Background: Following complete resection of pN2 non-small cell lung cancer (NSCLC), national guidelines recommend either sequential (sCRT) or concurrent chemoradiotherapy (cCRT). This is the largest study to date evaluating survival between both approaches. In sCRT patients, sequencing ‘chemotherapy first’ versus ‘radiotherapy first’ was also addressed. Methods: The National Cancer Data Base (NCDB) was queried for patients with primary NSCLC undergoing surgery (without neoadjuvant radiotherapy or chemotherapy), pN2 disease with negative surgical margins, and receiving postoperative CRT. Multivariable logistic regression ascertained factors associated with cCRT administration. Kaplan–Meier analysis evaluated overall survival (OS), and Cox proportional hazards modeling determined variables associated with OS. Propensity matching was performed to address group imbalances and indication biases. Results: Of 1924 total patients, 1115 (58%) received sCRT and 809 (42%) underwent cCRT. Median OS in the sCRT and cCRT cohorts was 53 months versus 37 months (p < 0.001); differences persisted following propensity matching (p = 0.002). In the sCRT population, there was a trend for higher OS in the ‘chemotherapy first’ group, relative to ‘radiotherapy first’ (55 vs. 44 months, p = 0.079), but there were no statistically apparent differences following propensity matching (p = 0.302). Conclusions: For completely resected pN2 NSCLC, delivering adjuvant sCRT was associated with improved survival over cCRT. Toxicity-related factors may help to explain these results but need to be better addressed in further investigations. Differential sequencing of sCRT did not appear to affect survival.
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