Pathologic nodal clearance and complete response following neoadjuvant chemoradiation for clinical N2 non-small cell lung cancer: Predictors and long-term outcomes

Purpose: From prospective studies, pathologic nodal clearance (PNC, ypNO) and pathologic complete response (pCR, ypTONO) correlate with overall survival (OS) following neoadjuvant chemoradiation for cN2 non-small cell lung cancer (NSCLC). Contemporary cooperative group trials attempt to increase radiation doses to achieve nodal clearance and/or pCR. However, long-term comparative outcomes of dose-escalated neoadjuvant chemoradiation are lacking. The goal of this study was to evaluate rates of PNC and pCR in a large population of cN2 NSCLC, predictors thereof, and long-term outcomes thereafter. Methods: The National Cancer Database was queried (2004-2015) for histologically-confirmed cT1-4N2M0 NSCLC undergoing neoadjuvant chemoradiation followed by lobectomy. Statistics included multivariable logistic regression, Kaplan-Meier OS analysis before and following propensity matching, Cox proportional hazards modeling, and sensitivity analysis when varying neoadjuvant radiation dose. Results: Of 1750 patients, the pCR and PNC rates were 17% and 37%, respectively. Radiation dose > 54 Gy independently predicted for pCR. Patients achieving pCR experienced significantly higher OS than non-pCR cases (p < 0.001) and ypT + ypNO cases (p < 0.001). In the subset of non-PNC patients, there was a trend towards higher OS in patients in whom ypTO was achieved (p = 0.059). On sensitivity analysis, when separating the cohort into doses of 45.0-50.4 Gy, 50.5-54.0 Gy, 54.1-59.4 Gy, and > 59.4 Gy, 30-day mortality rates in the respective groups were 2.9%, 1.8%, 1.2%, and 3.4%. Conclusions: Although neoadjuvant dose-escalation increases pCR rates, there is no OS benefit with dose-escalation, and high dose-escalation (i.e., > 59.4 Gy) was associated with numerically higher mortality rates, indicating the importance of careful multidisciplinary discussion.