Concurrent chemoradiotherapy, in which chemotherapy drugs and radiation therapy are used together, is a standard treatment for many locally advanced cancers. However, this approach is associated with severe side effects, including nausea, vomiting, significant weight loss, and radiation-induced lung injury that can lead to hospitalization.
For decades, concurrent chemoradiotherapy has been administered using photon-based radiotherapy. Now, a US research team has investigated whether irradiation using protons instead of photons can reduce this toxicity, by reducing the radiation dose to normal tissues (JAMA Oncol. 10.1001/jamaoncol.2019.4889).
The retrospective study – led by researchers at Washington University School of Medicine in St. Louis and the University of Pennsylvania – included 1483 patients with non-metastatic, locally advanced cancer. Common tumour sites included head-and-neck, lung, brain, oesophagus/gastric tract, rectum and pancreas. All patients received concurrent chemoradiotherapy with curative intent: 391 undergoing proton therapy and 1092 photon therapy (1016 of whom received intensity-modulated radiotherapy). Both patient groups received a similar integral radiation dose to the planning target volume. However, proton therapy delivered a lower integral dose to tissues outside the target.
The researchers note that patients treated with protons were, on average, significantly older and had more medical problems than those receiving standard photon therapy. Despite this, they found that proton therapy reduced the number of 90-day severe adverse events that caused unplanned hospitalizations by almost two-thirds: from 301 (27.6% of patients) in the photon cohort to 45 (11.5%) in the proton group.
Proton chemoradiotherapy also led to significantly less decline in performance status during treatment, and a significantly lower risk of adverse events that impaired the patient’s daily activities.
“We observed significantly fewer unplanned hospitalizations in the proton therapy group, which suggests the treatment may be better for patients and, perhaps, less taxing on the healthcare system,” says first author Brian Baumann in a press release from Washington University. “If proton therapy can reduce hospitalizations, that has a real impact on improving quality-of-life for both our patients and their caregivers.”
Importantly, the team saw no differences in disease-free or overall survival between the two groups. implying that proton therapy is as effective as photon therapy for treating the cancer.
The researchers suggest that the study has three important implications for future research. First, the lower observed toxicity of proton therapy raises the possibility that its higher up-front cost may be offset by savings from reduced hospitalizations and enhanced productivity from patients and caregivers. Second, this lower toxicity offers an opportunity to combine proton therapy with intensified systemic therapy or dose-escalated radiotherapy, which could improve survival. Third, proton therapy may allow older, sicker patients to receive the most effective combined-modality treatments.
As such, the team concludes that prospective clinical trials of proton versus photon chemoradiotherapy are warranted to validate these results.
