Comparative Effectiveness of Proton vs Photon Therapy as Part of Concurrent Chemoradiotherapy for Locally Advanced Cancer

1. Compared to standard photon therapy, proton chemoradiotherapy resulted in significantly reduced reduction in adverse events without changing disease-free or overall survival rates.

Evidence Rating Level: 2 (Good)

The standard of care for many cancers is concurrent chemoradiotherapy, which can be associated with significant morbidity. The administration of proton therapy as opposed to photon therapy, may result in reduced toxicity and improved outcomes through differences in radiation dose to surrounding tissues. This non-randomized, retrospective, comparative effectiveness study of 1,483 adult patients with non-metastatic, locally advanced cancer was conducted from 2011 through 2016 to determine differences between concurrent proton (n=391) and photon (n=1,092) chemoradiotherapy. Critical outcome data included 90-day adverse events associated with hospitalizations (CTCAEv4 grade >=3), performance status decline during treatment established by Eastern Cooperative Oncology Group (ECOG), and 90-day adverse events of at least CTCAEv4 grade 2 limiting activities of daily living (ADLs), and disease-free and overall survival. Researchers found that patients receiving proton therapy were significantly older than those undergoing photon therapy (p<0.01), exhibited less favorable Charlson-Deyo comorbidity scores (median difference 3.0, p<0.01), and had lower integral radiation dose to non-target tissues (mean volume difference –5.0 cGy/CC x 107, p<0.01). Baseline toxicity and ECOG performance status were not significantly different between treatment groups. Following propensity score weighted-analyses, proton therapy was found to be associated with a significant reduction in relative risk of grade 3 or worse adverse events during the 90-day time frame (RR 0.31, 95% CI 0.15 to 0.66, p = 0.002), grade 2 adverse events (RR 0.78, 95% CI 0.65 to 0.93, p=0.006), and reduced ECOG performance during treatment (RR 0.51, 95% CI 0.37 to 0.71, p<0.001). There were no significant differences in disease-free and overall survival rates. Nonetheless, this study found that proton chemoradiotherapy reduced acute adverse events leading to unplanned hospitalizations. As such, further studies are warranted to replicate these findings, as the results of this study suggest that proton therapy may be less harmful than conventional photon therapy.