At its opening a decade ago, the Indiana University Health Proton Therapy Center was one of four such facilities in the U.S.
Alas, money woes struck immediately. The center has run at a deficit for most of its existence—recently losing over $3.5 million in operating costs in fiscal 2013. And now the center is a landmark once again: On Jan. 1, 2015, it will become the first proton beam center in the U.S. to be closed.
“Predominantly this was a business decision,” said Patrick Loehrer, director of the Indiana University Melvin & Bren Simon Cancer Center, who served on a committee that recommended closing the facility. “The other factor had to be geographic, by the way. From a translational research component, to have a facility that is an hour away [from the Indianapolis-based cancer center] was not ideal.”
A conversation with Loehrer appears here.
The final phase of the Bloomington-based center is all the more remarkable because it’s playing out against the backdrop of a building boom of such centers.
The center will be shut down pursuant to recommendation from an independent review committee that concluded that an upgrade would require significant investment, and would not decrease costs sufficiently to enable the center to break even.
But money and distance were not the only issues.
In its unanimous recommendation to close the center, the six-member panel cited growing competition, falling reimbursement rates, and the lack of conclusive evidence for superior safety and efficacy of proton beam therapy over conventional radiation therapy.
“[Investigators have failed] to demonstrate in a scientifically robust fashion the putative benefits of this therapy,” the committee wrote. “There have, to date, been no completed randomized trials at any site demonstrating ‘proof of principle.’
“There have been very few prospective quality-of-life studies documenting advantage, even in children. Proton beam does not, therefore, feature in most national guidelines for cancer care.”
A copy of the committee report was obtained by The Cancer Letter, and is posted here.
According to the committee, there are 15 centers in operation in the U.S., with at least 20 more in the construction or planning stages. A larger facility can cost up to $200 million to build. A smaller one-room unit can cost about $30 million.
In the Washington, D.C.-Baltimore region alone, three centers are being built in close proximity to each other. When completed, the centers—located at the University of Maryland, Georgetown University Hospital, and Sibley Memorial Hospital—will have a combined capacity of treating 3,225 patients per year (The Cancer Letter, Oct. 25, 2013).
“Indiana University clearly has some issues that are unique to their situation, based on the facility and how it was designed and built,” said Kevin Cullen, director of the University of Maryland Marlene and Stewart Greenebaum Cancer Center. “However, their report raises a lot of important questions that are applicable to the oncology community and the radiation oncology community in general, that I think led them to this very difficult situation.
“A lot of factors that the committee cites are relevant to centers anywhere in the country.”
Formed by Jay Hess, vice-president for university clinical affairs and dean of the IU School of Medicine, the review committee consisted of:
• Committee chair Theodore Lawrence, the Isadore Lampe Professor and chair of the University of Michigan Cancer Center Department of Radiation Oncology;
• Stephen Hahn, chair of the University of Pennsylvania Department of Radiation Oncology, director of the Photodynamic Therapy Program, and co-program leader of radiation biology;
• Patrick Loehrer, associate dean for cancer research, director of the Indiana University Melvin & Bren Simon Cancer Center, associate director of clinical research, and H. H. Gregg senior professor of oncology;
• Dennis Murphy, chief operating officer of Indiana University Health;
• Anthony Zietman, associate director of the Harvard University Radiation Oncology Residency Program at the Massachusetts General Hospital, and Jenot W. and William U. Shipley Professor of radiation oncology at Harvard Medical School; and
• Ellen Burton, university clinical affairs program manager at Indiana University.
“We were given a number of charges,” Loehrer said to The Cancer Letter. “First and foremost was basically whether or not this facility’s model is financially feasible, and whether or not this is something that the health care system needs, going forward. We also assessed the status of proton therapy, and whether or not it is critical to the mission of the IU Simon Cancer Center and IU Health.”
Minesh Mehta, medical director of the University of Maryland Proton Treatment Center, said the IU decision is understandable.
