We conducted a phase III randomized clinical trial to assess whether Radical Hemithoracic Radiotherapy (RHR) compared to palliative radiotherapy (PR), may achieve overall survival (OS) advantages in malignant pleural mesothelioma (MPM) patients.

from August 2014 to May 2018, patients with hystologically diagnosed non-metastatic MPM, who underwent non-radical lung-sparing surgery and chemotherapy (CHT) were randomly assigned (1:1) to receive RHR or PR. RHR total dose to the involved pleural cavity was 50Gy in 25 fractions and the gross residual disease received a simultaneous integrated boost of 60Gy. The primary end-point was OS. Secondary end points were: local control, distant metastasis free survival, progression free survival, acute and late toxicity rates. A total sample size of 108 patients considering a type I error (α) of 0.05 and a statistical power of 80% was calculated to prove that RHR could improve the 2-year OS. OS was estimated with the Kaplan-Meier method and the log-rank test (two-sided) tested differences between arms. The univariate and multivariate analyses were performed by using Cox proportional hazard model. Possible prognostic factors investigated: age, sex, performance status, lung surgery, gross residual disease and histology.

108 patients were randomized: 53 to PR arm and 55 to RHR arm. Median follow-up was 14.6 months. The 2-year OS rate was 58% in RHR arm vs. 28% in PR arm (HR 0.54, 95% CI 0.31-0.95, p=0.031). In RHR arm: 11 patients experienced Grade≥ 3 acute toxicity, 17 had Grade 3-4 late toxicity. Nine patients experience a Grade ≥2 pneumonitis, including 1 Grade 5.

RHR significantly improves survival in MPM patients treated with non-radical lung sparing surgery and CHT compared to palliative treatments, although associated to a not negligible toxicity profile.