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

Abstract

Purpose: 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 and methods: 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).

Results: 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.

Conclusions: 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.

Trial registration: ClinicalTrials.gov NCT00715611.

Fig 1.

Consort diagram of the phase II study. EPP, extrapleural pneumonectomy; IMRT, intensity-modulated radiation therapy.

Fig 2.

Example of hemithoracic pleural intensity-modulated radiation therapy (IMRT) in a patient with (A) a resected and (B) an unresectable tumor. (A) Resected tumor image is from a 70-year-old man with left-sided pT3N0M0 epithelioid malignant pleural mesothelioma (MPM) treated with four cycles of carboplatin-pemetrexed, macroscopic gross total resection by pleurectomy-decortication and hemithoracic pleural IMRT to 50.4 Gy in 28 fractions. The red line is the planning target volume. (B) Unresectable tumor image is from a 63-year-old man with right-sided pT2N2M0 epithelioid MPM treated with four cycles of cisplatin-pemetrexed; unresectable disease noted on exploratory thoracotomy and hemithoracic pleural IMRT to 48.6 Gy in 27 fractions. The red line is the planning target volume.

Fig 3.

Overall survival and progression-free survival: (A) intent-to-treat analysis and (B) analysis of evaluable patients.

Fig 4.

Overall survival on the basis of (A) resection status and (B) response to chemotherapy.

Fig A1.

Pre-radiation therapy (RT) pulmonary function tests among patients with and without grade 2 or greater radiation pneumonitis. DLCO, diffusing capacity of the lung for carbon monoxide.