Adjuvant Chemotherapy, Not Radiotherapy, Prolongs Survival for Node-negative Non-small Cell Lung Cancer with Positive Surgical Margins
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Objective: The study objective was to determine differences in survival depending on adjuvant therapy type, timing, and sequence in node-negative disease with positive margins after non-small cell lung cancer resection.
Methods: The National Cancer Database was queried for patients with positive margins after surgical resection of treatment-naïve cT1-4N0M0 pN0 non-small cell lung cancer who underwent adjuvant radiotherapy or chemotherapy from 2010 to 2016. Adjuvant treatment groups were defined as surgery alone, chemotherapy alone, radiotherapy alone, concurrent chemoradiotherapy, sequential chemotherapy then radiotherapy, and sequential radiotherapy then chemotherapy. The impact of adjuvant radiotherapy initiation timing on survival was evaluated using multivariable Cox regression. Kaplan-Meier curves were generated to compare 5-year survival.
Results: A total of 1713 patients met inclusion criteria. Five-year survival estimates differed significantly between cohorts: surgery alone, 40.7%; chemotherapy alone, 47.0%; radiotherapy alone, 35.1%; concurrent chemoradiotherapy, 45.7%; sequential chemotherapy then radiotherapy, 36.6%; and sequential radiotherapy then chemotherapy, 32.2% ( = .033). Compared with surgery alone, adjuvant radiotherapy alone had a lower estimated survival at 5 years, although overall survival did not differ significantly ( = .8). Chemotherapy alone improved 5-year survival compared with surgery alone ( = .0016) and provided a statistically significant survival advantage over adjuvant radiotherapy ( = .002). Compared with radiotherapy-inclusive multimodal therapies, chemotherapy alone yielded similar 5-year survival ( = .066). Multivariable Cox regression showed an inverse linear association between time to adjuvant radiotherapy initiation and survival, but with an insignificant trend (10-day hazard ratio, 1.004; = .90).
Conclusions: In treatment-naïve cT1-4N0M0 pN0 non-small cell lung cancer with positive surgical margins, only adjuvant chemotherapy was associated with a survival improvement compared with surgery alone, with no radiotherapy-inclusive treatment providing additional survival benefit. Delayed timing of radiotherapy initiation was not associated with a survival reduction.