Low Cardiopulmonary Toxicity With Use of IMRT When Delivering Postoperative Radiation Therapy (PORT) in Patients With NSCLC.

Purpose/Objective(s) The role of PORT for patients with resected stage IIIA (N2) NSCLC is controversial. Recently, the Phase III LungART trial reported a significant improvement in mediastinal control with PORT but failed to show an overall survival (OS) benefit, due in part to cardiopulmonary (CP) toxicity (7% early and 20% late grade (G) 3-5). However, LungART employed 3D conformal radiotherapy (3D-CRT) in 90% of patients as well as elective treatment of mediastinal nodal stations. We evaluated the risk of CP toxicity associated with use of postoperative IMRT for this population. Materials/Methods We conducted a retrospective study of consecutive patients with NSCLC treated with postoperative IMRT between 2008 and 2019. Patients were eligible if they were found to have incidental pN2 or an R1/2 resection. Targets of PORT for pN2 were bronchial stump, ipsilateral hilum, and involved mediastinal station(s). The primary objective was incidence of CTCAE (v4) G3+ CP toxicities. Secondary objectives were major adverse cardiac events (MACE), defined as cardiac death, myocardial infarction, coronary revascularization or hospitalization due to heart failure; disease-free survival (DFS); and OS. Cumulative incidence and Kaplan-Meier method were used as appropriate. Results 73 patients received PORT with IMRT. Median follow-up was 54 months. Median age at diagnosis was 65 years (range 36 - 81); 33 patients (45%) had pre-existing cardiovascular disease and 48 (65.8%) were current/former smokers. 50 patients had pN2 disease and 23 patients had R1/R2 resection. Among patients with pN2, the median number of involved mediastinal nodes was 1 (range 1 – 12). All patients with pN2 and 70% of patients with R1/R2 resection received chemotherapy, the majority of which was sequential (n = 52, 71.2%). Median RT dose was 54 Gy (range 45 – 66 Gy) in 27 fractions for patients with pN2 and 59.4 Gy (range 45 – 66 Gy) in 30 fractions for patients with R1/R2 resection. 3-year cumulative incidence of G3+ CP toxicity was 2.7%, with an overall incidence of 6.8% (5 events in 73 patients). The rate of G3+ CP toxicity in patients with pN2 was 8%. Three patients developed ≥1 MACE: one died of a cardiac arrest and two underwent coronary revascularization. Two of these patients had a history of coronary artery disease. Two episodes of G3+ toxicity involved valve replacements in patients with pre-existing valvular disease. 3-year DFS was 51.4% (95% CL 46.9 – 55.1%). Two patients with pN2 developed mediastinal failures. 3-year OS was 62.3% (95% CL 50.2 – 74.4%). Conclusion PORT for pN2 NSCLC using IMRT and no elective nodal irradiation is associated with a low rate of G3+ CP toxicity in patients with pN2, comparable to the chemotherapy only arm of the LungART trial. Our data suggest that highly conformal radiation techniques should be prospectively assessed for their potential to translate the known local control benefit of PORT into a survival advantage.