Adjuvant Radiation Therapy for Pleural Mesothelioma after Extrapleural Pneumonectomy (EPP) or Pleurectomy and Decortication (P+D)

Abstract

The optimal treatment sequence for localized malignant pleural mesothelioma (MPM) is controversial. We hypothesized that pleurectomy and decortication (P+D) followed by adjuvant intensity modulated radiation therapy (IMRT) has equivalent cancer control with less morbidity than extrapleural pneumonectomy (EPP) followed by adjuvant radiation therapy (RT). Forty-four patients treated with curative intent surgery and adjuvant RT for MPM at a single institution were included. Prior to September 2013, patients were treated with EPP followed by adjuvant RT (n = 24, 54%). After September 2013, standard treatment was P+D followed by adjuvant IMRT (n = 20, 45%). We compared oncologic outcomes and toxicities (CTCAE version 5.0) between these two approaches. Median age at diagnosis was 64 years (range 26-76); patients receiving EPP were significantly younger (median age 60 vs. 70, p<0.01). Most patients were AJCC 8th edition clinical stage T1 (80%) and N0 (91%). Thirty-seven patients (84%) received neoadjuvant chemotherapy. At surgery, pathologic T stage was most commonly T3 (64%), with 30% node positive. Forty-two patients (95%) had epithelioid histology at surgery, and the remaining two had biphasic histology (5%). Median total RT dose to the entire pleura was 45 Gy (range 30-60 Gy), delivered over a median 27 fractions (range 20-33). Median follow-up for the entire cohort was 3.9 years (range 0.6-20.0 years). Median OS was 2.6 years for P+D compared to 1.1 years for EPP (HR: 0.52, 95% CI: 0.25-1.09, p = .08). Two-year OS was 63% for P+D versus 21% for EPP. On univariate analysis, male sex, pre-operative FEV1% <80, and clinically positive nodes were significantly associated with risk of death. There was no difference in locoregional control (LRC) or progression-free survival (PFS) between P+D and EPP. LRC at 2 and 5 years for the entire cohort was 48% and 39%. PFS at 2 and 5 years was 34% and 17%. Acute Grade 2+ pneumonitis was seen in 0% of EPP patients compared to 35% for P+D, with one grade 3 (5%), one grade 4 (5%), and no grade 5 (0%) pneumonitis. Mean lung dose was significantly associated with development of any grade pneumonitis (odds ratio: 1.46, 95% CI: 1.02-2.11, p = 0.04). Patients who developed pneumonitis had a mean total lung mean dose of 20.4 Gy, compared to 12.9 Gy in those who did not. Total lung V20% was also significantly associated with development of any grade pneumonitis (odds ratio: 1.11, 95% CI: 1.01-1.22, p = 0.03). Mean total lung V20% was 38% for those who developed pneumonitis, compared to 20% for those who did not. FEV1% declined by 27% after P+D and 32% after EPP, while DLCO% declined by 22% after P+D and 28% after EPP. Modern treatment with pleurectomy and decortication followed by adjuvant hemithoracic IMRT appears to provide favorable survival compared to EPP followed by RT, though more non-fatal pneumonitis was seen after P+D with adjuvant IMRT.