Surgical complications and clinical outcomes after dose-escalated trimodality therapy for non-small cell lung cancer in the era of intensity-modulated radiotherapy.

BACKGROUND: Trimodality therapy (TMT) with preoperative chemoradiation followed by surgical resection is used for 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. METHODS: A retrospective analysis of patients who received planned TMT with IMRT for LA-NSCLC at Brigham and Women's Hospital/Dana-Farber Cancer Institute between 2008 and 2017 was performed. Clinical and treatment characteristics, pathologic response, and surgical toxicity were assessed. Kaplan-Meier method and log-rank test was used for survival outcomes. Cox proportional-hazards regression was used for multivariable analysis. RESULTS: Forty-six patients received less than definitive doses of <60 Gy and 30 patients received definitive doses ≥60 Gy. Surgical outcomes, pathologic complete response, and postoperative toxicity did not differ significantly between the groups. With median follow-up of 3.6 years (range: 0.4-11.4), three-year locoregional recurrence-free survival (78.0% vs. 68.3%, p = 0.51) and overall survival (OS) (61.0% vs. 69.4%, p = 0.32) was not significantly different between patients receiving <60 Gy and ≥60 Gy, respectively. On multivariable analysis, older age, clinical stage, and length of hospital stay (LOS) >7 days were associated with OS. CONCLUSIONS: With IMRT, there was no increased rate of surgical complications in patients receiving higher doses of radiation. 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.