publication date: Jul. 31, 2020
FDA, Syapse real-world study reveal higher risk of hospitalization and death among cancer patients with COVID-19, underscore health disparities
The FDA’s Oncology Center of Excellence and Syapse presented data at the American Association of Clinical Research COVID-19 and Cancer meeting on an analysis of more than 212,000 health records of people living with cancer across two major health systems in the Midwestern United States.
The analysis found that cancer patients who also had COVID-19 are more likely—compared to those without COVID-19—to have: (1) other health conditions (e.g., kidney failure, obesity and heart disease), (2) increased rates of hospitalization and invasive mechanical ventilation, and (3) a 16-fold increased mortality risk. The researchers also underscored evidence for health care disparities among cancer patients with COVID-19.
This presentation is part of OCE’s partnerships with experts in healthcare data and analytics to investigate characteristics and clinical outcomes of patients with cancer who are infected with SARS-CoV-2, the virus that causes COVID-19.
This work builds upon several initiatives underway across FDA that leverage real-world data to improve understanding of COVID-19. These efforts include FDA’s participation in the COVID-19 Evidence Accelerator, organized by the Reagan-Udall Foundation for the FDA in collaboration with Friends of Cancer Research.
ACS updates guideline for cervical cancer screening
An updated cervical cancer screening guideline from the American Cancer Society reflects the rapidly changing landscape of cervical cancer prevention in the United States, calling for less and more simplified screening.
The guideline appears in CA: A Cancer Journal for Clinicians.
The updated guideline recommends that individuals with a cervix initiate cervical cancer screening at age 25, continuing through age 65, and that primary human papillomavirus testing every 5 years be the preferred method of testing.
The guideline says using HPV testing in combination with a Pap test (called cotesting) every five years or Pap tests alone every three years are acceptable options for now, as not all labs have transitioned to primary HPV testing.
“These streamlined recommendations can improve compliance and reduce potential harms,” Debbie Saslow, managing director of HPV & GYN Cancers for ACS, said in a statement. “They are made possible by some important developments that have allowed us to transform our approach to cervical cancer screening, primarily a deeper understanding of the role of HPV and the development of tools to address it.”
Virtually all cases of cervical cancer are caused by infection with high-risk strains of HPV. Evidence shows the HPV test is more accurate than the Pap test and can be done less often; one HPV test every five years is more effective than a Pap test every three years, and even every year as was recommended in the 1980’s and 1990’s, in reducing the risk of cervical cancer.
A negative HPV test is linked to a very low cervical cancer risk. In addition, a vaccine for HPV has been in use for nearly 15 years, and more women of screening age are now vaccinated and protected from the majority of cervical cancers.
The previous ACS guideline, released in 2012, called for screening starting at age 21. Since then, HPV vaccination rates have improved in the United States. Data suggest vaccination has led to a drop in rates of precancerous cervical changes, the precursors to cancer. In addition, cervical cancer incidence is low in this age group. Cancer registry data from 2011 to 2015 indicates an estimated 108 cases of invasive cervical cancer in women 20 to 24 years in the U.S. each year, a number that is expected to continue to fall as vaccine use increases.
There are also potential harms related to the treatment of precancerous cells identified by screening including preterm birth, and screening has not been shown to lower the rate of cancer in women in this age group. Also, most HPV infections in women in this age group become undetectable in 1-2 years. Those factors led the ACS to move the recommended age to initiate cervical cancer screening to 25.
“We estimate that compared with the currently recommended strategy of cytology (Pap testing) alone beginning at age 21 and switching to co-testing at age 30 years, starting with primary HPV testing at age 25 will prevent 13% more cervical cancers and 7% more cervical cancer deaths,” Saslow said. “Our model showed we could do that with a 9% increase in follow-up procedures, but with 45% fewer tests required overall.”
Clinical trial tests oral cancer drug to combat respiratory symptoms of COVID-19
Researchers at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute and The Ohio State University Wexner Medical Center are conducting a clinical trial to determine if ibrutinib (Imbruvica) can help patients with cancer or other immunocompromised conditions recover from COVID-19.
Imbruvica is sponsored by Janssen Scientific Affairs.
For this phase II clinical trial, physicians at the OSUCCC – James will enroll up to 78 patients with cancer or a precancerous condition who have been hospitalized as a result of a COVID-19 infection. Patients will be randomized to receive either 14 days of standard treatment plus the study drug ibrutinib, or standard treatment alone.
Ibrutinib is an oral therapy in a class of drugs known as Bruton’s tyrosine kinase inhibitors. These drugs work by blocking specific chemical reactions in the body involved in cellular processes. Use of this drug is considered experimental for this study; however, ibrutinib is approved by FDA for treatment of certain cancers, including mantle cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma and others.
Jennifer Woyach, an OSUCCC – James hematologist and co-principal investigator of the study, said preliminary data suggests ibrutinib has the potential to reduce rates of respiratory failure and death in COVID-19-infected patients.
“Ibrutinib targets and blocks a specific kinase related to lung inflammation, so we believe it could have real potential to help decrease this inflammation by shutting down the inappropriate cytokine release we see in COVID-19—a sort of overreaction from the immune system that can cause many problems, including life-threatening respiratory challenges,” Woyach said in a statement.
Patients will be monitored throughout study treatment with bloodwork to measure inflammatory markers, immune response and other bodily functions.
“Individuals with cancer or certain precancerous conditions can have lower immunity to diseases and infection, due to treatment or the nature of the disease. It is critically important that we perform clinical trials to try to improve COVID-19 care in these patients, because a COVID-19 infection can be even more dangerous for those who are immunocompromised,” Zeinab El Boghdadly, infectious disease physician at the Ohio State University Wexner Medical Center and co-principal Investigator for the trial, said in a statement.
