Accelerated hypofractionated hemithoracic intensity modulated radiation therapy (IMRT) followed by extrapleural pneumonectomy (EPP) for malignant pleural mesothelioma (MPM): Results of a phase I/II study.

Abstract

7526 Background: We developed a protocol with accelerated hypofractionated hemithoracic IMRT followed by EPP for MPM. Advantages include optimal delivery of radiation to the whole tumor bed in a short period limiting the risk of viable tumor cell spread during surgery. Methods: Patients with resectable clinical T1-3N0M0 histology proven MPM were eligible for the study. 25 Gy in 5 daily fractions over 1 week was delivered to the entire ipsilateral hemithorax by IMRT with concomitant boost of 5 Gy to volumes at high risk based on CT and PET scan findings. EPP was performed one week after the end of radiation. Adjuvant chemotherapy was offered to patients with ypN2 on final pathology. The primary end-point was treatment related mortality. Secondary endpoint included overall survival and disease-free survival (DFS). Initial sites of recurrence were also recorded. Results: Twenty five patients were accrued between 11/2008 and 10/2012. Patients had a median age of 64 years (range, 45-75), 76% were males, 64% had epithelioid histology. All patients completed IMRT and EPP. IMRT was well tolerated with no grade 3-5 toxicity. EPP was performed 6±2 days after completion of IMRT. Surgical complications occurred in 18 patients. One patient died from empyema at 88 days. All but one patient (stage IB) had stage III (n=11) or IV (n=13) disease on final pathology. Five out of 13 patients with ypN2 disease underwent adjuvant chemotherapy. After a median follow-up of 19 months (range, 3-51), the estimated 3-year survival reached 62%. Survival was significantly better in epithelioid compared to biphasic pathologic subtypes (83% survival at 3 years vs 19%, respectively; p=0.004). 14 patients remain disease free after a median follow-up of 17 months (range, 3-37). 2-year DFS was 85% in stage III and 37% in stage IV disease (p=0.03). Recurrences occurred in the ipsilateral chest only (n=2), ipsilateral chest and distant sites (n=2), and distant sites only (n=6). Conclusions: Accelerated hypofractionated hemithoracic IMRT followed by EPP is feasible. This treatment could improve survival in selected patients with epithelial subtype. Clinical trial information: NCT00797719.