Less Toxicity With Proton Beam vs Photon Chemoradiotherapy

CHICAGO — There are few direct comparisons of proton beam therapy with conventional photon radiotherapy, so any study that looks at both is worth noting.

One such study was presented (abstract 6521) here at the American Society of Clinical Oncology (ASCO) 2019 Annual Meeting. This was a comparative effectiveness study of proton beamversus traditional photon chemoradiotherapy in a cohort of 1483 patients (391 proton/1092 photon) with nonmetastatic cancer who were treated with curative intent at the University of Pennsylvania.

Researchers found that survival outcomes were similar regardless of which radiotherapy the patient received, but the incidence of adverse events was significantly reduced with proton beam therapy.

"The future is here — if the side effects are much lower, then you can potentially intensify therapy," said lead author Brian Baumann, MD, adjunct assistant professor of radiation oncology, Perelman School of Medicine, University of Pennsylvania, Pittsburgh, and an assistant professor of radiation oncology at Washington University School of Medicine, St Louis, Missouri.

"If you can give a higher dose of chemo or give chemo that an oncologist normally would not feel comfortable giving with radiation, then we might see a survival benefit," he told Medscape Medical News. "Or you can give higher doses of radiation safely, which could also improve survival."

"The real take-home message here is that the 90-day toxicity is lower," said Baumann. "Grade 3 and higher toxicity usually requires hospitalization. It means a trip to the ER, getting admitted, and a possibly worse outcome."

Proton beam therapy was associated with a significant reduction in those events with a relative risk (RR) of 0.31, he explained. "They were 69% less likely to have a grade 3 or over event, and the significance was really high."

"I think this is meaningful because patients care about toxicity, there is a lot of associated costs of side effects, and reducing toxicity improves quality of life," Baumann added. "And there are implications of how we may treat patients going forward, as protons seem to cause much less toxicity."

Similar Survival, Lower Toxicity

In this study, data on adverse events and survival were obtained prospectively, and the primary endpoint was 90-day adverse events associated with unplanned hospitalizations for grade 3 or worse adverse events. Secondary endpoints included a decline in ECOG performance status during treatment, 90-day grade ≥ 2 adverse events, disease-free survival, and overall survival.

Patients in the proton beam versus the photon chemoradiotherapy group were significantly older (median 66 vs 61 years), had less favorable Charlson-Deyo comorbidity scores (median 3.0 vs 2.0), and had a lower integral radiation dose to tissues outside the target (P < .05 for all). Baseline toxicity and performance status were similar (P > .05).

Overall, the authors found that proton beam compared with photon chemoradiotherapy was associated with a significantly lower RR of 90-day grade 3 or worse adverse events (11.5% vs 27.6%; RR 0.31; P < .01).

The use of proton beam chemoradiotherapy was also associated with a lower risk of 90-day grade ≥ 2 adverse events (RR, 0.78; P < .01) and decline in performance status during treatment (RR, 0.51; P < .01).

There was no difference in disease-free survival or overall survival between the groups.

Baumann explained the results were what his team had hypothesized and they had not expected to see survival differences. "That's because the patients were treated by the same doctors, with the same chemotherapy, at the same radiation dose, and there was no escalation of therapy," he said.

"But these results suggest that therapy can be escalated [with proton beam, because of the lower toxicity], and we may be able to show a difference in survival outcomes," he said.

The other implication that is important, he continued, is that the patients were primarily on Medicare and so the cohort was older and had more comorbidities. "The fact that they had lower rates of side effects, even though they were older and sicker, is a notable finding," said Baumann. "It shows that you can offer chemoradiation to older, sicker patients who were initially excluded from the clinical trials that established a benefit."

The Patient Voice

During a discussion of the results, John Vernon Cox, DO, MBA, Parkland Health System, University of Texas Southwestern, Dallas, emphasized that "effectiveness research is badly needed. We have a lot of therapies that we rely on and we don't have a good way of valuing them. And proton beam therapy is high on this list."

He reiterated that the authors analyzed a group of patients at their own institution, adverse event data were collected prospectively, and although there were significant differences in quality of life, outcomes were similar.

"The physics of protons cannot be argued, and this is a more accurate way of providing radiation therapy," he said. "But there are questions out there: Are these meaningful clinical differences? The data suggest that there are key quality of life differences."

Cox pointed out that there are issues with the study, as there are with any study that uses real-world data. It wasn't a randomized study, and the proton beam chemoradiotherapy group had a higher symptom burden and comorbidity score.

"The highlight for me was that they prospectively collected data on adverse events as part of routine care and that allowed them to do the study," he added. "All of us in practice need to be prospectively collecting the patient voice in a systematic way, and this really allows for a robust real-world experience to be reflected in real-world data."

Baumann has reported no relevant financial relationships. Several coauthors have disclosed financial relationships with industry. Cox has reported multiple disclosures.

ASCO 2019. Presented June 1, 2019. Abstract 6521.

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