of folks who are out there and who say we must get more minorities in the clinical trials.
But they ignore the fact that 97% of Americans don’t go on the cancer trials, by the way, Black or white, 95% plus don’t. And those who don’t go on the trials, frequently, if they’re a minority, or poor white as well, don’t get adequate care.
They push clinical trials, but forget about the fact that a lot of folks aren’t getting adequate care. They push screening programs that are of low yield.
Yes, they do save lives, but they’re of low yield when you look at the community as a whole. They tie up resources like CT scanners and pathologists and so forth and bog down the system and make care for other diseases worse. And we got to think about all of these things.
And then, of course, there’s the folks who are heavily into the biological differences amongst the races, which we’ve just talked about. All of these things to me—and I’m linking this to Tyre Nichols—those -isms that caused those police officers to beat that poor man.
We have our own version of those -isms in medicine, a lot of them—a lot of them that lead to biases that lead to misapplication of science.
Keep in mind, sometimes it’s the willing who do the wrong thing even; I mean good people who want to do the right thing, and they just don’t understand.
RW: Or, it’s attributed to Mark Twain. “It ain’t what you don’t know that gets you into trouble. It’s what you know for sure that just ain’t so.”
And frequently, we go in without the flexibility, the curiosity, the humility of being able to set these programs up. For example, I still think that there is a role for not only screening, but prevention—the resources and the voices needed to garner the resources.
We need to employ not just prevention in well-to-do places, but prevention all over is a good strategy.
Second, we do have to think about the reality that there are a bunch of -isms. We have -isms for “This person won’t go on trial. Well, because they’re Black.”
We have the -ism of, “Well, even if we screen this person, what are we going to do,” without actually saying, “If you’re going to screen, you ought to actually have the arc of screening that leads to the diagnostic screen, then to the therapy, and the treatment already in place.”
These -isms are frequently in the way of why—as we know through history and literature—people are offered certain therapies and others are not.
Not because they could or couldn’t, but because they were never asked.
And by the way, at the end of the day, in addition to race issues, there are class issues.
And what’s not being talked about with Tyre as well, is not only his African American status, but class.
When you start looking at both of those intersectionalities of being Black in America as well as being poor, whether you’re talking about the hollers of Beattyville, Kentucky, or you’re talking about the South Side of Chicago, there are more similarities in those two groups. And yet, we fail frequently to speak about that.
When it comes to policing—the data’s there to vet it out—African Americans certainly got pulled over more and treated more harshly, whether they have money or don’t have money.
But I guarantee that if you’re Black and you’re poor, that becomes an issue. The structural issues that we go in with our pre-biases, that extends well beyond law enforcement into what we do also in medicine.
The way to fight it is to first be cognizant of it, and then be able to hopefully develop these conversations where policies will help us get through this that don’t exist today. Hopefully with some thoughtfulness and some action, we can do better.
OB: Wrapping this up, you said a word that I just want to reemphasize, and that was humility.
I should point out, I don’t think you have to be Black to take care of Blacks.
As a matter of fact, my uncle, who was not a very educated man, but had some experiences in the health care system, used to always talk about how Jewish doctors understood him and took care of him well, because they cared.
He would talk about the history of what Jews have gone through in terms of persecution and so forth as one of the reasons why they cared, understood, and felt what the patient in front of him felt.
Now, that may be a little racist in itself, what he was doing, but I actually do think the point about humility, the point about caring about people, or just giving a damn, and the awareness that you might have some of these prejudices, and we all have them, is really important.
Humility, caring about the patient, and awareness that we all have these prejudices—we need to overcome them. I think that’s the solution to giving good high-quality care, no matter if you are a physician, a surgeon, a nurse, a medical student, a respiratory therapist, or a lab tech. Humility, caring about the patient, and then having awareness that we have these problems and trying to tamp them down.
I’m going to let you have the last word, Dr. Winn.
RW: Thank you for that. I’ll add only one thing, and that is having diversity at the table. I think when you can see your neighbor, whether they look like you or they don’t, and you can see their humanity, we tend to be much better off than when we don’t see each other’s humanity.
The only way to do that is by being mindful that access, not only to care, but access to becoming physicians, access to becoming directors of cancer centers, access to becoming deans, all that put together matter. We can disagree, but if you’re my neighbor, and I see you, and I get to hear you and your unique different viewpoints, I’m more likely to hear you and your differences. I’m more likely to hear a counter-argument from someone who I know and have humility and respect for than from someone who I don’t.
Michelle Obama said it better: “We have to do a better job of getting to know our neighbors, even those that we don’t actually agree with.”
We need to hear counterpoints so that we may actually be able to sharpen even our own ideals about why we think the way we do.
So, thank you for the opportunity, Dr. Brawley, to talk about this. The last word for me is not only may Tyre rest in peace, but hopefully, this déjà vu will be different. We will, hopefully, at a minimum, come out of this with some reasonable, practical laws that should have been put in place after George Floyd’s death.
We can only hope that it not only stimulates a change in law, but we can learn that there are also areas in health care that we need to work on so we can be our best selves for the patients we serve.
OB: Thank you. This has been a discussion about health care and lessons for health care from the unfortunate events of the last several weeks involving the beating of Tyre Nichols.
I want to thank Dr. Robert Winn, the director of the Massey Cancer Center at Virginia Commonwealth University and professor in the medical school at Virginia Commonwealth University, and February’s guest editor of The Cancer Letter.
I’m Otis Brawley. I’m the Bloomberg Distinguished Professor of Oncology and Epidemiology at Johns Hopkins, and I am the co-founder of the Cancer History Project. Thank you.
[post_title] => Otis Brawley & Robert Winn discuss the killing of Tyre Nichols and the power dynamics in policing—and health care [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_1 [to_ping] => [pinged] => [post_modified] => 2023-02-03 18:07:26 [post_modified_gmt] => 2023-02-03 22:07:26 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52415 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52415 ) [1] => Array ( [ID] => 52416 [post_author] => 2768 [post_date] => 2023-02-03 11:54:22 [post_date_gmt] => 2023-02-03 15:54:22 [post_content] =>Ten miles south of my job at the Chao Family Comprehensive Cancer Center, an Asian American elder opened fire and killed one person at the Taiwanese Presbyterian Church in Laguna Woods, CA.
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Six miles south of my home, an Asian American elder killed 11 people at a dance studio in Monterey Park, CA.
Four hundred miles north, another Asian American elder killed seven farmworkers in Half Moon Bay, CA.
As we continue to mourn for the victims and their families, the Asian American community is coping with a new reality. An elder that looks like our father, uncle, with a similar immigrant background, has killed several people that also look like us. Three recent mass shootings have forced the Asian American community to contend with the trauma and pain inflicted on us.
I intentionally use the racial term Asian American and not Asian. Owning guns and gun violence is not Asian, it is very much American.
This violence is not new, but it looks different. Many of us are still grappling from the increase in anti-Asian hate since the start of COVID-19—often with Chinese-looking elders as victims. For some Asian Americans, peace of mind now means owning a gun. Since 2021, there has been a 30% increase in gun ownership among Asian Americans.
I intentionally use the racial term Asian American and not Asian. Owning guns and gun violence is not Asian, it is very much American.
Our Office of Community Outreach and Engagement (COE) at the University of California, Irvine Chao Family Comprehensive Cancer Center (UCI CFCCC) has been on the frontlines of confronting extremism and anti-Asian hate. In June 2020, we coordinated a series of webinars in multiple Asian and Pacific Islander languages about anti-Asian hate, mortality and incidence of COVID-19, prevention, and access to care and services.
In May 2020, our COE office received a grant from Bristol Myers Squibb Foundation that helped form our coalition, Love our Vulnerable and Elderly (LOVE). Together with our community partners, we purchased, packaged, and delivered thousands of bags of rice, noodles, toilet paper, and Asian pantry items for cancer patients and isolated Asian American and Pacific Islander elders.
Like many COE offices, we pivoted and conducted cancer outreach and education by telephone in Korean, Mandarin, and Vietnamese. HIPAA-compliant virtual tools like Zoom are neither available in Asian languages nor user-friendly for Asian elders.
The community members we called expressed fear about going to the clinic for their routine cancer screening, and we observed that they were scared to leave the house.
In 2021, we helped set up several community COVID-19 vaccine clinics in the Asian American and Pacific Islander communities, particularly for elders and their caregivers. I asked a group of Cantonese elders in line for their vaccine why they each had a walking cane as they seemed able to walk without one. They said in case they were attacked on their walk over to the clinic, they would hit the perpetrator with their cane. My elderly mother has a cane for the same reasons as well.
Despite these disparities and the documented lack of funding to Asian American researchers, Asian Americans are still not considered an underrepresented population by the NCI and NIH. Currently, the NIH policy states that Blacks or African Americans, Hispanics or Latinos, American Indians or Alaska Natives, Native Hawaiians, and other Pacific Islanders are underrepresented.
I asked a group of Cantonese elders in line for their vaccine why they each had a walking cane as they seemed able to walk without one. They said in case they were attacked on their walk over to the clinic, they would hit the perpetrator with their cane. My own elderly mother also does the same.
Individuals from other racial and ethnic groups need to “demonstrate convincingly to be underrepresented by the grantee institution” (https://diversity.nih.gov/about-us/population-underrepresented). This places the burden on us, as Asian American cancer researchers, to continually educate and convince NCI, our own institutions, and journals that Asian Americans experience racial violence and health disparities.
How many more Asian Americans must die from gun violence and cancer for us to be heard, seen, and cared for?
天下太平 was written on a sign at the site of the Monterey Park mass shooting. It is a Chinese proverb that means “peace under the celestial sky.” Monterey Park is a city built by first-generation Cantonese and Toisan (Chinese dialects) immigrants who came to this country to flee war, starvation, and poverty. It is one of the few cities in the country with a majority of Asian Americans, 65%. It is a city built on grit, resilience, and perseverance.
As a child, I would regularly go with my parents to buy groceries in Monterey Park. The Chinese market we went to is still there and is next door to the Star Dance Studio, where the mass shooting occurred. As I recently walked the dance studio parking lot, I saw the outpouring of care, rows of flowers, incense, cards, and messages of love, peace, and safe journeys to the next life.
Three days after the Half Moon Bay mass shooting, I attended a statewide Asian American, Native Hawaiian, and Pacific Islander Health Equity Summit. Many of us in the room have been in the frontlines, translating and interpreting health information in 20+ languages, patient navigation, hate crime assistance, advocacy, civic engagement, mental health services, social services, the list goes on.
I didn’t need to explain myself in this room, we all collectively felt the edges and rawness of the moment. We have done so much, needed to do more, and find space to grieve and heal together.
“What does love look like in a time of hate?”
Celeste Ng answered this question in a 2021 article in The New York Times, showing a series of photos and stories about Asian Americans. I reread this article and it reminded me about the power we have as a community.
This moment will not define us, but instead our photos and stories of resilience, community, care, and LOVE will.
Cancer Treatment Centers of America will “fully transition” to City of Hope’s brand, giving the southern California-based cancer care health system a national footprint.
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As the widely recognized CTCA brand ceases to exist, its former outposts will become City of Hope Atlanta, City of Hope Chicago, and City of Hope Phoenix, City of Hope officials announced Feb. 1.
The name change will be communicated in a national advertising campaign, officials said.
“City of Hope undertook a thoughtful, collaborative integration period to ensure a smooth transition across operational, clinical, and administrative workstreams,” a City of Hope spokesperson said to The Cancer Letter. “As we form a national identity and create ‘One City of Hope’ across our clinical network, we see a number of benefits as we raise our profile with influential audiences, advocates and patients.
“Thanks to many recent accolades, including our top 10 ranking in US News & World Report Best Hospitals for Cancer list, City of Hope is becoming better known with national audiences. Patients coming to these CTCA locations are specifically interested in how CTCA doctors collaborate with City of Hope.”
City of Hope completed the $390 million acquisition of CTCA a year ago, with the goal of combining their strengths to create a national cancer research and treatment system with locations across the country. CTCA has been a for-profit, family-owned business that owned cancer centers in Chicago, Atlanta, and Phoenix (The Cancer Letter, Jan. 21, 2022).
“We saw that Cancer Treatment Centers of America is one of the most trusted brands among health care consumers in the country,” Robert Stone, president and CEO of City of Hope, said at the time to The Cancer Letter. “The CTCA acquisition will now mean we have care locations across four states and 41 care locations, with approximately 575 physicians and 11,000 employees. The combined organization will serve approximately 115,000 patients every year.”
After decades of aggressive marketing, CTCA has become one of the most recognized brands in the U.S. For example, the YouGov America survey of most popular hospitals continues to rank CTCA second, below Mayo Clinic and above Johns Hopkins Health.
We also continue to strengthen our leadership and operating model as we transform into a fully integrated, national system.
“City of Hope continues to invest in its clinical network, recruit new physicians and enhance the capabilities of all locations in its cancer research and treatment system,” the cancer center’s spokesperson said earlier this week. “We are in strong financial standing and building for the future with this announcement. For example, we’ve brought our world-renowned expertise in bone marrow and blood stem cell transplants and CAR T-cell therapy to our Phoenix and Chicago locations.
“To further support clinical consistency and the highest quality of care throughout the system, we are also scheduled to complete our Epic implementation across these locations in 2023.”
CTCA locations now function as nonprofit organizations, and City of Hope is implementing clinical and quality policies across all locations, with joint quality reviews and tumor boards.
To ensure a consistent patient experience throughout the national system, City of Hope has hired Kevin Manemann as chief integration officer for the clinical enterprise. Manemann joins City of Hope after 20 years with Providence St. Joseph Health, where he most recently served as the chief executive of the southern division and was responsible for 17 hospitals, a physician organization, surgery centers, immediate care centers, community care agencies, and a health plan with 700,000 lives covered.
“City of Hope is adding more talent across its clinical network. Since the acquisition, a number of cancer experts and outstanding clinicians have joined our Atlanta, Chicago, and Phoenix locations to be part of our transformation into a national cancer research and treatment system,” the City of Hope spokesperson said. “We want to fully realize the value of, and build on, the skills and expertise of our people to benefit patients and fulfill our strategic vision.
“We also continue to strengthen our leadership and operating model as we transform into a fully integrated, national system. Kevin joins Jo Ann Escasa-Haigh, who recently joined City of Hope as its chief business officer, and Phil Okala, who joined City of Hope in September 2022 as system president.”
City of Hope has grown over the past few years with the expansion of its clinical network in Southern California, the addition of the Translational Genomics Research Institute, the launch of its employer cancer care benefits offering AccessHope, the acquisition of CTCA and the opening of a new cancer center in Orange County.
“We’ve made substantial progress with the integration of CTCA and have served more patients than anticipated in the first year, with 134,000 patients treated by our shared organization in 2022,” the spokesperson said.
[post_title] => Exercising owner’s prerogative, City of Hope retires the Cancer Treatment Centers of America brand [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_3 [to_ping] => [pinged] => [post_modified] => 2023-02-03 18:01:11 [post_modified_gmt] => 2023-02-03 22:01:11 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52417 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52417 ) [3] => Array ( [ID] => 52418 [post_author] => 2768 [post_date] => 2023-02-03 11:52:26 [post_date_gmt] => 2023-02-03 15:52:26 [post_content] =>The National Cancer Institute defines precision medicine in cancer as a strategy that “uses specific information about a person’s tumor to help make a diagnosis, plan treatment, find out how well treatment is working, or make a prognosis.”1
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A quick perusal of the table of contents from the latest issues of any major oncology journal or a survey of ongoing cooperative group trials will underscore that a large proportion of clinical and basic investigation is focused on how oncologists might leverage precision medicine to improve treatment outcomes for patients.
Less often recognized, but critically important nonetheless, is the concept of physical precision. This is particularly relevant in radiation oncology, where the balance between delivering adequate tumoricidal doses of radiation must be balanced with the risk of damaging adjacent normal structures.
Built into this calculus is the inherent physical uncertainty with radiation therapy, particularly external beam radiotherapy. That is, the location and shape of the target, as well as the nearby normal tissues, can vary not only from day to day, but also during the delivery of a single dose of radiation. Because of these uncertainties, radiation oncologists often prescribe radiation not just to the intended clinical target, but rather to that target plus a margin around it. This total volume constitutes the “planning target volume” (PTV), and often overlaps with nearby organs. Within the context of radiation oncology, enhanced physical precision might lead to reducing the overall PTV, therefore potentially leading to reduced toxicity.
This concept is extremely relevant for patients with prostate cancer specifically. Approximately 288,000 American men will be diagnosed with prostate cancer in 2023.2 Thankfully, the vast majority will be diagnosed with clinically localized disease, and many men can be cured with either surgery or radiotherapy. Given the high cure rate and long life-expectancy following treatment for prostate cancer, quality of life (QOL) often remains paramount in decision making.3,4
When treating the prostate with radiotherapy, the major potential QOL declines are in the genitourinary (GU), gastrointestinal (GI), and sexual domains.5 With the exception of the prostatic urethra, the organs-at-risk with respect to GU, GI, and sexual toxicity after radiotherapy are presumed to be structures adjacent to the prostate (i.e., the bladder, rectum, and neurovascular structures). The PTV margin needed to ensure adequate dosing of the prostate will necessitate that portions of these organs-at-risk are included in the target volume.
Arguably, the importance of precision and accuracy becomes greater as the dose of radiation delivered per treatment session increases. Importantly, prostate cancer appears to be more sensitive than most cancers to the dose of radiation delivered per day, suggesting that condensing the radiation into a few high dose sessions might yield results that are, at minimum, equivalent to longer courses of radiation.6
Emerging clinical trial data have cemented stereotactic body radiotherapy (SBRT), a form of radiation in which ≤5 daily doses are delivered with high precision in generally five or fewer treatments, as a curative option for most men with localized prostate cancer.7 As suggested by the term “stereotactic”, SBRT relies on advanced imaging and treatment delivery techniques to ensure precise delivery of radiation to the PTV while minimizing dose outside the PTV.
What, precisely, contributes to the PTV?
The major sources of uncertainty that are considered when deciding on the required PTV margin are uncertainties related to prostate delineation and prostate motion.8 The prostate is best delineated using magnetic resonance imaging (MRI), but due to concerns related to electromagnetic interference, most linear accelerators (LINACs) delivering radiotherapy have only been equipped with computed-tomography (CT) or X-ray based imaging tools.
As such, prostate MRIs are often fused to CT-based imaging to help design the target for radiation, which imbues a small uncertainty into the prostate. To account for motion between individual doses of radiation, implanted markers are placed inside the prostate to provide a proxy for prostate position. Typically, these are radiopaque metallic markers that can be visualized on CT or X-ray. Motion during treatment can be managed either by shifting treatment based on frequent X-ray images focused on the fiducials, or limiting the treatment time as much as possible.
Having performed CT-guided SBRT for over a decade, we were able to query our institutional database to develop a margin formulation for the PTV that was based not just on theory, but on our own empirical observations.9 We found that a 3 mm margin around the prostate would be necessary to account for motion alone, and another 1 mm should be added for other residual uncertainties—this would translate a 4 mm total margin around the prostate.
By using volumetric arc therapy on an advanced CT-guided LINAC, an SBRT plan could be delivered in roughly 3-4 minutes. This margin formulation is well within the parameters of the standard-of-care margins used internationally. For instance, the large PACE-B and NRG-005 randomized trials recommend margins of 5 mm in all directions, with an option to narrow these to 3 mm in the posterior dimension.
Recently, two MRI-guided LINACs have become commercially available: the ViewRay MRIdian and the Elekta Unity. Both units have solved the aforementioned long-standing technical dilemma of integrating an MRI with a LINAC. MRI-guidance offers several theoretical advantages in the context of prostate radiotherapy.10
First, MRI-guided LINACs can monitor prostate motion directly, rather than relying on fiducial markers that are proxies for prostatic motion and require an invasive procedure to place.
Second, and perhaps most importantly, the frequency of monitoring is extremely high, and a “cine” MRI can be used to “gate” treatments on prostatic position. For instance, the MRIdian obtains an MRI four times per second. If a set percentage of the prostate target (say, 10%) is outside of a preset margin around the prostate (say, 3 mm), the radiation beam can be held automatically.
Third, the improved soft tissue contrast from an on-board MRI also improved the accuracy of alignment prior to radiation.
Fourth, residual errors resulting from fusing an MRI to a CT scan for accurate target delineation can be minimized if the on-board MRI is used directly for target delineation.
Given these enhanced imaging capabilities, we estimated that we could now use a PTV margin of only 2 mm – essentially 1 mm for motion, and 1 mm for residual uncertainty. But a salient question remained: would reducing these margins actually help patients?
While it may seem self-evident that radiating a smaller volume of tissues will lead to lower toxicity, not all apparently “obvious” truths can withstand the rigors of randomized testing. Indeed, oncologic literature is rife with examples where perfectly rational treatment strategies were ultimately found not to improve outcomes when tested in a randomized trial.10
When faced with a more complicated and costly intervention—even one with very limited risks, such as MRI-guided radiotherapy—the benefits to patients should be rigorously evaluated to assess the true value that is being achieved.2 Thus, the importance of randomized trials to rigorously evaluate whether a theoretical advantage can be actually realized in the clinic cannot be overstated.
Indeed, it is because of the importance of randomization that we designed the MIRAGE trial shortly after acquiring the MRIdian linear accelerator in the fourth quarter of 2019. The trial was designed to be a pragmatic, single-center randomized trial with a clearly defined early endpoint: acute moderate grade or greater genitourinary (GU) toxicity (i.e., grade ≥2) as measured on the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 scale. This endpoint was chosen because it could be scored within 90 days of treating a patient and because it occurs frequently enough that a single center trial could be reasonably powered to identify a change in its incidence.
Reliable estimates of the rate of grade ≥2 GU toxicity after CT-guided SBRT and MRI-guided SBRT were taken from the PACE-B trial1 (29.2%) and a single arm phase II trial from Amsterdam University Medical Centers29 (19%). Because the MRI-guided SBRT plan in Amsterdam trial used a 3 mm margin, we estimated that our toxicity rate might be lower, at 15%. The MIRAGE trial was thus designed to detect a 14% reduction in acute grade ≥2 GU from 29% to 15%. To detect this difference with 83.7% power with a one-sided, two sample Z-test at a 0.025 significance level would require 300 patients.
However, the target dosing we sought to employ in MIRAGE was more aggressive than had been used in either of the previous studies. Specifically, we planned to deliver 40 Gy to the entire PTV, while the PACE-B trial delivered 36.25 Gy to the PTV and the Amsterdam trial delivered 36.25 Gy to the PTV but reduced the dose around the urethra to 32.5 Gy. This escalated dose was chosen because we anticipated that we would treat patients with more aggressive disease than those treated on these prior studies, and our own research as well as work from others have suggested a dose-response with respect to biochemical control after prostate SBRT.11,12
Importantly, however, all trials of dose-escalation in prostate radiation oncology have identified that an increase in dose also leads to an increase in toxicity.13 Notably, toxicity following radiation depends not only on the total dose of radiation, but also the dose per fraction. As such, the effective difference for the bladder, urethra, and rectum between the MIRAGE target dose and the earlier doses ranges anywhere from 8 Gy to 14 Gy depending on assumptions about tissue radiosensitivity.
We know from multiple studies of radiation dose escalation that such large increases in dose will lead to increased toxicity.14 Therefore, we pre-specified that after 100 patients were eligible for analysis, we would perform an interim “futility” analysis to assess conditional power and re-estimate sample size. As it so happened, by the time 100 patients were eligible for this analysis (which occurred 90 days after the 100th patient was treated), 156 patients had already been enrolled and treated.
The analysis found that acute grade ≥2 GU toxicity was significantly reduced in men receiving MRI-guided SBRT versus CT-guided SBRT (22.4% vs. 47.1%, vs P = .01).15 It was concluded that 154 patients would be needed to have a conditional power of 89% to detect the hypothesized difference in toxicity, and therefore the trial was closed to accrual early.
While trials are always vulnerable to the vicissitudes of fate and fortune, it is important to underscore in this case that the trial was closed because the effect size observed on interim analysis (24.7% absolute difference) exceeded the hypothesized difference (14% absolute difference), suggesting enough patients had already been enrolled to detect the superiority of MRI-guided SBRT.
Of the 156 patients who received prostate SBRT on the MIRAGE trial, only 19% had favorable intermediate risk disease, supporting our decision to treat to a higher dose on this trial. With regards to other relevant variables, 44% had placement of a rectal hydrogel spacer, 24% received nodal radiation, 26% received a simultaneous integrated boost to the dominant lesion, and 68% received hormonal therapy, with no significant differences between arms for any of these parameters.
Prior to randomization, we stratified based on baseline International Prostate Symptom Score (IPSS) and prostate gland size, which are both known to impact post-treatment toxicity; these were thus also balanced between arms.
Before discussing the results of the final analysis, it is particularly important to discuss blinding. Ideally, a randomized trial would be double-blind to limit biases. In this case, the interventions being investigated were different enough (one requiring an invasive procedure to place fiducial markers, the other requiring multiple MRIs) that patient blinding would be impractical.
For similar reasons, the treating physician could not be blinded, as the treating physician would need to order, manage, and coordinate different procedures and different scans for patients on the different arms. In theory, an independent physician reviewer could have been used to adjudicate toxicity. However, this would also have been impractical for two major reasons.
First, the treatments are significantly different enough that an off-hand comment by the patient would immediately lead to unintentional unblinding (e.g., a comment about “being treated inside a tube” [only done on the MRI-guided SBRT arm] or about “having seeds put in my prostate” [referring to fiducial markers, only placed in the CT-guided SBRT arm]).
Second, the trial was designed and launched at the height of the COVID-19 pandemic. In fact, two patients (one on each arm) died of COVID-19-related complications before the 90-day window to assess toxicity was complete, leading to a final effective sample size of 154 patients. Thus, axillary patient-physician encounters for purely independent-adjudication in the context of clinical research would have been highly impractical, if even ethically permissible.
To attempt to mitigate this limitation, as well as the limitation of whether physician-scored toxicity is a relevant endpoint for patients, we also collected patient-reported outcomes. Specifically, all patients received IPSS and Expanded Prostate Cancer Index Composite-26 (EPIC-26) questionnaires at 1- and 3-months post-treatment. These were used to evaluate changes in urinary and bowel quality of life.
The primary endpoint results of the trial, published inJAMA Oncology on Jan. 12, 2023,6 therefore included not only physician-scored GU (and gastrointestinal, or GI) toxicity, but also IPSS and EPIC-26 changes. Overall, the primary endpoint of the trial was met and rates of grade ≥2 GU toxic effects were significantly lower with MRI vs CT guidance (24.4% vs. 43.4%, P = .01). Additionally, rates of grade ≥2 toxic effects were also significantly lower with MRI guidance vs CT guidance (0.0% vs 10.5%, P = .003).
After SBRT, urinary incontinence subdomain scores decreased significantly more with CT guidance vs MRI guidance at 1 month (11.3-point vs 6.2-point decrement; P = .01), but were no longer significantly different at 3 months). The percentage of patients with a clinically relevant increase in IPSS (>15 points) was significantly greater with CT guidance at 1 month (19.4% vs 6.8%, P = .01), but not at 3 months (1.4% vs 4.1%, P = .30).
Magnetic resonance imaging guidance vs CT guidance also resulted in a significantly smaller decrement in EPIC-26 bowel domain subscores at 1 month (4.1-point vs 18.2-point decrement, P < .001) but not at 3 months. A significantly larger percentage of patients treated with CT guidance experienced a clinically relevant (≥12-point) decrement in EPIC-26 bowel domain scores (50.0% vs 25.0%, P = .001).
Finally, a numerically greater decrement in EPIC-26 sexual domain scores was seen with CT guidance vs MRI guidance at 3 months (13.2-point vs 3-point decrement, P = .04; analysis restricted to men who did not receive androgen-deprivation therapy). Though the arms of the trial were well-balanced with respect to relevant variables like hydrogel use, nodal radiation, simultaneous integrated boost, and gland size, we did perform a post-hoc exploratory analysis to see whether the benefit of MRI-guidance still persisted after adjusting for these points. The results of this analysis suggested that trial arm remained associated with a 60% reduction in odds of grade ≥2 GU toxicity.
An open question, and one for which we encourage study, is whether alternative imaging and treatment delivery platforms could facilitate a similar reduction in PTV margins. A major challenge in designing and executing the MIRAGE trial was the need to randomize between two significantly different treatment platforms – a simple margin reduction trial conducted with both arms using the same technology would be significantly more straightforward to execute, in theory. However, to our knowledge, no such trial has been launched. We are actively exploring other aspects of treatment delivery, such as the frequency of beam-holds necessary due to prostate motion, which might be important factors with respect toxicity. We will also be reporting data on long-term side effects and oncologic outcomes.
In summary, the MIRAGE trial primary analysis demonstrates that the use of MRI-guidance in the context of prostate SBRT leads to reduced physician-scored and patient-reported urinary and bowel toxicity. This advantage is attributable to the fact that MRI-guidance allows enhanced physical precision, with a 2 mm PTV margin around the prostate being targeted rather than a standard-of-care 4 mm PTV margin.
Based on the positive results of the MIRAGE trial, we have changed our practice to offering MRI-guided SBRT as our preferred institutional standard of care. Patients who have implanted metallic objects or shrapnel, are extremely claustrophobic, or are completely pacemaker-dependent are not candidates for MRI-guided SBRT and still receive CT-guided SBRT (with 4 mm margins). Patients with minor claustrophobia, or who have implanted devices that are MRI compatible, can be treated with anxiolytic medications and appropriate supervision.
Perhaps the biggest takeaway from the trial is that as we enter the era of precision medicine in oncology, our definition of precision can and should extend beyond the biological precision that comes from a deeper understanding of cancer physiology. The physical precision of improved radiation planning and delivery devices, such as MRI-guided radiotherapy platforms, can also translate into meaningful benefits for patients. Indeed, the MIRAGE trial has shown us that the benefits of physical precision are not illusory, but tangible.
Amar Kishan is an associate professor of radiation and urology at the University of California, Los Angeles. He also serves as the Vice Chair of Clinical and Translational Research within the department of radiation oncology. He is responsible for running a clinical service focused on treating patients with genitourinary malignancies, as well as leading a clinical and translational research program designed to improve post-treatment quality of life and treatment efficacy for patients with prostate cancer. He has received grant funding from the Department of Defense, the American Society for Radiation Oncology, the Prostate Cancer Foundation, the National Institutes of Health, and Kure-It. He has also received research support from ViewRay Inc. (outside the scope of the MIRAGE trial), as well as honoraria from ViewRay Inc.
References
Richard Silvera is working to build trust between doctors Bronx communities that have a heavy burden of anal cancer.
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“There are higher rates of anal cancer among people with HIV. There are higher rates of anal cancer and poor anal cancer outcomes among Black populations as well,” Silvera, assistant professor of infectious disease at Icahn School of Medicine at Mount Sinai, said to The Cancer Letter. “Both of these communities have a lot of well-earned medical distrust, and that needs to be overcome, and actively overcome, by the people providing care. Or else, no matter how good the technology is, no one’s going to be there to receive it.”
Silvera, a recipient of a grant from the Robert A. Winn Diversity in Clinical Trials Award Program established in 2020 by the Bristol Myers Squibb Foundation, spoke with Winn, director and Lipman Chair in Oncology at VCU Massey, and senior associate dean for cancer innovation and professor of pulmonary disease and critical care medicine at VCU School of Medicine, about his work in the program.
For the third year, Winn is guest editor of The Cancer Letter during Black History Month. His interview with Silvera is the first of this year’s series documenting the the impact of Black doctors in the field this February.
A video of their conversation appears here.
What’s the first step to overcoming the distrust that Silvera speaks of?
“We need to have more diverse research professionals, not just physicians, but research assistants, aides, nurses, all these people need to be members of the community they’re caring for,” he said. “It gives you a common language to speak with your patients—yes, you can try to connect with people who come from different backgrounds than you do, but having a common experience is really a quick entry into a shared language of that person, a shared experience.”
With grant funds from the Winn Diversity in Clinical Trials Award Program, Silvera said he hopes to bridge advocacy and research.
“This program is nurturing my research career to get those first steps taken to be an established independent researcher,” he said. “Advocacy can be built into research questions if you ask the question correctly. I really would like to be a fully-formed, independent researcher, so I can have the ability to form those questions and ask those questions.”
Diversity in the workforce is key to advocating for patients in underserved communities—like patients with anal cancer who Dr. Silvera is treating in the Bronx.
“It also lets you bring the concerns of that community into the planning room, into the research protocol development room,” he said. “It lets you consider, what do these people care about? And can we represent those cares when we design this trial, when we recruit for this trial, when we think about how the trial is going to be set up? There are some things that are just really hard to know by reading a paper.
“You have to really live that life, and we need to have people with those experiences in those rooms when we develop these trials. Diversity of the workforce is also really, really important.”
Silvera lives in East Harlem, where the Young Lords—a group of revolutionary Afro-Latino activists—were once active.
“I live across the street from where their headquarters used to be, so I walk by it every day,” he said. “By commitment to their community, and by being innovative and being dedicated to what they were doing, they were able to accomplish so much—but they started with so little.
“And this reminds me, as a junior researcher, I feel like I have no funding. Well, you don’t need money. You just really have to try. Trying is more than half the effort,” he said. “While I may not have a multimillion-dollar research budget, I can accomplish something with what I do have.”
