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

We conducted a two-center phase II study to determine the safety of hemithoracic intensitymodulated pleural radiation therapy (IMPRINT) after chemotherapy and pleurectomy-decortication (P/D) as part of a multimodality lung-sparing treatment. Patients and MethodsPatients 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). ResultsA 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 followup, 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. ConclusionsHemithoracic 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.

A Randomized Phase II Trial of Adjuvant Galinpepimut-S, WT-1 Analogue Peptide Vaccine, After Multimodality Therapy for Patients with Malignant Pleural Mesothelioma

“…All but one patient received chemotherapy and all regimens contained pemetrexed and platinum. The vast majority of patients, 76%, received intensity modulated pleural radiation therapy (IMPRINT) 2,16 with 7% receiving a different type of radiation and 17% receiving no radiation prior to enrollment. Twenty patients were randomized to galinpepimut-S and 21 to the control arm.…”

“…For patients with early stage disease, multimodality therapy is a preferred approach which includes cytoreductive surgery (such as extended pleurectomy/decortication), pemetrexed-based chemotherapy, and, in some cases, thoracic radiation. 2 However, even with this aggressive approach to early stage disease, the majority of patients experience recurrence due to persistent microscopic disease. Therefore, it is imperative that efforts continue to further improve outcomes.…”

Immunotherapy for malignant pleural mesothelioma: current status and future directions

“…As such, adjuvant radiation therapy is used to control microscopic disease (7). Intensity-modulated pleural radiation therapy (IMPRINT) has been developed to target pleural surfaces directly while limiting lung exposure; it has been shown to be safe with no reported episodes of severe radiation pneumonitis (8).…”

The role of radical radiotherapy in the management of malignant pleural mesothelioma: A systematic review

“…Local recurrence was the predominant pattern of failure, most often in areas of previous bulk disease. [62]…”