Fox Chase researchers examine treatment toxicities in older esophageal cancer patients
Researchers at Fox Chase Cancer Center found that older patients who underwent chemoradiation therapy followed by removal of their esophagus due to cancer had toxicities and outcomes similar to younger patients.
The study, “Treatment-Related Toxicity and Outcomes in Older Versus Younger Patients With Esophageal Cancer Treated With Neoadjuvant Chemoradiation,” was published in the Journal of Geriatric Oncology.
Chemoradiation followed by an esophagectomy is considered the standard of care for locally advanced esophageal cancer.
“Clinical trials tend to enroll younger patients. Therefore, it’s hard to extrapolate and treat older patients based on the results of trials in younger patients,” Rishi Jain, lead author on the study and assistant professor in the Department of Hematology/Oncology at Fox Chase, said in a statement.
“We wanted to take a closer look at how older patients did with esophageal cancer, specifically in terms of side effects or toxicities and survivals. These results are important to know, because unfortunately sometimes people use age to decide how to treat patients and maybe older patients aren’t offered aggressive treatments,” Jain said.
Jain worked on the study with Joshua E. Meyer, an associate professor in the Department of Radiation Oncology, Efrat Dotan, an associate professor in the Department of Hematology/Oncology, and other researchers at Fox Chase.
The study examined 125 patients with early stage esophageal cancer who were treated at Fox Chase. Patients were split into age groups of individuals over 65 and individuals under 65. Of those 125 patients, Jain said 58 were over the age of 65 and 25 percent of the trial population were over 70.
Researchers compared side effects of the age groups, which were broken down into categories of hospitalizations related to the treatment, hematologic toxicities—or blood count issues—as well as others.
Similar toxicities and outcomes between younger and older patients in the study suggest that preliminary chemoradiation before esophagectomy is safe in select older adults with esophageal cancer, Jain said.
Additionally, the researchers found that older patients did have a higher rate of blood count issues, specifically lower platelets. Jain said, however, that this can be expected because older individuals have lower reserves of bone marrow with which to rebound after a blood count issue. Researchers said platelet-to-lymphocyte ratios and neutrophil-to-lymphocyte ratios may be able to serve as prognostic markers of aging, toxicity, and outcomes.
Jain said the study highlights the fact that by using practices like comprehensive geriatric assessments, physicians can effectively assess what problems an older patient may have and make sure they are addressed while treatment for cancer is being pursued.
“It’s helpful to know that if you carefully select older patients, you can safely get them through the treatment without putting them at much higher risk for complications in comparison to younger patients who are almost always treated aggressively,” said Jain.
Artificial intelligence identifies prostate cancer with near-perfect accuracy
A study by UPMC and University of Pittsburgh School of Medicine researchers demonstrates the highest accuracy to date in recognizing and characterizing prostate cancer using an artificial intelligence program.
The results were published in the Lancet Digital Health.
“Humans are good at recognizing anomalies, but they have their own biases or past experience,” senior author Rajiv Dhir, chief pathologist and vice chair of pathology at UPMC Shadyside and professor of biomedical informatics at Pitt, said in a statement. “Machines are detached from the whole story. There’s definitely an element of standardizing care.”
To train the AI to recognize prostate cancer, Dhir and his colleagues provided images from more than a million parts of stained tissue slides taken from patient biopsies. Each image was labeled by expert pathologists to teach the AI how to discriminate between healthy and abnormal tissue. The algorithm was then tested on a separate set of 1,600 slides taken from 100 consecutive patients seen at UPMC for suspected prostate cancer.
During testing, the AI demonstrated 98% sensitivity and 97% specificity at detecting prostate cancer—significantly higher than previously reported for algorithms working from tissue slides.
This is the first algorithm to extend beyond cancer detection, reporting high performance for tumor grading, sizing and invasion of the surrounding nerves. These all are clinically important features required as part of the pathology report.
AI also flagged six slides that were not noted by the expert pathologists.
But Dhir explained that this doesn’t necessarily mean that the machine is superior to humans. For example, in the course of evaluating these cases, the pathologist could have simply seen enough evidence of malignancy elsewhere in that patient’s samples to recommend treatment. For less experienced pathologists, though, the algorithm could act as a failsafe to catch cases that might otherwise be missed.
“Algorithms like this are especially useful in lesions that are atypical,” Dhir said. “A non-specialized person may not be able to make the correct assessment. That’s a major advantage of this kind of system.”
While these results are promising, Dhir cautions that new algorithms will have to be trained to detect different types of cancer. The pathology markers aren’t universal across all tissue types. But he didn’t see why that couldn’t be done to adapt this technology to work with breast cancer, for example.
Additional authors on the study include Liron Pantanowitz, of the University of Michigan; Gabriela Quiroga-Garza, of UPMC; Lilach Bien, Ronen Heled, Daphna Laifenfeld, Chaim Linhart, Judith Sandbank, Manuela Vecsler, of Ibex Medical Analytics; Anat Albrecht-Shach, of Shamir Medical Center; Varda Shalev, of Maccabbi Healthcare Services; and Pamela Michelow, and Scott Hazelhurst, of the University of the Witwatersrand.
Funding for this study was provided by Ibex, which also created this commercially available algorithm.
Pantanowitz, Shalev and Albrecht-Shach report fees paid by Ibex, and Pantanowitz and Shalev serve on the medical advisory board. Bien and Linhart are authors on pending patents US 62/743,559 and US 62/981,925. Ibex had no influence over the design of the study or the interpretation of the results.