Robert A. Winn: We’re going to talk today about the Bristol Myers Squibb Foundation Program. To start off, how and why did you get into medicine?
Richard Silvera: My path to medicine was a little bit circuitous. I initially started my academic work as an English major.
I studied literature with this idea in the back of my head. I wanted to do medicine, but I didn’t have a real plan of how to do that. And then I finished my undergraduate training and didn’t really know what I wanted to do. I actually ended up working in clinical research—and I fell in love with clinical research.
I really wedded my love of stories, and taking individual stories, and finding the essential truth of those stories, and weaving them together into a larger truth that we applied to a whole population.
It let me find a way with that English major mindset to make medicine into a story that could be used to help multiple people. I found my way back to medicine that way, particularly the care of people with HIV.
That’s how I got back into medicine.
That’s a wonderful path. Now explain more about the HIV-and-cancer link.
RS: I got into the care of people with HIV, because I was really drawn to the complexity of their care. Not just the medical complexity, but the social complexity, the political complexity that all patients with that illness had that surrounding their care.
The complexities really attracted me, because of their interaction with the doctor-patient relationship. And then, as part of that, I always looked at medicine through a primary care lens. I really wanted to take care of people, become a part of their lives, and take care of them over a long period of time.
And as I got into HIV primary care, I learned more and more about the toll of anal cancer among people with HIV. It was affecting people with HIV regardless of the kind of life they were living or regardless of their exposures in the past.
There was a much higher rate of anal cancer in people with HIV. And it was so common that it was something that really needed to be addressed in primary care.
That really made the light go off in my head, because I loved research. I also loved primary care, and this wedded all the things I was interested in medicine. We’re caring for people with HIV, doing so in a primary care setting, and trying to do preventive medicine and keep people living longer.
I’m glad you said that. It’s interesting to me how you weave that complexity of the people in the communities and the various issues that are happening within them, and bring them closer to having the therapies that would be able to impact their lives favorably.
I was thinking about how the treatment has changed for anal cancers recently. Can you comment on the evolution, from when you started to your treatment right now? And what’s your hope in the future when it comes to anal cancer?
RS: There have been great innovations in treatments for anal cancers, but I think that ideally what I’m focusing on is prevention.
An ounce of prevention is really worth a pound of cure. While there’ve been great strides in treatment modalities, having less invasive treatments with better outcomes, I would rather prevent that cancer from happening in the first place if I could. That’s really the goal of my research right now.
We could have strides in anal cancer screening throughout even my career, because there’s a lot of new innovation happening in that field.
Since I’ve entered into this world of research, we are working to perfect our ways of screening for anal pre-cancers so we can then remove those anal pre-cancers before they become anal cancers. That approach has been validated recently in the ANCHOR trial. It’s a large, multi-site trial, which showed that removing pre-cancers effectively prevented anal cancer from developing.
That’s great, that’s wonderful. That tells us we have a way of preventing these cancers from happening before we have to worry about treatment outcomes. But we have to find those pre-cancers before we can treat them. And that is what my research is looking at, new ways to find those anal pre-cancers.
As you start thinking about how to find them, it actually depends on two areas: the technology and the ability to find them. It also depends on the community and their level of trust to be participants. How are you addressing those issues?
RS: We can have the most amazing technology in the world, but if people don’t trust you enough to come to your clinic to receive that technology, it’s pointless.
Building an infrastructure of research in these communities is going to be a step towards building their trust because it takes generations to build trust, and you can’t just do it in one afternoon.
Particularly in the populations that have a heavier burden of anal cancer, there’s a lot of very justified systemic distrust of the medical establishment. There are higher rates of anal cancer among people with HIV.
There are higher rates of anal cancer and poor anal cancer outcomes among Black populations as well.
Both of these communities have a lot of well-earned medical distrust, and that needs to be overcome, and actively overcome, by the people providing care. Or else, no matter how good the technology is, no one’s going to be there to receive it. There are many ways we can address this.
First of all—who is doing this research?
We need to have more diverse research professionals, not just physicians, but research assistants, aides, nurses, all these people need to be members of the community they’re caring for.
It gives you a common language to speak with your patients—yes, you can try to connect with people who come from different backgrounds than you do, but having a common experience is really a quick entry into a shared language of that person, a shared experience. It really is hard to duplicate otherwise.
It also lets you bring the concerns of that community into the planning room, into the research protocol development room. It lets you consider, what do these people care about? And can we represent those cares when we design this trial, when we recruit for this trial, when we think about how the trial is going to be set up? There are some things that are just really hard to know by reading a paper.
You have to really live that life, and we need to have people with those experiences in those rooms when we develop these trials.
Diversity of the workforce is also really, really important.
Until recently, there hasn’t been an emphasis on outreach and engagement for the community, even in social determinants of health. Can you tell me how that’s evolved for you?
I know you’re part of The Robert A. Winn Diversity in Clinical Trials Award Program established in 2020 by the Bristol Myers Squibb Foundation as part of its commitment to health equity, inclusion and diversity.
Can you talk about your participation and where you think trials are now and where development can ultimately go?
RS: So I’ve been fortunate enough to be one of the first recipients of The Robert A. Winn Diversity in Clinical Trials Award Program.
But I’d argue that I am honored, and I am actually benefiting from your getting out there and doing it.
RS: Good on both sides, for everyone. I’m part of the initial cohort, and this program does two really, really important things for the success of these studies.
First, from my perspective as a young investigator trying to learn the ropes of this world, a lot of what we need to know to be a successful researcher—how to develop a research trail, how to inform a research question, how to write a manuscript appropriately—all of those things are not necessarily taught in classrooms.
They’re a shadow curriculum that you have to learn from the people around you. People from diverse backgrounds may not have access to those shadow curriculums and those networks.
I think creating an infrastructure to get that information to people who may or may not have access to it, depending on their environment or their connections, is really important. It gives them entry into the places where they can do really important research.
Secondly, the focus on actual, tangible skills and thinking critically about how to engage diverse communities, how to build clinical trust, how to move clinical trials into non-traditional settings to try to meet patients where they are—not just have that be a line somewhere on a slide that they are just going to breeze over.
Having it be worthy of discussion and focus is a really important skill to do research on people who are often excluded from research because research structures are not built to cater to them.
Learning how to leverage those resources you might get, as a junior researcher, to engage these communities that so often are overlooked, I think is going to be really important for getting more people involved in research on both sides, both as the patient as well as as the investigator.
You said something that really resonated with me—it is building trust.
As you’re thinking about the importance of it in various communities—African American communities, Latino communities, LGBTQ communities—how can you, as an individual, help to build more trust? How can it then transition from the Winn Awards Program, so that our institutions become more trustworthy?
RS: If I had the answer to this question, I would already be on a world tour. But I think I have some ideas of how to work towards this.
The first step is just showing up and being present. And being present, not just when it’s helpful to you, but being present consistently.
In the world of research, where funding may be temporary, that can be really tough to accomplish. I think that’s one thing that the Winn Program is addressing—having it be a continuous stream of researchers from these communities, interested in these communities, being present in these communities.
We can create a continuous research presence in these communities that will then be a step towards proving that you’re not just there to exploit that community for a particular research question and then taking your pick of the data and leaving.
Instead, you’re there to actually invest in long-term solution building for these communities. Not just being one person’s random research question, but to have it be structured where there’s continued investment, continued presence, multiple research questions.
Building an infrastructure of research in these communities is going to be a step towards building their trust, because it takes generations to build trust, and you can’t just do it in one afternoon.
Also, having a commitment from institutions to make that investment, I think is going to be really important.
Changing gears just a bit, talking about history during Black History Month. If you could pick an historical figure who continues to inspire you to this day, who would that be and why?
RS: History is tough, because, in many ways, I think the experience of being a minority in America, you get divorced from your own history.
It has a disconnect where it doesn’t really feel like it’s your own. But I would say that—I’ll pick something a little controversial—this is something I learned about more recently.
The proximity to my experiences is actually really important. I did my residency training in the Bronx, here in New York.
As part of that, we learned a lot about the history of the Bronx and the history of healthcare in New York City. Before doing my training, I had never heard of the Young Lords, who were a group of revolutionary, Afro-Latino activists in East Harlem.
They’re very inspired by the Black Panthers, doing similar revolutionary work. But what they were able to accomplish for their community is really inspiring.
I live across the street from where their headquarters used to be, so I walk by it every day. To think that they really came from nothing. But by commitment to their community, and by being innovative and being dedicated to what they were doing, they were able to accomplish so much—but they started with so little.
And this reminds me, as a junior researcher, I feel like I have no funding. Well, you don’t need money. You just really have to try. Trying is more than half the effort.
I can take inspiration from them. They were able to build so much and have such a lasting impact, but they really started with so little. I’m lucky. While I may not have a multimillion dollar research budget, I can accomplish something with what I do have. And I find I can draw inspiration from that.
You bring up a good point that sometimes when we go back, we don’t really fully recognize the impact of some of the community activators and the community activists.
RS: Having people from those communities, being interested in people within those communities for the good of those communities, was something that happened in the ‘50s and ‘60s that manifests itself differently today.
Why can’t we get health and science closer and more open to our communities?
In that context, what is the long-term impact that you’re trying to achieve with both your research, and after completing this program? What does success look like for you?
RS: Participating in the Winn Awards Program and doing this research is going to let me engage with success in a few different ways.
This program is nurturing my research career to get those first steps taken to be an established independent researcher.
None of this work happens in isolation, but I don’t want to just be one researcher on an island by myself. I want to be part of a community of researchers doing this work.
To be able to do this, to address these research questions, to let me be the one who designs the questions, to let me be the one who asks the questions, and to be the one who decides how those questions will be asked.
Advocacy can be built into research questions if you ask the question correctly. I really would like to be a fully-formed, independent researcher, so I can have the ability to form those questions and ask those questions.
That’s one form of success. And I think that the Winn Awards Program has well-poised me to be able to do that by letting me get my feet off the ground and start moving in the direction to gather data, get some research accomplished, and to show that these issues are worthwhile.
Part of success is also building a legacy. Not just having it be an island, but having an influence on the next generation. One thing that attracted me to the Winn Awards Program was that there was a mentoring aspect of it.
Being able to work with medical students has created a network where there will be, two or three years from now, a new round of researchers who have already gotten their taste for this. They will then come in to be able to take over these studies, be my junior researcher, and be the fellow I work with on these next steps.
That is also a mark of success to not just be one person doing something, but be the beginning of a community of people doing something. This Winn Awards Program is a step towards doing that.
None of this work happens in isolation, but I don’t want to just be one researcher on an island by myself. I want to be part of a community of researchers doing this work.
There has already been some great collaboration with other people I’ve met in this program and the network that we’ve been able to develop.
It’s wonderful just being part of a community of researchers who care about these issues, focus on these issues, and make these issues a fundamental part of the research questions that we ask.
I love that. Really, it’s a fantastic response. The Robert A. Winn Diversity in Clinical Trials Award Program is unique in that it’s pioneering, bringing together the design implementation and bringing in awareness of the community. How does it feel to be part of a program in which you’re pioneering, or trying to blaze new paths?
RS: It really feels like coming home in many ways. That first day when we met all the other members—other people who were part of the program, other people who really were passionate about the same things that you were passionate about and cared about, and were upset or energized about the same things that they’d seen in the news or read. Like you’d found your people.
And so, while this is pioneering, it also felt really comfortable and felt right. It’s been surprisingly easy to be able to do this.
It’s been great to find those other researchers out there working in the same world with an interest in advocacy and equity. It has felt really comforting and great. It’s been really easy to be a pioneer in that regard.
I’m going to come through and give you a Zoom hug, man.
Last question:
What would you like to tell future applicants of the Bristol Myers Squibb Foundation’s Winn Awards Program? If you had any advice for them, what would that be?
RS: The biggest advice I would have is to bring your whole self to your research.
Don’t feel like you have to cut yourself away, or cut parts of your personality, or parts of your history, or parts of your interests that you think are not what a researcher is supposed to be, or what a researcher’s supposed to look like, or kinds of questions a researcher’s supposed to care about.
Don’t try to edit those out of yourself when you present yourself professionally.
I would encourage you to bring your whole self, bring all of your experiences, bring your whole history, bring all the things you’ve experienced, both positive and negative, the questions that you ask, to the applications that you present.
We may have been subconsciously told that those things aren’t valuable, but they are valuable in certain places. They’re valuable here.
And I think that this is a place where I would encourage you to bring your whole experience and your whole self and the questions you ask. They want all of you, not just the paper writing part of you.
They want everything. I would encourage you to just bring your whole self to the application.
That’s part of this mission we have with the program, to not only move and pursue academic excellence, but to also move towards academic relevance. It’s relevant to us, and it’s relevant to the communities we serve.
I appreciate that you took the time to talk with us today and reflect. Not just on the program, but you reflected on really what it is that we’re all trying to do, particularly during this Black History month. We are making sure that our communities are impacted not only today, but every day.
Is there anything else that’s on your mind?
RS: Just a happy Black History Month to everyone, and I hope that we can continue moving upward and forward. Other than that, just keep plugging away every day. No matter how dark things look, things are getting better slowly. Keep working at it.
Keep working at it. Exactly.
Thank you for taking time and keep up the good fight and keep blazing the trails. Great work. I am so proud and honored to be able to know that I know you as you are starting to do this work through the Winn Awards Program. You started some good things, and there’s some even greater things for you to accomplish. It will get done. Of that, I’m absolutely confident. I appreciate you.
RS: Thank you, Dr. Winn. I appreciate you, as well.
[post_title] => Richard Silvera is bridging advocacy and research through the Robert A. Winn Diversity in Clinical Trials Award Program [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_5 [to_ping] => [pinged] => [post_modified] => 2023-02-03 18:03:48 [post_modified_gmt] => 2023-02-03 22:03:48 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52419 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52419 ) [5] => Array ( [ID] => 52420 [post_author] => 2768 [post_date] => 2023-02-03 11:50:30 [post_date_gmt] => 2023-02-03 15:50:30 [post_content] =>Nearly three years ago, Robert A. Winn and Otis Brawley provided their unforgettable personal perspectives on the murder of George Floyd by Minneapolis police.
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Both recounted harrowing instances where structural bias in policing nearly cost them their lives.
Winn is director and Lipman Chair in Oncology at VCU Massey Cancer Center and senior associate dean for cancer innovation, professor of pulmonary disease and critical care medicine at VCU School of Medicine, and guest editor of The Cancer Letter for the duration of Black History Month. Brawley is the Bloomberg Distinguished Professor of Oncology and Epidemiology at Johns Hopkins University, and co-editor of the Cancer History Project.
This week, after the murder of Tyre Nichols by police in Memphis, Winn and Brawley engaged in a conversation about how systemic racism is present in law enforcement and health care. The story appears here.
As we see evidence of another killing by police, it’s important to revisit the editorials Winn and Brawley penned in 2020.
I am almost certain that no other director of an NCI-designated cancer center can claim the distinction of having had a gun pulled on them by police.
I‘ve had that experience not once, but twice.
I struggled a great deal in deciding whether to put something together this week in response to the senseless killing of Mr. George Floyd. His untimely death has stirred up a number of complex issues, which I thought I had wrestled under control.
If there is anything we’ve learned from the COVID-19 crisis, it’s that the boundaries between cancer and non-cancer can be porous. And health disparities come in bunches, bouquets of injustice. And, as a pulmonologist, I hear Floyd’s last words—“I can’t breathe.” Don’t tell me that chokeholds, literal and figurative, are anything other than a public health issue.
The past ten days have seen an outpouring of emotions as American society, devastated by the tragic murder of George Floyd by four Minneapolis police officers, plunges into a crisis of conscience.
Floyd’s death may be a pivotal point in America, similar to the televised beating of peaceful civil rights marchers by police on the Edmund Pettus Bridge in 1965. It has led to a number of protests and, unfortunately, some violence, including an attack by federal law enforcement as they beat and pepper-sprayed peaceful protesters in front of the White House.
The use of force against demonstrators in front of the White House is particularly ironic, considering that this entire series of events stems from an act of police brutality.
The police brutality is the tip of the iceberg. The fact is, it is the most obvious and dangerous aspect of systemic racism. There are a number of social injustices that collectively make blacks feel that their lives are not valued, and these issues are not being addressed by American society as a whole. Many Americans simply do not care, or aren’t aware.
If they are not aware, they are not listening.
Those who simply say, ‘I am not a racist’ are complicit in perpetrating the inequity. It is time for reflection, it is time for awareness, it is time for listening, it is time for empathy and caring.
Otis W. Brawley
A panel convened by the Cancer History Project for Black History Month started with a discussion of mentorship, and concluded with a big underlying concept—justice.
Edith Mitchell came a long way from growing up on a Tennessee farm, to becoming a brigadier general and serving on the President’s Cancer Panel.
“It was making a plan, having a plan, and all of us had similar type plans that we needed to leave the farm—yes I grew up on a farm—and get out of town,” Mitchell, member of the President’s Cancer Panel, clinical professor of medicine and medical oncology, director of the Center to Eliminate Cancer Disparities, and associate director of diversity affairs at Sidney Kimmel Cancer Center at Jefferson, Thomas Jefferson University. “Yes, you have success, but look back and pull somebody behind you, pull them up.”
Harold Freeman had big plans after he finished his residency at Memorial Sloan Kettering Cancer Center in 1968. He planned to cut cancer out of Harlem.
“I’m ready to do it. I’m skilled. I know how to cut cancer out. I want to cut it out of Harlem. I can’t do that. I can’t cut it out. It won’t yield. It won’t yield to the surgeon’s knife. It won’t yield to what we call the Bard-Parker, which was the name of the surgeon’s knife. Cancer wouldn’t yield,” Freeman said to The Cancer Letter in an interview with Robert A. Winn, director of VCU Massey Cancer Center, and John Stewart, founding director of LSU Health/LCMC Health Cancer Center. “Then I get to the reality, I can’t cut it out. Why? Because the people were coming in too late with cancer for me to be able to cut it out.”
Freeman made his career out of asking why it was that his patients, who were poor and Black, sought treatment too late. As president of the American Cancer Society in 1988-89, he published a study, “Cancer in the socioeconomically disadvantaged,” and made an unprecedented conclusion—“that the principal reason that Black people were dying from cancer was because they were poor.”
“It was a socioeconomic invasion that was deeper than the cancer invasion in the community,” Freeman said.
“In many ways, I would say he became a father to me. I didn’t anticipate having such a close personal relationship, but that’s what occurred, as I lost my own dad at that time,” said Wayne A.I. Frederick, president of Howard University, remembering his mentor, LaSalle Leffall, Jr.
“Dr. Leffall, in many ways, I think, went above and beyond just being a mentor. That shaped me in terms of my own experience being a father and my relationships with my 17-year-old son and my 15-year-old daughter. So much of this comes from that same attention to detail he put into my relationship.”
This column features the latest posts to the Cancer History Project by our growing list of contributors.
The Cancer History Project is a free, web-based, collaborative resource intended to mark the 50th anniversary of the National Cancer Act and designed to continue in perpetuity. The objective is to assemble a robust collection of historical documents and make them freely available.
Access to the Cancer History Project is open to the public at CancerHistoryProject.com. You can also follow us on Twitter at @CancerHistProj, or follow our podcast.
Is your institution a contributor to the Cancer History Project? Eligible institutions include cancer centers, advocacy groups, professional societies, pharmaceutical companies, and key organizations in oncology.
To apply to become a contributor, please contact admin@cancerhistoryproject.com.
The Mark Foundation for Cancer Research has given two new Drug Discovery Awards.
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Launched in 2020, The Mark Foundation Drug Discovery Awards support high-risk, high-reward research and bridge the substantial gap in advancing promising academic discoveries to novel therapies. Based on key milestones along the continuum from target identification to preclinical development and initial regulatory filings, up to $25M is expected to be awarded over the next 5 years.
The two latest Mark Foundation Drug Discovery projects selected for more than $2 million in funding are:
Identifying small molecule inhibitors of SLC38A2/SNAT2 to treat pancreatic cancer
A group led by Alec Kimmelman at New York University Grossman School of Medicine and Seth Parker at the University of British Columbia is working to identify molecules that inhibit the amino acid transporter SLC38A2.
Kimmelman, Parker, and colleagues recently identified that pancreatic cancer cells express and depend on SLC38A2 for tumor initiation and growth. Now, they will carry out a screening campaign against SLC38A2 to identify inhibitors of the transporter. The hits from this screen represent the first step toward future medicinal chemistry with the goal of entering clinical development for the treatment of pancreatic cancer, the foundation said.
Developing CDK11B inhibitors as a novel anti-cancer strategy
A group led by Jason Sheltzer at Yale University and Jane Endicott at Newcastle University will expand upon Sheltzer’s recent discovery of a selective CDK11 inhibitor to further understand how targeting this enzyme could be used to treat cancer. CDK11 is a member of the cyclin-dependent kinase family, a group of enzymes important for cell cycle progression that are critical for tumor proliferation in many cancer types.
While they represent attractive targets for therapeutics, these enzymes have traditionally been difficult to inhibit in a selective manner, making drug development challenging. Sheltzer and his team previously determined that a compound which was thought to inhibit a different enzyme, was in fact inhibiting CDK11, making it one of the first selective CDK11 inhibitors described.
Now, by using this insight, this project will expand our understanding of CDK11 biology and provide a crucial foundation for future work directed at generating a first-in-class CDK11 inhibitor for patient testing.
“Most companies engaged in cancer drug discovery research are looking for projects that fit within narrowly defined criteria that align with their internal portfolio strategies and risk tolerance,” Ryan Schoenfeld, CEO of The Mark Foundation, said in a statement. “The Mark Foundation Drug Discovery Award program is a way for us to step in and fill a gap in academia that’s not being met by today’s drug companies nor by the traditional governmental funding programs. We have the flexibility to take risks earlier on promising, innovative ideas and approach cancer research funding on a broader scale.”
“In addition to providing funding, The Mark Foundation scientific team provides scientific and technical guidance to our grantees so that we can accelerate their ideas into the clinic,” Schoenfeld said. “We take advantage of our experience working with contract research organizations and other industry partners to provide grantees access to state-of-the-art drug discovery and development capabilities, as well as access to expert advice from our extensive network of experienced and highly accomplished industry advisors and consultants.”
Since the launch of the Drug Discovery Award program in 2020, more than $15 million has been awarded for drug discovery projects.
[post_title] => Teams led by Alec Kimmelman & Seth Parker, Jason Sheltzer & Jane Endicott receive $2M from The Mark Foundation [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_7a [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:26:01 [post_modified_gmt] => 2023-02-03 19:26:01 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52421 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52421 ) [7] => Array ( [ID] => 52422 [post_author] => 2768 [post_date] => 2023-02-03 11:44:34 [post_date_gmt] => 2023-02-03 15:44:34 [post_content] =>
Laleh Amiri-Kordestani was named acting associate director for cardio-oncology in the FDA Oncology Center of Excellence. She will also continue her role as the division director for the Division of Oncology 1.
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Amiri-Kordestani joined FDA in 2012 as a clinical reviewer in the Division of Oncology Products 1. She served as the breast cancer team leader before serving as associate division director. She has served as the division director of DO1 since 2019, overseeing drug development for breast cancers, genitourinary cancers, gynecologic malignancies, and supportive care.
Amiri-Kordestani has had an active interest in cardio-oncology throughout her career at FDA and has represented FDA on numerous projects, external working groups, and publications focused on cardio-oncology. Cardio-oncology is an interdisciplinary field of medicine that focuses on the prevention, detection, monitoring, and treatment of cardiovascular disease occurring as a side effect of cancer therapy.
Amiri-Kordestani also has served as OCE’s scientific liaison for cardio-oncology. In this role, she has actively engaged with the international cardio-oncology community, chairing public cardio-oncology workshops.
In her new role in the OCE, Amiri-Kordestani will work closely with external stakeholders and other OCE programs and FDA Centers and Offices to provide direction, coordination, and oversight for scientific and policy efforts related to cardio-oncology.
[post_title] => Laleh Amiri-Kordestani named acting associate director for cardio-oncology at FDA OCE [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_7b [to_ping] => [pinged] => [post_modified] => 2023-07-10 14:39:37 [post_modified_gmt] => 2023-07-10 18:39:37 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52422 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52422 ) [8] => Array ( [ID] => 52423 [post_author] => 2768 [post_date] => 2023-02-03 11:43:37 [post_date_gmt] => 2023-02-03 15:43:37 [post_content] =>
Sven Davisson was named associate director of administration at Louisiana Cancer Research Center.
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Since 2015, Davisson has served as chief administrative officer for the LCRC. Founded in 2002, the LCRC is a partnership bringing together the cancer research efforts of Louisiana State University Health New Orleans, Tulane University School of Medicine, Xavier University of Louisiana, and Ochsner Health.
Prior to joining the LCRC, Davisson spent 14 years at The Jackson Laboratory, an NCI-designated cancer center in Bar Harbor, ME, where he assisted with the submission of two P30 Cancer Center Support Grant competitive renewals. His final position at JAX was as senior director of sponsored programs, overseeing the research portfolio and support staff of JAX’s two primary research campuses in Bar Harbor and West Hartford, CT.
In his expanded role at LCRC, Davisson will support the director in ensuring that all cancer center activities meet NCI Cancer Center Support Grant guidelines in order to achieve and maintain a National Cancer Institute cancer center designation.
[post_title] => Sven Davisson named associate director of administration at Louisiana Cancer Research Center [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_7c [to_ping] => [pinged] => [post_modified] => 2023-07-10 14:39:34 [post_modified_gmt] => 2023-07-10 18:39:34 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52423 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52423 ) [9] => Array ( [ID] => 52424 [post_author] => 2768 [post_date] => 2023-02-03 11:42:38 [post_date_gmt] => 2023-02-03 15:42:38 [post_content] =>Moffitt Cancer Center, Weill Cornell Medicine, and the University of North Carolina School of Medicine received a $3.5 million, five-year grant from NCI to improve screening and preventative treatment of cervical cancer for women living with HIV in low-resource countries.
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Women living with HIV are more vulnerable to cervical cancer, especially in the low- and middle-income countries. Eighty-five percent of cervical cancer deaths occur in these settings, where high quality preventative services are often lacking.
As part of the HIV/Cervical Cancer Prevention ‘CASCADE’ Clinical Trials Network, investigators from the three institutions will develop trials to be conducted at clinical sites in Kenya, Uganda, and Botswana that were selected by NCI to be in the CASCADE Network. Cervical cancer is a preventable disease, but women in these areas of the world often present with advanced cancer that causes hardship and dramatically raises the likelihood of death.
“We have the tools already to make an immediate impact for these women. The challenge is how do we deploy them optimally? How do we sustain these services and engage women to accept them?” Timothy Wilkin, multiple principal investigator for CASCADE, professor of medicine in the Division of Infectious Diseases at Weill Cornell Medicine and an infectious disease specialist at NewYork-Presbyterian/Weill Cornell Medical Center, said in a statement.
To address these goals, Anna R. Giuliano, MPI of CASCADE, and founding director of Moffitt’s Center for Immunization and Infection Research in Cancer is collaborating with Wilkin and Carla Chibwesha, an associate professor of obstetrics and gynecology in the University of North Carolina’s Division of Global Women’s Health and the Lineberger Comprehensive Cancer Center, who is based in Johannesburg, South Africa.
“Since 2018, the World Health Organization has had elimination of cervical cancer as a global goal. The strategy to achieve this goal was approved by the World Health Assembly, a strategy that clearly highlights the importance of cervical cancer screening and treatment,” Giuliano said in a statement. “As each community has unique challenges to implementing screening and treatment, adaptation and innovation is required to assure that we can meet the ambitious goal that has been set. Hence the importance of continued research.”
The investigators are working with providers at study sites to identify challenges to screening patients for precancerous changes to the cervix, and to treating those patients found to be at risk.
[post_title] => Moffitt, Weill Cornell & UNC collaborate to improve HIV-related cancer care in low-resource countries [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_7d [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:26:16 [post_modified_gmt] => 2023-02-03 19:26:16 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52424 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52424 ) [10] => Array ( [ID] => 52425 [post_author] => 2768 [post_date] => 2023-02-03 11:41:41 [post_date_gmt] => 2023-02-03 15:41:41 [post_content] =>The International Cardio-Oncology Society has awarded University Hospitals Harrington Heart & Vascular Institute a Center of Excellence designation in recognition of its ongoing support of cancer patients facing heart issues. This Gold Status certification, the society’s highest designation, recognizes the institute for its commitment to cardiology services for cancer patients in whom life-saving treatments may cause cardiac problems.
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The innovative cardio-oncology program, founded in 2013, is a collaboration between UH Harrington Heart & Vascular Institute and UH Seidman Cancer Center.
The society awards this Gold Status Center of Excellence designation to programs with excellence in quality of care, standards of care, quality metrics, and program improvements. The designation is intended to not only acknowledge exceptional programs in cardio-oncology patient care, but to also award programs that contribute to local, regional, state, and national level education in cardio-oncology.
While cancer therapy has improved dramatically over the past several decades with a notable increase in survival rates, some cancer treatments such as chemotherapy and radiation can potentially cause heart problems. The development of unexpected heart issues can cause interruption and even discontinuation of cancer treatments. Therefore, keeping the heart healthy during cancer treatment is essential to delivering optimal patient care and achieving good outcomes. Cardio-oncologists are devoted to screening, monitoring, and treating any heart problem before, during, or after cancer therapy.
“Cancer treatments often result in significant physiologic changes to cells in the heart muscle, and patients have better health outcomes when their heart is monitored,” Zeeshan Hussain, advanced heart failure, heart transplantation, and cardio-oncology specialist with UH Harrington Heart & Vascular Institute, said in a statement. “Our cardio-oncologists are familiar with the medications, radiation treatments, and immunotherapies oncology patients receive—and how they may adversely affect their hearts, so we can proactively address any damage.”
The cardio-oncology program at UH provides comprehensive cardiovascular care for all cancer patients; more than 1,500 patients annually and between 60 to 100 new patients every month.
The program strives to provide high quality and accessible care in a variety of ways including same day appointment capability and an average time to appointment of less than one week. The program also features dedicated cardio-oncology nurse navigators to streamline patient triage and improve care coordination. It features three satellite clinics in the community in addition to the main location at UH Cleveland Medical Center.
[post_title] => University Hospitals awarded Gold Status certification for cardiovascular care of cancer patients [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_7e [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:26:19 [post_modified_gmt] => 2023-02-03 19:26:19 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52425 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52425 ) [11] => Array ( [ID] => 52427 [post_author] => 2768 [post_date] => 2023-02-03 11:30:45 [post_date_gmt] => 2023-02-03 15:30:45 [post_content] =>The V Foundation has established a grant program aimed at increasing female representation and female-led innovation in cancer research.
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A Grant of Her Own: The Women Scientists Innovation Award for Cancer Research is one of a few gender-specific grant programs designed to address gender inequities in cancer research funding. Awards will be given to outstanding female researchers at different stages in their careers.
The V Foundation will fund at least $8 million in grants.
The V Foundation will be awarding two separate grants as part of the inaugural award:
“By providing self-identified female investigators the necessary resources to begin and sustain impactful research and careers, A Grant of Her Own: The Women Scientists Innovation Award for Cancer Research will help address systemic gender disparities which have long existed and were further widened during the pandemic. These factors have kept women from fully contributing to the field of cancer research,” Susanna F. Greer, chief scientific officer of the V Foundation, said in a statement.
Compared to their male counterparts, women are paid less in comparable academic positions, receive lower startup funds for research with women scientists at some major institutes receiving 38% less in funding, and receive fewer awards from NIH grant programs at all points in their careers.
A survey of researchers found that female scientists and those with young children experienced a substantial decline in time devoted to research due to COVID-19. Given that time is of the essence in research, especially for scientists in the early stages of their careers, the losses experienced during the pandemic could have lasting effects on the number of women represented in cancer research.
“These female-specific grants expand on the V Foundation’s work to level the playing field by providing funds to support the research of all-star women scientists and those of color whose contributions are desperately needed to help us accelerate Victory Over Cancer,” Shane Jacobson, CEO of the V Foundation, said in a statement. “This year marks the 30th anniversary of the V Foundation, and from day one we have always been committed to female-led cancer research.”
V Foundation grants are awarded to researchers nominated by NCI-designated Cancer Centers and other exceptional research institutions and then selected by the Foundation’s Scientific Advisory Board.
Institutional nominations for A Grant of Her Own: The Women Scientists Innovation Award for Cancer Research must be submitted to the V Foundation by Feb. 15. Candidate applications are due to the Foundation on March 16.
[post_title] => The V Foundation establishes $8M grant program to increase female representation in cancer research [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_8 [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:19:39 [post_modified_gmt] => 2023-02-03 19:19:39 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52427 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52427 ) [12] => Array ( [ID] => 52428 [post_author] => 2768 [post_date] => 2023-02-03 11:25:47 [post_date_gmt] => 2023-02-03 15:25:47 [post_content] =>Age-based heuristics can lead to large differences in breast cancer treatment based on small differences in chronologic age, according to a new analysis of more than 500,000 patient records.
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Radiation therapy often is given after breast-conserving surgery to help prevent a patient’s cancer from returning. While post-surgical radiation may be omitted for certain patients with early-stage breast cancer—including older patients with lower-risk disease—it remains standard-of-care for patients with a higher risk of cancer recurrence.
In this analysis of nationwide data, however, researchers found that patients in this higher-risk subset who were age 70 at the time of diagnosis “were nearly twice as likely to be passed over for radiation” as those age 69.
