In a single-institution phase IIb trial reported in the Journal of Clinical Oncology, Steven H. Lin, MD, PhD, and colleagues found that proton beam therapy was associated with less toxicity and similar progression-free survival vs intensity-modulated radiation therapy in patients with locally advanced esophageal cancer.
“For locally advanced esophageal cancer, proton beam therapy reduced the risk and severity of adverse events compared with intensity-modulated radiation therapy while maintaining similar [progression-free survival].”— Steven H. Lin, MD, PhD, and colleagues
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Study Details
In the trial, 145 patients were randomly assigned to proton beam therapy (n = 73) or intensity-modulated radiation therapy at 50.4 Gy (n = 72). The co-primary endpoints were total toxicity burden and progression-free survival; total toxicity burden was defined by 13 possible instances of 11 separate adverse events, including 7 postoperative complications measured up to 30 days postoperatively and 6 potentially recurrent toxicities measured up to 12 months after random assignment. To quantify total toxicity burden, a numerical weight (0–100) was assigned to the severity/occurrence of each grade of each type of toxicity. Total toxicity burden was represented as Bayesian posterior mean values with 95% highest posterior density intervals.
Key Findings
The trial, which began in April 2012, was approved for closure and analysis upon activation of NRG-GI006, a larger study in this setting, in March 2019, just prior to the predefined (third and last) interim analysis at 67% of planned enrollment.
Among the 145 randomly assigned patients, 107 were evaluable, consisting of 46 in the proton beam therapy group and 61 in the intensity-modulated radiation therapy group. Proton beam therapy consisted of passive scattering in 80% of patients. Overall, 21 patients in the proton beam therapy group and 30 in the intensity-modulated radiation therapy group underwent esophagectomy.
Median follow-up was 44.1 months. The posterior mean total toxicity burden was 2.3 times higher in the intensity-modulated radiation therapy group (39.9, 95% highest posterior density interval = 26.2–54.9) vs the proton beam therapy group (17.4, 95% highest posterior density interval = 10.5–25.0). The mean postoperative complication score was 7.6 times higher in the intensity-modulated radiation therapy group (19.1, 95% highest posterior density interval = 7.3–32.3) vs the proton beam therapy group (2.5, 95% highest posterior density interval = 0.3–5.2).
The posterior probability that mean total toxicity burden was lower for proton beam therapy vs intensity-modulated radiation therapy was 0.9989, which exceeded the stopping boundary of 0.9942 at the 67% interim analysis.
At 3 years, progression-free survival was 44.5% in the proton beam therapy group vs 44.5% in the intensity-modulated radiation therapy group and median progression-free survival was 28.5 months vs 18.1 months (P = .70). At 3 years, overall survival was 51.2% vs 50.8% and median overall survival was 42.1 months vs 73.6 months (P = .60).
The investigators concluded: “For locally advanced esophageal cancer, proton beam therapy reduced the risk and severity of adverse events compared with intensity-modulated radiation therapy while maintaining similar [progression-free survival].”
Dr. Lin, of the Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by grants from the National Cancer Institute. For full disclosures of the study authors, visit ascopubs.org.
