Why randomized trials for proton therapy are difficult to complete (and what we can do about it)

July 11, 2018, Perelman School of Medicine at the University of Pennsylvania
Treatment room at the Roberts Proton Therapy Center at the University of Pennsylvania. Credit: Penn Medicine

Randomized clinical trials are the gold standard of cancer research and can shed light on whether innovative, new therapies with great potential actually have clear benefits over usual care for patients. However, the seven randomized trials funded by the National Cancer Institute (NCI) and the Patient Centered Outcomes Research Institute (PCORI) to test proton therapy are enrolling more slowly than expected. Commercial insurance medical policies that do not cover treatment with proton therapy can make it difficult for patients to participate in randomized clinical trials funded by the NCI, part of the National Institutes of Health, that are evaluating the therapy. That's the message from an expert at the Perelman School of Medicine at the University of Pennsylvania and colleagues at the NCI who are calling attention to what the authors say is a major barrier these trials face. The authors publish their commentary, and proposed solutions, this week in the Journal of Clinical Oncology.

"Most commercial insurers and state Medicaid plans do not cover for the cancers under study," said lead author Justin E. Bekelman, MD, an associate professor of Radiation Oncology and Medical Ethics and Health Policy and senior fellow in the Leonard Davis Institute for Health Economics at the University of Pennsylvania's Perelman School of Medicine. Bekelman is also the principal investigator of one of these trials, the RadComp trial for breast , which is funded by PCORI and the NCI. "While coverage denial is used to reduce inappropriate use of medical technologies, a downside when applied to proton is that cannot participate in randomized designed to answer crucial questions about its benefits and harms."

Co-authors include Andrea Denicoff, MS, RN, head of Clinical Trials Operations for the NCI's National Clinical Trials Network, and senior author Jeffrey Buchsbaum, MD, Ph.D., AM, medical officer and program director in the Radiation Research Branch at the NCI.

"Some research has shown the benefits of proton therapy, but other studies have demonstrated expected and sometimes unexpected toxicities in certain cancers," said Buchsbaum. "That's why these randomized trials are so important. We need the evidence from these trials to determine whether proton therapy is better than usual care at reducing side effects or extending survival."

There are currently six comparing proton therapy to photon (X-ray) therapy funded by the NCI and one by PCORI. All of these trials have faced enrollment challenges. For example, in the RadComp trial for breast cancer, nearly two-thirds of patients have insurance coverage policies that do not cover proton therapy for ; thus, the majority of patients eligible for RadComp cannot actually enroll and participate in the clinical study. In contrast, Medicare typically does cover proton therapy through local coverage determinations, thus allowing patients to participate in trials. However, inclusion of only Medicare eligible patients over 65 significantly limits the number of patients who can participate in the trials and may reduce the generalizability of the results.

"NCI's randomized trial program for proton and photon therapy is designed to provide evidence comparing these two therapeutic options," said Denicoff. "Future patients will benefit directly from the knowledge gained. If we can complete the trials in a timely fashion, the results will enable patients to make more informed treatment decisions."

All stakeholders are aware of the dilemma and are attempting to find solutions. Some commercial insurers and some proton centers have made arrangements to cover proton therapy for selected cancers under study. For example, some insurers cover proton therapy for selected cancers under study or have established coverage with study participation policies. The researchers are proposing an approach that leverages lessons learned from these successful experiences—bringing together public and private insurers, proton therapy centers, hospitals, radiation therapy equipment vendors and patient advocates to establish a program of coverage that includes trial participation in one of the seven trials. The NCI is hosting a meeting with insurers later this month to consider opportunities and challenges to establish such a program. Other barriers will be addressed, including physician and patient engagement in the clinical trials.

"The seven trials that are currently enrolling patients will definitively compare cancer control and side effects between proton and photon therapy across prevalent cancers," Bekelman said. "To complete these , we need a coalition of patients, clinicians, payers, vendors, hospitals, and funders. If we are successful, our efforts could serve as a model to evaluate new advanced technologies in the future."

Explore further: Proton therapy for prostate cancer is advantageous to imrt according to new study

More information: Justin E. Bekelman et al, Randomized Trials of Proton Therapy: Why They Are at Risk, Proposed Solutions, and Implications for Evaluating Advanced Technologies to Diagnose and Treat Cancer, Journal of Clinical Oncology (2018). DOI: 10.1200/JCO.2018.77.7078

Related Stories

Proton therapy for prostate cancer is advantageous to imrt according to new study

October 25, 2017
Proton therapy treatment for prostate cancer is associated with higher survival rates and decreased risk of complications compared to intensity-modulated radiation therapy (IMRT) according to a new study by researchers at ...

97 percent of insurance denials in pediatric proton patients overturned on appeal

August 7, 2017
Insurance companies end up covering proton therapy treatment for pediatric cancer patients in 97 percent of the cases they originally deny once those decisions are appealed. Researchers from the Perelman School of Medicine ...

Clinical trial matching project sees higher enrollment in breast cancer trials through use of artificial intelligence

March 8, 2018
Mayo Clinic and IBM Watson Health today unveiled results from early use of the Watson for Clinical Trial Matching, an IBM cognitive computing system. Use of this system in the Mayo Clinic oncology practice has been associated ...

More patients OK'd for cancer trials under Obamacare: study

July 20, 2017
(HealthDay)—The Affordable Care Act has enabled more privately insured patients to enroll in clinical trials for new cancer treatments, a new study contends.

Insurance approval rates for clinical trial participation rose under Affordable Care Act

July 20, 2017
Approval rates for privately insured patients seeking to enroll in oncology clinical trials increased after the passage of the Affordable Care Act.

Proton therapy shown to be less costly than some alternative radiotherapy techniques

October 31, 2014
In terms of duration of treatment and cost, patients with early stage breast cancer may benefit from accelerated partial breast irradiation (APBI) with proton therapy versus whole breast irradiation (WBI), according to new ...

Recommended for you

Daily low-dose aspirin may be weapon against ovarian cancer

July 20, 2018
(HealthDay)— One low-dose aspirin a day could help women avoid ovarian cancer or boost their survival should it develop, two new studies suggest.

Discovery of kidney cancer driver could lead to new treatment strategy

July 19, 2018
University of North Carolina Lineberger Comprehensive Cancer Center scientists have uncovered a potential therapeutic target for kidney cancers that have a common genetic change. Scientists have known this genetic change ...

High fruit and vegetable consumption may reduce risk of breast cancer, especially aggressive tumors

July 19, 2018
Women who eat a high amount of fruits and vegetables each day may have a lower risk of breast cancer, especially of aggressive tumors, than those who eat fewer fruits and vegetables, according to a new study led by researchers ...

Sunscreen reduces melanoma risk by 40 per cent in young people

July 19, 2018
A world-first study led by University of Sydney has found that Australians aged 18-40 years who were regular users of sunscreen in childhood reduced their risk of developing melanoma by 40 percent, compared to those who rarely ...

Analysis of prostate tumors reveals clues to cancer's aggressiveness

July 19, 2018
Using genetic sequencing, scientists have revealed the complete DNA makeup of more than 100 aggressive prostate tumors, pinpointing important genetic errors these deadly tumors have in common. The study lays the foundation ...

Complementary medicine for cancer can decrease survival

July 19, 2018
People who received complementary therapy for curable cancers were more likely to refuse at least one component of their conventional cancer treatment, and were more likely to die as a result, according to researchers from ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.