Malignant Pleural Mesothelioma and Radiotherapy: Lung Toxicity Results of an Interim Analysis in Prospective Pilot Trial

Abstract

Malignant Pleural Mesothelioma (MPM) is a rare but aggressive intrathoracic malignancy with an overall poor prognosis. Neoadjuvant chemotherapy, surgery and then radiotherapy is the standard of care in early-stage disease. Our study aim is to evaluate the feasibility and toxicity of the novel adjuvant RT in accelerated hypofractionation. We report the lung toxicity preliminary results of the first patients entreated. Starting in 2017, 29 MPM patients were enrolled in the trial (IRST trial 163). All patients were treated with accelerated hypofractionated radiotherapy using a helical 3-D CRT and IMRT system and intensity-modulated arc therapy. We conducted a prospective mono-institutional clinical trial enrolling cyto-histological proven, MPM patients. The major exclusion criteria were: previous thorax radiotherapy, contralateral mediastinum involvement (N3) and/or M1, interstitial pneumopathy, active pneumonitis, and fissural disease. The prescription dose was 30 Gy in five daily fractions, while an inhomogeneous dose escalation to 40 Gy was prescribed based solely upon the presence of gross residual tumor. All patients were treated in a 3-D CRT and IMRT system. Patients underwent functional lung study before to start radiotherapy treatment, 2 months and 6 months after the end of the treatment. The organs at risk dose-volume histograms were converted to a 2-Gy equivalent dose, and we closely adhered to the dose constraints of the literature data. We in particular analyzed lung toxicity of the first 20 patients. No G3/G4 lung toxicity was found. We reported 65.0% G1 pneumonitis and 10% G2 as acute lung toxicity. The majority of the G1 patients had only mild symptoms and pneumonitis was described only for radiologic features with no need for medical therapy. Other respiratory toxicities were G1-G2 cough in 50% of the patients; G1 dyspnea occurred in 65% of the patients and G2 in the 15%. The total lung mean dose was 18 Gy (range 13 Gy-23 Gy), and the contralateral lung mean dose was 2 Gy (range 1 Gy-2 Gy). The median value of Forced Expired Volume in one second (FEV1) recorded was 75.5% (range: 46%-137%) before the treatment was started, the median value of Forced Vital Capacity (FVC) at baseline was 74 (range 46-123) with progressive decreasing values through time. DLCO has also been reported with a progressive decrease over time after radiotherapy treatment. No case of respiratory failure was reported after treatment. Treatment of the intact lung with pleural intensity-modulated arc irradiation is a novel treatment strategy that appears to be safe, feasible, and without a high grade of lung toxicity. More investigations are mandatory. The protocol is ongoing.