Patients diagnosed at age 70 were 53% less likely to be recommended post-operative radiation and 39% less likely to receive it, compared to patients age 69. There were no similar gaps between other year-over-year age groups (68 vs 69, 70 vs 71, etc.).
The study, which is published in the International Journal of Radiation Oncology•Biology•Physics, is among “the first to demonstrate an age cutoff heuristic in oncology.”
“Our findings suggest that cognitive heuristics, or ‘rules of thumb,’ play a greater role in physician decision-making than we previously realized. It’s important that we center individual patients, with the unique characteristics of their cancer, as well as their individual preferences, in treatment decisions,” Suzanne B. Evans, senior author of the study and a professor of therapeutic radiology at Yale Cancer Center, said in a statement.
“While we would expect recommendations for this treatment to decline gradually as expected lifespan shortens, there seems to be a steep cliff when a patient moves from their 60s to their 70s. In breast oncology, physicians seem to anchor on a patient entering their 70s as a signal to de-escalate care, even in situations where evidence does not support this practice,” said Wesley J. Talcott, lead author of the study and a radiation oncologist with Northwell Health. “Our study indicates that physicians should be mindful of how we factor age into treatment decisions and adopt a more nuanced approach, extending beyond defining patients as simply ’young’ or ’elderly.’”
[post_title] => Study finds large gap in breast cancer treatment recommendations for patients aged 70 vs 69 [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_9a [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:16:55 [post_modified_gmt] => 2023-02-03 19:16:55 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52428 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52428 ) [13] => Array ( [ID] => 52429 [post_author] => 2768 [post_date] => 2023-02-03 11:24:49 [post_date_gmt] => 2023-02-03 15:24:49 [post_content] =>Although widespread use of immune checkpoint inhibitors in patients with advanced lung cancer has led to meaningful improvements in survival in younger patients, older patients have not experienced similar survival benefits, new research from Yale Cancer Center shows.
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The study was published in JAMA Oncology.
“There has been a great deal of excitement in the cancer community regarding the potential of immune checkpoint inhibitors to improve survival in patients with lung cancer,” Teja Voruganti, first author of the study, said in a statement. “The initial clinical trials that led to FDA approval for these treatments suggested impressive benefits. Now that these medications have been used in clinical practice for several years, it is critical to assess the survival benefits for patients in routine clinical practice, outside of the clinical trial setting.”
Prior work by senior author Cary Gross, professor of medicine and of epidemiology (chronic diseases) at Yale, and his team, demonstrated that patients enrolled in initial clinical trials that led to FDA approval of ICIs are often younger and healthier than patients with cancer in “real world” clinical practice.
“It is unclear whether the substantial benefits that we see in pre-marketing trials of cancer therapies in fact bear out when the treatments are used in everyday practice,” Gross said. “That’s what patients care about—they’re not just asking ‘What did the initial study show?’ They want to know, ‘What happens when people like me take this treatment?’”
For the study, the authors analyzed a large database of patients with advanced-stage lung cancer who were diagnosed from 2011 (which was prior to the discovery of ICI treatments) through 2019. They found that by the end of the study period, there was no difference in the use of ICIs between younger patients (age 55 and younger) and older patients (age 75 and older); just under half of the patients in each group were receiving ICIs. But the effect on survival outcomes differed dramatically: After ICIs were approved in 2015, survival increased from 11.5 months to 16 months among younger patients in 2019. However, in older patients the median survival increased from 9.1 months to 10.2 months over the same time interval. Notably, this is below the 2-3 month threshold for clinical benefit that the American Society of Clinical Oncology has defined as a “clinically meaningful” survival improvement for lung cancer.
Not only have ICIs opened new avenues of treatment in many different cancers, but the side effects of ICIs are often more well-tolerated than traditional chemotherapy. However, Gross cautions, “Any cancer treatment has a cost. Estimates of the cost of pembrolizumab, one of the ICIs used to treat advanced lung cancer, can be over $100,000 annually. Therefore, we need to critically look at the benefits of these treatments in our patients.”
“The use of immune checkpoint inhibitors has been touted as a ‘game changer’ in the treatment of lung cancer, but our findings show that the impact on older adults may not actually be clinically meaningful,” Gross said. “This is a wake-up call for patients, researchers, and policy-makers: We need to determine which cancer treatments are effective in older patients, rather than relying on assumptions. These are life and death questions—we need evidence.”
[post_title] => Older patients left behind in progress against lung cancer, Yale study shows [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_9b [to_ping] => [pinged] => [post_modified] => 2023-02-03 18:23:55 [post_modified_gmt] => 2023-02-03 22:23:55 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52429 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52429 ) [14] => Array ( [ID] => 52431 [post_author] => 2768 [post_date] => 2023-02-03 11:23:52 [post_date_gmt] => 2023-02-03 15:23:52 [post_content] =>Results from the SWOG S1416 clinical trial showed that adding veliparib to chemotherapy can significantly extend progression-free survival times in patients with TNBC that has a “BRCA-like” phenotype.
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Veliparib belongs to a class of drugs known as PARP inhibitors, which have been shown to be effective in treating breast cancer with germline mutations in the BRCA1 or BRCA2 gene. But this is the first trial to demonstrate a PARP inhibitor benefit in breast cancer that is not BRCA1/2-mutated, but is BRCA-like based on the presence of other changes that similarly affect cells’ DNA repair abilities.
Results from the trial, which was led by researchers from SWOG Cancer Research Network, a cancer clinical trials group funded by NCI, are published in Lancet Oncology.
Priyanka Sharma, a SWOG investigator who is professor of medicine at the University of Kansas Medical Center was co-lead author on the paper with Eve Rodler, associate professor of medicine at University of California, Davis.
“SWOG S1416 is the first trial to report benefit of a PARP inhibitor in metastatic TNBC with a BRCA-like phenotype in absence of germline mutations in BRCA1 or BRCA2 genes,” Sharma said in a statement. “BRCA-like phenotype is noted in 40-50% of triple negative breast cancers, making these findings and BRCA-like classification relevant for a substantial proportion of patients with TNBC.”
The researchers randomized 320 patients with metastatic breast cancer to either cisplatin chemotherapy plus the PARP inhibitor veliparib or cisplatin chemotherapy plus a placebo. Patients had breast cancer that was either triple-negative (without estrogen or progesterone receptors or HER2 overexpression) or was HER2 negative and suspected to be associated to germline mutations in BRCA1 or BRCA2.
After patients were randomized, researchers tested their blood and tumor tissue for biomarkers and, based on the results, assigned patients to one of three distinct groups describing their type of breast cancer: BRCA-mutated, BRCA-like, or non-BRCA-like.
The S1416 team found that among patients who had BRCA-like breast cancer, those treated on the veliparib arm had statistically significantly longer median PFS than those on the placebo arm: 5.9 months versus 4.2 months. These patients had a numerically better median overall survival time and objective response rate than patients on the placebo arm, however, these differences did not achieve statistical significance.
The researchers further reported higher overall rates of grade 3/4 treatment-related adverse events on the veliparib arm than on the placebo arm (74% versus 52%), including higher rates of grade 3/4 neutropenia, anemia, and thrombocytopenia.
“While these results are not immediately practice changing, since veliparib is not FDA approved,” Sharma said, “S1416 findings open new clinical trial directions by extending the patient population that could benefit from PARPi therapy. With demonstration of efficacy in BRCA-like phenotype TNBC, S1416 results provide a basis for expanding the therapeutic role of PARP inhibitors (e.g., veliparib) beyond germline BRCA mutation in breast cancer.”
Study S1416 is supported by the NCI, led by SWOG Cancer Research Network, and conducted by the NIH-funded NCI National Clinical Trials Network. AbbVie, Inc. provided veliparib through a collaborative agreement with the NCI.
This work was funded by the NIH/NCI through grants CA180888, CA180819, CA180820, CA180821, and CA180868 and National Institute of General Medical Sciences grant P20 GM130423. Additional support was provided by AbbVie, Inc. and Myriad Genetics, Inc. The work was also supported in part by funding from a Biomarker, Imaging, & QOL Studies Funding Program award from the NCI.
[post_title] => SWOG S1416 study results show PARP inhibitor benefit in “BRCA-like” breast cancer [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_9c [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:16:54 [post_modified_gmt] => 2023-02-03 19:16:54 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52431 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52431 ) [15] => Array ( [ID] => 52433 [post_author] => 2768 [post_date] => 2023-02-03 11:22:02 [post_date_gmt] => 2023-02-03 15:22:02 [post_content] =>Data from a Yale Cancer Center-led clinical trial show improved rates of survival and reduced risk of recurrence in patients taking Tagrisso (osimertinib), a targeted therapy for non-small cell lung cancer.
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The phase III ADAURA clinical trial assessed the safety and efficacy of Tagrisso in patients with completely resected stage 1B-2A NSCLC, who were previously treated with or without adjuvant chemotherapy. The updated trial results were published in the Journal of Clinical Oncology on Jan. 31.
The new data show there are ongoing benefits for patients with NSCLC taking Tagrisso, including prolonged disease-free survival over placebo, reduced risk of local and distant metastases, and improved central nervous system DFS.
“These data demonstrate a new paradigm demonstrating the importance of using targeted therapy against epidermal growth-factor-driven tumors as early as possible in the course of a patient’s disease,” Roy S. Herbst, lead author and principal investigator of the trial, Ensign Professor of Medicine (Medical Oncology), and professor of pharmacology and deputy director at Yale Cancer Center, said in a statement. “The results have led to a new standard of care in this disease setting.”
Herbst is also chief of medical oncology and director of the Center for Thoracic Cancers at Smilow Cancer Hospital and the Yale Cancer Center, and assistant dean for translational research at Yale School of Medicine.
The trial enrolled 682 patients with stage 1B-2A NSCLC, who were randomly assigned to receive Tagrisso once daily or a placebo. Herbst and his research team found that fewer patients treated with Tagrisso experience recurrence. Data also showed that fewer patients had distant metastases when compared to the placebo group.
The study found that disease-free survival over four years was 73% for the Tagrisso group and 38% for the placebo group. Fewer patients who were randomly assigned Tagrisso had disease recurrence (27%) than those in the placebo group (60%). The data from this study demonstrate prolonged DFS and reduced local- and distant-recurrence of symptoms, supporting Tagrisso as a highly effective treatment in patients with resected EGFR-mutated stage 1B-2A NSCLC.
“This therapy was well tolerated and prevented patients from developing metastasis to distant sites such as the brain, bone, and other areas of the lungs,” Herbst said. “This has truly impacted the lives of our patients.”
The study was supported by AstraZeneca, the manufacturer of Tagrisso.
[post_title] => Yale-led trial shows significant disease-free survival in NSCLC [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_9d [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:16:59 [post_modified_gmt] => 2023-02-03 19:16:59 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52433 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52433 ) [16] => Array ( [ID] => 52434 [post_author] => 2768 [post_date] => 2023-02-03 11:21:03 [post_date_gmt] => 2023-02-03 15:21:03 [post_content] =>Merck will stop the phase III KEYNOTE-991 trial investigating Keytruda (pembrlizumab), Merck’s anti-PD-1 therapy, in combination with Xtandi (enzalutamide) and androgen deprivation therapy for the treatment of patients with metastatic, hormone-sensitive prostate cancer.
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Merck said it’s discontinuing the study based on the recommendation of an independent Data Monitoring Committee which reviewed data from a planned interim analysis. At the interim analysis, Keytruda in combination with Xtandi and ADT did not demonstrate an improvement in overall survival or radiographic progression-free survival, the trial’s dual primary endpoints, compared to placebo plus Xtandi and ADT.
The safety profile of Keytruda in this trial was consistent with that observed in previously reported studies, the company said. No new safety signals were identified; however, the combination was associated with a higher incidence of grade 3-5 adverse events and serious adverse events compared to the control arm.
Merck’s clinical development program is evaluating Keytruda as monotherapy and in combination with other anti-cancer therapies in the phase II trials KEYNOTE-199 and KEYNOTE-365 and the phase III registrational trial KEYNOTE-641. Additionally, in July 2022, Merck entered into a global development and commercialization agreement with Orion Corp. for Orion’s investigational candidate ODM-208 (MK-5684), which is currently being evaluated in a phase II clinical trial for the treatment of patients with metastatic castration-resistant prostate cancer.
[post_title] => KEYNOTE-991 trial evaluating Keytruda + Xtandi + androgen deprivation therapy in hormone-sensitive prostate cancer is stopped for futility [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_9e [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:16:57 [post_modified_gmt] => 2023-02-03 19:16:57 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52434 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52434 ) [17] => Array ( [ID] => 52435 [post_author] => 2768 [post_date] => 2023-02-03 11:20:05 [post_date_gmt] => 2023-02-03 15:20:05 [post_content] =>Patients with myelofibrosis had clinically significant improvement in disease-related symptoms, including anemia and spleen enlargement, when treated with the targeted therapy momelotinib, according to results from the international phase III MOMENTUM trial led by researchers at MD Anderson Cancer Center.
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Momelotinib is sponsored by GSK.
The findings, published in The Lancet, support the use of momelotinib—a potent ACVR1/ALK2 and JAK1/2 inhibitor—over the standard therapy danazol in treating myelofibrosis patients that were resistant, refractory, or intolerant to firstline therapy, especially symptomatic patients and those with anemia.
“Current options for managing anemia in our myelofibrosis patients provide only modest and temporary benefits, so we are excited about these findings,” study lead Srdan Verstovsek, professor of leukemia, said in a statement. “The trial results suggest that momelotinib is safe, well-tolerated, and can improve one of the most common and debilitating clinical problems for this patient population.”
Myelofibrosis is an uncommon bone marrow cancer that is part of a group of diseases known as myeloproliferative neoplasms. A hallmark of the disease is dysregulated JAK signaling, which disrupts the body’s normal production of blood cells and leads to common symptoms, including an enlarged spleen and anemia. Chronic anemia in these patients is associated with poor prognoses.
Currently approved JAK inhibitors can improve spleen responses and other disease-related symptoms, but they also can worsen anemia. In this trial, momelotinib improved anemia and reduced transfusion dependency in myelofibrosis patients previously treated with a JAK inhibitor. Momelotinib can be administered and maintained at full dose because it does not suppress bone marrow activity like other JAK inhibitors.
The MOMENTUM trial is the first randomized phase III study to evaluate a JAK1/2 and ACVR1/ALK2 inhibitor in patients with myelofibrosis and anemia. The trial was designed to compare the clinical benefits of momelotinib to danazol, a synthetic androgen currently used to treat anemia in symptomatic myelofibrosis patients.
The study enrolled 195 adult patients from 107 research sites across 21 countries. Trial participants were randomly assigned (2:1) to receive momelotinib plus placebo or danazol plus placebo. Sixty-three percent of participants were male and 37% were female. The median age of participants for the momelotinib group was 71 years and for the danazol group 72 years.
The trial’s primary endpoint was symptom reduction after 24 weeks of treatment, defined as a 50% or more reduction in Myelofibrosis Symptom Assessment Form Total Symptom Score. A significantly greater proportion of patients who received momelotinib saw benefits in their disease symptoms (25%) compared to those receiving danazol (9%).
Patients treated with momelotinib also experienced a significant reduction in their spleen size, with 25% responding after 24 weeks of therapy. Additionally, these patients required fewer blood transfusions compared to those receiving danazol.
The safety profile of momelotinib was comparable to previous clinical trials, the company said. The most common non-hematological side effects experienced by trial participants in the momelotinib group included diarrhea, nausea, weakness, and itching or irritated skin.
[post_title] => Momelotinib provides significant symptom and anemia improvements for myelofibrosis [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_9f [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:14:48 [post_modified_gmt] => 2023-02-03 19:14:48 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52435 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52435 ) [18] => Array ( [ID] => 52437 [post_author] => 2768 [post_date] => 2023-02-03 11:19:08 [post_date_gmt] => 2023-02-03 15:19:08 [post_content] =>A proof-of-concept, single-arm, phase II clinical trial, led by investigators from the Mass General Cancer Center, reported a long-lasting response among patients who responded to the combined treatment and reveals how a targeted therapy may cooperate with an immunotherapy for better results.
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The paper, published in Nature Medicine, included 37 patients with BRAF V600 mutations, which are found in about 10% of colorectal cancers. The work represents the first clinical trial combining immunotherapy and targeted therapy for this patient population.
“By combining [immunotherapy and targeted therapy], we saw a dramatic increase in patients who responded to treatment and unprecedented durability, with 18% of patients staying in the trial for a year or more,” co-corresponding author Ryan Corcoran, director of the Gastrointestinal Cancer Center Program and physician-investigator in the Mass General Cancer Center, said in a statement.
The findings suggest the potential for these two therapies to cooperate when given together, meriting further clinical investigation and pre-clinical experiments to determine the best targeted approach to increase immune reactivity against colorectal cancer with mutated BRAF, co-corresponding author Nir Hacohen, director of the MGH Center for Cancer Immunotherapy, said.
BRAF mutations occur in many kinds of cancers, most commonly in melanoma. However, response to BRAF inhibitors occurs in less than 5% of patients with colorectal cancer in which BRAF has been mutated. Immunotherapy—which has also been extremely effective against some types of cancer—has generally not worked well against colorectal cancers, with the exception of approximately 4% of cancers with an unusual feature known as microsatellite instability.
Corcoran, Hacohen, and colleagues drew inspiration for the clinical trial from observations seen in preclinical models. In these models, investigators saw signs that inhibitors targeting the MAPK pathway, including BRAF, might enhance the immune system’s response. Based on these observations, the team investigated whether combining a therapy targeting BRAF could enhance the effectiveness of the immunotherapy.
To investigate this potential cooperativity, the investigators analyzed samples collected from 71 patients before and during an earlier clinical study in which patients received BRAF targeted therapy only.
Using single-cell RNA sequencing, the team looked for molecular changes that occurred due to treatment. Based on what they saw, they initiated a clinical trial in which patients with a specific BRAF mutation known as V600E received the BRAF inhibitor Tafinlar (dabrafenib), the MEK inhibitor Mekinist (trametinib), and the immunotherapeutic drug spartalizumab.
The study met its primary endpoint, with a confirmed response rate of 24.3% of patients (compared to a response rate of only 7% in a prior trial where patients were treated with the same targeted therapies alone).
The team also saw promising results in one of the trial’s secondary endpoints: durability. When BRAF or MEK inhibitors have been given to colorectal cancer patients with BRAF mutations in the past, even among those who responded, the clinical benefit has been short-lived. But the combined treatment increased durability with a median progression-free survival of 5 months (versus 3.5 months with BRAF/MEK alone), with 57% of patients remaining on treatment for more than 6 months and 18% for more than a year.
The team also performed single-cell RNA sequencing on samples collected before and on day 15 of combined treatment. For patients who had better clinical outcomes, investigators saw an increase in tumor cell-intrinsic immune programs and more complete MAPK inhibition. This suggested that improving MAPK inhibition, perhaps by focusing on other treatment targets in the pathway, may drive a greater immune response and improve treatment overall. Other clinical trials are currently underway to further explore this.
Corcoran said that the implications of the work may go well beyond colorectal cancer.
“For almost every type of cancer, a large percentage of tumors will harbor mutations in the MAPK pathway,” he said. “Our work suggests that combining other treatments that target this pathway with an immunotherapy could lead to a cooperative, enhanced immune response that may improve outcomes for patients.”
[post_title] => Immunotherapy + targeted therapy for CRC shows positive phase II results [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_9g [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:17:06 [post_modified_gmt] => 2023-02-03 19:17:06 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52437 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52437 ) [19] => Array ( [ID] => 52436 [post_author] => 2768 [post_date] => 2023-02-03 11:18:06 [post_date_gmt] => 2023-02-03 15:18:06 [post_content] =>A study, led by Randy Vince Jr. and Daniel Spratt, demonstrated the link between cancer outcomes and social determinants of health, as opposed to only race.
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It is commonly known that Black men have worse prostate cancer outcomes than white men. This association is often described as being driven largely by race in biomedical research, as opposed to other factors such as institutional racism and SDOH.
Vince and Spratt recently published in the Journal of Clinical Oncology that less than 5% of studies throughout history acknowledge that race is a social construct, nor was there any acknowledgment that this association is potentially driven by racism and SDOH. These findings led to the present study, published by JAMA Network Open Jan. 11.
This was a meta-analysis of 47 studies of more than 1 million men with prostate cancer. Each individual study investigated the association of race with death from prostate cancer and overall survival between Black and white men. The authors developed a tool to capture the extent that SDOH were accounted for in each study.
In the studies with minimal accounting for SDOH, Black patients had significantly higher mortality than white patients.
However, Black men had significantly lower mortality from prostate disease (called prostate cancer-specific mortality—PCSM) in studies with greater accounting for SDOH. This powerful result highlights the importance of how racial disparities and health outcome research are conducted, as improper methods can lead to improper conclusions that inadvertently perpetuate racialization.
“These findings coincide with the commonly said phrase, ‘racism is the risk factor, not race,’” Vince, assistant professor of urology and director of Minority Men’s Health at University Hospitals, Case Western Reserve University School of Medicine and the lead author of the study, said in a statement. “I hope our results will motivate researchers and society to rethink how we analyze and attempt to address racial disparities. In order to address the current inequities at hand, we must acknowledge the past that has led us to this position. Any efforts to achieve equity that do not recognize and attempt to reverse the impact of various forms of racism will continue to be futile.”
“The scientific and biomedical fields have inadvertently perpetuated the notion that race, rather than racism, impacts cancer outcomes. This is especially true when it comes to the inferior outcomes for Black patients with cancer,” Spratt, senior author and Vincent K. Smith Chair in Radiation Oncology and professor in the Department of Radiation Oncology at UH Seidman Cancer Center and Case Western Reserve University, said in a statement. “Our study not only demonstrates that most health outcomes research conducted on race and prostate cancer outcomes adjusted for few if any confounding SDOH variables, but when accounting for SDOH even partially, Black men had similar to improved cancer outcomes compared to white men.
“As race is a social construct, this should not be surprising. However, medical education has been shown to rarely teach, and the biomedical scientific community to rarely report, that differences observed between Black and white patients are often driven by SDOH and racism, not race.”
[post_title] => UH Seidman study demonstrates importance of SDOH when evaluating the association of race and cancer outcomes [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_9h [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:17:10 [post_modified_gmt] => 2023-02-03 19:17:10 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52436 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52436 ) [20] => Array ( [ID] => 52439 [post_author] => 2768 [post_date] => 2023-02-03 11:17:10 [post_date_gmt] => 2023-02-03 15:17:10 [post_content] =>Phase I results from the phase I/II study of Rezlidhia (olutasidenib), an investigational, oral, small molecule inhibitor of mutant isocitrate dehydrogenase-1, suggests that Rezlidhia, with or without azacitidine, was well-tolerated and was associated with improvements in clinical efficacy endpoints in patients with mIDH1 acute myeloid leukemia.
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Rezlidhia is sponsored by Rigel Pharmaceuticals, Inc.
In the study, published in The Lancet Haematology, Rezlidhia was assessed as a monotherapy or in combination with azacitidine, in patients with mIDH1 AML or myelodysplastic syndrome.
Among patients receiving combination therapy, treatment-naïve AML patients saw a 77% overall response rate and a 54% complete response plus CR with partial hematological recovery. These results provide strong rationale for future evaluation of either sequential or triplet therapy in this setting.
In the MDS cohort, 4 of 9 responding patients achieved mutation clearance. CRs were observed with both monotherapy and combination therapy, including an 86% ORR and 57% CR rate in the combination arm.
The investigators noted, “To our knowledge, we also report the first available data on patients with myelodysplastic syndrome treated with an IDH1 inhibitor plus azacitidine, where we observed a strong preliminary activity signal.”
Rezlidhia was well-tolerated in patients with AML and MDS, either as monotherapy or in combination with azacitidine. No dose limiting toxicities occurred in the dose escalation cohorts. Overall, adverse events were similar and manageable across the monotherapy and combination arms. Transient QT prolongation was observed in 3 patients (4%). This study showed that Rezlidhia has the potential to provide an additional treatment option for mIDH1 AML.
[post_title] => Rezlidhia shows positive results for mIDH1 AML in phase I/II study [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_9i [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:17:12 [post_modified_gmt] => 2023-02-03 19:17:12 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52439 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52439 ) [21] => Array ( [ID] => 52438 [post_author] => 2768 [post_date] => 2023-02-03 11:16:09 [post_date_gmt] => 2023-02-03 15:16:09 [post_content] =>Patients who have intrahepatic cholangiocarcinoma caused by specific FGFR2 gene alterations may soon have a better treatment option that more successfully targets that mutation.
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That is the conclusion of a recent phase II study in The New England Journal of Medicine, co-authored by University Hospitals Seidman Cancer Center’s Amit Mahipal and colleagues across the country.
The research team tested the FGFR2 inhibitor Lytgobi (futibatinib) in 103 patients with unresectable or metastatic intrahepatic cholangiocarcinoma caused by specific FGFR2 gene alterations. These FGFR2 fusions or rearrangements occur in up to 14% of patients with this rare form of cancer. Patients in the study had previously received one or more types of systemic therapy. Results show that 42% of patients had a response to treatment with the new FGFR2 inhibitor, with the median duration of response of 9.7 months.
These results are especially important because of the limitations of other FGFR2 inhibitors in treating this poor-prognosis cancer, Mahipal said. Other FGFR2 inhibitors, Pemazyre (pemigatinib) and Truseltiq (infigratinib), have received accelerated approval from FDA for treating this form of cancer. But when they bind with receptors on the cancer cell, that binding process can sometimes be reversed and can result in new mutations in resistance to the therapy.
“The irreversible nature of binding and its distinct binding site make futibatinib less susceptible to on-target resistance mutations than pemigatinib and infigratinib,” Mahipal said in a statement. “In preclinical experiments, futibatinib showed stronger activity against a wider spectrum of FGFR2 mutations than other FGFR inhibitors. Furthermore, fewer drug-resistant clones emerged with futibatinib treatment. Data from this study establish futibatinib as having measurable clinical benefit in patients with this disease and show the value of molecular profiling in identifying tumors that are likely to respond to FGFR2 inhibition.”
[post_title] => Phase II study shows positive results for new treatment for a form of intrahepatic cholangiocarcinoma [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_9j [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:17:14 [post_modified_gmt] => 2023-02-03 19:17:14 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52438 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52438 ) [22] => Array ( [ID] => 52441 [post_author] => 2768 [post_date] => 2023-02-03 11:15:13 [post_date_gmt] => 2023-02-03 15:15:13 [post_content] =>A drug that recently received accelerated approval from FDA to treat a form of non-small cell lung cancer caused by a unique genetic mutation also appears to be effective against advanced pancreatic cancer caused by the same uncommon mutation.
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The study, published in The New England Journal of Medicine, was co-authored by UH Seidman Cancer Center’s David Bajor.
The safety and efficacy of the study medicine sotorasib, a KRAS G12C inhibitor, had previously been unknown among previously treated patients with KRAS p.G12C–mutated pancreatic cancer. Study results show that sotorasib showed anticancer activity and had an acceptable safety profile in patients with KRAS p.G12C–mutated advanced pancreatic cancer who had received previous treatment.
KRAS p.G12C mutation occurs in approximately 1-2% of pancreatic cancers.
The research team says that these results are quite promising and suggest that inhibitors could even be developed for KRAS mutations that are linked to more common forms of pancreatic cancer.
[post_title] => UH Seidman discovers newly-approved NSCLC could also treat rare advanced pancreatic cancer [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_9k [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:17:19 [post_modified_gmt] => 2023-02-03 19:17:19 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52441 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52441 ) [23] => Array ( [ID] => 52440 [post_author] => 2768 [post_date] => 2023-02-03 11:14:11 [post_date_gmt] => 2023-02-03 15:14:11 [post_content] =>An analysis led by a researcher at UT Southwestern Medical Center, which looked at costs for patients with Hepatocellular carcinoma in the first year after diagnosis, found that median Medicare payments exceeded $65,000 and out-of-pocket costs were more than $10,000—significantly more than costs for patients with cirrhosis alone.
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The study, led by Amit Singal, professor of internal medicine in the Division of Digestive and Liver Diseases and a member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern, was published in Clinical Gastroenterology and Hepatology.
“As has been shown for other cancer types, we found patients with liver cancer suffer from high cancer-related financial burden. Financial toxicity of cancer therapy can negatively impact patients, resulting in medical debt and even bankruptcy for some patients,” said Singal, who is also the medical director of UTSW’s Liver Tumor Program and a Dedman Family Scholar in Clinical Care.
The team chose to investigate outcomes in liver cancer given its rising incidence and mortality rate. Liver cancer mortality is accelerating, in part due to continued detection at late stages, and it is expected to be the third-leading cause of cancer deaths by 2040, according to Singal and his team.
The cost of liver cancer treatment has been little studied, the researchers said. Several treatments have become available for patients in the past decade, including new surgeries, radiation-based therapies, and immunotherapies, making it essential to understand the financial impact of treatment. Although these therapies can be effective, they also can be quite expensive and difficult for patients to afford.
Using data from the Surveillance, Epidemiology, and End Results Medicare database, the study looked at first-year treatment costs for 4,525 patients ages 68 and older who were diagnosed with liver cancer between 2011 and 2015. The study compared costs for patients with HCC with those for a matched set of patients with cirrhosis.
Sixty-seven percent of the patients in the study were male; 72% were white, 7.5% Black, 3.7% Hispanic, and 16.7% other ethnicities. Medication claims were not included because they were not available for all patients covered by Medicare parts A and B.
The analysis found that patients with liver cancer had significantly higher inpatient, outpatient, and physician costs compared with the cirrhosis-only patients. Median out-of-pocket costs for the first year of treatment were more than $7,000 higher than the costs for the cirrhosis patients.
The analysis found that patients with early-stage liver cancer had lower costs. Patients with certain co-existing conditions, such as non-alcoholic fatty liver disease and ascites (fluid in the abdomen), experienced higher costs. These differences in costs across subgroups are notable because most patients are found beyond an early stage, and non-alcoholic fatty liver disease is an increasingly common underlying factor for liver cancer.
The study was supported by grants through the Cancer Prevention and Research Institute of Texas (RP170259), the NIH (R01 MD012565 and U01 CA230694), the Population Informatics Lab, and the Texas Virtual Data Library at Texas A&M University.
[post_title] => Liver cancer treatment costly for Medicare patients, UT Southwestern study finds [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_9l [to_ping] => [pinged] => [post_modified] => 2023-08-21 11:14:49 [post_modified_gmt] => 2023-08-21 15:14:49 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52440 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52440 ) [24] => Array ( [ID] => 52442 [post_author] => 2768 [post_date] => 2023-02-03 11:13:14 [post_date_gmt] => 2023-02-03 15:13:14 [post_content] =>Scientists at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, collaborating with international researchers, have developed an AI algorithm that performs advanced computational analysis to identify potential therapeutic targets for glioblastoma multiforme and other cancers.
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Their research is described in the Feb. 2 issue of Nature Cancer and could affect future treatment of GBM, an aggressive, usually fatal type of brain cancer, and certain breast, lung, and pediatric cancers.
“Our work represents translational science that offers immediate opportunities to change the way glioblastoma patients are routinely managed in the clinic,” Antonio Iavarone, deputy director of Sylvester Comprehensive Cancer Center and senior author of the study, said in a statement. “Our algorithm offers applications to precision cancer medicine, giving oncologists a new tool to battle this deadly disease and other cancers as well.”
The AI algorithm, known as SPHINKS—Substrate PHosphosite-based Inference for Network of KinaseS—deployed deep-machine learning to help the researchers identify and experimentally
validate two protein kinases (PKCδ and DNAPKcs) as the culprits associated with tumor progression in two GBM subtypes and as potential therapeutic targets for other cancers.
Protein kinases are the key targets currently used in precision cancer medicine to tailor treatment to a patient’s specific cancer properties. The most active kinases, which the researchers labeled “master kinases” in their paper, are those for which clinicians direct targeted drugs as a hallmark of current cancer treatment.
In addition to identifying the master kinases, Iavarone and colleagues used tumor organoids grown in the laboratory from patient samples—what they called “patient-derived tumor avatars”—to show that targeted drugs that interfere with the activity of master kinases can thwart tumor growth.
Previously, Iavarone and team had reported a new glioblastoma classification by capturing key tumor cell traits and grouping GBM patients based on their likelihood of survival and their tumor’s vulnerability to drugs. In the new study, these classifications were independently confirmed through several omics platforms: genomics, proteomics, lipidomics, acetylomics, metabolomics, and others.
SPHINKS leverages machine learning to refine these omics datasets and create an interactome—a complete set of biological interactions—to pinpoint the kinases that generate aberrant growth and treatment resistance in each glioblastoma subtype. These findings show multi-omics data can generate new algorithms that predict which targeted therapies can provide the best therapeutic options based on each patient’s glioblastoma subtype.
“We can now stratify glioblastoma patients based on biological features that are common between different omics,” Iavarone said. “Reading the genome alone has not been enough. We have needed more comprehensive data to identify tumor vulnerabilities.”
The SPHINKS algorithm and related methods can be readily incorporated into molecular pathology labs, according to the researchers. Their paper includes a clinical classifier that can help assign the appropriate glioblastoma subtype to each patient. The team has also established an online portal to access the algorithm. The authors believe this approach can produce insightful information that could benefit as many as 75% of glioblastoma patients.
