Long-term outcomes of intensity-modulated radiotherapy following extra-pleural pneumonectomy for malignant pleural mesothelioma

Abstract

Background: The purpose was to evaluate safety and efficacy of intensity-modulated radiotherapy (IMRT) following extra-pleural pneumonectomy (EPP) for malignant pleural mesothelioma (MPM).Material and methods: Patients with MPM of clinical stage I–III, which were macroscopic completely resected with EPP were eligible for this prospective study. The ipsilateral hemithorax was irradiated with a prescribed dose of 50.4 Gy. When the high-risk surgical margins or FDG-avid regions were identified, simultaneous integrated boost (SIB) with 56.0 Gy or 61.6 Gy was applied.Results: Twenty-one patients were enrolled. SIB was applied to five patients. The planned IMRT fractions were completed in all, but four patients who suffered from severe fatigue or radiation pneumonitis. With a potential median follow-up of 6.3 years, overall survival was 37.5% at 3 years since the IMRT. The median survival time was 17.5 and 27.0 months since the IMRT and the initial treatment, respectively. Three patients have survived for more than 5 years. Distant metastasis was observed in 15 patients. Local recurrence was also observed in 2 of the 15 patients. Acute toxicities of Grade 3 or worse were observed in 15 patients, including 9 with hematological, 3 with pneumonitis and 6 with fatigue, nausea or vomiting. Five patients developed Grade 3 or worse late toxicities associated with IMRT, consisting of one with persistent Grade 4 thrombocytopenia, one with brain infarction and congestive liver dysfunction, and three with elevation of serum transaminase or biliary enzyme. No Grade 5 toxicity was observed. Patients with N2 showed significantly worse survival than those with N0–1 (18.2% vs. 60.0% at 3 years, p = .014).Conclusion: IMRT following EPP achieved excellent local control for MPM, that might lead to the long-term survival in selected patients. However, treatment burden including acute and late toxicities should be considered in this treatment approach.