Induction chemotherapy, extrapleural pneumonectomy, and adjuvant radiotherapy for malignant pleural mesothelioma: experience of Guy’s and St Thomas’ hospitals

Abstract

The treatment of malignant pleural mesothelioma (MPM) remains controversial. We present a prospective study of patients treated at our institution with neoadjuvant chemotherapy, extrapleural pneumonectomy (EPP), and radical radiotherapy. Patients with MPM who were eligible for EPP and multimodality therapy were included in this study. Staging was through computed tomography and positron emission tomography and computed tomography (PET/CT) scanning, video-assisted thoracoscopic surgery (VATS), and mediastinoscopy. Our protocol involved three cycles of cisplatin-based neoadjuvant chemotherapy followed by extrapleural pneumonectomy and adjuvant radiotherapy (54 Gy). All patients were followed up every 3-6 months until death. From March 2004 through October 2008, 25 patients were referred for EPP following neoadjuvant chemotherapy. EPP was performed in all but three patients, who were found to have T4 disease at surgery. Surgical complications included arrhythmias (28%), bronchopleural fistulas (12 %), reoperations for bleeding (8%), acute respiratory distress syndrome (4%), pneumonia (4%), septicemia (4%), vocal cord palsy (4%), and Horner's syndrome (4%). The 30-day mortality was 4%. Adjuvant radiotherapy was administered to 81% of patients after EPP. Radiotherapy toxicities included thrombocytopenia, radiation pneumonitis, pulmonary embolus, radiation hepatitis, herpes zoster, transverse myelitis, and late constrictive pericarditis. Median survival from diagnosis was 12.8 months (95% confidence interval 7.8-17.7 months). One-year survival was 54.5%; 2-year survival was 18.2%. Disease progression occurred in 77.3% of patients. Nodal status (N0 disease versus N1-N2) or histology (epithelioid versus biphasic) had no significant impact on survival. Despite recent advances in chemotherapy, surgery, and radiotherapy, survival rates remain low for patients with MPM completing multimodality therapy including EPP.