“This classifier can be used in basically any lab,” Anna Lasorella, professor of biochemistry and molecular biology at Sylvester CCC and co-senior author on the study, said in a statement. “By importing the omics information into the web portal, pathologists receive classification information for one tumor, ten tumors, however many they import. These classifications can be applied immediately to patient care.”
While SPHINKS was first tested on glioblastoma, the algorithm is equally applicable to several other cancers. The team found the same cancer-driving kinases in breast, lung, and
pediatric brain tumors. Iavarone, Lasorella, and colleagues believe this finding could be the impetus for a new type of clinical trial.
“We are exploring the concept of basket trials,” Iavarone said, “which would include patients with the same biological subtype but not necessarily the same cancer types. If patients with glioblastoma or breast or lung cancer have similar molecular features, they could be included in the same trial. Rather than doing multiple trials for a single agent, we could conduct one combined trial and potentially bring more effective drugs to more patients faster.”
[post_title] => Sylvester scientists develop AI to gain insight into glioblastoma [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_9m [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:17:26 [post_modified_gmt] => 2023-02-03 19:17:26 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52442 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52442 ) [25] => Array ( [ID] => 52444 [post_author] => 2768 [post_date] => 2023-02-03 11:12:16 [post_date_gmt] => 2023-02-03 15:12:16 [post_content] =>Yale Cancer Center scientists have developed a technology that enables massively parallel DNA substitutions (known as “knock-ins”) into human cells by taking advantage of messenger RNA, a platform now well-known from its use as the COVID vaccine vehicle.
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This new technology, named CLASH, allows scientists to generate tens of thousands of different variants of cells with different genetic modifications and pick the best one for desired purposes, such as using them in cell therapies for cancer treatment.
The study was published Jan. 26 in the journal Nature Biotechnology.
“While there are different ways to modify the genome, inserting pieces of DNA has historically been more difficult than deleting pieces, and it’s even harder to insert many different pieces into various cells at the same time,” senior author Sidi Chen, an associate professor of genetics at Yale School of Medicine and member of Yale Cancer Center, said in a statement. “We have been working hard over the past five years and came up with a solution: designing and creating large pools of adeno-associated virus vectors and delivering them together with mRNA enabled us to achieve mass insertions instead of one-to-one gene substitutions.”
Chen’s research team first applied this technology in human T cells to solve the challenge of cell therapy for cancer. Cell therapy such as CAR-T therapy is successful and recently approved by FDA to treat blood cancers but faces major hurdles in solid tumors such as breast cancer, lung cancer, and colon cancer.
For the new study, the team used CLASH to modify the genome of T cells and created pools of new CAR-T variants, which they called “treasure islands.” They then tested these T cell variant pools against cancer, and let the best candidate emerge from selection. Researchers have found that a unique mutant can substantially enhance CAR-T against cancer in animals, and the effect is universal across different types of disease models.
“Although the proof-of-principle is in human T cells, the CLASH technology is in principle applicable to many different cell types, which allows us to rapidly create thousands of cell therapy candidates for diverse cancer treatment options,” Chen said. Future trials are needed before human application.
Chen is affiliated with the Systems Biology Institute and the Center for Cancer Systems Biology at Yale West Campus, the Yale Stem Cell Center, the Yale Center for Biomedical Data Science, and the Department of Genetics at Yale School of Medicine.
The research was primarily funded by the NIH and the U.S. Department of Defense.
[post_title] => Yale scientists enable massively parallel DNA insertions into human cells [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_9n [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:17:31 [post_modified_gmt] => 2023-02-03 19:17:31 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52444 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52444 ) [26] => Array ( [ID] => 52443 [post_author] => 2768 [post_date] => 2023-02-03 11:11:15 [post_date_gmt] => 2023-02-03 15:11:15 [post_content] =>In a study published in Cell Reports Medicine, a team of scientists at Baylor College of Medicine focused on the molecular pathways metastatic cancer cells use and identified four cancer subtypes according to the main genes expressed. The findings unveiled potential vulnerabilities of each subtype that have relevant implications for therapy.
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“We analyzed molecular data from the public domain collectively representing 38 studies and more than 3,000 patients and 4,000 tumors,” lead author Chad Creighton, professor of medicine and co-director of cancer bioinformatics at the Dan L Duncan Comprehensive Cancer Center at Baylor, said in a statement. “Our pan-cancer analysis looked to identify molecular pathways that are common to many different cancers, regardless of tumor origin.”
One challenge when studying cancer metastasis is that tumor samples have abundant non-cancer tissue. Samples tend to be a mixture of cancer and non-cancer cells, such as normal endothelial cells, fibroblasts and immune cells, that interfere with the molecular analysis of cancer cells.
To cut through all that noise, Creighton and his colleagues worked with data obtained from PDX cancer models. In this model, human cancer tissues implanted in immune-deficient mouse models grew into a new tumor similar to a metastasis.
“The nice thing with the PDX model is that mouse cells are different enough that they cannot be confused with human cells and, therefore, they are not going to contribute to the cancer profile,” Creighton said.
By analyzing the data of the PDX models, the team was able to define four cancer molecular subtypes in the metastasis-like PDX samples. Importantly, the researchers determined that those four subtypes also are present in patient metastasis and are broadly represented among the different cancer types studied. These subtypes not only facilitate understanding the molecular underpinnings of metastases but also point at potential therapeutic interventions already under investigation.
The tumors in the first subtype have extensive alterations in gene copy number, higher expression of both DNA repair genes and transcription factor genes such as MYC. This suggests that tumors of this subtype might be susceptible to MYC-inhibiting compounds or BET inhibitors currently under clinical evaluation.
The second subtype has higher expression of genes involving metabolism, prostaglandin synthesis and regulation. Tumors in this group might be susceptible to COX-2 inhibitors.
The third subtype has evidence of neuronal differentiation and high expression of genes EZH2 and BCL2. In this case, such tumors might respond better to EZH2 or BCL2 inhibitors.
The fourth subtype has higher expression of immune checkpoint and Notch pathway genes, suggesting that these tumors could be affected by immunotherapy.
“When comparing a primary tumor with the metastatic tumor derived from it, we found that, in most cases, the primary and the metastatic tumors were not of the same subtype,” Creighton said. “This has important implications for therapy as it suggests that primary and metastatic tumors may not be treated in the same way. The findings provide valuable insights for the development of personalized treatments for metastatic cancer.”
Yiqun Zhang and Fengju Chen at Baylor College of Medicine also contributed to this work.
This study was supported by the NIH grant P30CA125123.
[post_title] => Study shows molecular pathways followed by metastatic cancer cells [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_9o [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:17:35 [post_modified_gmt] => 2023-02-03 19:17:35 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52443 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52443 ) [27] => Array ( [ID] => 52447 [post_author] => 2768 [post_date] => 2023-02-03 11:10:20 [post_date_gmt] => 2023-02-03 15:10:20 [post_content] =>Researchers at Baylor College of Medicine, the University of Michigan, and collaborating institutions working with animal models of graft-versus-host disease reported in Immunity that alterations in the gut microbiome are connected to an increase in the oxygen levels in the intestine that follows immune-mediated intestinal damage. Pharmacologically reducing intestinal oxygen levels alleviated the microbial imbalance and reduced the severity of the intestinal disease.
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The severity of immune-mediated intestinal diseases such as GVHD or inflammatory bowel diseases is known to be associated with alterations in the gut microbiome, but what leads to such disruption in the microbial community has remained unknown.
“There is a lot of data showing that microbes change in many diseases, but we do not understand how that happens,” leading author Pavan Reddy, professor and director of Baylor’s Dan L Duncan Comprehensive Cancer Center, who was at the University of Michigan during the development of this project, said in a statement. “This study is one of the first to provide an explanation and a potential solution for the imbalance in the gut microbiome that exacerbates GVHD and possibly other inflammatory intestinal conditions.”
GVHD is a potentially life-threatening complication of bone marrow transplantation. “It is the complication that can prevent us from using this therapy that has proven to be effective to treat many blood cancers and inherited blood diseases,” Reddy said.
Reddy and his colleagues discovered that the damage immune cells cause to intestinal cells prevents these cells from fully using oxygen to conduct their normal functions. Consequently, all the oxygen that is not being used by intestinal cells oozes into the intestine, changing the environment for the resident microbes.
“Most of the ‘good microbes’ we have in the intestine grow in oxygen-poor environments—oxygen is toxic to them. They are called anaerobic (without oxygen) bacteria,” Reddy said. “When oxygen levels in the intestine increase, these microbes tend to disappear, and oxygen-loving microbes tend to grow. An increase in oxygen level provides an explanation for the microbiome changes in the context of these inflammatory diseases.”
The findings suggested that restoring the normal environment by reducing the oxygen level in the intestine could help reestablish the balance of the microbial community and lead to attenuation of GVHD.
“Indeed, we discovered that reducing the intestinal oxygen level actually made a difference in the progression of GVHD in the animal models,” Reddy said. “We found that a commonly used drug to reduce iron overload, an iron chelator, mitigated the microbial imbalance and reduced the severity of GVHD.”
Iron chelators have been used for many years to treat conditions in which excess iron causes tissue damage, such as hemochromatosis. Iron chelators are compounds that bind to iron, pulling it out and removing it from the body. “We discovered that iron chelators also can act as oxygen sinks,” Reddy said. “In our animal models, iron chelators removed iron from the intestine and that facilitated the restoration of an oxygen-poor environment that gave anaerobic bacteria an opportunity to bloom. Importantly, this reduced the severity of GVHD.”
The researchers’ next steps include conducting studies to determine whether iron chelation can help control the severity of GVHD in patients who have received a bone marrow transplant.
Another advantage of iron chelation would be that it may reduce or avoid the use of immune suppressor medications that are usually used to control GVHD. Suppressing the immune system may control GVHD, but also favors infections, which can be life-threatening. “If iron chelation helps control the condition in patients, it would be a novel non-immunosuppressive approach to treat GVHD with seemingly little side effects,” Reddy said.
[post_title] => Study provides explanation and potential solution for severe GVHD [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_9p [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:17:39 [post_modified_gmt] => 2023-02-03 19:17:39 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52447 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52447 ) [28] => Array ( [ID] => 52508 [post_author] => 2768 [post_date] => 2023-02-03 11:09:38 [post_date_gmt] => 2023-02-03 15:09:38 [post_content] =>To mark World Cancer Day, researchers from the International Agency for Research on Cancer in collaboration with the Lalla Salma Foundation for Cancer Prevention and Treatment (Morocco) published a report that provides solutions to overcoming some of the common system-level barriers to implementation of cervical cancer screening, which are faced in many countries in sub-Saharan Africa.
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This new publication summarizes the outcomes of the Care4Afrique pilot project, which was initially implemented in Benin, Côte d’Ivoire, and Senegal in close collaboration with the ministries of health of those countries.
“Although the burden of cervical cancer is very high in Francophone sub-Saharan Africa, very little evidence is available on how best to integrate cervical cancer screening and treatment services, especially using new technologies such as thermal ablation, into routine primary health-care services,” IARC scientist Farida Selmouni, the coordinator
of the project, said in a statement. “The Care4Afrique project provides an implementation model that other countries may emulate in order to remain aligned with the World Health Organization (WHO) strategy to eliminate cervical cancer as a public health problem globally.”
The Care4Afrique pilot project demonstrated that implementation of cervical cancer screening by visual inspection with acetic acid followed by immediate treatment of precancerous lesions with thermal ablation in primary health-care services is feasible in resource-constrained settings.
The project also showed that treatment with thermal ablation is safe and highly acceptable to women.
The keys to the success of cervical cancer screening in any health setting, including in sub-Saharan Africa, are strong leadership, stakeholder engagement, appropriate coordination between the primary and secondary levels of health services, adequate investment
in training and refresher training of service providers, and stringent quality assurance.
Another ambition of the pilot project was to build capacity within the public health-care system in
the focus countries to deliver cervical cancer screening and treatment. Strong collaborations were established among multiple African countries to build capacity in the primary health-care facilities.
A team of master trainers was identified in each country and trained. These master trainers trained a large number of providers at the primary and secondary levels of care to deliver screening and treatment and also mentored them regularly.
IARC, in collaboration with the Lalla Salma Foundation for Cancer Prevention and Treatment (Morocco), launched the Care4Afrique pilot project in November 2017.
The project incorporated VIA as the screening test, thermal ablation as a novel technology to treat cervical precancers, and screen-and-treat as the management approach.
Between April 2018 and January 2021, a total of 16,530 women in the three focus countries were screened through the project. Overall, 8.1% of the women screened were VIA-positive, and among them, 0.2% of the women had lesions suspicious of cancer on VIA. A total of 60.7% of all VIA-positive women were eligible for thermal ablation; most of them (87.9%) received treatment on the same day as screening, and only 1.0% refused treatment.
The Care4Afrique project has now also been implemented in Cameroon, where screening of women has begun.
[post_title] => IARC, Lalla Salma Foundation report addresses barriers to cervical cancer screening in Benin, Côte d’Ivoire, Senegal [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_9q [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:17:43 [post_modified_gmt] => 2023-02-03 19:17:43 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52508 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52508 ) [29] => Array ( [ID] => 52446 [post_author] => 2768 [post_date] => 2023-02-03 11:05:19 [post_date_gmt] => 2023-02-03 15:05:19 [post_content] =>FDA granted accelerated approval to Jaypirca (pirtobrutinib) for relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor.
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Jaypirca is sponsored by Eli Lilly and Co. Full prescribing information for Jaypirca can be found here.
Efficacy was evaluated in BRUIN (NCT03740529), an open-label, multicenter, single-arm trial of Jaypirca monotherapy that included 120 patients with MCL previously treated with a BTK inhibitor. Patients had a median of 3 prior lines of therapy, with 93% having 2 or more prior lines. Eighty three percent of patients had discontinued their last BTK inhibitor due to refractory or progressive disease.
The main efficacy measures were overall response rate and duration of response, as assessed by an independent review committee using Lugano criteria. The ORR was 50% with a complete response rate of 13%. The estimated median DOR was 8.3 months, and the estimated DOR rate at 6 months was 65.3%.
The most common adverse reactions in patients with MCL were fatigue, musculoskeletal pain, diarrhea, edema, dyspnea, pneumonia, and bruising.
[post_title] => Jaypirca receives FDA accelerated approval for R/R mantle cell lymphoma [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_10a [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:00:24 [post_modified_gmt] => 2023-02-03 19:00:24 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52446 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52446 ) [30] => Array ( [ID] => 52445 [post_author] => 2768 [post_date] => 2023-02-03 11:04:18 [post_date_gmt] => 2023-02-03 15:04:18 [post_content] =>FDA approved Orserdu (elacestrant) for postmenopausal women or adult men with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy.
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Orserdu is sponsored by Stemline Therapeutics Inc.
FDA also approved the Guardant360 CDx assay as a companion diagnostic device to identify patients with breast cancer for treatment with Orserdu.
Full prescribing information for Orserdu can be found here.
Efficacy was evaluated in EMERALD (NCT03778931), a randomized, open-label, active-controlled, multicenter trial that enrolled 478 postmenopausal women and men with ER-positive, HER2-negative, advanced or metastatic breast cancer of which 228 patients had ESR1 mutations.
Patients were required to have disease progression on one or two prior lines of endocrine therapy, including one line containing a CDK4/6 inhibitor. Eligible patients could have received up to one prior line of chemotherapy in the advanced or metastatic setting.
Patients were randomized (1:1) to receive Orserdu (n=239) or investigator’s choice of endocrine therapy (n=239), which included fulvestrant (n=166) or an aromatase inhibitor (n=73).
Randomization was stratified by ESR1 mutation status, prior treatment with fulvestrant, and visceral metastasis. ESR1 mutational status was determined by blood circulating tumor DNA using the Guardant360 CDx assay and was limited to ESR1 missense mutations in the ligand binding domain.
The major efficacy outcome measure was progression-free survival, assessed by a blinded imaging review committee. A statistically significant difference in PFS was observed in the intention to treat population and in the subgroup of patients with ESR1 mutations.
In the 228 (48%) patients with ESR1 mutations, median PFS was 3.8 months in the Orserdu arm and 1.9 months in the fulvestrant or aromatase inhibitor arm,
An exploratory analysis of PFS in the 250 (52%) patients without ESR1 mutations showed a HR 0.86 indicating that the improvement in the ITT population was primarily attributed to the results seen in the ESR1 mutated population.
The most common adverse events, including laboratory abnormalities, were musculoskeletal pain, nausea, increased cholesterol, increased AST, increased triglycerides, fatigue, decreased hemoglobin, vomiting, increased ALT, decreased sodium, increased creatinine, decreased appetite, diarrhea, headache, constipation, abdominal pain, hot flush, and dyspepsia.
[post_title] => Orserdu & companion diagnostic for ER+, HER2-, ESR1-mutated advanced breast cancer receive FDA approval [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_10b [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:00:28 [post_modified_gmt] => 2023-02-03 19:00:28 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52445 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52445 ) [31] => Array ( [ID] => 52448 [post_author] => 2768 [post_date] => 2023-02-03 11:03:21 [post_date_gmt] => 2023-02-03 15:03:21 [post_content] =>FDA granted first marketing clearance for RefleXion Medical’s SCINTIX biology-guided radiotherapy, a cutting-edge treatment applicable for early and late-stage cancers.
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The FDA cleared SCINTIX biology-guided radiotherapy to treat patients with lung and bone tumors. These tumors may arise from primary cancers or from metastatic lesions spread from other cancers in the body.
SCINTIX is the first and only radiotherapy that allows each cancer’s unique biology to autonomously determine where and how much radiation to deliver, second-by-second, during actual treatment delivery. This expands the RefleXion X1 into the only dual-treatment modality platform that can treat patients with indicated solid tumors of any stage.
The SCINTIX biologic modality tracks tumor motion from all types of movement, including expected motion from internal processes such as breathing and digestion or unexpected movement by a patient. The X1 also has a state-of-the-art anatomic modality previously cleared by the FDA for solid tumors located anywhere in the body.
“SCINTIX ushers in a new era of external-beam radiotherapy by harnessing data produced from the biologic process of cancer cells, which until now has been untapped,” Terence Williams, chair of City of Hope’s Department of Radiation Oncology, said in a statement. “We are excited to be among the early adopters of SCINTIX and to help develop this therapy for all cancer patients, especially those with stage 4 disease, where treatment options often remain very limited.
“With SCINTIX, the X1 machine and the tumor communicate continuously via a live data stream produced during patient treatment,” Williams said. “This precision should enable us to treat less surrounding tissue and may enable the treatment of more tumors in the same course of therapy.”
Previously granted Breakthrough Device designation by the FDA for treating lung tumors, the breakthrough nature of SCINTIX technology lies in its ability to detect and then treat multiple moving tumors. Initially cleared for use with the radiopharmaceutical fluorodeoxyglucose F 18—commonly known as FDG—the company plans to adapt SCINTIX therapy to work with the full array of novel radiopharmaceuticals under development for different cancer types.
SCINTIX therapy (formerly referred to as BgRT) is delivered through the RefleXion X1 machine, which combines positron emission tomography with a linear accelerator to deliver a radiation dose that tracks the cancer’s motion. Immediately prior to treatment, the patient is injected with a radiopharmaceutical that interacts with cancer cells to produce signals or emissions.
The X1 continuously constructs a map from the detected emissions data that determines where to aim beamlets of radiation. This crosstalk between the tumor and the X1 requires the system to rotate at 60 rpm—making it the first and only radiotherapy machine to spin at this speed.
[post_title] => RefleXion receives FDA clearance for SCINTIX biology-guided radiotherapy [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_10c [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:00:31 [post_modified_gmt] => 2023-02-03 19:00:31 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52448 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52448 ) [32] => Array ( [ID] => 52449 [post_author] => 2768 [post_date] => 2023-02-03 11:02:23 [post_date_gmt] => 2023-02-03 15:02:23 [post_content] =>FLAG-003, an investigational small molecule therapy developed by FLAG Therapeutics Inc. for the treatment of diffuse intrinsic pontine glioma—a rare, highly aggressive and difficult to treat brain tumor found in children—has been granted Rare Pediatric Disease designation from FDA.
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FLAG-003, the company’s lead program for the treatment of all gliomas, is engineered to cross the blood brain barrier and specifically target and kill cancer cells by simultaneously blocking the formation of a tumor vascular system and disrupting cancer cell replication by inhibiting tubulin.
RPD designation is granted to drugs in development for the treatment of rare childhood diseases—diseases affecting children 18 years of age and younger and fewer than 200,000 people in the U.S.
Under the RPD program, the sponsor may qualify for a priority review voucher if the drug is initially approved for the disease for which the RPD designation was granted. Holders of a PRV can redeem the voucher to obtain priority review for any subsequent marketing application, or they can sell or transfer it to other developers.
FLAG-003 was previously granted Orphan Drug Designation for the treatment of all gliomas, including glioblastoma multiforme and DIPG, by FDA.
FLAG-003 is a novel multi-specific small molecule therapeutic designed to target, bind, and kill cancer cells through two well-established mechanisms of action: anti-angiogenesis and tubulin inhibition.
Diffuse intrinsic pontine glioma is a highly aggressive, difficult to treat malignant brain tumor that is usually diagnosed in children between the ages of five and nine. It accounts for nearly 10% of all childhood central nervous system tumors. In the U.S., approximately 300 children are diagnosed with DIPG each year. Due to its location in the brain stem, surgery is not an option; results of first line treatment with radiation are typically short lived, lasting on average approximately six to nine months. At present, there are no approved drug therapies for the treatment of DIPG.
[post_title] => FLAG Therapeutics’s FLAG-003 receives Rare Pediatric Disease Designation for diffuse intrinsic pontine glioma [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_10d [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:00:34 [post_modified_gmt] => 2023-02-03 19:00:34 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52449 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52449 ) [33] => Array ( [ID] => 52450 [post_author] => 2768 [post_date] => 2023-02-03 11:00:24 [post_date_gmt] => 2023-02-03 15:00:24 [post_content] =>The National Cancer Institute approved the following clinical research studies last month.
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For further information, contact the principal investigator listed.
Phase I/II - NRG-GY028
A Phase IB and Randomized Phase II Trial of Megestrol Acetate with or Without Ipatasertib in Recurrent or Metastatic Endometrioid Endometrial Cancer
NRG Oncology
Grinsfelder, Michaela Onstad
(713) 745-7418
Phase II - A222101
An Early Phase and Phase II Clinical trial to evaluate ganglioside-monosialic acid (GM1) for preventing paclitaxel-associated neuropathy
Alliance for Clinical Trials in Oncology
Cathcart-Rake, Elizabeth
(816) 932-4565
Phase II/III - AOST2032
A Feasibility and Randomized Phase 2/3 Study of the VEFGR2/MET Inhibitor Cabozantinib in Combination with Cytotoxic Chemotherapy for Newly Diagnosed Osteosarcoma
Children’s Oncology Group
Bishop, Michael William
(901) 595-2220
Phase III - A022101
A Pragmatic Randomized Phase III Trial Evaluating Total Ablative Therapy for Patients with Limited Metastatic Colorectal Cancer: Evaluating Radiation, Ablation, and Surgery (ERASur)
Alliance for Clinical Trials in Oncology
Miller, Eric David
(614) 685-4922
Phase III - A022102
Randomized Phase III Trial of mFOLFIRINOX +/- Nivolumab vs. FOLFOX +/- Nivolumab for First-Line Treatment of Metastatic HER2-Negative Gastroesophageal Adenocarcinoma
Alliance for Clinical Trials in Oncology
Park, Haeseong
(617) 632-3000
Phase III - NRG-BR008
A Phase III Randomized Trial of Radiotherapy Optimization for Low-Risk HER2-Positive Breast Cancer (HERO*) *Her2 Radiation Optimization (HERO)
NRG Oncology
Braunstein, Lior Zvi
(201) 775-7446
Phase III - NRG-LU008
Phase III Prospective Randomized Trial of Primary Lung Tumor Stereotactic Body Radiation Therapy Followed by Concurrent Mediastinal Chemoradiation for Locally-Advanced Non-Small Cell Lung Cancer
NRG Oncology
Simone, Charles B.
(646) 968-9052
Phase III - URCC-22053
High-dose Vitamin D Supplementation for ADT-Induced Bone Loss in Older Prostate Cancer Patients
University of Rochester NCORP Research Base
Peppone, Luke Joseph
(585) 275-7827
Phase Other - ALTE21C1
Assessment of Clonal Hematopoiesis and its Relationship to Cardiovascular Disease in Hodgkin Lymphoma Survivors
Children’s Oncology Group
Hayashi, Robert J.
(314) 454-6018
On May 25, 2020, George Floyd said “I can’t breathe” more than 20 times before he suffocated on a street in Minneapolis. On Jan. 7, 2023, Tyre Nichols repeatedly screamed, “Mom, mom, mom” as he was beaten to death on a street in Memphis.
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Both were Black men. Both died at the hands of police officers wielding the power of life and death.
“This is like déjà vu all over again. That’s only two years ago,” said Robert Winn, director and Lipman Chair in Oncology at the Virginia Commonwealth University Massey Cancer Center, a professor of pulmonary disease and critical care medicine at the VCU School of Medicine, and the guest editor of The Cancer Letter during February, Black History Month.
“It’s a cultural problem. It’s some kind of bias. It’s a disrespect,” said Otis Brawley, Bloomberg Distinguished Professor of Oncology and Epidemiology at Johns Hopkins University, and co-editor of the Cancer History Project.
Both physicians have had life-threatening encounters with police—Brawley was thrown to the ground and held at gunpoint for standing in the garage of his own home; Winn was thrown to the ground and held at gunpoint for walking toward his own car.
“We both happen to be Black men. With the events in the last several weeks involving Tyre Nichols in Memphis, we thought we should have a chat, because both of us have in the past talked about our experiences with police, our experiences in society growing up,” Brawley said.
The Cancer Letter invited Winn and Brawley to discuss the structural biases and racism in law enforcement as well as in health care.
This conversation is also available as a video and podcast.
It’s important for physicians and public health professionals, as individuals in positions of power, to reflect on the problems in policing in America, and identify areas where these problems are also present in health care, Brawley and Winn said.
“Someone had said the other day, ‘The Tyre thing is very different than the thing from George Floyd, because, well, with George Floyd, the policemen that were doing that were predominantly white, and in this case, the policemen were all African American,’” Winn said.
For me, the only time I’ve had guns pulled out on me has been when I was encountering law enforcement. It wasn’t by a gang or anything like that.
Robert Winn
“And I essentially said that that is actually incorrect,” Winn said. “Policemen still see, even whether they’re Black, Asian, or white, based on the way sometimes that unit is taught or the culture of that unit, that they would treat an African American different than they would treat a white person for the same traffic stop violation. It’s a power dynamic.”
“And I worry about that power dynamic in medicine as well,” Brawley said.
Race is one dimension of that power dynamic.
“We have a medical system that is segregated by socioeconomics, and separate cannot be equal. Separate is not equal,” Brawley said.
Class is another dimension, albeit less talked about, Winn said.
“Class does not protect, whether it’s in law enforcement nor, actually, in medicine,” Winn said. “But I guarantee you this: if you’re Black and you’re poor, that becomes an issue.
“I hope that with Tyre’s death that one of the good things that could come out of this would be for us to take a pause and be all recommitted, as many of us were at the time that George Floyd actually was also murdered in front of all of our eyes.”
The conversation between Brawley and Winn follows:
Otis Brawley: Hello. I’m Otis Brawley, and I’m a medical oncologist. I’m here with my good friend Rob Winn, who is director of the Massey Cancer Center at Virginia Commonwealth University. And we are two major players in oncology. We both happen to be Black men.
With the events in the last several weeks involving Tyre Nichols in Memphis, TN, we thought we should have a chat, because both of us have in the past talked about our experiences with police, our experiences in society growing up.
I’ll start out by simply saying, I personally think that there is a problem in the United States with police and policing, and it’s a cultural problem. It has to do with biases and disrespect. We can talk about whether it’s biases and disrespect because of race or because of social positioning.
There is a problem in policing, and unfortunately, the police are not ready to deal with it.
Now, we are in medicine, and I think it’s a good time to actually think if some of these problems that we see in policing that actually do go into the rest of society, actually transcend into medicine. And that’s an area where we actually can do something about it and can be leaders in bringing about change.
So, Brother Winn, thank you for joining me in this conversation. It’s been two years since George Floyd, and now we’ve seen Tyre Nichols. And along the way, we’ve had Breonna Taylor and so many others who have been abused by police.
My first question for you is why do you think it’s important that we, as physicians and public health professionals, have an understanding of these issues in depth and think about them broadly?
Robert Winn: Dr. Brawley, I want to thank you for all that you have and continue to do, particularly in bringing light to these issues that really impact our communities and our patients.
I was thinking, as you were talking, about a line—and just for transparency’s sake, my brother just retired from the police force as a state trooper—I remember when we had been talking at some point it came up, the saying that “When you’re Black in America, there is no such thing as a routine traffic stop.”
That extends to when you are Black in America and you wind up going to an ER for certain problems; that many things that should be routine are not; that are really impacted by historical things that have happened long before us and continue to impact both, not only policing.
But I still think what we do in making sometimes unconscious, biased decisions about, for example, the lack of African Americans wanting to be on clinical trials.
I think that is a myth. I still think, to this day, that if you were to ask first and be able to communicate effectively, we’d have many more people from African American and many other communities, including rural communities, wanting to be on clinical trials.
So, I’ll start there by saying that it did make me think this weekend that 32 years after Rodney King, two years after George Floyd, that this is like déjà vu all over again, except for I think this time it may be a little different.
OB: Now, some of the folks who are listening to this or reading this may not be aware, but two years ago, you and I both wrote pieces for The Cancer Letter, talking about our negative experiences with the police throughout our years.
I, in particular, was an aide to the Surgeon General and a tenured researcher at the NIH, but I found myself face down in my driveway handcuffed for opening my garage door.
Yes. And then, when they saw that I had a military ID, one of the police—and by the way, one was Black, one was white—actually challenged my military ID’s validity, because they decided that I was too young to be the rank on my ID.
Some of these things get really, really stupid that the police do. And unfortunately, we see a lot of these things. And it’s some kind of bias. It’s a disrespect.
And it’s not all police. There’s three kinds of police. There’s the police who do this, the police who let it happen, and the police who are ignorant to the fact that it’s happening. I’m worried about that in medicine... We’ve recently had an article that medical students at a major university—I’ll tell you, it was the University of Virginia—thought that Black people don’t feel pain the way white people feel.
Black people do it, too. I hear about Black breast cancer as if it’s a proud thing among Black women. They’re talking about triple-negative disease. Last time I looked at it, 20% of Black women have it, and 12% of white women have it. Now, we’re going to claim it as Black breast cancer.
Help me out here. We’ve got to get away from some of these labels, and the bias, and we need to start respecting each other, and being concerned about each other.
RW: I absolutely couldn’t agree with you more. Going back to your first point, it was senseless. The use of appropriate policing is always in order.
In fact, my brother would say that the people who dislike that kind of bad policing are good police.
For me, the only time I’ve had guns pulled out on me has been when I was encountering law enforcement. It wasn’t by a gang or anything like that.
And Henry Louis Gates, remember, when [he was] trying to get into his own house? I only say that to say that class does not protect, whether it’s in law enforcement nor, actually, in medicine.
You and I have talked about that sometimes we have these feelings like African Americans do less well from things like multiple myeloma, until we actually have studies like the ones out of the University of Wisconsin-Madison, and others that are looking at multiple myeloma.
They actually show that if you give the appropriate access to care, it may not be-all-end-all, but it certainly reduces the disparities.
It’s not so much that biology is a major driver, but those things around the biology. I hope that not only will we grow as a society in being much more thoughtful around policing, but I also think that we will take this moment of Tyre’s death to figure out how many of us in the medical community said, or at least stated, that we wanted to be better; that we wanted to do things better after George Floyd’s death. That’s only two years ago.
The reality is, I hope that with Tyre’s death that one of the good things that could come out of this would be for us to take a pause and be all recommitted, as many of us were at the time that George Floyd was also murdered in front of all of our eyes.
And that extends to health care. I think many of us in the cancer world said, “How could we make access to care better? And how can we address these issues?”
Because sometimes, there’s the DWB—driving while Black—but I think that there’s also these same phenomena when we’re talking about our patients. That just simply being Black means that you, in some cases, say, “It’s our biology,” and don’t look at other issues that happen in the context of the ZNA, or the ZIP code-neighborhood association.
Other factors also play a role.
OB: You and I are great believers that the ZNA, or the ZIP code, is far more important than the DNA in many of these issues. And indeed, there are studies going back to the 1990s that show that equal treatment yields equal outcome amongst equal people, but there is not equal treatment.
Let me just go into my disease. Black men who have stage 3 prostate cancer are twice as likely to die as white men in the United States. When they’re treated in American College of Surgeons-certified hospitals that have a cancer program, they’re only one and a half times as likely to die.
When they’re treated in some of the premier hospitals in the United States, equal treatment yields equal outcomes. It’s Black and white one-to-one in terms of outcome.
And so, here we have in prostate cancer, clearly, a problem that a large number of Black men, actually some white men too, don’t get good treatment.
I suspect the same is true in breast cancer. I suspect the same is true in a myriad of cancers. I think the way to overcome implicit bias—and all of us have it—is to realize that these disparities exist, number one.
And two, try to do your best, to give your best care to every patient in front of you. Get back to basic principles. Who was it? Was it [Francis] Peabody who said, “The secret in caring for the patient is caring for the patient?”
