Clinical Outcomes After Trimodality Therapy With Dose-Escalated Neoadjuvant Intensity-Modulated Radiotherapy for Locally Advanced Non-Small Cell Lung Cancer.

Abstract

PURPOSE/OBJECTIVE(S)\nTrimodality therapy (TMT) with preoperative chemoradiation followed by surgical resection is used in the management of locally-advanced non-small cell lung cancer (LA-NSCLC). Traditionally, preoperative radiation doses ≤54 Gy are used due to concerns regarding excess morbidity, but little is known about outcomes and toxicities after TMT with intensity-modulated radiotherapy (IMRT) to higher doses. We investigated whether clinical outcomes were different after TMT with IMRT using less than definitive doses of < 60 Gy and definitive doses ≥60 Gy for LA-NSCLC.\n\n\nMATERIALS/METHODS\nWe conducted an Institutional Review Board-approved retrospective cohort analysis of patients who received planned TMT using IMRT for LA-NSCLC between 2008 and 2017 at one institution. We recorded clinical and treatment characteristics, pathologic response, and surgical toxicity within 30 days. Toxicity was graded using Common Terminology Criteria for Adverse Events version 5.0. Chi-square or Fisher exact tests were used for categorical variables. Survival outcomes were analyzed by Kaplan-Meier method and log-rank test. Univariate and multivariate analyses were performed using Cox proportional-hazards regression.\n\n\nRESULTS\nWe identified 46 patients receiving doses < 60 Gy and 30 patients receiving doses ≥60 Gy. Distribution of clinical nodal stage was different between the two groups with more cases of N0 and N3 disease in the higher dose group (P\u202f=\u202f0.015), but other factors, including age, comorbidities, clinical stage, and surgical approach, were not different. Rates of R0 resection, pathologic complete response, and postoperative toxicity, including cardiovascular toxicity, post-operative infection, intensive care unit (ICU) admission, and length of hospital stay (LOS), were not significantly different between the two groups. Three patients died within 30 days of surgery with two receiving doses ≥60 Gy. Mean esophageal (24.2 vs. 20.2 Gy, P\u202f=\u202f0.029) and lung (16.7 vs. 13.6 Gy, P\u202f=\u202f0.005) doses were significantly higher for patients receiving doses ≥60 Gy. With median follow-up of 3.6 years (range: 0.4-11.4), 3-year locoregional recurrence-free survival (78.0% vs. 68.3%) and overall survival (OS) (61.0% vs. 69.4%) was not different between patients receiving < 60 Gy and ≥60 Gy. On multivariate analysis, older age, clinical stage, and LOS > 7 days were significantly associated with decreased OS when controlling for sex, surgical approach, post-operative grade ≥3 toxicity, and mean lung dose.\n\n\nCONCLUSION\nWe found no increased rate of post-TMT complications in patients receiving higher doses using IMRT. Survival outcomes or LOS did not differ based on radiation dose, but increased LOS was associated with worse OS. Larger prospective studies are needed to further examine outcomes after IMRT in patients with LA-NSCLC receiving TMT.