“I don’t think the closure is surprising, that they made the decision that their facility has gotten to a point of obsolescence,” Mehta said to The Cancer Letter. “Rather than being an isolated event, because you can probably find one factor or more that are relevant, IU was probably caught in a situation analogous to a perfect storm, where all of the factors came together.”
The Bloomington facility now faces competition from newer centers in nearby metropolitan areas.
“For instance, the center in Chicago that now exists, was not there when the Bloomington center was built,” Mehta said. “IU probably had patients coming in from the Chicago area in the past, and presumably those patients are now getting their care in Chicago. St. Louis has also opened a proton therapy center, and those patients would no longer be coming in to Bloomington.”
Conventional Therapies Catching Up
Conventional radiation therapies and alternative treatment options to proton beam have improved, the review committee wrote, adding that those advances were important considerations in deciding the fate of the Bloomington facility.
“Photon beam (i.e. standard) radiation therapy did not stand still, and ‘intensity-modulated’ techniques (which can turn one beam into hundreds of ‘beamlets’) of external radiation or stereotactic radiation therapy (which uses many relatively low intensity beams focused on the tumor, thus producing an ablative treatment with little toxicity) have closed the gap with proton beam to an unanticipated degree,” the committee wrote.
Loehrer said the scientific value of proton therapy in comparison to conventional therapies was a factor in IU’s decision.
“When one compares proton therapy to historical data on photon therapy, it’s clear that proton therapy comes way ahead,” Loehrer said to The Cancer Letter. “However, there’s been evolution in how photon therapy is now delivered including stereotactic radiotherapy and IMRT. These modalities come much closer to the advantages from normal tissue damage seen with proton therapy at the present time.
“The other concern is that randomized trials comparing photon vs. proton have not been completed. There have been a couple trials that have been initiated, and I do look forward to the completion of those trials. I will be particularly interested in potential long-term side effects of protons, and assurances that there are no other side effects that we believe many [patients] develop.”
Trials comparing proton and conventional therapies are underway, said Walter Curran, chair of the Department of Radiation Oncology at Emory University, director of the Winship Cancer Institute, and a co-chair of NRG Oncology, a group within the new NCI-supported National Clinical Trials Network.
“At the moment, we’re conducting a phase III trial comparing proton therapy with chemotherapy to intensity-modulated radiation therapy with chemotherapy for patients with stage III non-small cell lung cancer,” Curran said to The Cancer Letter. “We’re about to activate a study evaluating proton therapy vs. IMRT with chemotherapy for patients with glioblastoma multiforme and having a number of other studies evaluating proton therapy for patients with other malignancies—like, would it be open within NRG Oncology over the next few years.”
The Emory Winship Cancer Institute in Atlanta is constructing a five-room proton beam center, similar to the upcoming University of Maryland facility in Baltimore. Both institutions are partnering with a private company, Advanced Particle Therapy, LLC of San Diego.
“There’s a lot of emerging data that points to a clear clinical benefit in many other disease sites, and some of these data is already reported, some of it is already out there, and I think we’ll see more and more over the next few years,” Curran said. “There’s very interesting new data suggesting decreased toxicity for patients receiving such treatment for head-neck cancer, lung cancer, and potential benefit in liver tumors.”
There are benefits in using proton beam therapy for the treatment of pediatric and eye and skull-base tumors, but those benefits are, for now, largely limited to those sites, IU’s review committee wrote.
“At present, we can say that there are sites where a clinically meaningful advantage likely exists, those where it likely does not exist (most breast or GI cancers), and those where it needs formal investigation (liver and lung),” the committee wrote. “The future of proton therapy will depend in part upon the demonstration of a meaningful clinical advantage in some, any, or all of these clinical sites, and in part on technological advances that will allow it to ‘pull away’ from the competition once again.”
Maryland’s Cullen agrees.
“I think there is certainly the strongest evidence for use in those sites,” Cullen said to The Cancer Letter. “But it will be awhile before we know for certain how much benefit proton therapy will have compared to photon for other diseases at other sites.”
It will take large-scale collaborations to achieve those results, said Emory’s Curran.