RW: Is caring for the patient. Yes.
Otis, you bring up a good point. And you bring up a good point that I think is, as we started this conversation, the broad range of how we can address this issue. Number one, it turns out that just sensitivity training alone for policemen and “sensitivity” or diversity equity modules that get just taught about unconscious bias may not be enough.
What we really ought to get to is what you just said. And some of that can’t be policed, and some of that can’t be driven by law. Some of that’s going to have to be instilled in a culture, of medicine and hopefully, in policing, that every person does count, and that the truth of the matter is to see the person in front of you, not your image of what you think about them.
Now, someone had said the other day, “The Tyre thing is very different than the thing from George Floyd, because, well, with George Floyd, the policemen that were doing that were predominantly white, and in this case, the policemen were all African American.”
And I essentially said that that is actually incorrect. Policemen still see, even whether they’re Black, Asian, or white, based on the way sometimes that unit is taught or the culture of that unit, that they would treat an African American differently than they would treat a white person for the same traffic stop violation. It’s a power dynamic.
OB: And I worry about that power dynamic in medicine as well.
RW: Exactly. And these tags of Black men just come out, “they do worse from prostate cancer,” as if it’s a gospel truth, without understanding that it probably takes more data.
Or that we do worse in lung cancer. We have the data to show it, but the question is, what’s the why? And the why is not frequently as easy as “Well, because I’m Black.”
We usually are fascinated, and we push lots of dollars towards really getting down to the molecular and submolecular levels of science, and molecular therapies. We’re always asking the additional why question.
But it turns out, when it comes to issues around population health, health delivery, implementation sciences, sometimes we don’t have the same patience, and particularly when it comes to health systems—and they’re dealing with collecting data, using data in appropriate ways, and making sure that all people have the access to the same care, in the same manner—those are actually also important questions. I’m not sure that we do that as well as we could.
OB: I’m also concerned that in medicine we are letting the perception of biological differences amongst the races—keep in mind, I think race is a sociopolitical categorization.
Area of geographic origin, there’s some biological differences there, but when we started talking about area of geographic origin, when we talk about Black people or people of dark skin, there’s well over 100 of those in Africa.
When we talk about areas of geographic origin amongst Caucasians, there’s more than 600 of those that have been identified in Europe and Eurasia. So, I think race is just too big a thing, and it’s really sociopolitical.
But getting back to my original point, I think we worry too much about racial differences in biology and not the true racial issue, which is getting all people adequate care.
RW: Recognizing that structure matters. And as we get adequate care, we also have to account for the structures that are sometimes even creating and contributing to the disease.
I am so happy that what you just said is that when we now talk about ancestry and we talk about African Americans with ancestry, we don’t recognize that everyone has ancestry.
If you trace some of this back to ancestral markers as opposed to just Black—for example, I thought that the work from Lisa Newman and Melissa Davis were actually important about women.
African Americans who were considered African Americans with triple-negative breast cancer. What they said about having more Eastern African descent or ancestry as opposed to Western African ancestry, there was a difference in outcome.
I actually think that goes beyond just people who were “Black,” which is a social construct to fit everyone, whether you’re Asian, Latino, or Caucasian.
An awakening and an awareness of that idea will be helpful as we try to come up with new therapies as opposed to using the shorthand Black and using the shorthand white for everything.
As we progress, those tags hopefully will become relics of the past.
OB: I wanted to talk about this later on in this talk, but since you brought up two extraordinary scientists... I personally am very pleased with the young folks coming up and their absolutely amazing contributions in this area to help us understand it better.
I’m especially fond of Lisa because I’ve been able to watch her grow over the last 25 to 30 years.
But what do you think senior leaders in health care, Black and white, need to be doing in this area? And tell me a little about what you think about the next generation of health care. Then I’m going to go back to what I was originally going to talk to you about or ask you about.
RW: Thank you for asking that question. I think that I’m going to make a parallel to what’s happening in law enforcement to medicine.
The first is the reality that more diverse voices at the table do matter, and ultimately, understanding that you’re picking the best and the brightest to be able to fill the jobs matters.
I think in law enforcement, it’s becoming clearer that what happened in Memphis, and the speed in which it happened—of getting the information out, of being able to deal with things—in large part, was because there was a different type of leader at the helm.
I would say that when I think about Massey Cancer Center and I think about the next generation of leaders, having the first woman of color now be the cancer center director at University of New Mexico doesn’t guarantee, but allows for a different voice to be at the table and different perspectives.
Humility, caring about the patient, and awareness that we all have these prejudices—we need to overcome them. I think that’s the solution to giving good high-quality care
Otis Brawley
It doesn’t mean that, as I told someone as a cancer center director here at VCU Massey, that just because I’m an African American doesn’t mean that all I’m focused on is African Americans.
As if I were the governor of the state, I have multiple constituencies to be concerned about, including white rural, and people who are well off.
My number one goal is to make sure that anybody with cancer certainly benefits from having our cancer center. But I don’t want to pretend that I come in different than some of my colleagues—from not just being an African American, but from a class perspective—with also understanding some of the structural issues that are contributing to disease.
Maybe in a more nuanced way than others.
Having said that, I think our future is bright. You have folks like John Carpten. You have, like I said, Melissa Davis, Lisa Newman, Brian Rivers, Chanita Hughes-Halbert. There is a host of new and up-and-coming researchers in the basic science, translational, clinical, and data field.
And I’m feeling very comfortable that if you look at cancer center directors in 1971 and you now look at 2023, we have women, we have people from underrepresented groups.
And as a result of that, I think we’ve made over the last several years significant strides in progress in “normalizing” the concept that while people may look different on the outside, there are some core things that we all have to do to deliver the best, the highest care, and our research matters for all of them.
OB: Getting back to where I was going to go first, tell me what you think of this: I worry about people who mean well, but don’t understand the entire situation. We have people who are pro-life, but once the child is born, they don’t care about the child’s upbringing, and education, and grooming, and health care.
You might say, in so being pro-life, they should say they’re “pro-birth,” because they’re not really pro-life, because life is taking care of the person after they’re born.
We have people who are nowadays going to very resource-poor hospitals that take care of a lot of people who are from socioeconomically deprived backgrounds, and they’re pushing programs on these resource-poor programs to try to help poor people.
For example, I was director of the cancer center at Grady Hospital, which is an inner-city, county facility. It’s a safety net hospital. It’s common now for people to try to go and get places like Grady to do lung cancer screening.
Lung cancer screening is wonderful. It saves lives. It does have some drawbacks that we don’t talk about enough, but it does save lives.
I like to point out the study that shows that it works was done in 30 of the finest hospitals in the country. It showed that for every 5.4 lives you save, you kill one person; so, benefits and harms.
But if you go down to Grady, and you start doing lung cancer screening, you make the line for those four CT scanners at Grady longer. You actually create disparities and worsen the care of people who need that CT scanner by making the line longer.
And by the way, the current director of the cancer center at Grady constantly has folks saying, “Why aren’t you doing lung cancer screening?” I just told you why. That’s just one example. We have a medical system that is segregated by socioeconomics, and separate cannot be equal. Separate is not equal.
People who are poor who go to these resource-strapped hospitals and clinics do not get the same quality of care as people who go to the places that accept the private insurances. And I’ve been preaching, you can respond to that.
RW: Your point is well made. 85% of the people don’t wind up in NCI-designated cancer centers and academic centers. They’re being treated in the community setting.
And yet, these folks in the community setting frequently are under-resourced. As you just said, we’re layering on top what they should be doing without layering on additional resources for them to get the job done. Dr. Brawley, you know this.
We first met when I was in Chicago at University of Illinois where I had a dual role of being a cancer center director there. I was director of the University of Illinois Cancer Center, but I was also the associate vice president at that time of community-based practice, which is a fancy title.
I ran the network of Federally Qualified Health Centers, which came to be as part of the act on making sure in the 1960s that people had access to care, poor people in particular. There would be well-intentioned scientists who wanted to do studies within the FQHC settings.
When they would come in, well-meaning, well-intentioned, they would never-ever come with additional resources that wouldn’t disrupt my team.
Once I remember famously saying to someone, “I love your research. I’m sure it’s going to be of value, but the reality is the number one job of my team in this FQHC, at this site is to see patients that are, by the way, lined up in the hallway to be seen. If they’re not seen here, then they wind up in the emergency room. So, if you want to do research, what additional resources are you going to bring to the table so that you don’t disrupt?”
I would actually say the same thing is true with most of our community hospitals. The ACCC is doing a wonderful job in shedding light that there are community hospitals that have resources, but there are other community hospitals that do not. We are fooling ourselves that we’re giving the same care. It’s not even separate and equal. It’s separate and unequal in most cases.
And we have to do a better job from policy perspectives on how the academic centers can partner better, how there will be better policies, how we can get more resources that are used appropriately to do those things that we know can help.
But until we bring resources to the table, I think it’s unrealistic to have our community hospitals be mini, if you will, NCI-designated cancer centers. It just will not work.
OB: We’ve covered a couple of issues here, Dr. Winn. There’s a bunch of folks who are out there and who say we must get more minorities in the clinical trials.
But they ignore the fact that 97% of Americans don’t go on the cancer trials, by the way, Black or white, 95% plus don’t. And those who don’t go on the trials, frequently, if they’re a minority, or poor white as well, don’t get adequate care.
They push clinical trials, but forget about the fact that a lot of folks aren’t getting adequate care. They push screening programs that are of low yield.
Yes, they do save lives, but they’re of low yield when you look at the community as a whole. They tie up resources like CT scanners and pathologists and so forth and bog down the system and make care for other diseases worse. And we got to think about all of these things.
And then, of course, there’s the folks who are heavily into the biological differences amongst the races, which we’ve just talked about. All of these things to me—and I’m linking this to Tyre Nichols—those -isms that caused those police officers to beat that poor man.
We have our own version of those -isms in medicine, a lot of them—a lot of them that lead to biases that lead to misapplication of science.
Keep in mind, sometimes it’s the willing who do the wrong thing even; I mean good people who want to do the right thing, and they just don’t understand.
RW: Or, it’s attributed to Mark Twain. “It ain’t what you don’t know that gets you into trouble. It’s what you know for sure that just ain’t so.”
And frequently, we go in without the flexibility, the curiosity, the humility of being able to set these programs up. For example, I still think that there is a role for not only screening, but prevention—the resources and the voices needed to garner the resources.
We need to employ not just prevention in well-to-do places, but prevention all over is a good strategy.
Second, we do have to think about the reality that there are a bunch of -isms. We have -isms for “This person won’t go on trial. Well, because they’re Black.”
We have the -ism of, “Well, even if we screen this person, what are we going to do,” without actually saying, “If you’re going to screen, you ought to actually have the arc of screening that leads to the diagnostic screen, then to the therapy, and the treatment already in place.”
These -isms are frequently in the way of why—as we know through history and literature—people are offered certain therapies and others are not.
Not because they could or couldn’t, but because they were never asked.
And by the way, at the end of the day, in addition to race issues, there are class issues.
And what’s not being talked about with Tyre as well, is not only his African American status, but class.
When you start looking at both of those intersectionalities of being Black in America as well as being poor, whether you’re talking about the hollers of Beattyville, Kentucky, or you’re talking about the South Side of Chicago, there are more similarities in those two groups. And yet, we fail frequently to speak about that.
When it comes to policing—the data’s there to vet it out—African Americans certainly got pulled over more and treated more harshly, whether they have money or don’t have money.
But I guarantee that if you’re Black and you’re poor, that becomes an issue. The structural issues that we go in with our pre-biases, that extends well beyond law enforcement into what we do also in medicine.
The way to fight it is to first be cognizant of it, and then be able to hopefully develop these conversations where policies will help us get through this that don’t exist today. Hopefully with some thoughtfulness and some action, we can do better.
OB: Wrapping this up, you said a word that I just want to reemphasize, and that was humility.
I should point out, I don’t think you have to be Black to take care of Blacks.
As a matter of fact, my uncle, who was not a very educated man, but had some experiences in the health care system, used to always talk about how Jewish doctors understood him and took care of him well, because they cared.
He would talk about the history of what Jews have gone through in terms of persecution and so forth as one of the reasons why they cared, understood, and felt what the patient in front of him felt.
Now, that may be a little racist in itself, what he was doing, but I actually do think the point about humility, the point about caring about people, or just giving a damn, and the awareness that you might have some of these prejudices, and we all have them, is really important.
Humility, caring about the patient, and awareness that we all have these prejudices—we need to overcome them. I think that’s the solution to giving good high-quality care, no matter if you are a physician, a surgeon, a nurse, a medical student, a respiratory therapist, or a lab tech. Humility, caring about the patient, and then having awareness that we have these problems and trying to tamp them down.
I’m going to let you have the last word, Dr. Winn.
RW: Thank you for that. I’ll add only one thing, and that is having diversity at the table. I think when you can see your neighbor, whether they look like you or they don’t, and you can see their humanity, we tend to be much better off than when we don’t see each other’s humanity.
The only way to do that is by being mindful that access, not only to care, but access to becoming physicians, access to becoming directors of cancer centers, access to becoming deans, all that put together matter. We can disagree, but if you’re my neighbor, and I see you, and I get to hear you and your unique different viewpoints, I’m more likely to hear you and your differences. I’m more likely to hear a counter-argument from someone who I know and have humility and respect for than from someone who I don’t.
Michelle Obama said it better: “We have to do a better job of getting to know our neighbors, even those that we don’t actually agree with.”
We need to hear counterpoints so that we may actually be able to sharpen even our own ideals about why we think the way we do.
So, thank you for the opportunity, Dr. Brawley, to talk about this. The last word for me is not only may Tyre rest in peace, but hopefully, this déjà vu will be different. We will, hopefully, at a minimum, come out of this with some reasonable, practical laws that should have been put in place after George Floyd’s death.
We can only hope that it not only stimulates a change in law, but we can learn that there are also areas in health care that we need to work on so we can be our best selves for the patients we serve.
OB: Thank you. This has been a discussion about health care and lessons for health care from the unfortunate events of the last several weeks involving the beating of Tyre Nichols.
I want to thank Dr. Robert Winn, the director of the Massey Cancer Center at Virginia Commonwealth University and professor in the medical school at Virginia Commonwealth University, and February’s guest editor of The Cancer Letter.
I’m Otis Brawley. I’m the Bloomberg Distinguished Professor of Oncology and Epidemiology at Johns Hopkins, and I am the co-founder of the Cancer History Project. Thank you.
[post_title] => Otis Brawley & Robert Winn discuss the killing of Tyre Nichols and the power dynamics in policing—and health care [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_1 [to_ping] => [pinged] => [post_modified] => 2023-02-03 18:07:26 [post_modified_gmt] => 2023-02-03 22:07:26 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52415 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52415 ) [1] => Array ( [ID] => 52416 [post_author] => 2768 [post_date] => 2023-02-03 11:54:22 [post_date_gmt] => 2023-02-03 15:54:22 [post_content] =>Ten miles south of my job at the Chao Family Comprehensive Cancer Center, an Asian American elder opened fire and killed one person at the Taiwanese Presbyterian Church in Laguna Woods, CA.
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Six miles south of my home, an Asian American elder killed 11 people at a dance studio in Monterey Park, CA.
Four hundred miles north, another Asian American elder killed seven farmworkers in Half Moon Bay, CA.
As we continue to mourn for the victims and their families, the Asian American community is coping with a new reality. An elder that looks like our father, uncle, with a similar immigrant background, has killed several people that also look like us. Three recent mass shootings have forced the Asian American community to contend with the trauma and pain inflicted on us.
I intentionally use the racial term Asian American and not Asian. Owning guns and gun violence is not Asian, it is very much American.
This violence is not new, but it looks different. Many of us are still grappling from the increase in anti-Asian hate since the start of COVID-19—often with Chinese-looking elders as victims. For some Asian Americans, peace of mind now means owning a gun. Since 2021, there has been a 30% increase in gun ownership among Asian Americans.
I intentionally use the racial term Asian American and not Asian. Owning guns and gun violence is not Asian, it is very much American.
Our Office of Community Outreach and Engagement (COE) at the University of California, Irvine Chao Family Comprehensive Cancer Center (UCI CFCCC) has been on the frontlines of confronting extremism and anti-Asian hate. In June 2020, we coordinated a series of webinars in multiple Asian and Pacific Islander languages about anti-Asian hate, mortality and incidence of COVID-19, prevention, and access to care and services.
In May 2020, our COE office received a grant from Bristol Myers Squibb Foundation that helped form our coalition, Love our Vulnerable and Elderly (LOVE). Together with our community partners, we purchased, packaged, and delivered thousands of bags of rice, noodles, toilet paper, and Asian pantry items for cancer patients and isolated Asian American and Pacific Islander elders.
Like many COE offices, we pivoted and conducted cancer outreach and education by telephone in Korean, Mandarin, and Vietnamese. HIPAA-compliant virtual tools like Zoom are neither available in Asian languages nor user-friendly for Asian elders.
The community members we called expressed fear about going to the clinic for their routine cancer screening, and we observed that they were scared to leave the house.
In 2021, we helped set up several community COVID-19 vaccine clinics in the Asian American and Pacific Islander communities, particularly for elders and their caregivers. I asked a group of Cantonese elders in line for their vaccine why they each had a walking cane as they seemed able to walk without one. They said in case they were attacked on their walk over to the clinic, they would hit the perpetrator with their cane. My elderly mother has a cane for the same reasons as well.
Despite these disparities and the documented lack of funding to Asian American researchers, Asian Americans are still not considered an underrepresented population by the NCI and NIH. Currently, the NIH policy states that Blacks or African Americans, Hispanics or Latinos, American Indians or Alaska Natives, Native Hawaiians, and other Pacific Islanders are underrepresented.
I asked a group of Cantonese elders in line for their vaccine why they each had a walking cane as they seemed able to walk without one. They said in case they were attacked on their walk over to the clinic, they would hit the perpetrator with their cane. My own elderly mother also does the same.
Individuals from other racial and ethnic groups need to “demonstrate convincingly to be underrepresented by the grantee institution” (https://diversity.nih.gov/about-us/population-underrepresented). This places the burden on us, as Asian American cancer researchers, to continually educate and convince NCI, our own institutions, and journals that Asian Americans experience racial violence and health disparities.
How many more Asian Americans must die from gun violence and cancer for us to be heard, seen, and cared for?
天下太平 was written on a sign at the site of the Monterey Park mass shooting. It is a Chinese proverb that means “peace under the celestial sky.” Monterey Park is a city built by first-generation Cantonese and Toisan (Chinese dialects) immigrants who came to this country to flee war, starvation, and poverty. It is one of the few cities in the country with a majority of Asian Americans, 65%. It is a city built on grit, resilience, and perseverance.
As a child, I would regularly go with my parents to buy groceries in Monterey Park. The Chinese market we went to is still there and is next door to the Star Dance Studio, where the mass shooting occurred. As I recently walked the dance studio parking lot, I saw the outpouring of care, rows of flowers, incense, cards, and messages of love, peace, and safe journeys to the next life.
Three days after the Half Moon Bay mass shooting, I attended a statewide Asian American, Native Hawaiian, and Pacific Islander Health Equity Summit. Many of us in the room have been in the frontlines, translating and interpreting health information in 20+ languages, patient navigation, hate crime assistance, advocacy, civic engagement, mental health services, social services, the list goes on.
I didn’t need to explain myself in this room, we all collectively felt the edges and rawness of the moment. We have done so much, needed to do more, and find space to grieve and heal together.
“What does love look like in a time of hate?”
Celeste Ng answered this question in a 2021 article in The New York Times, showing a series of photos and stories about Asian Americans. I reread this article and it reminded me about the power we have as a community.
This moment will not define us, but instead our photos and stories of resilience, community, care, and LOVE will.
Cancer Treatment Centers of America will “fully transition” to City of Hope’s brand, giving the southern California-based cancer care health system a national footprint.
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As the widely recognized CTCA brand ceases to exist, its former outposts will become City of Hope Atlanta, City of Hope Chicago, and City of Hope Phoenix, City of Hope officials announced Feb. 1.
The name change will be communicated in a national advertising campaign, officials said.
“City of Hope undertook a thoughtful, collaborative integration period to ensure a smooth transition across operational, clinical, and administrative workstreams,” a City of Hope spokesperson said to The Cancer Letter. “As we form a national identity and create ‘One City of Hope’ across our clinical network, we see a number of benefits as we raise our profile with influential audiences, advocates and patients.
“Thanks to many recent accolades, including our top 10 ranking in US News & World Report Best Hospitals for Cancer list, City of Hope is becoming better known with national audiences. Patients coming to these CTCA locations are specifically interested in how CTCA doctors collaborate with City of Hope.”
City of Hope completed the $390 million acquisition of CTCA a year ago, with the goal of combining their strengths to create a national cancer research and treatment system with locations across the country. CTCA has been a for-profit, family-owned business that owned cancer centers in Chicago, Atlanta, and Phoenix (The Cancer Letter, Jan. 21, 2022).
“We saw that Cancer Treatment Centers of America is one of the most trusted brands among health care consumers in the country,” Robert Stone, president and CEO of City of Hope, said at the time to The Cancer Letter. “The CTCA acquisition will now mean we have care locations across four states and 41 care locations, with approximately 575 physicians and 11,000 employees. The combined organization will serve approximately 115,000 patients every year.”
After decades of aggressive marketing, CTCA has become one of the most recognized brands in the U.S. For example, the YouGov America survey of most popular hospitals continues to rank CTCA second, below Mayo Clinic and above Johns Hopkins Health.
We also continue to strengthen our leadership and operating model as we transform into a fully integrated, national system.
“City of Hope continues to invest in its clinical network, recruit new physicians and enhance the capabilities of all locations in its cancer research and treatment system,” the cancer center’s spokesperson said earlier this week. “We are in strong financial standing and building for the future with this announcement. For example, we’ve brought our world-renowned expertise in bone marrow and blood stem cell transplants and CAR T-cell therapy to our Phoenix and Chicago locations.
“To further support clinical consistency and the highest quality of care throughout the system, we are also scheduled to complete our Epic implementation across these locations in 2023.”
CTCA locations now function as nonprofit organizations, and City of Hope is implementing clinical and quality policies across all locations, with joint quality reviews and tumor boards.
To ensure a consistent patient experience throughout the national system, City of Hope has hired Kevin Manemann as chief integration officer for the clinical enterprise. Manemann joins City of Hope after 20 years with Providence St. Joseph Health, where he most recently served as the chief executive of the southern division and was responsible for 17 hospitals, a physician organization, surgery centers, immediate care centers, community care agencies, and a health plan with 700,000 lives covered.
“City of Hope is adding more talent across its clinical network. Since the acquisition, a number of cancer experts and outstanding clinicians have joined our Atlanta, Chicago, and Phoenix locations to be part of our transformation into a national cancer research and treatment system,” the City of Hope spokesperson said. “We want to fully realize the value of, and build on, the skills and expertise of our people to benefit patients and fulfill our strategic vision.
“We also continue to strengthen our leadership and operating model as we transform into a fully integrated, national system. Kevin joins Jo Ann Escasa-Haigh, who recently joined City of Hope as its chief business officer, and Phil Okala, who joined City of Hope in September 2022 as system president.”
City of Hope has grown over the past few years with the expansion of its clinical network in Southern California, the addition of the Translational Genomics Research Institute, the launch of its employer cancer care benefits offering AccessHope, the acquisition of CTCA and the opening of a new cancer center in Orange County.
“We’ve made substantial progress with the integration of CTCA and have served more patients than anticipated in the first year, with 134,000 patients treated by our shared organization in 2022,” the spokesperson said.
[post_title] => Exercising owner’s prerogative, City of Hope retires the Cancer Treatment Centers of America brand [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_3 [to_ping] => [pinged] => [post_modified] => 2023-02-03 18:01:11 [post_modified_gmt] => 2023-02-03 22:01:11 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52417 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52417 ) [3] => Array ( [ID] => 52418 [post_author] => 2768 [post_date] => 2023-02-03 11:52:26 [post_date_gmt] => 2023-02-03 15:52:26 [post_content] =>The National Cancer Institute defines precision medicine in cancer as a strategy that “uses specific information about a person’s tumor to help make a diagnosis, plan treatment, find out how well treatment is working, or make a prognosis.”1
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A quick perusal of the table of contents from the latest issues of any major oncology journal or a survey of ongoing cooperative group trials will underscore that a large proportion of clinical and basic investigation is focused on how oncologists might leverage precision medicine to improve treatment outcomes for patients.
Less often recognized, but critically important nonetheless, is the concept of physical precision. This is particularly relevant in radiation oncology, where the balance between delivering adequate tumoricidal doses of radiation must be balanced with the risk of damaging adjacent normal structures.
Built into this calculus is the inherent physical uncertainty with radiation therapy, particularly external beam radiotherapy. That is, the location and shape of the target, as well as the nearby normal tissues, can vary not only from day to day, but also during the delivery of a single dose of radiation. Because of these uncertainties, radiation oncologists often prescribe radiation not just to the intended clinical target, but rather to that target plus a margin around it. This total volume constitutes the “planning target volume” (PTV), and often overlaps with nearby organs. Within the context of radiation oncology, enhanced physical precision might lead to reducing the overall PTV, therefore potentially leading to reduced toxicity.
This concept is extremely relevant for patients with prostate cancer specifically. Approximately 288,000 American men will be diagnosed with prostate cancer in 2023.2 Thankfully, the vast majority will be diagnosed with clinically localized disease, and many men can be cured with either surgery or radiotherapy. Given the high cure rate and long life-expectancy following treatment for prostate cancer, quality of life (QOL) often remains paramount in decision making.3,4
When treating the prostate with radiotherapy, the major potential QOL declines are in the genitourinary (GU), gastrointestinal (GI), and sexual domains.5 With the exception of the prostatic urethra, the organs-at-risk with respect to GU, GI, and sexual toxicity after radiotherapy are presumed to be structures adjacent to the prostate (i.e., the bladder, rectum, and neurovascular structures). The PTV margin needed to ensure adequate dosing of the prostate will necessitate that portions of these organs-at-risk are included in the target volume.
Arguably, the importance of precision and accuracy becomes greater as the dose of radiation delivered per treatment session increases. Importantly, prostate cancer appears to be more sensitive than most cancers to the dose of radiation delivered per day, suggesting that condensing the radiation into a few high dose sessions might yield results that are, at minimum, equivalent to longer courses of radiation.6
Emerging clinical trial data have cemented stereotactic body radiotherapy (SBRT), a form of radiation in which ≤5 daily doses are delivered with high precision in generally five or fewer treatments, as a curative option for most men with localized prostate cancer.7 As suggested by the term “stereotactic”, SBRT relies on advanced imaging and treatment delivery techniques to ensure precise delivery of radiation to the PTV while minimizing dose outside the PTV.
What, precisely, contributes to the PTV?
The major sources of uncertainty that are considered when deciding on the required PTV margin are uncertainties related to prostate delineation and prostate motion.8 The prostate is best delineated using magnetic resonance imaging (MRI), but due to concerns related to electromagnetic interference, most linear accelerators (LINACs) delivering radiotherapy have only been equipped with computed-tomography (CT) or X-ray based imaging tools.
As such, prostate MRIs are often fused to CT-based imaging to help design the target for radiation, which imbues a small uncertainty into the prostate. To account for motion between individual doses of radiation, implanted markers are placed inside the prostate to provide a proxy for prostate position. Typically, these are radiopaque metallic markers that can be visualized on CT or X-ray. Motion during treatment can be managed either by shifting treatment based on frequent X-ray images focused on the fiducials, or limiting the treatment time as much as possible.
Having performed CT-guided SBRT for over a decade, we were able to query our institutional database to develop a margin formulation for the PTV that was based not just on theory, but on our own empirical observations.9 We found that a 3 mm margin around the prostate would be necessary to account for motion alone, and another 1 mm should be added for other residual uncertainties—this would translate a 4 mm total margin around the prostate.
By using volumetric arc therapy on an advanced CT-guided LINAC, an SBRT plan could be delivered in roughly 3-4 minutes. This margin formulation is well within the parameters of the standard-of-care margins used internationally. For instance, the large PACE-B and NRG-005 randomized trials recommend margins of 5 mm in all directions, with an option to narrow these to 3 mm in the posterior dimension.
Recently, two MRI-guided LINACs have become commercially available: the ViewRay MRIdian and the Elekta Unity. Both units have solved the aforementioned long-standing technical dilemma of integrating an MRI with a LINAC. MRI-guidance offers several theoretical advantages in the context of prostate radiotherapy.10
First, MRI-guided LINACs can monitor prostate motion directly, rather than relying on fiducial markers that are proxies for prostatic motion and require an invasive procedure to place.
Second, and perhaps most importantly, the frequency of monitoring is extremely high, and a “cine” MRI can be used to “gate” treatments on prostatic position. For instance, the MRIdian obtains an MRI four times per second. If a set percentage of the prostate target (say, 10%) is outside of a preset margin around the prostate (say, 3 mm), the radiation beam can be held automatically.
Third, the improved soft tissue contrast from an on-board MRI also improved the accuracy of alignment prior to radiation.
Fourth, residual errors resulting from fusing an MRI to a CT scan for accurate target delineation can be minimized if the on-board MRI is used directly for target delineation.
Given these enhanced imaging capabilities, we estimated that we could now use a PTV margin of only 2 mm – essentially 1 mm for motion, and 1 mm for residual uncertainty. But a salient question remained: would reducing these margins actually help patients?
While it may seem self-evident that radiating a smaller volume of tissues will lead to lower toxicity, not all apparently “obvious” truths can withstand the rigors of randomized testing. Indeed, oncologic literature is rife with examples where perfectly rational treatment strategies were ultimately found not to improve outcomes when tested in a randomized trial.10
When faced with a more complicated and costly intervention—even one with very limited risks, such as MRI-guided radiotherapy—the benefits to patients should be rigorously evaluated to assess the true value that is being achieved.2 Thus, the importance of randomized trials to rigorously evaluate whether a theoretical advantage can be actually realized in the clinic cannot be overstated.
Indeed, it is because of the importance of randomization that we designed the MIRAGE trial shortly after acquiring the MRIdian linear accelerator in the fourth quarter of 2019. The trial was designed to be a pragmatic, single-center randomized trial with a clearly defined early endpoint: acute moderate grade or greater genitourinary (GU) toxicity (i.e., grade ≥2) as measured on the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 scale. This endpoint was chosen because it could be scored within 90 days of treating a patient and because it occurs frequently enough that a single center trial could be reasonably powered to identify a change in its incidence.
Reliable estimates of the rate of grade ≥2 GU toxicity after CT-guided SBRT and MRI-guided SBRT were taken from the PACE-B trial1 (29.2%) and a single arm phase II trial from Amsterdam University Medical Centers29 (19%). Because the MRI-guided SBRT plan in Amsterdam trial used a 3 mm margin, we estimated that our toxicity rate might be lower, at 15%. The MIRAGE trial was thus designed to detect a 14% reduction in acute grade ≥2 GU from 29% to 15%. To detect this difference with 83.7% power with a one-sided, two sample Z-test at a 0.025 significance level would require 300 patients.
However, the target dosing we sought to employ in MIRAGE was more aggressive than had been used in either of the previous studies. Specifically, we planned to deliver 40 Gy to the entire PTV, while the PACE-B trial delivered 36.25 Gy to the PTV and the Amsterdam trial delivered 36.25 Gy to the PTV but reduced the dose around the urethra to 32.5 Gy. This escalated dose was chosen because we anticipated that we would treat patients with more aggressive disease than those treated on these prior studies, and our own research as well as work from others have suggested a dose-response with respect to biochemical control after prostate SBRT.11,12
Importantly, however, all trials of dose-escalation in prostate radiation oncology have identified that an increase in dose also leads to an increase in toxicity.13 Notably, toxicity following radiation depends not only on the total dose of radiation, but also the dose per fraction. As such, the effective difference for the bladder, urethra, and rectum between the MIRAGE target dose and the earlier doses ranges anywhere from 8 Gy to 14 Gy depending on assumptions about tissue radiosensitivity.
We know from multiple studies of radiation dose escalation that such large increases in dose will lead to increased toxicity.14 Therefore, we pre-specified that after 100 patients were eligible for analysis, we would perform an interim “futility” analysis to assess conditional power and re-estimate sample size. As it so happened, by the time 100 patients were eligible for this analysis (which occurred 90 days after the 100th patient was treated), 156 patients had already been enrolled and treated.
The analysis found that acute grade ≥2 GU toxicity was significantly reduced in men receiving MRI-guided SBRT versus CT-guided SBRT (22.4% vs. 47.1%, vs P = .01).15 It was concluded that 154 patients would be needed to have a conditional power of 89% to detect the hypothesized difference in toxicity, and therefore the trial was closed to accrual early.
While trials are always vulnerable to the vicissitudes of fate and fortune, it is important to underscore in this case that the trial was closed because the effect size observed on interim analysis (24.7% absolute difference) exceeded the hypothesized difference (14% absolute difference), suggesting enough patients had already been enrolled to detect the superiority of MRI-guided SBRT.
Of the 156 patients who received prostate SBRT on the MIRAGE trial, only 19% had favorable intermediate risk disease, supporting our decision to treat to a higher dose on this trial. With regards to other relevant variables, 44% had placement of a rectal hydrogel spacer, 24% received nodal radiation, 26% received a simultaneous integrated boost to the dominant lesion, and 68% received hormonal therapy, with no significant differences between arms for any of these parameters.
