B C John Cho1, Laura Donahoe2, Penelope A Bradbury3, Natasha Leighl3, Shaf Keshavjee2, Andrew Hope4, Prodipto Pal5, Michael Cabanero5, Kasia Czarnecka6, Karen McRae7, Ming-Sound Tsao5, Marc de Perrot2. 1. Department of Radiation Oncology, University Health Network, University of Toronto, ON, Canada. Electronic address: john.cho@rmp.uhn.ca. 2. Princess Margaret Cancer Centre, Division of Thoracic Surgery, Toronto General Hospital, University Health Network, University of Toronto, ON, Canada. 3. Division of Medical Oncology, University Health Network, University of Toronto, ON, Canada. 4. Department of Radiation Oncology, University Health Network, University of Toronto, ON, Canada. 5. Department of Pathology, Laboratory Medicine Program, University Health Network, University of Toronto, ON, Canada. 6. Princess Margaret Cancer Centre, Division of Thoracic Surgery, Toronto General Hospital, University Health Network, University of Toronto, ON, Canada; Division of Respirology, Department of Medicine, University Health Network, University of Toronto, ON, Canada. 7. Department of Anesthesia and Pain Management, University Health Network, University of Toronto, ON, Canada.
Abstract
BACKGROUND: A novel approach for managing malignant pleural mesothelioma, surgery for mesothelioma after radiotherapy (SMART), consisting of a short accelerated course of high-dose, hemithoracic, intensity modulated radiotherapy (IMRT) followed by extrapleural pneumonectomy was developed. The aim of this study was to evaluate the clinical feasibility of the SMART protocol. METHODS: In this single-centre, phase 2 trial, patients aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-2, with histologically proven, resectable, cT1-3N0M0 disease who had previously untreated malignant pleural mesothelioma were eligible for inclusion. Patients received 25 Gy in five daily fractions over 1 week to the entire ipsilateral hemithorax with a concomitant 5 Gy boost to high risk areas followed by extrapleural pneumonectomy within 1 week. Adjuvant chemotherapy was offered to patients with ypN+ disease on final pathology. The primary endpoint was feasibility, which was defined as the number of patients with 30-day perioperative treatment-related death (grade 5 events) or morbidity (grade 3 or 4 events). A key secondary endpoint was cumulative incidence of distant recurrence. The final analysis was done on an intention-to-treat basis (including all eligible patients). This trial is registered with ClinicalTrials.gov, NCT00797719. FINDINGS: Between Nov 1, 2008, and Oct 31, 2019, 102 patients were enrolled onto the trial and 96 eligible patients were treated with SMART on protocol and included in the analysis. Extrapleural pneumonectomy was done at a median of 5 days (range 2-12) after completing IMRT. 47 (49%) patients had 30-day perioperative grade 3-4 events and one (1%) patient died within 30 days perioperatively (grade 5 event; pneumonia). After a median follow-up of 46·8 months (IQR 13·4-61·2), the 5-year cumulative incidence of distant recurrence was 62 (63·3% [95% CI 52·3-74·4]). The most common first sites of recurrence were the contralateral chest (33 [46%] of 72 patients) and the peritoneal cavity (32 [44%]). INTERPRETATION: Results from this study suggest that extrapleural pneumonectomy after radiotherapy can be done with good early and long-term results. However, minimising grade 4 events on the protocol is technically demanding and might affect survival beyond the post-operative period. FUNDING: Princess Margaret Hospital Foundation Mesothelioma Research Fund.
BACKGROUND: A novel approach for managing malignant pleural mesothelioma, surgery for mesothelioma after radiotherapy (SMART), consisting of a short accelerated course of high-dose, hemithoracic, intensity modulated radiotherapy (IMRT) followed by extrapleural pneumonectomy was developed. The aim of this study was to evaluate the clinical feasibility of the SMART protocol. METHODS: In this single-centre, phase 2 trial, patients aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-2, with histologically proven, resectable, cT1-3N0M0 disease who had previously untreated malignant pleural mesothelioma were eligible for inclusion. Patients received 25 Gy in five daily fractions over 1 week to the entire ipsilateral hemithorax with a concomitant 5 Gy boost to high risk areas followed by extrapleural pneumonectomy within 1 week. Adjuvant chemotherapy was offered to patients with ypN+ disease on final pathology. The primary endpoint was feasibility, which was defined as the number of patients with 30-day perioperative treatment-related death (grade 5 events) or morbidity (grade 3 or 4 events). A key secondary endpoint was cumulative incidence of distant recurrence. The final analysis was done on an intention-to-treat basis (including all eligible patients). This trial is registered with ClinicalTrials.gov, NCT00797719. FINDINGS: Between Nov 1, 2008, and Oct 31, 2019, 102 patients were enrolled onto the trial and 96 eligible patients were treated with SMART on protocol and included in the analysis. Extrapleural pneumonectomy was done at a median of 5 days (range 2-12) after completing IMRT. 47 (49%) patients had 30-day perioperative grade 3-4 events and one (1%) patient died within 30 days perioperatively (grade 5 event; pneumonia). After a median follow-up of 46·8 months (IQR 13·4-61·2), the 5-year cumulative incidence of distant recurrence was 62 (63·3% [95% CI 52·3-74·4]). The most common first sites of recurrence were the contralateral chest (33 [46%] of 72 patients) and the peritoneal cavity (32 [44%]). INTERPRETATION: Results from this study suggest that extrapleural pneumonectomy after radiotherapy can be done with good early and long-term results. However, minimising grade 4 events on the protocol is technically demanding and might affect survival beyond the post-operative period. FUNDING: Princess Margaret Hospital Foundation Mesothelioma Research Fund.
Authors: Thomas Henzi; Kim-Long Diep; Anne Oberson; Valerie Salicio; Christian G Bochet; Beat Schwaller Journal: Int J Mol Sci Date: 2022-04-02 Impact factor: 5.923
Authors: Caroline Rodrigues; Hagit Peretz Soroka; Agostino Pierro; Reto M Baertschiger; Marcelo Cypel; Laura Donahoe; Derek S Tsang; John Cho; Marc De Perrot; Thomas K Waddell; Abha A Gupta Journal: Curr Oncol Date: 2022-06-15 Impact factor: 3.109