Fewer Side Effects With Proton Beam vs Traditional Radiotherapy

Roxanne Nelson, RN, BSN

December 31, 2019

One of the main advantages claimed for proton beam radiotherapy is that it has fewer adverse effects than traditional radiotherapy. A new study suggests that that is so.

The retrospective comparative effectiveness study involved 1483 patients with nonmetastatic cancer (various types, including brain, head and neck, lung, gastrointestinal, gynecologic) who were treated with curative intent.

Slightly less than a third of these patients (n = 391) were treated with proton beam radiotherapy; the remaining patients (n = 1092) underwent traditional radiotherapy.

The results show that among the patients who were treated with proton therapy, there was a significantly lower risk for serious side effects: 11.5% experienced events of grade 3 or higher within 90 days of treatment, compared to 27.6% of patients in the traditional radiotherapy group.

"We know from our clinical experience that proton therapy can have this benefit, but even we did not expect the effect to be this sizeable," said senior author James Metz, MD, chair of radiation oncology, leader of the Roberts Proton Therapy Center at the University of Pennsylvania, and a member of Penn's Abramson Cancer Center.

Importantly, there was no difference in cancer outcomes between the two groups; both disease-free and overall survival were similar.

"It shows that proton therapy offers a way for us to reduce the serious side effects of chemoradiation and improve patient health and well-being without sacrificing the effectiveness of the therapy," said lead author Brian Baumann, MD. He is an adjunct assistant professor of radiation oncology at Penn and an assistant professor of radiation oncology at the Washington University School of Medicine in St. Louis.

The study was published online December 26 in JAMA Oncology.

It provides a "compelling hypothesis that patients undergoing chemoradiotherapy for locally advanced cancer may benefit from the use of proton therapy, potentially leading to major cost savings for patients, payers, and society at large," comment the authors of an accompanying editorial.

They are Henry S. Park, MD, MPH, and James B. Yu, MD, MHS, both from Yale University School of Medicine, New Haven, Connecticut.

Need for Randomized Clinical Trials

The results from this study were initially presented at the 2019 annual meeting of the American Society of Clinical Oncology and were reported by Medscape Medical News at that time.

At the meeting, Baumann commented that, if the side effects are reduced, then it may be possible to intensify therapy, which in turn could improve survival.

But the "real take-home message here is that the 90-day toxicity is lower," he said. "Grade 3 and higher toxicity usually requires hospitalization. It means a trip to the ER [emergency room], getting admitted, and a possibly worse outcome."

Baumann emphasized that an important next step is to conduct randomized clinical trials of proton therapy vs proton chemoradiotherapy. "Efforts are already underway to do these studies for some cancers," he said. "I think it's important that we support these trials and encourage accrual on these trials."

There is now a need to study the cost implications for proton therapy. "Whether the cost savings in terms of reduced hospitalizations and ER visits would cover the higher upfront cost for proton therapy is an important next step," he added.

The editorialists agree about the need for randomized clinical trials. They say that trials are especially needed in order "to truly justify the expense incurred with proton therapy.

"Thus far, results from prospective studies has been mixed," the editorialists point out. As an example, one multicenter trial found no difference between proton and photon therapies with respect to grade 3 radiation pneumonitis among patients with locally advanced lung cancer, nor in local recurrence following concurrent chemoradiotherapy (J Clin Oncol. 2018;36:1813-1822).

Another example was a single center trial that found an improvement in physician-reported total treatment burden among patients with locally advanced esophageal cancer who received proton therapy, but there was no difference in patient-reported outcomes or progression-free survival (Int J Radiat Oncol Biol Phys. 2019;105:680-681).

"This latter study, however, was limited by a significant proportion of patients randomized to proton therapy who had to be treated off trial owing to insurance denial," Park and Yu write. "The paradox lies in the fact that insurance companies increasingly require more evidence to prove the value and cost-effectiveness of proton therapy before paying for it yet often deny coverage for patients who are randomly assigned to proton therapy in clinical trials."

Insurance coverage is really a sticking point if phase 3 trials are going to be successful in accruing patients. "We must insist that these trials are adequately supported by the payers who demand them," they write.

The study was supported exclusively by research development funds from the Department of Radiation Oncology, University of Pennsylvania. Baumann has reported no relevant financial relationships. Several coauthors have disclosed financial relationships with industry. Yu reported receiving consulting and speaking fees from Augmenix and Inc/Boston Scientific and has participated on an advisory board for Galera Pharmaceuticals, Inc. Park reported receiving honoraria from RadOncQuestions.

JAMA Oncol. Published online December 26, 2019. Abstract, Editorial

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