Phase II Study of Hemithoracic Intensity-Modulated Pleural Radiation Therapy (IMPRINT) As Part of Lung-Sparing Multimodality Therapy in Patients With Malignant Pleural Mesothelioma

• Published in: Journal of clinical oncology Vol. 34; no. 23; pp. 2761 - 2768
• Main Authors: Rimner, Andreas, Zauderer, Marjorie G, Gomez, Daniel R, Adusumilli, Prasad S, Parhar, Preeti K, Wu, Abraham J, Woo, Kaitlin M, Shen, Ronglai, Ginsberg, Michelle S, Yorke, Ellen D, Rice, David C, Tsao, Anne S, Rosenzweig, Kenneth E, Rusch, Valerie W, Krug, Lee M
• Format: Journal Article
• Language: English
• Published: United States American Society of Clinical Oncology 10.08.2016
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Carboplatin - administration & dosage; Cisplatin - administration & dosage; Disease-Free Survival; Dose Fractionation; Female; Humans; Lung; Male; Mesothelioma - surgery; Mesothelioma - therapy; Middle Aged; Organ Sparing Treatments; ORIGINAL REPORTS; Pemetrexed - administration & dosage; Pleural Neoplasms - surgery; Pleural Neoplasms - therapy; Prospective Studies; Radiation Pneumonitis - etiology; Radiotherapy, Intensity-Modulated - adverse effects; Radiotherapy, Intensity-Modulated - methods; Radn; Survival Rate
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2016.67.2675

We conducted a two-center phase II study to determine the safety of hemithoracic intensity-modulated pleural radiation therapy (IMPRINT) after chemotherapy and pleurectomy-decortication (P/D) as part of a multimodality lung-sparing treatment. Patients received up to four cycles of pemetrexed plus platinum. If feasible, P/D was performed. Hemithoracic IMPRINT was administered to a planned dose of 50.4 Gy in 28 fractions. The primary end point was the incidence of grade 3 or greater radiation pneumonitis (RP). A total of 45 patients were enrolled; 18 were not evaluable (because of disease progression before radiation therapy [RT], n = 9; refusal of surgery or RT, n = 5; extrapleural pneumonectomy at time of surgery, n = 2; or chemotherapy complications, n = 2). A total of 26 patients received pemetrexed plus cisplatin, 18 received pemetrexed plus carboplatin, and four received a combination. Thirteen patients (28.9%) had a partial response, 15 patients (33.3%) experienced disease progression, one patient died during chemotherapy, and all others had stable disease. Eight patients underwent P/D or an extended P/D, and 13 underwent a partial P/D. A total of 27 patients started IMPRINT (median dose, 46.8 Gy; range, 28.8 to 50.4 Gy) and were evaluable for the primary end point (median follow-up, 21.6 months). Six patients experienced grade 2 RP, and two patients experienced grade 3 RP; all recovered after corticosteroid initiation. No grade 4 or 5 radiation-related toxicities were observed. The median progression-free survival and overall survival (OS) were 12.4 and 23.7 months, respectively; the 2-year OS was 59% in patients with resectable tumors and was 25% in patients with unresectable tumors. Hemithoracic IMPRINT for malignant pleural mesothelioma (MPM) is safe and has an acceptable rate of RP. Its incorporation with chemotherapy and P/D forms a new lung-sparing treatment paradigm for patients with locally advanced MPM.