Proton vs. Photon Therapy in Cancer Patients: A Comparison

A newly published study compared proton therapy versus photon therapy, both in the setting of concurrent chemoradiotherapy, to determine which was associated with fewer adverse outcomes.

“Concurrent chemoradiotherapy is the standard-of-care curative treatment for many cancers but is associated with substantial morbidity,” the study authors wrote. “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.”

The goal of this study—a retrospective, nonrandomized comparison effectiveness trial—was to compare the rates of 90-day unplanned hospitalizations (Common Terminology Criteria for Adverse Events, version 4 [CTCAEv4], grade ≥3) and other adverse events as well as disease-free and overall survival between the two therapies.

A total of 1,483 adult patients were included in the comparison. Patients had nonmetastatic, locally advanced cancer and underwent concurrent chemoradiotherapy with curative intent between Jan. 1, 2011, and Dec. 31, 2016. In addition to chemoradiotherapy patients also received either proton therapy (n = 391) or photon therapy (n = 1,092). Patient data were analyzed from Oct. 15, 2018, through Feb. 1, 2019. The study’s main end point was the rate of 90-day adverse events (AEs) correlated with unplanned hospitalizations (CTCAEv4 grade ≥3). Additional outcomes included Eastern Cooperative Oncology Group (ECOG) performance status decline during treatment, 90-day AEs of at least CTCAEv4 grade 2, and disease-free and overall survival.

The median (range) age of the total study population was 62 (18-93) years, and the study was primarily male (n = 935, 63.0%). The proton therapy group was older than the photon therapy group (median [range] age, 66 [18-93] years vs. 61 [19-91] years; P<0.01). The proton group also had poorer Charlson-Deyo comorbidity scores (median 3.0 vs. 2.0; P<0.01) and lower integral radiation dose to tissues outside the target (mean [SD] volume, 14.1 [6.4] cGy/cc × 107 vs. 19.1 [10.6] cGy/cc × 107; P<0.01). There were no significant between-group differences in the proton and photon groups regarding baseline grade ≥2 toxicity (22% vs. 24%; P=0.37( and ECOG performance status (mean [SD], 0.62 [0.74] vs. 0.68 [0.80]; P=0.16). Propensity score-weighted analyses unveiled a significant association between proton chemoradiotherapy and a reduced relative risk of 90-day AEs of at least grade 3 (0.31; 95% confidence interval [CI], 0.15-0.66; P=0.002), 90-day AEs of at least grade 2 (0.78; 95% CI, 0.65-0.93; P=0.006), and decline in performance status during treatment (0.51; 95% CI, 0.37-0.71; P<0.001). Disease-free and overall survival did not differ between the groups.

The study was published in JAMA Oncology.

In their conclusion the authors recommended that future prospective studies be conducted to confirm their findings.