Prior to randomization, we stratified based on baseline International Prostate Symptom Score (IPSS) and prostate gland size, which are both known to impact post-treatment toxicity; these were thus also balanced between arms.
Before discussing the results of the final analysis, it is particularly important to discuss blinding. Ideally, a randomized trial would be double-blind to limit biases. In this case, the interventions being investigated were different enough (one requiring an invasive procedure to place fiducial markers, the other requiring multiple MRIs) that patient blinding would be impractical.
For similar reasons, the treating physician could not be blinded, as the treating physician would need to order, manage, and coordinate different procedures and different scans for patients on the different arms. In theory, an independent physician reviewer could have been used to adjudicate toxicity. However, this would also have been impractical for two major reasons.
First, the treatments are significantly different enough that an off-hand comment by the patient would immediately lead to unintentional unblinding (e.g., a comment about “being treated inside a tube” [only done on the MRI-guided SBRT arm] or about “having seeds put in my prostate” [referring to fiducial markers, only placed in the CT-guided SBRT arm]).
Second, the trial was designed and launched at the height of the COVID-19 pandemic. In fact, two patients (one on each arm) died of COVID-19-related complications before the 90-day window to assess toxicity was complete, leading to a final effective sample size of 154 patients. Thus, axillary patient-physician encounters for purely independent-adjudication in the context of clinical research would have been highly impractical, if even ethically permissible.
To attempt to mitigate this limitation, as well as the limitation of whether physician-scored toxicity is a relevant endpoint for patients, we also collected patient-reported outcomes. Specifically, all patients received IPSS and Expanded Prostate Cancer Index Composite-26 (EPIC-26) questionnaires at 1- and 3-months post-treatment. These were used to evaluate changes in urinary and bowel quality of life.
The primary endpoint results of the trial, published inJAMA Oncology on Jan. 12, 2023,6 therefore included not only physician-scored GU (and gastrointestinal, or GI) toxicity, but also IPSS and EPIC-26 changes. Overall, the primary endpoint of the trial was met and rates of grade ≥2 GU toxic effects were significantly lower with MRI vs CT guidance (24.4% vs. 43.4%, P = .01). Additionally, rates of grade ≥2 toxic effects were also significantly lower with MRI guidance vs CT guidance (0.0% vs 10.5%, P = .003).
After SBRT, urinary incontinence subdomain scores decreased significantly more with CT guidance vs MRI guidance at 1 month (11.3-point vs 6.2-point decrement; P = .01), but were no longer significantly different at 3 months). The percentage of patients with a clinically relevant increase in IPSS (>15 points) was significantly greater with CT guidance at 1 month (19.4% vs 6.8%, P = .01), but not at 3 months (1.4% vs 4.1%, P = .30).
Magnetic resonance imaging guidance vs CT guidance also resulted in a significantly smaller decrement in EPIC-26 bowel domain subscores at 1 month (4.1-point vs 18.2-point decrement, P < .001) but not at 3 months. A significantly larger percentage of patients treated with CT guidance experienced a clinically relevant (≥12-point) decrement in EPIC-26 bowel domain scores (50.0% vs 25.0%, P = .001).
Finally, a numerically greater decrement in EPIC-26 sexual domain scores was seen with CT guidance vs MRI guidance at 3 months (13.2-point vs 3-point decrement, P = .04; analysis restricted to men who did not receive androgen-deprivation therapy). Though the arms of the trial were well-balanced with respect to relevant variables like hydrogel use, nodal radiation, simultaneous integrated boost, and gland size, we did perform a post-hoc exploratory analysis to see whether the benefit of MRI-guidance still persisted after adjusting for these points. The results of this analysis suggested that trial arm remained associated with a 60% reduction in odds of grade ≥2 GU toxicity.
An open question, and one for which we encourage study, is whether alternative imaging and treatment delivery platforms could facilitate a similar reduction in PTV margins. A major challenge in designing and executing the MIRAGE trial was the need to randomize between two significantly different treatment platforms – a simple margin reduction trial conducted with both arms using the same technology would be significantly more straightforward to execute, in theory. However, to our knowledge, no such trial has been launched. We are actively exploring other aspects of treatment delivery, such as the frequency of beam-holds necessary due to prostate motion, which might be important factors with respect toxicity. We will also be reporting data on long-term side effects and oncologic outcomes.
In summary, the MIRAGE trial primary analysis demonstrates that the use of MRI-guidance in the context of prostate SBRT leads to reduced physician-scored and patient-reported urinary and bowel toxicity. This advantage is attributable to the fact that MRI-guidance allows enhanced physical precision, with a 2 mm PTV margin around the prostate being targeted rather than a standard-of-care 4 mm PTV margin.
Based on the positive results of the MIRAGE trial, we have changed our practice to offering MRI-guided SBRT as our preferred institutional standard of care. Patients who have implanted metallic objects or shrapnel, are extremely claustrophobic, or are completely pacemaker-dependent are not candidates for MRI-guided SBRT and still receive CT-guided SBRT (with 4 mm margins). Patients with minor claustrophobia, or who have implanted devices that are MRI compatible, can be treated with anxiolytic medications and appropriate supervision.
Perhaps the biggest takeaway from the trial is that as we enter the era of precision medicine in oncology, our definition of precision can and should extend beyond the biological precision that comes from a deeper understanding of cancer physiology. The physical precision of improved radiation planning and delivery devices, such as MRI-guided radiotherapy platforms, can also translate into meaningful benefits for patients. Indeed, the MIRAGE trial has shown us that the benefits of physical precision are not illusory, but tangible.
Amar Kishan is an associate professor of radiation and urology at the University of California, Los Angeles. He also serves as the Vice Chair of Clinical and Translational Research within the department of radiation oncology. He is responsible for running a clinical service focused on treating patients with genitourinary malignancies, as well as leading a clinical and translational research program designed to improve post-treatment quality of life and treatment efficacy for patients with prostate cancer. He has received grant funding from the Department of Defense, the American Society for Radiation Oncology, the Prostate Cancer Foundation, the National Institutes of Health, and Kure-It. He has also received research support from ViewRay Inc. (outside the scope of the MIRAGE trial), as well as honoraria from ViewRay Inc.
References
Richard Silvera is working to build trust between doctors Bronx communities that have a heavy burden of anal cancer.
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“There are higher rates of anal cancer among people with HIV. There are higher rates of anal cancer and poor anal cancer outcomes among Black populations as well,” Silvera, assistant professor of infectious disease at Icahn School of Medicine at Mount Sinai, said to The Cancer Letter. “Both of these communities have a lot of well-earned medical distrust, and that needs to be overcome, and actively overcome, by the people providing care. Or else, no matter how good the technology is, no one’s going to be there to receive it.”
Silvera, a recipient of a grant from the Robert A. Winn Diversity in Clinical Trials Award Program established in 2020 by the Bristol Myers Squibb Foundation, spoke with Winn, director and Lipman Chair in Oncology at VCU Massey, and senior associate dean for cancer innovation and professor of pulmonary disease and critical care medicine at VCU School of Medicine, about his work in the program.
For the third year, Winn is guest editor of The Cancer Letter during Black History Month. His interview with Silvera is the first of this year’s series documenting the the impact of Black doctors in the field this February.
A video of their conversation appears here.
What’s the first step to overcoming the distrust that Silvera speaks of?
“We need to have more diverse research professionals, not just physicians, but research assistants, aides, nurses, all these people need to be members of the community they’re caring for,” he said. “It gives you a common language to speak with your patients—yes, you can try to connect with people who come from different backgrounds than you do, but having a common experience is really a quick entry into a shared language of that person, a shared experience.”
With grant funds from the Winn Diversity in Clinical Trials Award Program, Silvera said he hopes to bridge advocacy and research.
“This program is nurturing my research career to get those first steps taken to be an established independent researcher,” he said. “Advocacy can be built into research questions if you ask the question correctly. I really would like to be a fully-formed, independent researcher, so I can have the ability to form those questions and ask those questions.”
Diversity in the workforce is key to advocating for patients in underserved communities—like patients with anal cancer who Dr. Silvera is treating in the Bronx.
“It also lets you bring the concerns of that community into the planning room, into the research protocol development room,” he said. “It lets you consider, what do these people care about? And can we represent those cares when we design this trial, when we recruit for this trial, when we think about how the trial is going to be set up? There are some things that are just really hard to know by reading a paper.
“You have to really live that life, and we need to have people with those experiences in those rooms when we develop these trials. Diversity of the workforce is also really, really important.”
Silvera lives in East Harlem, where the Young Lords—a group of revolutionary Afro-Latino activists—were once active.
“I live across the street from where their headquarters used to be, so I walk by it every day,” he said. “By commitment to their community, and by being innovative and being dedicated to what they were doing, they were able to accomplish so much—but they started with so little.
“And this reminds me, as a junior researcher, I feel like I have no funding. Well, you don’t need money. You just really have to try. Trying is more than half the effort,” he said. “While I may not have a multimillion-dollar research budget, I can accomplish something with what I do have.”
Robert A. Winn: We’re going to talk today about the Bristol Myers Squibb Foundation Program. To start off, how and why did you get into medicine?
Richard Silvera: My path to medicine was a little bit circuitous. I initially started my academic work as an English major.
I studied literature with this idea in the back of my head. I wanted to do medicine, but I didn’t have a real plan of how to do that. And then I finished my undergraduate training and didn’t really know what I wanted to do. I actually ended up working in clinical research—and I fell in love with clinical research.
I really wedded my love of stories, and taking individual stories, and finding the essential truth of those stories, and weaving them together into a larger truth that we applied to a whole population.
It let me find a way with that English major mindset to make medicine into a story that could be used to help multiple people. I found my way back to medicine that way, particularly the care of people with HIV.
That’s how I got back into medicine.
That’s a wonderful path. Now explain more about the HIV-and-cancer link.
RS: I got into the care of people with HIV, because I was really drawn to the complexity of their care. Not just the medical complexity, but the social complexity, the political complexity that all patients with that illness had that surrounding their care.
The complexities really attracted me, because of their interaction with the doctor-patient relationship. And then, as part of that, I always looked at medicine through a primary care lens. I really wanted to take care of people, become a part of their lives, and take care of them over a long period of time.
And as I got into HIV primary care, I learned more and more about the toll of anal cancer among people with HIV. It was affecting people with HIV regardless of the kind of life they were living or regardless of their exposures in the past.
There was a much higher rate of anal cancer in people with HIV. And it was so common that it was something that really needed to be addressed in primary care.
That really made the light go off in my head, because I loved research. I also loved primary care, and this wedded all the things I was interested in medicine. We’re caring for people with HIV, doing so in a primary care setting, and trying to do preventive medicine and keep people living longer.
I’m glad you said that. It’s interesting to me how you weave that complexity of the people in the communities and the various issues that are happening within them, and bring them closer to having the therapies that would be able to impact their lives favorably.
I was thinking about how the treatment has changed for anal cancers recently. Can you comment on the evolution, from when you started to your treatment right now? And what’s your hope in the future when it comes to anal cancer?
RS: There have been great innovations in treatments for anal cancers, but I think that ideally what I’m focusing on is prevention.
An ounce of prevention is really worth a pound of cure. While there’ve been great strides in treatment modalities, having less invasive treatments with better outcomes, I would rather prevent that cancer from happening in the first place if I could. That’s really the goal of my research right now.
We could have strides in anal cancer screening throughout even my career, because there’s a lot of new innovation happening in that field.
Since I’ve entered into this world of research, we are working to perfect our ways of screening for anal pre-cancers so we can then remove those anal pre-cancers before they become anal cancers. That approach has been validated recently in the ANCHOR trial. It’s a large, multi-site trial, which showed that removing pre-cancers effectively prevented anal cancer from developing.
That’s great, that’s wonderful. That tells us we have a way of preventing these cancers from happening before we have to worry about treatment outcomes. But we have to find those pre-cancers before we can treat them. And that is what my research is looking at, new ways to find those anal pre-cancers.
As you start thinking about how to find them, it actually depends on two areas: the technology and the ability to find them. It also depends on the community and their level of trust to be participants. How are you addressing those issues?
RS: We can have the most amazing technology in the world, but if people don’t trust you enough to come to your clinic to receive that technology, it’s pointless.
Building an infrastructure of research in these communities is going to be a step towards building their trust because it takes generations to build trust, and you can’t just do it in one afternoon.
Particularly in the populations that have a heavier burden of anal cancer, there’s a lot of very justified systemic distrust of the medical establishment. There are higher rates of anal cancer among people with HIV.
There are higher rates of anal cancer and poor anal cancer outcomes among Black populations as well.
Both of these communities have a lot of well-earned medical distrust, and that needs to be overcome, and actively overcome, by the people providing care. Or else, no matter how good the technology is, no one’s going to be there to receive it. There are many ways we can address this.
First of all—who is doing this research?
We need to have more diverse research professionals, not just physicians, but research assistants, aides, nurses, all these people need to be members of the community they’re caring for.
It gives you a common language to speak with your patients—yes, you can try to connect with people who come from different backgrounds than you do, but having a common experience is really a quick entry into a shared language of that person, a shared experience. It really is hard to duplicate otherwise.
It also lets you bring the concerns of that community into the planning room, into the research protocol development room. It lets you consider, what do these people care about? And can we represent those cares when we design this trial, when we recruit for this trial, when we think about how the trial is going to be set up? There are some things that are just really hard to know by reading a paper.
You have to really live that life, and we need to have people with those experiences in those rooms when we develop these trials.
Diversity of the workforce is also really, really important.
Until recently, there hasn’t been an emphasis on outreach and engagement for the community, even in social determinants of health. Can you tell me how that’s evolved for you?
I know you’re part of The Robert A. Winn Diversity in Clinical Trials Award Program established in 2020 by the Bristol Myers Squibb Foundation as part of its commitment to health equity, inclusion and diversity.
Can you talk about your participation and where you think trials are now and where development can ultimately go?
RS: So I’ve been fortunate enough to be one of the first recipients of The Robert A. Winn Diversity in Clinical Trials Award Program.
But I’d argue that I am honored, and I am actually benefiting from your getting out there and doing it.
RS: Good on both sides, for everyone. I’m part of the initial cohort, and this program does two really, really important things for the success of these studies.
First, from my perspective as a young investigator trying to learn the ropes of this world, a lot of what we need to know to be a successful researcher—how to develop a research trail, how to inform a research question, how to write a manuscript appropriately—all of those things are not necessarily taught in classrooms.
They’re a shadow curriculum that you have to learn from the people around you. People from diverse backgrounds may not have access to those shadow curriculums and those networks.
I think creating an infrastructure to get that information to people who may or may not have access to it, depending on their environment or their connections, is really important. It gives them entry into the places where they can do really important research.
Secondly, the focus on actual, tangible skills and thinking critically about how to engage diverse communities, how to build clinical trust, how to move clinical trials into non-traditional settings to try to meet patients where they are—not just have that be a line somewhere on a slide that they are just going to breeze over.
Having it be worthy of discussion and focus is a really important skill to do research on people who are often excluded from research because research structures are not built to cater to them.
Learning how to leverage those resources you might get, as a junior researcher, to engage these communities that so often are overlooked, I think is going to be really important for getting more people involved in research on both sides, both as the patient as well as as the investigator.
You said something that really resonated with me—it is building trust.
As you’re thinking about the importance of it in various communities—African American communities, Latino communities, LGBTQ communities—how can you, as an individual, help to build more trust? How can it then transition from the Winn Awards Program, so that our institutions become more trustworthy?
RS: If I had the answer to this question, I would already be on a world tour. But I think I have some ideas of how to work towards this.
The first step is just showing up and being present. And being present, not just when it’s helpful to you, but being present consistently.
In the world of research, where funding may be temporary, that can be really tough to accomplish. I think that’s one thing that the Winn Program is addressing—having it be a continuous stream of researchers from these communities, interested in these communities, being present in these communities.
We can create a continuous research presence in these communities that will then be a step towards proving that you’re not just there to exploit that community for a particular research question and then taking your pick of the data and leaving.
Instead, you’re there to actually invest in long-term solution building for these communities. Not just being one person’s random research question, but to have it be structured where there’s continued investment, continued presence, multiple research questions.
Building an infrastructure of research in these communities is going to be a step towards building their trust, because it takes generations to build trust, and you can’t just do it in one afternoon.
Also, having a commitment from institutions to make that investment, I think is going to be really important.
Changing gears just a bit, talking about history during Black History Month. If you could pick an historical figure who continues to inspire you to this day, who would that be and why?
RS: History is tough, because, in many ways, I think the experience of being a minority in America, you get divorced from your own history.
It has a disconnect where it doesn’t really feel like it’s your own. But I would say that—I’ll pick something a little controversial—this is something I learned about more recently.
The proximity to my experiences is actually really important. I did my residency training in the Bronx, here in New York.
As part of that, we learned a lot about the history of the Bronx and the history of healthcare in New York City. Before doing my training, I had never heard of the Young Lords, who were a group of revolutionary, Afro-Latino activists in East Harlem.
They’re very inspired by the Black Panthers, doing similar revolutionary work. But what they were able to accomplish for their community is really inspiring.
I live across the street from where their headquarters used to be, so I walk by it every day. To think that they really came from nothing. But by commitment to their community, and by being innovative and being dedicated to what they were doing, they were able to accomplish so much—but they started with so little.
And this reminds me, as a junior researcher, I feel like I have no funding. Well, you don’t need money. You just really have to try. Trying is more than half the effort.
I can take inspiration from them. They were able to build so much and have such a lasting impact, but they really started with so little. I’m lucky. While I may not have a multimillion dollar research budget, I can accomplish something with what I do have. And I find I can draw inspiration from that.
You bring up a good point that sometimes when we go back, we don’t really fully recognize the impact of some of the community activators and the community activists.
RS: Having people from those communities, being interested in people within those communities for the good of those communities, was something that happened in the ‘50s and ‘60s that manifests itself differently today.
Why can’t we get health and science closer and more open to our communities?
In that context, what is the long-term impact that you’re trying to achieve with both your research, and after completing this program? What does success look like for you?
RS: Participating in the Winn Awards Program and doing this research is going to let me engage with success in a few different ways.
This program is nurturing my research career to get those first steps taken to be an established independent researcher.
None of this work happens in isolation, but I don’t want to just be one researcher on an island by myself. I want to be part of a community of researchers doing this work.
To be able to do this, to address these research questions, to let me be the one who designs the questions, to let me be the one who asks the questions, and to be the one who decides how those questions will be asked.
Advocacy can be built into research questions if you ask the question correctly. I really would like to be a fully-formed, independent researcher, so I can have the ability to form those questions and ask those questions.
That’s one form of success. And I think that the Winn Awards Program has well-poised me to be able to do that by letting me get my feet off the ground and start moving in the direction to gather data, get some research accomplished, and to show that these issues are worthwhile.
Part of success is also building a legacy. Not just having it be an island, but having an influence on the next generation. One thing that attracted me to the Winn Awards Program was that there was a mentoring aspect of it.
Being able to work with medical students has created a network where there will be, two or three years from now, a new round of researchers who have already gotten their taste for this. They will then come in to be able to take over these studies, be my junior researcher, and be the fellow I work with on these next steps.
That is also a mark of success to not just be one person doing something, but be the beginning of a community of people doing something. This Winn Awards Program is a step towards doing that.
None of this work happens in isolation, but I don’t want to just be one researcher on an island by myself. I want to be part of a community of researchers doing this work.
There has already been some great collaboration with other people I’ve met in this program and the network that we’ve been able to develop.
It’s wonderful just being part of a community of researchers who care about these issues, focus on these issues, and make these issues a fundamental part of the research questions that we ask.
I love that. Really, it’s a fantastic response. The Robert A. Winn Diversity in Clinical Trials Award Program is unique in that it’s pioneering, bringing together the design implementation and bringing in awareness of the community. How does it feel to be part of a program in which you’re pioneering, or trying to blaze new paths?
RS: It really feels like coming home in many ways. That first day when we met all the other members—other people who were part of the program, other people who really were passionate about the same things that you were passionate about and cared about, and were upset or energized about the same things that they’d seen in the news or read. Like you’d found your people.
And so, while this is pioneering, it also felt really comfortable and felt right. It’s been surprisingly easy to be able to do this.
It’s been great to find those other researchers out there working in the same world with an interest in advocacy and equity. It has felt really comforting and great. It’s been really easy to be a pioneer in that regard.
I’m going to come through and give you a Zoom hug, man.
Last question:
What would you like to tell future applicants of the Bristol Myers Squibb Foundation’s Winn Awards Program? If you had any advice for them, what would that be?
RS: The biggest advice I would have is to bring your whole self to your research.
Don’t feel like you have to cut yourself away, or cut parts of your personality, or parts of your history, or parts of your interests that you think are not what a researcher is supposed to be, or what a researcher’s supposed to look like, or kinds of questions a researcher’s supposed to care about.
Don’t try to edit those out of yourself when you present yourself professionally.
I would encourage you to bring your whole self, bring all of your experiences, bring your whole history, bring all the things you’ve experienced, both positive and negative, the questions that you ask, to the applications that you present.
We may have been subconsciously told that those things aren’t valuable, but they are valuable in certain places. They’re valuable here.
And I think that this is a place where I would encourage you to bring your whole experience and your whole self and the questions you ask. They want all of you, not just the paper writing part of you.
They want everything. I would encourage you to just bring your whole self to the application.
That’s part of this mission we have with the program, to not only move and pursue academic excellence, but to also move towards academic relevance. It’s relevant to us, and it’s relevant to the communities we serve.
I appreciate that you took the time to talk with us today and reflect. Not just on the program, but you reflected on really what it is that we’re all trying to do, particularly during this Black History month. We are making sure that our communities are impacted not only today, but every day.
Is there anything else that’s on your mind?
RS: Just a happy Black History Month to everyone, and I hope that we can continue moving upward and forward. Other than that, just keep plugging away every day. No matter how dark things look, things are getting better slowly. Keep working at it.
Keep working at it. Exactly.
Thank you for taking time and keep up the good fight and keep blazing the trails. Great work. I am so proud and honored to be able to know that I know you as you are starting to do this work through the Winn Awards Program. You started some good things, and there’s some even greater things for you to accomplish. It will get done. Of that, I’m absolutely confident. I appreciate you.
RS: Thank you, Dr. Winn. I appreciate you, as well.
[post_title] => Richard Silvera is bridging advocacy and research through the Robert A. Winn Diversity in Clinical Trials Award Program [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_5 [to_ping] => [pinged] => [post_modified] => 2023-02-03 18:03:48 [post_modified_gmt] => 2023-02-03 22:03:48 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52419 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52419 ) [5] => Array ( [ID] => 52420 [post_author] => 2768 [post_date] => 2023-02-03 11:50:30 [post_date_gmt] => 2023-02-03 15:50:30 [post_content] =>Nearly three years ago, Robert A. Winn and Otis Brawley provided their unforgettable personal perspectives on the murder of George Floyd by Minneapolis police.
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Both recounted harrowing instances where structural bias in policing nearly cost them their lives.
Winn is director and Lipman Chair in Oncology at VCU Massey Cancer Center and senior associate dean for cancer innovation, professor of pulmonary disease and critical care medicine at VCU School of Medicine, and guest editor of The Cancer Letter for the duration of Black History Month. Brawley is the Bloomberg Distinguished Professor of Oncology and Epidemiology at Johns Hopkins University, and co-editor of the Cancer History Project.
This week, after the murder of Tyre Nichols by police in Memphis, Winn and Brawley engaged in a conversation about how systemic racism is present in law enforcement and health care. The story appears here.
As we see evidence of another killing by police, it’s important to revisit the editorials Winn and Brawley penned in 2020.
I am almost certain that no other director of an NCI-designated cancer center can claim the distinction of having had a gun pulled on them by police.
I‘ve had that experience not once, but twice.
I struggled a great deal in deciding whether to put something together this week in response to the senseless killing of Mr. George Floyd. His untimely death has stirred up a number of complex issues, which I thought I had wrestled under control.
If there is anything we’ve learned from the COVID-19 crisis, it’s that the boundaries between cancer and non-cancer can be porous. And health disparities come in bunches, bouquets of injustice. And, as a pulmonologist, I hear Floyd’s last words—“I can’t breathe.” Don’t tell me that chokeholds, literal and figurative, are anything other than a public health issue.
The past ten days have seen an outpouring of emotions as American society, devastated by the tragic murder of George Floyd by four Minneapolis police officers, plunges into a crisis of conscience.
Floyd’s death may be a pivotal point in America, similar to the televised beating of peaceful civil rights marchers by police on the Edmund Pettus Bridge in 1965. It has led to a number of protests and, unfortunately, some violence, including an attack by federal law enforcement as they beat and pepper-sprayed peaceful protesters in front of the White House.
The use of force against demonstrators in front of the White House is particularly ironic, considering that this entire series of events stems from an act of police brutality.
The police brutality is the tip of the iceberg. The fact is, it is the most obvious and dangerous aspect of systemic racism. There are a number of social injustices that collectively make blacks feel that their lives are not valued, and these issues are not being addressed by American society as a whole. Many Americans simply do not care, or aren’t aware.
If they are not aware, they are not listening.
Those who simply say, ‘I am not a racist’ are complicit in perpetrating the inequity. It is time for reflection, it is time for awareness, it is time for listening, it is time for empathy and caring.
Otis W. Brawley
A panel convened by the Cancer History Project for Black History Month started with a discussion of mentorship, and concluded with a big underlying concept—justice.
Edith Mitchell came a long way from growing up on a Tennessee farm, to becoming a brigadier general and serving on the President’s Cancer Panel.
“It was making a plan, having a plan, and all of us had similar type plans that we needed to leave the farm—yes I grew up on a farm—and get out of town,” Mitchell, member of the President’s Cancer Panel, clinical professor of medicine and medical oncology, director of the Center to Eliminate Cancer Disparities, and associate director of diversity affairs at Sidney Kimmel Cancer Center at Jefferson, Thomas Jefferson University. “Yes, you have success, but look back and pull somebody behind you, pull them up.”
Harold Freeman had big plans after he finished his residency at Memorial Sloan Kettering Cancer Center in 1968. He planned to cut cancer out of Harlem.
“I’m ready to do it. I’m skilled. I know how to cut cancer out. I want to cut it out of Harlem. I can’t do that. I can’t cut it out. It won’t yield. It won’t yield to the surgeon’s knife. It won’t yield to what we call the Bard-Parker, which was the name of the surgeon’s knife. Cancer wouldn’t yield,” Freeman said to The Cancer Letter in an interview with Robert A. Winn, director of VCU Massey Cancer Center, and John Stewart, founding director of LSU Health/LCMC Health Cancer Center. “Then I get to the reality, I can’t cut it out. Why? Because the people were coming in too late with cancer for me to be able to cut it out.”
Freeman made his career out of asking why it was that his patients, who were poor and Black, sought treatment too late. As president of the American Cancer Society in 1988-89, he published a study, “Cancer in the socioeconomically disadvantaged,” and made an unprecedented conclusion—“that the principal reason that Black people were dying from cancer was because they were poor.”
“It was a socioeconomic invasion that was deeper than the cancer invasion in the community,” Freeman said.
“In many ways, I would say he became a father to me. I didn’t anticipate having such a close personal relationship, but that’s what occurred, as I lost my own dad at that time,” said Wayne A.I. Frederick, president of Howard University, remembering his mentor, LaSalle Leffall, Jr.
“Dr. Leffall, in many ways, I think, went above and beyond just being a mentor. That shaped me in terms of my own experience being a father and my relationships with my 17-year-old son and my 15-year-old daughter. So much of this comes from that same attention to detail he put into my relationship.”
This column features the latest posts to the Cancer History Project by our growing list of contributors.
The Cancer History Project is a free, web-based, collaborative resource intended to mark the 50th anniversary of the National Cancer Act and designed to continue in perpetuity. The objective is to assemble a robust collection of historical documents and make them freely available.
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The Mark Foundation for Cancer Research has given two new Drug Discovery Awards.
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Launched in 2020, The Mark Foundation Drug Discovery Awards support high-risk, high-reward research and bridge the substantial gap in advancing promising academic discoveries to novel therapies. Based on key milestones along the continuum from target identification to preclinical development and initial regulatory filings, up to $25M is expected to be awarded over the next 5 years.
The two latest Mark Foundation Drug Discovery projects selected for more than $2 million in funding are:
Identifying small molecule inhibitors of SLC38A2/SNAT2 to treat pancreatic cancer
A group led by Alec Kimmelman at New York University Grossman School of Medicine and Seth Parker at the University of British Columbia is working to identify molecules that inhibit the amino acid transporter SLC38A2.
Kimmelman, Parker, and colleagues recently identified that pancreatic cancer cells express and depend on SLC38A2 for tumor initiation and growth. Now, they will carry out a screening campaign against SLC38A2 to identify inhibitors of the transporter. The hits from this screen represent the first step toward future medicinal chemistry with the goal of entering clinical development for the treatment of pancreatic cancer, the foundation said.
Developing CDK11B inhibitors as a novel anti-cancer strategy
A group led by Jason Sheltzer at Yale University and Jane Endicott at Newcastle University will expand upon Sheltzer’s recent discovery of a selective CDK11 inhibitor to further understand how targeting this enzyme could be used to treat cancer. CDK11 is a member of the cyclin-dependent kinase family, a group of enzymes important for cell cycle progression that are critical for tumor proliferation in many cancer types.
While they represent attractive targets for therapeutics, these enzymes have traditionally been difficult to inhibit in a selective manner, making drug development challenging. Sheltzer and his team previously determined that a compound which was thought to inhibit a different enzyme, was in fact inhibiting CDK11, making it one of the first selective CDK11 inhibitors described.
Now, by using this insight, this project will expand our understanding of CDK11 biology and provide a crucial foundation for future work directed at generating a first-in-class CDK11 inhibitor for patient testing.
“Most companies engaged in cancer drug discovery research are looking for projects that fit within narrowly defined criteria that align with their internal portfolio strategies and risk tolerance,” Ryan Schoenfeld, CEO of The Mark Foundation, said in a statement. “The Mark Foundation Drug Discovery Award program is a way for us to step in and fill a gap in academia that’s not being met by today’s drug companies nor by the traditional governmental funding programs. We have the flexibility to take risks earlier on promising, innovative ideas and approach cancer research funding on a broader scale.”
“In addition to providing funding, The Mark Foundation scientific team provides scientific and technical guidance to our grantees so that we can accelerate their ideas into the clinic,” Schoenfeld said. “We take advantage of our experience working with contract research organizations and other industry partners to provide grantees access to state-of-the-art drug discovery and development capabilities, as well as access to expert advice from our extensive network of experienced and highly accomplished industry advisors and consultants.”
Since the launch of the Drug Discovery Award program in 2020, more than $15 million has been awarded for drug discovery projects.
[post_title] => Teams led by Alec Kimmelman & Seth Parker, Jason Sheltzer & Jane Endicott receive $2M from The Mark Foundation [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_7a [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:26:01 [post_modified_gmt] => 2023-02-03 19:26:01 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52421 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52421 ) [7] => Array ( [ID] => 52422 [post_author] => 2768 [post_date] => 2023-02-03 11:44:34 [post_date_gmt] => 2023-02-03 15:44:34 [post_content] =>Laleh Amiri-Kordestani was named acting associate director for cardio-oncology in the FDA Oncology Center of Excellence. She will also continue her role as the division director for the Division of Oncology 1.
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Amiri-Kordestani joined FDA in 2012 as a clinical reviewer in the Division of Oncology Products 1. She served as the breast cancer team leader before serving as associate division director. She has served as the division director of DO1 since 2019, overseeing drug development for breast cancers, genitourinary cancers, gynecologic malignancies, and supportive care.
Amiri-Kordestani has had an active interest in cardio-oncology throughout her career at FDA and has represented FDA on numerous projects, external working groups, and publications focused on cardio-oncology. Cardio-oncology is an interdisciplinary field of medicine that focuses on the prevention, detection, monitoring, and treatment of cardiovascular disease occurring as a side effect of cancer therapy.
Amiri-Kordestani also has served as OCE’s scientific liaison for cardio-oncology. In this role, she has actively engaged with the international cardio-oncology community, chairing public cardio-oncology workshops.
In her new role in the OCE, Amiri-Kordestani will work closely with external stakeholders and other OCE programs and FDA Centers and Offices to provide direction, coordination, and oversight for scientific and policy efforts related to cardio-oncology.
[post_title] => Laleh Amiri-Kordestani named acting associate director for cardio-oncology at FDA OCE [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_7b [to_ping] => [pinged] => [post_modified] => 2023-07-10 14:39:37 [post_modified_gmt] => 2023-07-10 18:39:37 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52422 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52422 ) [8] => Array ( [ID] => 52423 [post_author] => 2768 [post_date] => 2023-02-03 11:43:37 [post_date_gmt] => 2023-02-03 15:43:37 [post_content] =>Sven Davisson was named associate director of administration at Louisiana Cancer Research Center.
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Since 2015, Davisson has served as chief administrative officer for the LCRC. Founded in 2002, the LCRC is a partnership bringing together the cancer research efforts of Louisiana State University Health New Orleans, Tulane University School of Medicine, Xavier University of Louisiana, and Ochsner Health.
Prior to joining the LCRC, Davisson spent 14 years at The Jackson Laboratory, an NCI-designated cancer center in Bar Harbor, ME, where he assisted with the submission of two P30 Cancer Center Support Grant competitive renewals. His final position at JAX was as senior director of sponsored programs, overseeing the research portfolio and support staff of JAX’s two primary research campuses in Bar Harbor and West Hartford, CT.
