Postoperative Hemithoracic Intensity Modulated Radiation Therapy (Imrt) With An Optional Integrated Boost For Malignant Pleural Mesothelioma: Toxicity, Patterns Of Failure, And A Matched Survival Analysis

Hemithoracic intensity-modulated radiation therapy (IMRT) after pleurectomy/decortication (PD) is a novel paradigm for which there is limited data. We investigated the safety, efficacy and recurrence patterns in patients treated with this technique. We then compared the treatment related toxicity and survival of this cohort to patients treated with postoperative IMRT after extrapleural pneumonectomy (EPP). From 2009-2013, 22 patients (11 prospectively enrolled in an institutional protocol and 11 studied off protocol) with malignant pleural mesothelioma underwent PD followed by adjuvant IMRT to the involved hemithorax. Patients were treated to 45 Gy in 25 fractions, with 9 patients receiving a simultaneous boost to 60 Gy to high-risk areas. Twenty patients received chemotherapy (15 = induction, 2 = adjuvant, 3 = both). Toxicity was scored with CTCAE v4.0. Pulmonary function tests were compared within an individual patient at baseline, post-operatively, and within 7 months (median 3.0 months, range 1.5-6.3 months) after IMRT using a paired t-test. Kaplan-Meier analysis was used to calculate rates of overall survival (OS), progression-free survival (PFS), time to locoregional failure (tLRF), and time to distant metastasis (tDM). Locoregional patterns of failure were classified as infield, marginal or out-of-field. Treatment related toxicity, OS, PFS, tLRF, and tDM were compared to 22 patients who received postoperative IMRT after EPP utilizing a matched analysis on the following factors: age, nodal stage, performance status, and receipt of chemotherapy. Significance between groups was determined using the log-rank or Fisher’s exact test. Median follow up was 14.7 months after surgery (range 4.1-37.1 months). Rates of grade 2-3 toxicity were: fatigue 45%, upper GI 77%, skin 23%, and lung 41%. Two instances of grade 2 leukopenia and 1 case of grade 4 thrombocytopenia were observed. Median baseline % predicted FVC, FEV1, and DLCO were 90%, 84%, and 87%. The change in % predicted FVC, FEV1 and DLCO was -18%, -11% and-17% after surgery and -25% (p = 0.02), -18% (p = 0.01), and -27% (p = 0.01) after IMRT. Rates of OS and PFS were 73% and 60% at 1 year and 52% and 32% at 2 years. Outcomes for IMRT after PD compared to IMRT after EPP were as follows: grade 4-5 toxicity (0/22 vs 3/22, p = 0.23), median OS (28.4 vs 14.2 months, p = 0.14), median DFS (15.4 vs 10.2 months, p = 0.18), median tLRF (20.5 months vs not reached, p = 0.06), and median tDM (not reached vs 11.8 months, p = 0.15). IMRT after PD is associated with a low likelihood of high-grade toxicity, though with transient reductions in blood counts during RT and progressive declines in pulmonary function over time. When matched with similar patients who received IMRT after EPP, there does not appear to be inferiority with regard to PFS or OS.