January 07, 2020
3 min read

Proton chemoradiotherapy associated with reduced acute adverse events in locally advanced cancer

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Brian C. Baumann, MD
Brian C. Baumann

Proton chemoradiotherapy appeared associated with a substantial reduction in acute adverse events that caused unplanned hospitalizations compared with traditional photon chemoradiotherapy among adults with locally advanced cancer, according to results of a retrospective study published in JAMA Oncology.

Researchers also reported nearly identical PFS and OS rates with the two treatments.

“This is exciting because 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,” Brian C. Baumann, MD, adjunct assistant professor of radiation oncology at University of Pennsylvania and assistant professor of radiation oncology at Washington University School of Medicine in St. Louis, said in a press release.

Concurrent chemoradiotherapy using photon radiation is the standard of care for several locally advanced cancers, although it can result in substantial adverse events because photon therapy deposits radiation into normal tissues beyond the primary target.

Proton radiation therapy directly deposits protons to the target tissues, which could reduce toxicity. However, data comparing results of proton chemoradiotherapy and chemoradiotherapy delivered with photon therapy are lacking.

In their comparative effectiveness study, Baumann and colleagues retrospectively analyzed 1,483 adults (median age, 62 years; range, 18-93; 63% men) with nonmetastatic, locally advanced cancer who received curative-intent concurrent chemoradiotherapy between 2011 and 2016. Among these patients, 1,092 received photon therapy (median age, 61 years; range, 19-91) and 391 received proton therapy (median age, 66 years; range, 18-93).

Grade 3 or higher adverse events within 90 days of treatment, including unplanned hospitalizations, served as the study’s primary endpoint. Grade 2 or higher adverse events within 90 days of treatment, decline in ECOG performance status during treatment, DFS and OS served as secondary endpoints. Researchers gathered data on adverse events and survival prospectively.

Patients treated with photon therapy had less favorable Charlson-Deyo comorbidity scores (median, 3 vs. 2; P < .01), and lower integral radiation dose to tissues outside the target (mean volume, 14.1 cGy/cc × 10 vs. 19.1 cGy/cc × 10; P < .01).

The treatment groups had similar baseline grade 2 or higher toxicity (22% vs. 24%) and baseline ECOG performance status (mean, 0.62 vs. 0.68).

Within 90 days of treatment, 45 adverse events of grade 3 or higher occurred in the proton cohort, compared with 301 in the photon cohort.


Propensity score-weighted analyses showed that compared with photon chemoradiotherapy, proton chemoradiotherapy appeared associated with a significantly lower risk for 90-day adverse events of grade 3 or worse (RR = 0.31; 95% CI, 0.15-0.66), 90-day adverse events of grade 2 or worse (RR = 0.78; 95% CI, 0.65-0.93) and decline in performance status during treatment (RR = 0.51; 95% CI, 0.37-0.71).

“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,” James M. Metz, MD, chair of radiation oncology and leader of the Roberts Proton Therapy Center at University of Pennsylvania, said in the press release.

With median follow-up of 3.7 years for the proton cohort and 4.2 years for the photon cohort, researchers observed no significant difference in DFS (HR = 0.84; 95% CI, 0.48-1.48) or OS (HR = 0.73; 95% CI, 0.38-1.39).

Although the results of this study may lead to reduced adverse events and lower health care costs, phase 3 confirmatory studies are needed to rule out any potential biases, Henry S. Park, MD, MPH, assistant professor of therapeutic radiology at Yale University, and James B. Yu, MD, MHS, professor of therapeutic radiology, medical director of Smilow Radiation Oncology and director of the prostate and genitourinary cancer radiotherapy program at Yale University, wrote in a related editorial.

“Patients who undergo proton therapy may be more likely to be from privileged backgrounds and have stronger motivation than their counterparts receiving photon therapy,” Park and Yu wrote. “Although race, ethnicity, insurance type and comorbidity score are accounted for by Baumann [and colleagues], there may be differences in socioeconomic strata, functional status, social support and ability to navigate the complex U.S. health care system that favor patients who receive proton therapy.” – by John DeRosier

Disclosures: Baumann reports no relevant financial disclosures. Metz reports personal fees from Ion Beam Applications, Provision and Varian Medical Systems outside of the submitted work. Please see the study for all other authors’ relevant financial disclosures. Park reports honoraria from RadOncQuestions. Yu reports consultant/advisory and/or speakers bureau roles with Augmenix, Boston Scientific and Halera Pharmaceuticals.