In his expanded role at LCRC, Davisson will support the director in ensuring that all cancer center activities meet NCI Cancer Center Support Grant guidelines in order to achieve and maintain a National Cancer Institute cancer center designation.
[post_title] => Sven Davisson named associate director of administration at Louisiana Cancer Research Center [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_7c [to_ping] => [pinged] => [post_modified] => 2023-07-10 14:39:34 [post_modified_gmt] => 2023-07-10 18:39:34 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52423 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52423 ) [9] => Array ( [ID] => 52424 [post_author] => 2768 [post_date] => 2023-02-03 11:42:38 [post_date_gmt] => 2023-02-03 15:42:38 [post_content] =>Moffitt Cancer Center, Weill Cornell Medicine, and the University of North Carolina School of Medicine received a $3.5 million, five-year grant from NCI to improve screening and preventative treatment of cervical cancer for women living with HIV in low-resource countries.
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Women living with HIV are more vulnerable to cervical cancer, especially in the low- and middle-income countries. Eighty-five percent of cervical cancer deaths occur in these settings, where high quality preventative services are often lacking.
As part of the HIV/Cervical Cancer Prevention ‘CASCADE’ Clinical Trials Network, investigators from the three institutions will develop trials to be conducted at clinical sites in Kenya, Uganda, and Botswana that were selected by NCI to be in the CASCADE Network. Cervical cancer is a preventable disease, but women in these areas of the world often present with advanced cancer that causes hardship and dramatically raises the likelihood of death.
“We have the tools already to make an immediate impact for these women. The challenge is how do we deploy them optimally? How do we sustain these services and engage women to accept them?” Timothy Wilkin, multiple principal investigator for CASCADE, professor of medicine in the Division of Infectious Diseases at Weill Cornell Medicine and an infectious disease specialist at NewYork-Presbyterian/Weill Cornell Medical Center, said in a statement.
To address these goals, Anna R. Giuliano, MPI of CASCADE, and founding director of Moffitt’s Center for Immunization and Infection Research in Cancer is collaborating with Wilkin and Carla Chibwesha, an associate professor of obstetrics and gynecology in the University of North Carolina’s Division of Global Women’s Health and the Lineberger Comprehensive Cancer Center, who is based in Johannesburg, South Africa.
“Since 2018, the World Health Organization has had elimination of cervical cancer as a global goal. The strategy to achieve this goal was approved by the World Health Assembly, a strategy that clearly highlights the importance of cervical cancer screening and treatment,” Giuliano said in a statement. “As each community has unique challenges to implementing screening and treatment, adaptation and innovation is required to assure that we can meet the ambitious goal that has been set. Hence the importance of continued research.”
The investigators are working with providers at study sites to identify challenges to screening patients for precancerous changes to the cervix, and to treating those patients found to be at risk.
[post_title] => Moffitt, Weill Cornell & UNC collaborate to improve HIV-related cancer care in low-resource countries [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_7d [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:26:16 [post_modified_gmt] => 2023-02-03 19:26:16 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52424 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52424 ) [10] => Array ( [ID] => 52425 [post_author] => 2768 [post_date] => 2023-02-03 11:41:41 [post_date_gmt] => 2023-02-03 15:41:41 [post_content] =>The International Cardio-Oncology Society has awarded University Hospitals Harrington Heart & Vascular Institute a Center of Excellence designation in recognition of its ongoing support of cancer patients facing heart issues. This Gold Status certification, the society’s highest designation, recognizes the institute for its commitment to cardiology services for cancer patients in whom life-saving treatments may cause cardiac problems.
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The innovative cardio-oncology program, founded in 2013, is a collaboration between UH Harrington Heart & Vascular Institute and UH Seidman Cancer Center.
The society awards this Gold Status Center of Excellence designation to programs with excellence in quality of care, standards of care, quality metrics, and program improvements. The designation is intended to not only acknowledge exceptional programs in cardio-oncology patient care, but to also award programs that contribute to local, regional, state, and national level education in cardio-oncology.
While cancer therapy has improved dramatically over the past several decades with a notable increase in survival rates, some cancer treatments such as chemotherapy and radiation can potentially cause heart problems. The development of unexpected heart issues can cause interruption and even discontinuation of cancer treatments. Therefore, keeping the heart healthy during cancer treatment is essential to delivering optimal patient care and achieving good outcomes. Cardio-oncologists are devoted to screening, monitoring, and treating any heart problem before, during, or after cancer therapy.
“Cancer treatments often result in significant physiologic changes to cells in the heart muscle, and patients have better health outcomes when their heart is monitored,” Zeeshan Hussain, advanced heart failure, heart transplantation, and cardio-oncology specialist with UH Harrington Heart & Vascular Institute, said in a statement. “Our cardio-oncologists are familiar with the medications, radiation treatments, and immunotherapies oncology patients receive—and how they may adversely affect their hearts, so we can proactively address any damage.”
The cardio-oncology program at UH provides comprehensive cardiovascular care for all cancer patients; more than 1,500 patients annually and between 60 to 100 new patients every month.
The program strives to provide high quality and accessible care in a variety of ways including same day appointment capability and an average time to appointment of less than one week. The program also features dedicated cardio-oncology nurse navigators to streamline patient triage and improve care coordination. It features three satellite clinics in the community in addition to the main location at UH Cleveland Medical Center.
[post_title] => University Hospitals awarded Gold Status certification for cardiovascular care of cancer patients [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_7e [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:26:19 [post_modified_gmt] => 2023-02-03 19:26:19 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52425 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52425 ) [11] => Array ( [ID] => 52427 [post_author] => 2768 [post_date] => 2023-02-03 11:30:45 [post_date_gmt] => 2023-02-03 15:30:45 [post_content] =>The V Foundation has established a grant program aimed at increasing female representation and female-led innovation in cancer research.
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A Grant of Her Own: The Women Scientists Innovation Award for Cancer Research is one of a few gender-specific grant programs designed to address gender inequities in cancer research funding. Awards will be given to outstanding female researchers at different stages in their careers.
The V Foundation will fund at least $8 million in grants.
The V Foundation will be awarding two separate grants as part of the inaugural award:
“By providing self-identified female investigators the necessary resources to begin and sustain impactful research and careers, A Grant of Her Own: The Women Scientists Innovation Award for Cancer Research will help address systemic gender disparities which have long existed and were further widened during the pandemic. These factors have kept women from fully contributing to the field of cancer research,” Susanna F. Greer, chief scientific officer of the V Foundation, said in a statement.
Compared to their male counterparts, women are paid less in comparable academic positions, receive lower startup funds for research with women scientists at some major institutes receiving 38% less in funding, and receive fewer awards from NIH grant programs at all points in their careers.
A survey of researchers found that female scientists and those with young children experienced a substantial decline in time devoted to research due to COVID-19. Given that time is of the essence in research, especially for scientists in the early stages of their careers, the losses experienced during the pandemic could have lasting effects on the number of women represented in cancer research.
“These female-specific grants expand on the V Foundation’s work to level the playing field by providing funds to support the research of all-star women scientists and those of color whose contributions are desperately needed to help us accelerate Victory Over Cancer,” Shane Jacobson, CEO of the V Foundation, said in a statement. “This year marks the 30th anniversary of the V Foundation, and from day one we have always been committed to female-led cancer research.”
V Foundation grants are awarded to researchers nominated by NCI-designated Cancer Centers and other exceptional research institutions and then selected by the Foundation’s Scientific Advisory Board.
Institutional nominations for A Grant of Her Own: The Women Scientists Innovation Award for Cancer Research must be submitted to the V Foundation by Feb. 15. Candidate applications are due to the Foundation on March 16.
[post_title] => The V Foundation establishes $8M grant program to increase female representation in cancer research [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_8 [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:19:39 [post_modified_gmt] => 2023-02-03 19:19:39 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52427 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52427 ) [12] => Array ( [ID] => 52428 [post_author] => 2768 [post_date] => 2023-02-03 11:25:47 [post_date_gmt] => 2023-02-03 15:25:47 [post_content] =>Age-based heuristics can lead to large differences in breast cancer treatment based on small differences in chronologic age, according to a new analysis of more than 500,000 patient records.
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Radiation therapy often is given after breast-conserving surgery to help prevent a patient’s cancer from returning. While post-surgical radiation may be omitted for certain patients with early-stage breast cancer—including older patients with lower-risk disease—it remains standard-of-care for patients with a higher risk of cancer recurrence.
In this analysis of nationwide data, however, researchers found that patients in this higher-risk subset who were age 70 at the time of diagnosis “were nearly twice as likely to be passed over for radiation” as those age 69.
Patients diagnosed at age 70 were 53% less likely to be recommended post-operative radiation and 39% less likely to receive it, compared to patients age 69. There were no similar gaps between other year-over-year age groups (68 vs 69, 70 vs 71, etc.).
The study, which is published in the International Journal of Radiation Oncology•Biology•Physics, is among “the first to demonstrate an age cutoff heuristic in oncology.”
“Our findings suggest that cognitive heuristics, or ‘rules of thumb,’ play a greater role in physician decision-making than we previously realized. It’s important that we center individual patients, with the unique characteristics of their cancer, as well as their individual preferences, in treatment decisions,” Suzanne B. Evans, senior author of the study and a professor of therapeutic radiology at Yale Cancer Center, said in a statement.
“While we would expect recommendations for this treatment to decline gradually as expected lifespan shortens, there seems to be a steep cliff when a patient moves from their 60s to their 70s. In breast oncology, physicians seem to anchor on a patient entering their 70s as a signal to de-escalate care, even in situations where evidence does not support this practice,” said Wesley J. Talcott, lead author of the study and a radiation oncologist with Northwell Health. “Our study indicates that physicians should be mindful of how we factor age into treatment decisions and adopt a more nuanced approach, extending beyond defining patients as simply ’young’ or ’elderly.’”
[post_title] => Study finds large gap in breast cancer treatment recommendations for patients aged 70 vs 69 [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_9a [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:16:55 [post_modified_gmt] => 2023-02-03 19:16:55 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52428 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52428 ) [13] => Array ( [ID] => 52429 [post_author] => 2768 [post_date] => 2023-02-03 11:24:49 [post_date_gmt] => 2023-02-03 15:24:49 [post_content] =>Although widespread use of immune checkpoint inhibitors in patients with advanced lung cancer has led to meaningful improvements in survival in younger patients, older patients have not experienced similar survival benefits, new research from Yale Cancer Center shows.
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The study was published in JAMA Oncology.
“There has been a great deal of excitement in the cancer community regarding the potential of immune checkpoint inhibitors to improve survival in patients with lung cancer,” Teja Voruganti, first author of the study, said in a statement. “The initial clinical trials that led to FDA approval for these treatments suggested impressive benefits. Now that these medications have been used in clinical practice for several years, it is critical to assess the survival benefits for patients in routine clinical practice, outside of the clinical trial setting.”
Prior work by senior author Cary Gross, professor of medicine and of epidemiology (chronic diseases) at Yale, and his team, demonstrated that patients enrolled in initial clinical trials that led to FDA approval of ICIs are often younger and healthier than patients with cancer in “real world” clinical practice.
“It is unclear whether the substantial benefits that we see in pre-marketing trials of cancer therapies in fact bear out when the treatments are used in everyday practice,” Gross said. “That’s what patients care about—they’re not just asking ‘What did the initial study show?’ They want to know, ‘What happens when people like me take this treatment?’”
For the study, the authors analyzed a large database of patients with advanced-stage lung cancer who were diagnosed from 2011 (which was prior to the discovery of ICI treatments) through 2019. They found that by the end of the study period, there was no difference in the use of ICIs between younger patients (age 55 and younger) and older patients (age 75 and older); just under half of the patients in each group were receiving ICIs. But the effect on survival outcomes differed dramatically: After ICIs were approved in 2015, survival increased from 11.5 months to 16 months among younger patients in 2019. However, in older patients the median survival increased from 9.1 months to 10.2 months over the same time interval. Notably, this is below the 2-3 month threshold for clinical benefit that the American Society of Clinical Oncology has defined as a “clinically meaningful” survival improvement for lung cancer.
Not only have ICIs opened new avenues of treatment in many different cancers, but the side effects of ICIs are often more well-tolerated than traditional chemotherapy. However, Gross cautions, “Any cancer treatment has a cost. Estimates of the cost of pembrolizumab, one of the ICIs used to treat advanced lung cancer, can be over $100,000 annually. Therefore, we need to critically look at the benefits of these treatments in our patients.”
“The use of immune checkpoint inhibitors has been touted as a ‘game changer’ in the treatment of lung cancer, but our findings show that the impact on older adults may not actually be clinically meaningful,” Gross said. “This is a wake-up call for patients, researchers, and policy-makers: We need to determine which cancer treatments are effective in older patients, rather than relying on assumptions. These are life and death questions—we need evidence.”
[post_title] => Older patients left behind in progress against lung cancer, Yale study shows [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_9b [to_ping] => [pinged] => [post_modified] => 2023-02-03 18:23:55 [post_modified_gmt] => 2023-02-03 22:23:55 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52429 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52429 ) [14] => Array ( [ID] => 52431 [post_author] => 2768 [post_date] => 2023-02-03 11:23:52 [post_date_gmt] => 2023-02-03 15:23:52 [post_content] =>Results from the SWOG S1416 clinical trial showed that adding veliparib to chemotherapy can significantly extend progression-free survival times in patients with TNBC that has a “BRCA-like” phenotype.
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Veliparib belongs to a class of drugs known as PARP inhibitors, which have been shown to be effective in treating breast cancer with germline mutations in the BRCA1 or BRCA2 gene. But this is the first trial to demonstrate a PARP inhibitor benefit in breast cancer that is not BRCA1/2-mutated, but is BRCA-like based on the presence of other changes that similarly affect cells’ DNA repair abilities.
Results from the trial, which was led by researchers from SWOG Cancer Research Network, a cancer clinical trials group funded by NCI, are published in Lancet Oncology.
Priyanka Sharma, a SWOG investigator who is professor of medicine at the University of Kansas Medical Center was co-lead author on the paper with Eve Rodler, associate professor of medicine at University of California, Davis.
“SWOG S1416 is the first trial to report benefit of a PARP inhibitor in metastatic TNBC with a BRCA-like phenotype in absence of germline mutations in BRCA1 or BRCA2 genes,” Sharma said in a statement. “BRCA-like phenotype is noted in 40-50% of triple negative breast cancers, making these findings and BRCA-like classification relevant for a substantial proportion of patients with TNBC.”
The researchers randomized 320 patients with metastatic breast cancer to either cisplatin chemotherapy plus the PARP inhibitor veliparib or cisplatin chemotherapy plus a placebo. Patients had breast cancer that was either triple-negative (without estrogen or progesterone receptors or HER2 overexpression) or was HER2 negative and suspected to be associated to germline mutations in BRCA1 or BRCA2.
After patients were randomized, researchers tested their blood and tumor tissue for biomarkers and, based on the results, assigned patients to one of three distinct groups describing their type of breast cancer: BRCA-mutated, BRCA-like, or non-BRCA-like.
The S1416 team found that among patients who had BRCA-like breast cancer, those treated on the veliparib arm had statistically significantly longer median PFS than those on the placebo arm: 5.9 months versus 4.2 months. These patients had a numerically better median overall survival time and objective response rate than patients on the placebo arm, however, these differences did not achieve statistical significance.
The researchers further reported higher overall rates of grade 3/4 treatment-related adverse events on the veliparib arm than on the placebo arm (74% versus 52%), including higher rates of grade 3/4 neutropenia, anemia, and thrombocytopenia.
“While these results are not immediately practice changing, since veliparib is not FDA approved,” Sharma said, “S1416 findings open new clinical trial directions by extending the patient population that could benefit from PARPi therapy. With demonstration of efficacy in BRCA-like phenotype TNBC, S1416 results provide a basis for expanding the therapeutic role of PARP inhibitors (e.g., veliparib) beyond germline BRCA mutation in breast cancer.”
Study S1416 is supported by the NCI, led by SWOG Cancer Research Network, and conducted by the NIH-funded NCI National Clinical Trials Network. AbbVie, Inc. provided veliparib through a collaborative agreement with the NCI.
This work was funded by the NIH/NCI through grants CA180888, CA180819, CA180820, CA180821, and CA180868 and National Institute of General Medical Sciences grant P20 GM130423. Additional support was provided by AbbVie, Inc. and Myriad Genetics, Inc. The work was also supported in part by funding from a Biomarker, Imaging, & QOL Studies Funding Program award from the NCI.
[post_title] => SWOG S1416 study results show PARP inhibitor benefit in “BRCA-like” breast cancer [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_9c [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:16:54 [post_modified_gmt] => 2023-02-03 19:16:54 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52431 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52431 ) [15] => Array ( [ID] => 52433 [post_author] => 2768 [post_date] => 2023-02-03 11:22:02 [post_date_gmt] => 2023-02-03 15:22:02 [post_content] =>Data from a Yale Cancer Center-led clinical trial show improved rates of survival and reduced risk of recurrence in patients taking Tagrisso (osimertinib), a targeted therapy for non-small cell lung cancer.
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The phase III ADAURA clinical trial assessed the safety and efficacy of Tagrisso in patients with completely resected stage 1B-2A NSCLC, who were previously treated with or without adjuvant chemotherapy. The updated trial results were published in the Journal of Clinical Oncology on Jan. 31.
The new data show there are ongoing benefits for patients with NSCLC taking Tagrisso, including prolonged disease-free survival over placebo, reduced risk of local and distant metastases, and improved central nervous system DFS.
“These data demonstrate a new paradigm demonstrating the importance of using targeted therapy against epidermal growth-factor-driven tumors as early as possible in the course of a patient’s disease,” Roy S. Herbst, lead author and principal investigator of the trial, Ensign Professor of Medicine (Medical Oncology), and professor of pharmacology and deputy director at Yale Cancer Center, said in a statement. “The results have led to a new standard of care in this disease setting.”
Herbst is also chief of medical oncology and director of the Center for Thoracic Cancers at Smilow Cancer Hospital and the Yale Cancer Center, and assistant dean for translational research at Yale School of Medicine.
The trial enrolled 682 patients with stage 1B-2A NSCLC, who were randomly assigned to receive Tagrisso once daily or a placebo. Herbst and his research team found that fewer patients treated with Tagrisso experience recurrence. Data also showed that fewer patients had distant metastases when compared to the placebo group.
The study found that disease-free survival over four years was 73% for the Tagrisso group and 38% for the placebo group. Fewer patients who were randomly assigned Tagrisso had disease recurrence (27%) than those in the placebo group (60%). The data from this study demonstrate prolonged DFS and reduced local- and distant-recurrence of symptoms, supporting Tagrisso as a highly effective treatment in patients with resected EGFR-mutated stage 1B-2A NSCLC.
“This therapy was well tolerated and prevented patients from developing metastasis to distant sites such as the brain, bone, and other areas of the lungs,” Herbst said. “This has truly impacted the lives of our patients.”
The study was supported by AstraZeneca, the manufacturer of Tagrisso.
[post_title] => Yale-led trial shows significant disease-free survival in NSCLC [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_9d [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:16:59 [post_modified_gmt] => 2023-02-03 19:16:59 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52433 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52433 ) [16] => Array ( [ID] => 52434 [post_author] => 2768 [post_date] => 2023-02-03 11:21:03 [post_date_gmt] => 2023-02-03 15:21:03 [post_content] =>Merck will stop the phase III KEYNOTE-991 trial investigating Keytruda (pembrlizumab), Merck’s anti-PD-1 therapy, in combination with Xtandi (enzalutamide) and androgen deprivation therapy for the treatment of patients with metastatic, hormone-sensitive prostate cancer.
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Merck said it’s discontinuing the study based on the recommendation of an independent Data Monitoring Committee which reviewed data from a planned interim analysis. At the interim analysis, Keytruda in combination with Xtandi and ADT did not demonstrate an improvement in overall survival or radiographic progression-free survival, the trial’s dual primary endpoints, compared to placebo plus Xtandi and ADT.
The safety profile of Keytruda in this trial was consistent with that observed in previously reported studies, the company said. No new safety signals were identified; however, the combination was associated with a higher incidence of grade 3-5 adverse events and serious adverse events compared to the control arm.
Merck’s clinical development program is evaluating Keytruda as monotherapy and in combination with other anti-cancer therapies in the phase II trials KEYNOTE-199 and KEYNOTE-365 and the phase III registrational trial KEYNOTE-641. Additionally, in July 2022, Merck entered into a global development and commercialization agreement with Orion Corp. for Orion’s investigational candidate ODM-208 (MK-5684), which is currently being evaluated in a phase II clinical trial for the treatment of patients with metastatic castration-resistant prostate cancer.
[post_title] => KEYNOTE-991 trial evaluating Keytruda + Xtandi + androgen deprivation therapy in hormone-sensitive prostate cancer is stopped for futility [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_9e [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:16:57 [post_modified_gmt] => 2023-02-03 19:16:57 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52434 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52434 ) [17] => Array ( [ID] => 52435 [post_author] => 2768 [post_date] => 2023-02-03 11:20:05 [post_date_gmt] => 2023-02-03 15:20:05 [post_content] =>Patients with myelofibrosis had clinically significant improvement in disease-related symptoms, including anemia and spleen enlargement, when treated with the targeted therapy momelotinib, according to results from the international phase III MOMENTUM trial led by researchers at MD Anderson Cancer Center.
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Momelotinib is sponsored by GSK.
The findings, published in The Lancet, support the use of momelotinib—a potent ACVR1/ALK2 and JAK1/2 inhibitor—over the standard therapy danazol in treating myelofibrosis patients that were resistant, refractory, or intolerant to firstline therapy, especially symptomatic patients and those with anemia.
“Current options for managing anemia in our myelofibrosis patients provide only modest and temporary benefits, so we are excited about these findings,” study lead Srdan Verstovsek, professor of leukemia, said in a statement. “The trial results suggest that momelotinib is safe, well-tolerated, and can improve one of the most common and debilitating clinical problems for this patient population.”
Myelofibrosis is an uncommon bone marrow cancer that is part of a group of diseases known as myeloproliferative neoplasms. A hallmark of the disease is dysregulated JAK signaling, which disrupts the body’s normal production of blood cells and leads to common symptoms, including an enlarged spleen and anemia. Chronic anemia in these patients is associated with poor prognoses.
Currently approved JAK inhibitors can improve spleen responses and other disease-related symptoms, but they also can worsen anemia. In this trial, momelotinib improved anemia and reduced transfusion dependency in myelofibrosis patients previously treated with a JAK inhibitor. Momelotinib can be administered and maintained at full dose because it does not suppress bone marrow activity like other JAK inhibitors.
The MOMENTUM trial is the first randomized phase III study to evaluate a JAK1/2 and ACVR1/ALK2 inhibitor in patients with myelofibrosis and anemia. The trial was designed to compare the clinical benefits of momelotinib to danazol, a synthetic androgen currently used to treat anemia in symptomatic myelofibrosis patients.
The study enrolled 195 adult patients from 107 research sites across 21 countries. Trial participants were randomly assigned (2:1) to receive momelotinib plus placebo or danazol plus placebo. Sixty-three percent of participants were male and 37% were female. The median age of participants for the momelotinib group was 71 years and for the danazol group 72 years.
The trial’s primary endpoint was symptom reduction after 24 weeks of treatment, defined as a 50% or more reduction in Myelofibrosis Symptom Assessment Form Total Symptom Score. A significantly greater proportion of patients who received momelotinib saw benefits in their disease symptoms (25%) compared to those receiving danazol (9%).
Patients treated with momelotinib also experienced a significant reduction in their spleen size, with 25% responding after 24 weeks of therapy. Additionally, these patients required fewer blood transfusions compared to those receiving danazol.
The safety profile of momelotinib was comparable to previous clinical trials, the company said. The most common non-hematological side effects experienced by trial participants in the momelotinib group included diarrhea, nausea, weakness, and itching or irritated skin.
[post_title] => Momelotinib provides significant symptom and anemia improvements for myelofibrosis [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_9f [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:14:48 [post_modified_gmt] => 2023-02-03 19:14:48 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52435 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52435 ) [18] => Array ( [ID] => 52437 [post_author] => 2768 [post_date] => 2023-02-03 11:19:08 [post_date_gmt] => 2023-02-03 15:19:08 [post_content] =>A proof-of-concept, single-arm, phase II clinical trial, led by investigators from the Mass General Cancer Center, reported a long-lasting response among patients who responded to the combined treatment and reveals how a targeted therapy may cooperate with an immunotherapy for better results.
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The paper, published in Nature Medicine, included 37 patients with BRAF V600 mutations, which are found in about 10% of colorectal cancers. The work represents the first clinical trial combining immunotherapy and targeted therapy for this patient population.
“By combining [immunotherapy and targeted therapy], we saw a dramatic increase in patients who responded to treatment and unprecedented durability, with 18% of patients staying in the trial for a year or more,” co-corresponding author Ryan Corcoran, director of the Gastrointestinal Cancer Center Program and physician-investigator in the Mass General Cancer Center, said in a statement.
The findings suggest the potential for these two therapies to cooperate when given together, meriting further clinical investigation and pre-clinical experiments to determine the best targeted approach to increase immune reactivity against colorectal cancer with mutated BRAF, co-corresponding author Nir Hacohen, director of the MGH Center for Cancer Immunotherapy, said.
BRAF mutations occur in many kinds of cancers, most commonly in melanoma. However, response to BRAF inhibitors occurs in less than 5% of patients with colorectal cancer in which BRAF has been mutated. Immunotherapy—which has also been extremely effective against some types of cancer—has generally not worked well against colorectal cancers, with the exception of approximately 4% of cancers with an unusual feature known as microsatellite instability.
Corcoran, Hacohen, and colleagues drew inspiration for the clinical trial from observations seen in preclinical models. In these models, investigators saw signs that inhibitors targeting the MAPK pathway, including BRAF, might enhance the immune system’s response. Based on these observations, the team investigated whether combining a therapy targeting BRAF could enhance the effectiveness of the immunotherapy.
To investigate this potential cooperativity, the investigators analyzed samples collected from 71 patients before and during an earlier clinical study in which patients received BRAF targeted therapy only.
Using single-cell RNA sequencing, the team looked for molecular changes that occurred due to treatment. Based on what they saw, they initiated a clinical trial in which patients with a specific BRAF mutation known as V600E received the BRAF inhibitor Tafinlar (dabrafenib), the MEK inhibitor Mekinist (trametinib), and the immunotherapeutic drug spartalizumab.
The study met its primary endpoint, with a confirmed response rate of 24.3% of patients (compared to a response rate of only 7% in a prior trial where patients were treated with the same targeted therapies alone).
The team also saw promising results in one of the trial’s secondary endpoints: durability. When BRAF or MEK inhibitors have been given to colorectal cancer patients with BRAF mutations in the past, even among those who responded, the clinical benefit has been short-lived. But the combined treatment increased durability with a median progression-free survival of 5 months (versus 3.5 months with BRAF/MEK alone), with 57% of patients remaining on treatment for more than 6 months and 18% for more than a year.
The team also performed single-cell RNA sequencing on samples collected before and on day 15 of combined treatment. For patients who had better clinical outcomes, investigators saw an increase in tumor cell-intrinsic immune programs and more complete MAPK inhibition. This suggested that improving MAPK inhibition, perhaps by focusing on other treatment targets in the pathway, may drive a greater immune response and improve treatment overall. Other clinical trials are currently underway to further explore this.
Corcoran said that the implications of the work may go well beyond colorectal cancer.
“For almost every type of cancer, a large percentage of tumors will harbor mutations in the MAPK pathway,” he said. “Our work suggests that combining other treatments that target this pathway with an immunotherapy could lead to a cooperative, enhanced immune response that may improve outcomes for patients.”
[post_title] => Immunotherapy + targeted therapy for CRC shows positive phase II results [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_9g [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:17:06 [post_modified_gmt] => 2023-02-03 19:17:06 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52437 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52437 ) [19] => Array ( [ID] => 52436 [post_author] => 2768 [post_date] => 2023-02-03 11:18:06 [post_date_gmt] => 2023-02-03 15:18:06 [post_content] =>A study, led by Randy Vince Jr. and Daniel Spratt, demonstrated the link between cancer outcomes and social determinants of health, as opposed to only race.
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It is commonly known that Black men have worse prostate cancer outcomes than white men. This association is often described as being driven largely by race in biomedical research, as opposed to other factors such as institutional racism and SDOH.
Vince and Spratt recently published in the Journal of Clinical Oncology that less than 5% of studies throughout history acknowledge that race is a social construct, nor was there any acknowledgment that this association is potentially driven by racism and SDOH. These findings led to the present study, published by JAMA Network Open Jan. 11.
This was a meta-analysis of 47 studies of more than 1 million men with prostate cancer. Each individual study investigated the association of race with death from prostate cancer and overall survival between Black and white men. The authors developed a tool to capture the extent that SDOH were accounted for in each study.
In the studies with minimal accounting for SDOH, Black patients had significantly higher mortality than white patients.
However, Black men had significantly lower mortality from prostate disease (called prostate cancer-specific mortality—PCSM) in studies with greater accounting for SDOH. This powerful result highlights the importance of how racial disparities and health outcome research are conducted, as improper methods can lead to improper conclusions that inadvertently perpetuate racialization.
“These findings coincide with the commonly said phrase, ‘racism is the risk factor, not race,’” Vince, assistant professor of urology and director of Minority Men’s Health at University Hospitals, Case Western Reserve University School of Medicine and the lead author of the study, said in a statement. “I hope our results will motivate researchers and society to rethink how we analyze and attempt to address racial disparities. In order to address the current inequities at hand, we must acknowledge the past that has led us to this position. Any efforts to achieve equity that do not recognize and attempt to reverse the impact of various forms of racism will continue to be futile.”
“The scientific and biomedical fields have inadvertently perpetuated the notion that race, rather than racism, impacts cancer outcomes. This is especially true when it comes to the inferior outcomes for Black patients with cancer,” Spratt, senior author and Vincent K. Smith Chair in Radiation Oncology and professor in the Department of Radiation Oncology at UH Seidman Cancer Center and Case Western Reserve University, said in a statement. “Our study not only demonstrates that most health outcomes research conducted on race and prostate cancer outcomes adjusted for few if any confounding SDOH variables, but when accounting for SDOH even partially, Black men had similar to improved cancer outcomes compared to white men.
“As race is a social construct, this should not be surprising. However, medical education has been shown to rarely teach, and the biomedical scientific community to rarely report, that differences observed between Black and white patients are often driven by SDOH and racism, not race.”
[post_title] => UH Seidman study demonstrates importance of SDOH when evaluating the association of race and cancer outcomes [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_9h [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:17:10 [post_modified_gmt] => 2023-02-03 19:17:10 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52436 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52436 ) [20] => Array ( [ID] => 52439 [post_author] => 2768 [post_date] => 2023-02-03 11:17:10 [post_date_gmt] => 2023-02-03 15:17:10 [post_content] =>Phase I results from the phase I/II study of Rezlidhia (olutasidenib), an investigational, oral, small molecule inhibitor of mutant isocitrate dehydrogenase-1, suggests that Rezlidhia, with or without azacitidine, was well-tolerated and was associated with improvements in clinical efficacy endpoints in patients with mIDH1 acute myeloid leukemia.
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Rezlidhia is sponsored by Rigel Pharmaceuticals, Inc.
In the study, published in The Lancet Haematology, Rezlidhia was assessed as a monotherapy or in combination with azacitidine, in patients with mIDH1 AML or myelodysplastic syndrome.
Among patients receiving combination therapy, treatment-naïve AML patients saw a 77% overall response rate and a 54% complete response plus CR with partial hematological recovery. These results provide strong rationale for future evaluation of either sequential or triplet therapy in this setting.
In the MDS cohort, 4 of 9 responding patients achieved mutation clearance. CRs were observed with both monotherapy and combination therapy, including an 86% ORR and 57% CR rate in the combination arm.
The investigators noted, “To our knowledge, we also report the first available data on patients with myelodysplastic syndrome treated with an IDH1 inhibitor plus azacitidine, where we observed a strong preliminary activity signal.”
Rezlidhia was well-tolerated in patients with AML and MDS, either as monotherapy or in combination with azacitidine. No dose limiting toxicities occurred in the dose escalation cohorts. Overall, adverse events were similar and manageable across the monotherapy and combination arms. Transient QT prolongation was observed in 3 patients (4%). This study showed that Rezlidhia has the potential to provide an additional treatment option for mIDH1 AML.
[post_title] => Rezlidhia shows positive results for mIDH1 AML in phase I/II study [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_9i [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:17:12 [post_modified_gmt] => 2023-02-03 19:17:12 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52439 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52439 ) [21] => Array ( [ID] => 52438 [post_author] => 2768 [post_date] => 2023-02-03 11:16:09 [post_date_gmt] => 2023-02-03 15:16:09 [post_content] =>Patients who have intrahepatic cholangiocarcinoma caused by specific FGFR2 gene alterations may soon have a better treatment option that more successfully targets that mutation.
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That is the conclusion of a recent phase II study in The New England Journal of Medicine, co-authored by University Hospitals Seidman Cancer Center’s Amit Mahipal and colleagues across the country.
