1. DiGiulio, Sarah

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Proton beam radiation therapy has been around for decades and offers theoretical benefits over the current standard-photon therapy. But clinical trial data documenting the advantages of proton therapy has been lacking. Now a new randomized trial published earlier this year in the Journal of Clinical Oncology from a group of researchers at MD Anderson Cancer Center (MDACC) offers new data comparing the two treatment modalities, suggesting there are indeed benefits to proton beam therapy (Lin et al, 2020;38;1569-1579). The data shows there is a statistically significant reduction in total toxicity burden with proton therapy compared with photon therapy for patients with esophageal cancer.

Charles B. Simone, I... - Click to enlarge in new windowCharles B. Simone, II, MD. Charles B. Simone, II, MD

It's just one study, but in an editorial, Charles B. Simone, II, MD, Chief Medical Officer of the New York Proton Center and Research Professor in the Department of Radiation Oncology at Memorial Sloan Kettering Cancer Center, explains that this research is in fact significant (J Clin Oncol 2020; doi: 10.1200/JCO.20.01405).


"It is not enough to show that [proton beam radiation therapy] can better spare normal tissues. The proton community is committed to determining which patients truly benefit most from [it]. This esophageal trial and the other studies discussed above have helped to chip away at the criticism of lack of randomized [proton beam radiation therapy] data," Simone noted in the editorial.


In an interview with Oncology Times, here's what else Simone says about the research by Lin et al, and related ongoing work.


1 Why is the recent randomized controlled trial by the MD Anderson Cancer Center group significant?

"The first randomized trials in which patients received proton or photon radiation therapy were not directly comparing these modalities, and instead they were assessing if protons could be used to more safely allow for radiation dose escalation. The trial by Lin et al, is only the third reported trial directly comparing proton versus photon radiation therapy. The first two were single-institution lung cancer trials published in 2018 for locally advanced and for early-stage, non-small cell lung cancer-the latter of which closed early after only enrolling 19 evaluable patients.


"Given the limitations of those two lung cancer trials, the Lin et al, trial for esophageal cancer is the first proton versus photon randomized trial to show protons were superior to photons for the study's primary endpoint of total toxicity burden-and hence a positive trial.


"The primary endpoint used in this study, total toxicity burden, not being previously validated is the biggest limitation. While this measure is clinically meaningful and takes into account toxicities across a spectrum of different organs, the NRG-GI006 trial will need to assess if the toxicity advantage of proton therapy in the trial by Lin et al, translates to better progression-free survival or overall survival for patients. Proton therapy insurance denials and patients specifically wanting proton therapy instead of photon therapy also led to a high rate of unevaluable patients in the study, which has also been a limitation in prior and ongoing proton versus photon randomized trials."


2 You explain in the editorial that more research is still needed to answer questions about use of proton versus photon radiation therapy. What studies would you say are most urgent?

"NRG Oncology [a National Cancer Institute-funded oncology cooperative group] is leading the way in assessing the superiority of proton therapy relative to photon therapy and has ongoing trials comparing these modalities in locally advanced non-small cell lung cancer, esophageal cancer, glioblastoma multiforme, low- to intermediate-grade glioma, meningioma, and hepatocellular carcinoma. The Proton Collaborative Group is also activating a randomized trial comparing these modalities for postoperative lung cancer. Other multi-center randomized trials are also ongoing, including the RADCOMP trial for locally advanced breast cancer, the PARTIQoL and COMPPARE trials for prostate cancer, and the MDACC and TORPEdO trials for oropharyngeal cancer.


"Each of these multi-center, high-impact trials will be important in assessing which patient populations proton therapy is most beneficial in. And given the many reports of protons improving outcomes for hepatocellular cancer; the encouraging proton results by Lin et al, for esophageal cancer; the rapidly increasing use of proton therapy for breast cancer and esophageal cancer; how common lung cancer is; and how difficult it is to treat is glioblastoma multiforme-each of those trial results are highly anticipated."


3 What is the takeaway message that practicing oncologists and cancer care providers should know about your editorial and the research we've discussed?

"Esophageal cancer remains one of the more challenging cancers to treat. Patients are at high risks of pulmonary, gastrointestinal, and hematologic toxicities with chemoradiation alone. Additionally, as many patients also undergo surgical resection, trimodality therapy adds risks of cardiac arrythmias, postoperative pneumonias, effusions, acute respiratory distress syndrome, and more.


"As such, patients receiving radiation therapy as part of their multimodality therapy for esophageal cancer are at risk for significant and potentially life-threatening complications from their treatment, and advanced radiation modalities may help to reduce these risks and, therefore, improve outcomes for patients. Based on the findings of this trial, subsets of esophageal patients may have significant toxicity reductions when receiving proton therapy as compared with photon therapy."