“Until there is sufficient critical mass of centers with the very latest technology, until these centers really come together and do prospective research, it’s difficult to say that the benefit is less limited to these [pediatric, eye, and skull-base] tumors,” Curran said. “As the data emerge, it appears that the benefit’s going to be extending to more and more types of cancer, but it does require discipline on the part of the centers, which will have this technology, to systematically study it.
“That’s already happening at a number of centers that are open, and I’m quite certain that will also happen at the University of Maryland center as well as the Winship center in Atlanta.”
These collaborations will be difficult to put together, as many facilities will individually compete for the same patient populations, Cullen said.
“I personally think that there is a need to collaborate on the kind of research studies that will answer those questions as quickly as possible, and unfortunately, when multiple sites are building facilities in close proximity, it’s going to make that kind of important research harder to complete,” Cullen said.
The Question of Demand
The IU review committee pondered at length the survival of existing proton therapy facilities.
“It is quite possible that we are on the verge of a ‘proton bubble,’ with the more indebted centers or those without a strong patient supply line closing,” the committee wrote. “Those with less or no debt, or those built around academic institutions, will likely survive and continue to provide the care that pediatric and base of skull tumor patients need. It is hoped that they will develop the data necessary to define the exact role of proton beam therapy in oncology.”
Projected patient volume and revenue targets in Bloomington didn’t justify new investment in the center.
“These [targets] seem very difficult to achieve given the current proposed development of over 30 new facilities, particularly in current key referral markets like Ohio (Ohio State University) and Minnesota (The Mayo Clinic) where this facility draws the majority of its out of state referrals, and declining payer reimbursement rates,” the committee wrote.
Loehrer said he wonders whether many proton facilities are being built for marketing advantage.
“I would also have concerns that there is not much need assessment done for the country in terms of facilities,” Loehrer said. “How many do we need, and where should they be located to best serve our patients?”
Cullen said the U.S. is building far too many proton therapy centers.
“I think that there is the real risk that we are seeing, and will see, a ‘proton bubble’—as they described it—and I think it makes me feel more strongly that centers should really, wherever possible, collaborate and consolidate their efforts to develop and invest in these facilities,” Cullen said. “Otherwise, we’re going to have much more capacity than is justified, and ultimately, that’s going to be an unsustainable expense for the centers that are building these facilities.”
Cullen predicts vigorous competition for patients in the D.C.-Baltimore area.
“I’ve looked at the business plans for all three facilities as part of the District of Columbia certificate of need process—and I think it’s fair to say that all of them are very optimistic and don’t really take into significant account the possibility that additional facilities will be built in the immediate area,” Cullen said.
“It’s inconceivable to me that the three facilities will achieve their business projections, and if there are three facilities open in a small area, it seems very likely that none of them will meet their original volume projections.
“But Hopkins and MedStar had said, no, they don’t want to do it, they want to build their own.
“I’m very puzzled by the decision making at MedStar and Hopkins that makes them want to continue to develop their facilities independently given all of the economic issues that the closure of Indiana raised.”
The conclusion that there would be a capacity overload for proton beam therapy in the U.S. may be too simplistic, said Mehta, medical director of the University of Maryland center, which will have a capacity of treating 2,000 patients annually when all five rooms are completed in late 2016.
The center will be run by the Department of Radiation Oncology, which does not report to Cullen or the Greenebaum Cancer Center. No funds from the cancer center or the university is involved in the construction or maintenance of the proton facility, Cullen said.
“The assumption that the capacity has been exceeded implies that these so-called experts have a clear definition, in their minds, as to what the capacity is, and what represents excess capacity,” Mehta said. “And so the implications of that assumption would be, that I, as this expert—and I’m merely paraphrasing—although I’ve never actually used proton therapy myself, I’m somehow enough of an expert to know exactly what’s going to happen with proton therapy in the next three, four, five or 10 years, and can predict with precision, how many patients will benefit, and I can therefore give you a capacity rate, and tell you what the capacity is.
“You can very well imagine that there are so many assumptions in a scenario like that, that the likelihood that such a statement would be true is low.
“Believing that would be quite simplistic.”