Purpose/objectives: Data are conflicting on the effects of time interval from neoadjuvant chemoradiation (NCRT) to surgery for locally advanced non-small-cell lung cancer (LA-NSCLC). This study investigated the impact of surgical timing after NCRT and radiation dose on postoperative mortality and overall survival (OS).
Materials and methods: Using the National Cancer Database, we identified 3489 LA-NSCLC patients treated with NCRT and surgery. Multivariate Cox proportional hazards analysis (MVA) was used to examine the effects of surgery >7 weeks from NCRT completion on OS. Propensity score (PS)-matched survival analysis for surgery ≤7 and >7 weeks was performed. Postoperative mortality was assessed.
Results: Median OS for surgery ≤7 weeks and >7 weeks after NCRT were 56.9 versus 45.6 months (hazard ratio, HR 1.18 [1.07-1.30]; p < 0.001). Surgery >7 weeks correlated with decreased OS on MVA (HR 1.15 [1.04-1.27]; p = 0.009) and PS matching (HR 1.16 [1.049-1.29]; p = 0.004). Time as a continuous variable correlated with OS on MVA (HR 1.003 [1.001-1.006]; p = 0.0056) and PS matching (HR 1.004 [1.001-1.006]; p = 0.004). Among 2902 lobectomy patients, the mortality rate for surgery ≤66 days was 5.2% versus 8.1% for >66 days (MVA HR 1.59 [1.02-2.49]; p = 0.04). Higher neoadjuvant radiotherapy dose correlated with surgery >7 weeks and lobectomy >66 days on MVA.
Conclusions: Increased interval >7 weeks from NCRT to surgery for LA-NSCLC is correlated with worse OS and lobectomy ≤66 days correlated with improved OS. Surgery ≤7weeks may improve tumor control, whereas higher mortality for surgery >66 days may relate to late NCRT manifestations. Neoadjuvant doses of 44-50.4 Gy may minimize risks of radiation-induced lung injury and surgical complications and facilitate surgery within the optimal 7-week interval.
Keywords: lung cancer; radiation dose; surgical timing; survival; trimodality therapy.
© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.