The research team tested the FGFR2 inhibitor Lytgobi (futibatinib) in 103 patients with unresectable or metastatic intrahepatic cholangiocarcinoma caused by specific FGFR2 gene alterations. These FGFR2 fusions or rearrangements occur in up to 14% of patients with this rare form of cancer. Patients in the study had previously received one or more types of systemic therapy. Results show that 42% of patients had a response to treatment with the new FGFR2 inhibitor, with the median duration of response of 9.7 months.
These results are especially important because of the limitations of other FGFR2 inhibitors in treating this poor-prognosis cancer, Mahipal said. Other FGFR2 inhibitors, Pemazyre (pemigatinib) and Truseltiq (infigratinib), have received accelerated approval from FDA for treating this form of cancer. But when they bind with receptors on the cancer cell, that binding process can sometimes be reversed and can result in new mutations in resistance to the therapy.
“The irreversible nature of binding and its distinct binding site make futibatinib less susceptible to on-target resistance mutations than pemigatinib and infigratinib,” Mahipal said in a statement. “In preclinical experiments, futibatinib showed stronger activity against a wider spectrum of FGFR2 mutations than other FGFR inhibitors. Furthermore, fewer drug-resistant clones emerged with futibatinib treatment. Data from this study establish futibatinib as having measurable clinical benefit in patients with this disease and show the value of molecular profiling in identifying tumors that are likely to respond to FGFR2 inhibition.”
[post_title] => Phase II study shows positive results for new treatment for a form of intrahepatic cholangiocarcinoma [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_9j [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:17:14 [post_modified_gmt] => 2023-02-03 19:17:14 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52438 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52438 ) [22] => Array ( [ID] => 52441 [post_author] => 2768 [post_date] => 2023-02-03 11:15:13 [post_date_gmt] => 2023-02-03 15:15:13 [post_content] =>A drug that recently received accelerated approval from FDA to treat a form of non-small cell lung cancer caused by a unique genetic mutation also appears to be effective against advanced pancreatic cancer caused by the same uncommon mutation.
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The study, published in The New England Journal of Medicine, was co-authored by UH Seidman Cancer Center’s David Bajor.
The safety and efficacy of the study medicine sotorasib, a KRAS G12C inhibitor, had previously been unknown among previously treated patients with KRAS p.G12C–mutated pancreatic cancer. Study results show that sotorasib showed anticancer activity and had an acceptable safety profile in patients with KRAS p.G12C–mutated advanced pancreatic cancer who had received previous treatment.
KRAS p.G12C mutation occurs in approximately 1-2% of pancreatic cancers.
The research team says that these results are quite promising and suggest that inhibitors could even be developed for KRAS mutations that are linked to more common forms of pancreatic cancer.
[post_title] => UH Seidman discovers newly-approved NSCLC could also treat rare advanced pancreatic cancer [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_9k [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:17:19 [post_modified_gmt] => 2023-02-03 19:17:19 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52441 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52441 ) [23] => Array ( [ID] => 52440 [post_author] => 2768 [post_date] => 2023-02-03 11:14:11 [post_date_gmt] => 2023-02-03 15:14:11 [post_content] =>An analysis led by a researcher at UT Southwestern Medical Center, which looked at costs for patients with Hepatocellular carcinoma in the first year after diagnosis, found that median Medicare payments exceeded $65,000 and out-of-pocket costs were more than $10,000—significantly more than costs for patients with cirrhosis alone.
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The study, led by Amit Singal, professor of internal medicine in the Division of Digestive and Liver Diseases and a member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern, was published in Clinical Gastroenterology and Hepatology.
“As has been shown for other cancer types, we found patients with liver cancer suffer from high cancer-related financial burden. Financial toxicity of cancer therapy can negatively impact patients, resulting in medical debt and even bankruptcy for some patients,” said Singal, who is also the medical director of UTSW’s Liver Tumor Program and a Dedman Family Scholar in Clinical Care.
The team chose to investigate outcomes in liver cancer given its rising incidence and mortality rate. Liver cancer mortality is accelerating, in part due to continued detection at late stages, and it is expected to be the third-leading cause of cancer deaths by 2040, according to Singal and his team.
The cost of liver cancer treatment has been little studied, the researchers said. Several treatments have become available for patients in the past decade, including new surgeries, radiation-based therapies, and immunotherapies, making it essential to understand the financial impact of treatment. Although these therapies can be effective, they also can be quite expensive and difficult for patients to afford.
Using data from the Surveillance, Epidemiology, and End Results Medicare database, the study looked at first-year treatment costs for 4,525 patients ages 68 and older who were diagnosed with liver cancer between 2011 and 2015. The study compared costs for patients with HCC with those for a matched set of patients with cirrhosis.
Sixty-seven percent of the patients in the study were male; 72% were white, 7.5% Black, 3.7% Hispanic, and 16.7% other ethnicities. Medication claims were not included because they were not available for all patients covered by Medicare parts A and B.
The analysis found that patients with liver cancer had significantly higher inpatient, outpatient, and physician costs compared with the cirrhosis-only patients. Median out-of-pocket costs for the first year of treatment were more than $7,000 higher than the costs for the cirrhosis patients.
The analysis found that patients with early-stage liver cancer had lower costs. Patients with certain co-existing conditions, such as non-alcoholic fatty liver disease and ascites (fluid in the abdomen), experienced higher costs. These differences in costs across subgroups are notable because most patients are found beyond an early stage, and non-alcoholic fatty liver disease is an increasingly common underlying factor for liver cancer.
The study was supported by grants through the Cancer Prevention and Research Institute of Texas (RP170259), the NIH (R01 MD012565 and U01 CA230694), the Population Informatics Lab, and the Texas Virtual Data Library at Texas A&M University.
[post_title] => Liver cancer treatment costly for Medicare patients, UT Southwestern study finds [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_9l [to_ping] => [pinged] => [post_modified] => 2023-08-21 11:14:49 [post_modified_gmt] => 2023-08-21 15:14:49 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52440 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52440 ) [24] => Array ( [ID] => 52442 [post_author] => 2768 [post_date] => 2023-02-03 11:13:14 [post_date_gmt] => 2023-02-03 15:13:14 [post_content] =>Scientists at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine, collaborating with international researchers, have developed an AI algorithm that performs advanced computational analysis to identify potential therapeutic targets for glioblastoma multiforme and other cancers.
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Their research is described in the Feb. 2 issue of Nature Cancer and could affect future treatment of GBM, an aggressive, usually fatal type of brain cancer, and certain breast, lung, and pediatric cancers.
“Our work represents translational science that offers immediate opportunities to change the way glioblastoma patients are routinely managed in the clinic,” Antonio Iavarone, deputy director of Sylvester Comprehensive Cancer Center and senior author of the study, said in a statement. “Our algorithm offers applications to precision cancer medicine, giving oncologists a new tool to battle this deadly disease and other cancers as well.”
The AI algorithm, known as SPHINKS—Substrate PHosphosite-based Inference for Network of KinaseS—deployed deep-machine learning to help the researchers identify and experimentally
validate two protein kinases (PKCδ and DNAPKcs) as the culprits associated with tumor progression in two GBM subtypes and as potential therapeutic targets for other cancers.
Protein kinases are the key targets currently used in precision cancer medicine to tailor treatment to a patient’s specific cancer properties. The most active kinases, which the researchers labeled “master kinases” in their paper, are those for which clinicians direct targeted drugs as a hallmark of current cancer treatment.
In addition to identifying the master kinases, Iavarone and colleagues used tumor organoids grown in the laboratory from patient samples—what they called “patient-derived tumor avatars”—to show that targeted drugs that interfere with the activity of master kinases can thwart tumor growth.
Previously, Iavarone and team had reported a new glioblastoma classification by capturing key tumor cell traits and grouping GBM patients based on their likelihood of survival and their tumor’s vulnerability to drugs. In the new study, these classifications were independently confirmed through several omics platforms: genomics, proteomics, lipidomics, acetylomics, metabolomics, and others.
SPHINKS leverages machine learning to refine these omics datasets and create an interactome—a complete set of biological interactions—to pinpoint the kinases that generate aberrant growth and treatment resistance in each glioblastoma subtype. These findings show multi-omics data can generate new algorithms that predict which targeted therapies can provide the best therapeutic options based on each patient’s glioblastoma subtype.
“We can now stratify glioblastoma patients based on biological features that are common between different omics,” Iavarone said. “Reading the genome alone has not been enough. We have needed more comprehensive data to identify tumor vulnerabilities.”
The SPHINKS algorithm and related methods can be readily incorporated into molecular pathology labs, according to the researchers. Their paper includes a clinical classifier that can help assign the appropriate glioblastoma subtype to each patient. The team has also established an online portal to access the algorithm. The authors believe this approach can produce insightful information that could benefit as many as 75% of glioblastoma patients.
“This classifier can be used in basically any lab,” Anna Lasorella, professor of biochemistry and molecular biology at Sylvester CCC and co-senior author on the study, said in a statement. “By importing the omics information into the web portal, pathologists receive classification information for one tumor, ten tumors, however many they import. These classifications can be applied immediately to patient care.”
While SPHINKS was first tested on glioblastoma, the algorithm is equally applicable to several other cancers. The team found the same cancer-driving kinases in breast, lung, and
pediatric brain tumors. Iavarone, Lasorella, and colleagues believe this finding could be the impetus for a new type of clinical trial.
“We are exploring the concept of basket trials,” Iavarone said, “which would include patients with the same biological subtype but not necessarily the same cancer types. If patients with glioblastoma or breast or lung cancer have similar molecular features, they could be included in the same trial. Rather than doing multiple trials for a single agent, we could conduct one combined trial and potentially bring more effective drugs to more patients faster.”
[post_title] => Sylvester scientists develop AI to gain insight into glioblastoma [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_9m [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:17:26 [post_modified_gmt] => 2023-02-03 19:17:26 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52442 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52442 ) [25] => Array ( [ID] => 52444 [post_author] => 2768 [post_date] => 2023-02-03 11:12:16 [post_date_gmt] => 2023-02-03 15:12:16 [post_content] =>Yale Cancer Center scientists have developed a technology that enables massively parallel DNA substitutions (known as “knock-ins”) into human cells by taking advantage of messenger RNA, a platform now well-known from its use as the COVID vaccine vehicle.
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This new technology, named CLASH, allows scientists to generate tens of thousands of different variants of cells with different genetic modifications and pick the best one for desired purposes, such as using them in cell therapies for cancer treatment.
The study was published Jan. 26 in the journal Nature Biotechnology.
“While there are different ways to modify the genome, inserting pieces of DNA has historically been more difficult than deleting pieces, and it’s even harder to insert many different pieces into various cells at the same time,” senior author Sidi Chen, an associate professor of genetics at Yale School of Medicine and member of Yale Cancer Center, said in a statement. “We have been working hard over the past five years and came up with a solution: designing and creating large pools of adeno-associated virus vectors and delivering them together with mRNA enabled us to achieve mass insertions instead of one-to-one gene substitutions.”
Chen’s research team first applied this technology in human T cells to solve the challenge of cell therapy for cancer. Cell therapy such as CAR-T therapy is successful and recently approved by FDA to treat blood cancers but faces major hurdles in solid tumors such as breast cancer, lung cancer, and colon cancer.
For the new study, the team used CLASH to modify the genome of T cells and created pools of new CAR-T variants, which they called “treasure islands.” They then tested these T cell variant pools against cancer, and let the best candidate emerge from selection. Researchers have found that a unique mutant can substantially enhance CAR-T against cancer in animals, and the effect is universal across different types of disease models.
“Although the proof-of-principle is in human T cells, the CLASH technology is in principle applicable to many different cell types, which allows us to rapidly create thousands of cell therapy candidates for diverse cancer treatment options,” Chen said. Future trials are needed before human application.
Chen is affiliated with the Systems Biology Institute and the Center for Cancer Systems Biology at Yale West Campus, the Yale Stem Cell Center, the Yale Center for Biomedical Data Science, and the Department of Genetics at Yale School of Medicine.
The research was primarily funded by the NIH and the U.S. Department of Defense.
[post_title] => Yale scientists enable massively parallel DNA insertions into human cells [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_9n [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:17:31 [post_modified_gmt] => 2023-02-03 19:17:31 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52444 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52444 ) [26] => Array ( [ID] => 52443 [post_author] => 2768 [post_date] => 2023-02-03 11:11:15 [post_date_gmt] => 2023-02-03 15:11:15 [post_content] =>In a study published in Cell Reports Medicine, a team of scientists at Baylor College of Medicine focused on the molecular pathways metastatic cancer cells use and identified four cancer subtypes according to the main genes expressed. The findings unveiled potential vulnerabilities of each subtype that have relevant implications for therapy.
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“We analyzed molecular data from the public domain collectively representing 38 studies and more than 3,000 patients and 4,000 tumors,” lead author Chad Creighton, professor of medicine and co-director of cancer bioinformatics at the Dan L Duncan Comprehensive Cancer Center at Baylor, said in a statement. “Our pan-cancer analysis looked to identify molecular pathways that are common to many different cancers, regardless of tumor origin.”
One challenge when studying cancer metastasis is that tumor samples have abundant non-cancer tissue. Samples tend to be a mixture of cancer and non-cancer cells, such as normal endothelial cells, fibroblasts and immune cells, that interfere with the molecular analysis of cancer cells.
To cut through all that noise, Creighton and his colleagues worked with data obtained from PDX cancer models. In this model, human cancer tissues implanted in immune-deficient mouse models grew into a new tumor similar to a metastasis.
“The nice thing with the PDX model is that mouse cells are different enough that they cannot be confused with human cells and, therefore, they are not going to contribute to the cancer profile,” Creighton said.
By analyzing the data of the PDX models, the team was able to define four cancer molecular subtypes in the metastasis-like PDX samples. Importantly, the researchers determined that those four subtypes also are present in patient metastasis and are broadly represented among the different cancer types studied. These subtypes not only facilitate understanding the molecular underpinnings of metastases but also point at potential therapeutic interventions already under investigation.
The tumors in the first subtype have extensive alterations in gene copy number, higher expression of both DNA repair genes and transcription factor genes such as MYC. This suggests that tumors of this subtype might be susceptible to MYC-inhibiting compounds or BET inhibitors currently under clinical evaluation.
The second subtype has higher expression of genes involving metabolism, prostaglandin synthesis and regulation. Tumors in this group might be susceptible to COX-2 inhibitors.
The third subtype has evidence of neuronal differentiation and high expression of genes EZH2 and BCL2. In this case, such tumors might respond better to EZH2 or BCL2 inhibitors.
The fourth subtype has higher expression of immune checkpoint and Notch pathway genes, suggesting that these tumors could be affected by immunotherapy.
“When comparing a primary tumor with the metastatic tumor derived from it, we found that, in most cases, the primary and the metastatic tumors were not of the same subtype,” Creighton said. “This has important implications for therapy as it suggests that primary and metastatic tumors may not be treated in the same way. The findings provide valuable insights for the development of personalized treatments for metastatic cancer.”
Yiqun Zhang and Fengju Chen at Baylor College of Medicine also contributed to this work.
This study was supported by the NIH grant P30CA125123.
[post_title] => Study shows molecular pathways followed by metastatic cancer cells [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_9o [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:17:35 [post_modified_gmt] => 2023-02-03 19:17:35 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52443 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52443 ) [27] => Array ( [ID] => 52447 [post_author] => 2768 [post_date] => 2023-02-03 11:10:20 [post_date_gmt] => 2023-02-03 15:10:20 [post_content] =>Researchers at Baylor College of Medicine, the University of Michigan, and collaborating institutions working with animal models of graft-versus-host disease reported in Immunity that alterations in the gut microbiome are connected to an increase in the oxygen levels in the intestine that follows immune-mediated intestinal damage. Pharmacologically reducing intestinal oxygen levels alleviated the microbial imbalance and reduced the severity of the intestinal disease.
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The severity of immune-mediated intestinal diseases such as GVHD or inflammatory bowel diseases is known to be associated with alterations in the gut microbiome, but what leads to such disruption in the microbial community has remained unknown.
“There is a lot of data showing that microbes change in many diseases, but we do not understand how that happens,” leading author Pavan Reddy, professor and director of Baylor’s Dan L Duncan Comprehensive Cancer Center, who was at the University of Michigan during the development of this project, said in a statement. “This study is one of the first to provide an explanation and a potential solution for the imbalance in the gut microbiome that exacerbates GVHD and possibly other inflammatory intestinal conditions.”
GVHD is a potentially life-threatening complication of bone marrow transplantation. “It is the complication that can prevent us from using this therapy that has proven to be effective to treat many blood cancers and inherited blood diseases,” Reddy said.
Reddy and his colleagues discovered that the damage immune cells cause to intestinal cells prevents these cells from fully using oxygen to conduct their normal functions. Consequently, all the oxygen that is not being used by intestinal cells oozes into the intestine, changing the environment for the resident microbes.
“Most of the ‘good microbes’ we have in the intestine grow in oxygen-poor environments—oxygen is toxic to them. They are called anaerobic (without oxygen) bacteria,” Reddy said. “When oxygen levels in the intestine increase, these microbes tend to disappear, and oxygen-loving microbes tend to grow. An increase in oxygen level provides an explanation for the microbiome changes in the context of these inflammatory diseases.”
The findings suggested that restoring the normal environment by reducing the oxygen level in the intestine could help reestablish the balance of the microbial community and lead to attenuation of GVHD.
“Indeed, we discovered that reducing the intestinal oxygen level actually made a difference in the progression of GVHD in the animal models,” Reddy said. “We found that a commonly used drug to reduce iron overload, an iron chelator, mitigated the microbial imbalance and reduced the severity of GVHD.”
Iron chelators have been used for many years to treat conditions in which excess iron causes tissue damage, such as hemochromatosis. Iron chelators are compounds that bind to iron, pulling it out and removing it from the body. “We discovered that iron chelators also can act as oxygen sinks,” Reddy said. “In our animal models, iron chelators removed iron from the intestine and that facilitated the restoration of an oxygen-poor environment that gave anaerobic bacteria an opportunity to bloom. Importantly, this reduced the severity of GVHD.”
The researchers’ next steps include conducting studies to determine whether iron chelation can help control the severity of GVHD in patients who have received a bone marrow transplant.
Another advantage of iron chelation would be that it may reduce or avoid the use of immune suppressor medications that are usually used to control GVHD. Suppressing the immune system may control GVHD, but also favors infections, which can be life-threatening. “If iron chelation helps control the condition in patients, it would be a novel non-immunosuppressive approach to treat GVHD with seemingly little side effects,” Reddy said.
[post_title] => Study provides explanation and potential solution for severe GVHD [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_9p [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:17:39 [post_modified_gmt] => 2023-02-03 19:17:39 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52447 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52447 ) [28] => Array ( [ID] => 52508 [post_author] => 2768 [post_date] => 2023-02-03 11:09:38 [post_date_gmt] => 2023-02-03 15:09:38 [post_content] =>To mark World Cancer Day, researchers from the International Agency for Research on Cancer in collaboration with the Lalla Salma Foundation for Cancer Prevention and Treatment (Morocco) published a report that provides solutions to overcoming some of the common system-level barriers to implementation of cervical cancer screening, which are faced in many countries in sub-Saharan Africa.
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This new publication summarizes the outcomes of the Care4Afrique pilot project, which was initially implemented in Benin, Côte d’Ivoire, and Senegal in close collaboration with the ministries of health of those countries.
“Although the burden of cervical cancer is very high in Francophone sub-Saharan Africa, very little evidence is available on how best to integrate cervical cancer screening and treatment services, especially using new technologies such as thermal ablation, into routine primary health-care services,” IARC scientist Farida Selmouni, the coordinator
of the project, said in a statement. “The Care4Afrique project provides an implementation model that other countries may emulate in order to remain aligned with the World Health Organization (WHO) strategy to eliminate cervical cancer as a public health problem globally.”
The Care4Afrique pilot project demonstrated that implementation of cervical cancer screening by visual inspection with acetic acid followed by immediate treatment of precancerous lesions with thermal ablation in primary health-care services is feasible in resource-constrained settings.
The project also showed that treatment with thermal ablation is safe and highly acceptable to women.
The keys to the success of cervical cancer screening in any health setting, including in sub-Saharan Africa, are strong leadership, stakeholder engagement, appropriate coordination between the primary and secondary levels of health services, adequate investment
in training and refresher training of service providers, and stringent quality assurance.
Another ambition of the pilot project was to build capacity within the public health-care system in
the focus countries to deliver cervical cancer screening and treatment. Strong collaborations were established among multiple African countries to build capacity in the primary health-care facilities.
A team of master trainers was identified in each country and trained. These master trainers trained a large number of providers at the primary and secondary levels of care to deliver screening and treatment and also mentored them regularly.
IARC, in collaboration with the Lalla Salma Foundation for Cancer Prevention and Treatment (Morocco), launched the Care4Afrique pilot project in November 2017.
The project incorporated VIA as the screening test, thermal ablation as a novel technology to treat cervical precancers, and screen-and-treat as the management approach.
Between April 2018 and January 2021, a total of 16,530 women in the three focus countries were screened through the project. Overall, 8.1% of the women screened were VIA-positive, and among them, 0.2% of the women had lesions suspicious of cancer on VIA. A total of 60.7% of all VIA-positive women were eligible for thermal ablation; most of them (87.9%) received treatment on the same day as screening, and only 1.0% refused treatment.
The Care4Afrique project has now also been implemented in Cameroon, where screening of women has begun.
[post_title] => IARC, Lalla Salma Foundation report addresses barriers to cervical cancer screening in Benin, Côte d’Ivoire, Senegal [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_9q [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:17:43 [post_modified_gmt] => 2023-02-03 19:17:43 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52508 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52508 ) [29] => Array ( [ID] => 52446 [post_author] => 2768 [post_date] => 2023-02-03 11:05:19 [post_date_gmt] => 2023-02-03 15:05:19 [post_content] =>FDA granted accelerated approval to Jaypirca (pirtobrutinib) for relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor.
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Jaypirca is sponsored by Eli Lilly and Co. Full prescribing information for Jaypirca can be found here.
Efficacy was evaluated in BRUIN (NCT03740529), an open-label, multicenter, single-arm trial of Jaypirca monotherapy that included 120 patients with MCL previously treated with a BTK inhibitor. Patients had a median of 3 prior lines of therapy, with 93% having 2 or more prior lines. Eighty three percent of patients had discontinued their last BTK inhibitor due to refractory or progressive disease.
The main efficacy measures were overall response rate and duration of response, as assessed by an independent review committee using Lugano criteria. The ORR was 50% with a complete response rate of 13%. The estimated median DOR was 8.3 months, and the estimated DOR rate at 6 months was 65.3%.
The most common adverse reactions in patients with MCL were fatigue, musculoskeletal pain, diarrhea, edema, dyspnea, pneumonia, and bruising.
[post_title] => Jaypirca receives FDA accelerated approval for R/R mantle cell lymphoma [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_10a [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:00:24 [post_modified_gmt] => 2023-02-03 19:00:24 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52446 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52446 ) [30] => Array ( [ID] => 52445 [post_author] => 2768 [post_date] => 2023-02-03 11:04:18 [post_date_gmt] => 2023-02-03 15:04:18 [post_content] =>FDA approved Orserdu (elacestrant) for postmenopausal women or adult men with ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy.
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Orserdu is sponsored by Stemline Therapeutics Inc.
FDA also approved the Guardant360 CDx assay as a companion diagnostic device to identify patients with breast cancer for treatment with Orserdu.
Full prescribing information for Orserdu can be found here.
Efficacy was evaluated in EMERALD (NCT03778931), a randomized, open-label, active-controlled, multicenter trial that enrolled 478 postmenopausal women and men with ER-positive, HER2-negative, advanced or metastatic breast cancer of which 228 patients had ESR1 mutations.
Patients were required to have disease progression on one or two prior lines of endocrine therapy, including one line containing a CDK4/6 inhibitor. Eligible patients could have received up to one prior line of chemotherapy in the advanced or metastatic setting.
Patients were randomized (1:1) to receive Orserdu (n=239) or investigator’s choice of endocrine therapy (n=239), which included fulvestrant (n=166) or an aromatase inhibitor (n=73).
Randomization was stratified by ESR1 mutation status, prior treatment with fulvestrant, and visceral metastasis. ESR1 mutational status was determined by blood circulating tumor DNA using the Guardant360 CDx assay and was limited to ESR1 missense mutations in the ligand binding domain.
The major efficacy outcome measure was progression-free survival, assessed by a blinded imaging review committee. A statistically significant difference in PFS was observed in the intention to treat population and in the subgroup of patients with ESR1 mutations.
In the 228 (48%) patients with ESR1 mutations, median PFS was 3.8 months in the Orserdu arm and 1.9 months in the fulvestrant or aromatase inhibitor arm,
An exploratory analysis of PFS in the 250 (52%) patients without ESR1 mutations showed a HR 0.86 indicating that the improvement in the ITT population was primarily attributed to the results seen in the ESR1 mutated population.
The most common adverse events, including laboratory abnormalities, were musculoskeletal pain, nausea, increased cholesterol, increased AST, increased triglycerides, fatigue, decreased hemoglobin, vomiting, increased ALT, decreased sodium, increased creatinine, decreased appetite, diarrhea, headache, constipation, abdominal pain, hot flush, and dyspepsia.
[post_title] => Orserdu & companion diagnostic for ER+, HER2-, ESR1-mutated advanced breast cancer receive FDA approval [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_10b [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:00:28 [post_modified_gmt] => 2023-02-03 19:00:28 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52445 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52445 ) [31] => Array ( [ID] => 52448 [post_author] => 2768 [post_date] => 2023-02-03 11:03:21 [post_date_gmt] => 2023-02-03 15:03:21 [post_content] =>FDA granted first marketing clearance for RefleXion Medical’s SCINTIX biology-guided radiotherapy, a cutting-edge treatment applicable for early and late-stage cancers.
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The FDA cleared SCINTIX biology-guided radiotherapy to treat patients with lung and bone tumors. These tumors may arise from primary cancers or from metastatic lesions spread from other cancers in the body.
SCINTIX is the first and only radiotherapy that allows each cancer’s unique biology to autonomously determine where and how much radiation to deliver, second-by-second, during actual treatment delivery. This expands the RefleXion X1 into the only dual-treatment modality platform that can treat patients with indicated solid tumors of any stage.
The SCINTIX biologic modality tracks tumor motion from all types of movement, including expected motion from internal processes such as breathing and digestion or unexpected movement by a patient. The X1 also has a state-of-the-art anatomic modality previously cleared by the FDA for solid tumors located anywhere in the body.
“SCINTIX ushers in a new era of external-beam radiotherapy by harnessing data produced from the biologic process of cancer cells, which until now has been untapped,” Terence Williams, chair of City of Hope’s Department of Radiation Oncology, said in a statement. “We are excited to be among the early adopters of SCINTIX and to help develop this therapy for all cancer patients, especially those with stage 4 disease, where treatment options often remain very limited.
“With SCINTIX, the X1 machine and the tumor communicate continuously via a live data stream produced during patient treatment,” Williams said. “This precision should enable us to treat less surrounding tissue and may enable the treatment of more tumors in the same course of therapy.”
Previously granted Breakthrough Device designation by the FDA for treating lung tumors, the breakthrough nature of SCINTIX technology lies in its ability to detect and then treat multiple moving tumors. Initially cleared for use with the radiopharmaceutical fluorodeoxyglucose F 18—commonly known as FDG—the company plans to adapt SCINTIX therapy to work with the full array of novel radiopharmaceuticals under development for different cancer types.
SCINTIX therapy (formerly referred to as BgRT) is delivered through the RefleXion X1 machine, which combines positron emission tomography with a linear accelerator to deliver a radiation dose that tracks the cancer’s motion. Immediately prior to treatment, the patient is injected with a radiopharmaceutical that interacts with cancer cells to produce signals or emissions.
The X1 continuously constructs a map from the detected emissions data that determines where to aim beamlets of radiation. This crosstalk between the tumor and the X1 requires the system to rotate at 60 rpm—making it the first and only radiotherapy machine to spin at this speed.
[post_title] => RefleXion receives FDA clearance for SCINTIX biology-guided radiotherapy [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_10c [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:00:31 [post_modified_gmt] => 2023-02-03 19:00:31 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52448 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52448 ) [32] => Array ( [ID] => 52449 [post_author] => 2768 [post_date] => 2023-02-03 11:02:23 [post_date_gmt] => 2023-02-03 15:02:23 [post_content] =>FLAG-003, an investigational small molecule therapy developed by FLAG Therapeutics Inc. for the treatment of diffuse intrinsic pontine glioma—a rare, highly aggressive and difficult to treat brain tumor found in children—has been granted Rare Pediatric Disease designation from FDA.
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FLAG-003, the company’s lead program for the treatment of all gliomas, is engineered to cross the blood brain barrier and specifically target and kill cancer cells by simultaneously blocking the formation of a tumor vascular system and disrupting cancer cell replication by inhibiting tubulin.
RPD designation is granted to drugs in development for the treatment of rare childhood diseases—diseases affecting children 18 years of age and younger and fewer than 200,000 people in the U.S.
Under the RPD program, the sponsor may qualify for a priority review voucher if the drug is initially approved for the disease for which the RPD designation was granted. Holders of a PRV can redeem the voucher to obtain priority review for any subsequent marketing application, or they can sell or transfer it to other developers.
FLAG-003 was previously granted Orphan Drug Designation for the treatment of all gliomas, including glioblastoma multiforme and DIPG, by FDA.
FLAG-003 is a novel multi-specific small molecule therapeutic designed to target, bind, and kill cancer cells through two well-established mechanisms of action: anti-angiogenesis and tubulin inhibition.
Diffuse intrinsic pontine glioma is a highly aggressive, difficult to treat malignant brain tumor that is usually diagnosed in children between the ages of five and nine. It accounts for nearly 10% of all childhood central nervous system tumors. In the U.S., approximately 300 children are diagnosed with DIPG each year. Due to its location in the brain stem, surgery is not an option; results of first line treatment with radiation are typically short lived, lasting on average approximately six to nine months. At present, there are no approved drug therapies for the treatment of DIPG.
[post_title] => FLAG Therapeutics’s FLAG-003 receives Rare Pediatric Disease Designation for diffuse intrinsic pontine glioma [post_excerpt] => [post_status] => publish [comment_status] => closed [ping_status] => closed [post_password] => [post_name] => 20230203_10d [to_ping] => [pinged] => [post_modified] => 2023-02-03 15:00:34 [post_modified_gmt] => 2023-02-03 19:00:34 [post_content_filtered] => [post_parent] => 0 [guid] => https://cancerletter.com/?p=52449 [menu_order] => 0 [post_type] => post [post_mime_type] => [comment_count] => 0 [pod_item_id] => 52449 ) [33] => Array ( [ID] => 52450 [post_author] => 2768 [post_date] => 2023-02-03 11:00:24 [post_date_gmt] => 2023-02-03 15:00:24 [post_content] =>The National Cancer Institute approved the following clinical research studies last month.
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For further information, contact the principal investigator listed.
Phase I/II - NRG-GY028
A Phase IB and Randomized Phase II Trial of Megestrol Acetate with or Without Ipatasertib in Recurrent or Metastatic Endometrioid Endometrial Cancer
NRG Oncology
Grinsfelder, Michaela Onstad
(713) 745-7418
Phase II - A222101
An Early Phase and Phase II Clinical trial to evaluate ganglioside-monosialic acid (GM1) for preventing paclitaxel-associated neuropathy
Alliance for Clinical Trials in Oncology
Cathcart-Rake, Elizabeth
(816) 932-4565
Phase II/III - AOST2032
A Feasibility and Randomized Phase 2/3 Study of the VEFGR2/MET Inhibitor Cabozantinib in Combination with Cytotoxic Chemotherapy for Newly Diagnosed Osteosarcoma
Children’s Oncology Group
Bishop, Michael William
(901) 595-2220
Phase III - A022101
A Pragmatic Randomized Phase III Trial Evaluating Total Ablative Therapy for Patients with Limited Metastatic Colorectal Cancer: Evaluating Radiation, Ablation, and Surgery (ERASur)
Alliance for Clinical Trials in Oncology
Miller, Eric David
(614) 685-4922
Phase III - A022102
Randomized Phase III Trial of mFOLFIRINOX +/- Nivolumab vs. FOLFOX +/- Nivolumab for First-Line Treatment of Metastatic HER2-Negative Gastroesophageal Adenocarcinoma
Alliance for Clinical Trials in Oncology
Park, Haeseong
(617) 632-3000
Phase III - NRG-BR008
A Phase III Randomized Trial of Radiotherapy Optimization for Low-Risk HER2-Positive Breast Cancer (HERO*) *Her2 Radiation Optimization (HERO)
NRG Oncology
Braunstein, Lior Zvi
(201) 775-7446
Phase III - NRG-LU008
Phase III Prospective Randomized Trial of Primary Lung Tumor Stereotactic Body Radiation Therapy Followed by Concurrent Mediastinal Chemoradiation for Locally-Advanced Non-Small Cell Lung Cancer
NRG Oncology
Simone, Charles B.
(646) 968-9052
Phase III - URCC-22053
High-dose Vitamin D Supplementation for ADT-Induced Bone Loss in Older Prostate Cancer Patients
University of Rochester NCORP Research Base
Peppone, Luke Joseph
(585) 275-7827
Phase Other - ALTE21C1
Assessment of Clonal Hematopoiesis and its Relationship to Cardiovascular Disease in Hodgkin Lymphoma Survivors
Children’s Oncology Group
Hayashi, Robert J.
(314) 454-6018
