Results from a comparative study suggest that proton therapy with concurrent chemoradiotherapy may significantly reduce severe adverse events (AEs) in adults with locally advanced cancer compared with photon therapy (JAMA Oncol. 2019 Dec 26. Epub ahead of print).

“Concurrent chemoradiotherapy is the standard-of-care curative treatment for many cancers but is associated with substantial morbidity,” said Brian C. Baumann, MD, Department of Radiation Oncology, University of Pennsylvania, Philadelphia, and colleagues.

“Concurrent chemoradiotherapy administered with proton therapy might reduce toxicity and achieve comparable cancer control outcomes compared with conventional photon radiotherapy by reducing the radiation dose to normal tissues,” they continued.

Thus, Dr Baumann et al conducted a retrospective, nonrandomized, comparative effectiveness study to determine whether proton therapy in the setting of concurrent chemoradiotherapy is tied to fewer 90-day unplanned hospitalizations or other AEs and similar disease-free survival (DFS) and overall survival (OS) than concurrent photon therapy and chemoradiotherapy.

A total of 1483 adults (median age, 62 years) with nonmetastatic, locally advanced cancer treated with concurrent chemoradiotherapy between January 1, 2011, and December 31, 2016, were included in the study. Of these patients, 391 received proton therapy and 1092 received photon therapy.

The primary end point of the study was 90-day AEs linked to unplanned hospitalizations, and secondary end points included a decline in Eastern Cooperative Oncology Group (ECOG) performance status during therapy, 90-day AEs limiting instrumental activities of daily living, and DFS and OS.

Dr Baumann and co-investigators prospectively collected AE and survival data, and performed their analysis between October 15, 2018, and February 1, 2019.

Those given proton therapy versus photon therapy were significantly older (median age, 66 years vs 61 years, respectively; P <.01), had less favorable Charlson-Deyo comorbidity scores (median, 3.0 vs 2.0, respectively; P <.01), and had lower integral radiation dose to tissues outside the target (mean volume, 14.1 vs 19.1 cGy/cc × 107; P <.01).

However, baseline grade ≥2 toxicity (22% vs 24%, respectively; P = .37) and ECOG performance status (mean, 0.62 vs 0.68, respectively; P = .16) were similar between the 2 treatment arms.

According to findings from propensity score weighted-analyses, proton chemoradiotherapy was tied to a significantly lower relative risk for 90-day AEs of at least grade 3 (0.31; 95% CI, 0.15-0.66; P = .002), 90-day AEs of at least grade 2 (0.78; 95% CI, 0.65-0.93; P = .006), and decline in performance status during therapy (0.51; 95% CI, 0.37-0.71; P <.001). The investigators observed no difference in DFS or OS.

“In this analysis, proton chemoradiotherapy was associated with significantly reduced acute adverse events that caused unplanned hospitalizations, with similar disease-free and [OS],” Dr Baumann and co-investigators concluded, adding that prospective studies should be conducted to validate these findings.—Hina Porcelli