Concurrent Chemoradiotherapy With Proton Radiation Reduces Short-Term Side Effects

Concurrent chemoradiotherapy with proton radiation can reduce short-term side effects that caused unplanned hospitalizations, with similar disease-free and overall survival, compared with photon radiation, according to study results published in JAMA Oncology.

“These findings suggest that, in adults with locally advanced cancer, proton therapy with concurrent chemoradiotherapy may significantly reduce severe adverse events compared with photon therapy, with comparable oncologic outcomes,” the researchers wrote.

Concurrent chemoradiotherapy is a standard-of-care curative therapy for locally advanced cancers; however, this treatment option can be associated with significant morbidities like oral mucositis, esophagitis, nausea, vomiting, significant weight loss and radiation-induced lung injury that can all result in unplanned hospitalizations. In turn, these morbidities can diminish the effectiveness of treatment and decrease patient performance status.

Photon therapy has been administered for decades, but proton radiation therapy has emerged as an alternative. “Proton therapy as part of concurrent chemoradiotherapy may be able to reduce treatment toxicity, but limited data are available comparing results of proton chemoradiotherapy with chemoradiotherapy delivered with photon therapy, and proton therapy remains unproven in this setting,” the researchers wrote.

Therefore, they compared the rate of severe 90-day side effects associated with unplanned hospitalizations or other side effects and similar disease-free and overall survival for patients treated with proton (391 patients), versus photon chemoradiotherapy (1,092 patients) in 1,483 patients with nonmetastatic, locally advanced cancer.

The majority of patients were men (63%). Median age was 62 years; however, patients who received proton therapy were significantly older at a median age of 66 years. In addition, these patients had less favorable comorbidity scores and lower integral radiation dose to tissues outside the target tumor location.

Baseline grade 2 or higher toxicities and ECOG performance status, which describes a patient's level of functioning in terms of their ability to care for themselves, daily activity and physical ability, were similar among both groups.

Proton chemoradiotherapy was associated with a significantly lower relative risk of 90-day side effects of at least grade 3, 90-day side effects of at least grade 2 and decline in performance status during treatment. “We observed substantial morbidity associated with conventional photon chemoradiotherapy; 27.6% of patients developed severe 90-day adverse events associated with unplanned hospitalizations, whereas in the proton group, 11.5% of patients had severe 90-day adverse events,” the researchers explained.

There was no difference in disease-free or overall survival. “This finding is noteworthy because it suggests that, with careful delineation of the target volume, proton therapy is not associated with worse cancer control outcomes that could occur due to a marginal miss if the proton beam stops short of covering the full extent of the subclinical disease,” the researchers added.

They concluded that there are now three important implications for future research. “First, proton therapy’s lower observed toxicity and its more favorable association with performance status at least raises the tantalizing possibility that the higher up-front cost of proton therapy may be offset by cost savings from reduced hospitalizations and enhanced productivity from patients and caregivers,” the wrote.

“Second, the lower observed toxicity of proton therapy offers an opportunity to explore clinical trials combining proton therapy with intensified systemic therapy and/or dose-escalated radiotherapy, which may, in turn, improve survival outcomes,” the researchers added. “Third, in our study, older patients with more comorbid disease were more likely to receive proton therapy and experienced less toxicity; thus, proton therapy may allow older patients with more comorbidities to receive the most effective combined-modality treatments.”