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

• Published in: Lung cancer (Amsterdam, Netherlands) Vol. 130; pp. 93 - 100
• Main Authors: Haque, Waqar, Verma, Vivek, Butler, E. Brian, Teh, Bin S.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.04.2019
• Subjects: Aged; Carcinoma, Non-Small-Cell Lung - diagnosis; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - mortality; Chemoradiotherapy, Adjuvant - methods; Complete response; Dose-escalation; Female; Humans; Lung cancer; Lung Neoplasms - diagnosis; Lung Neoplasms - drug therapy; Lung Neoplasms - mortality; Lymph Nodes - pathology; Lymphatic Metastasis; Male; Neoadjuvant chemoradiation; Neoadjuvant Therapy - methods; Neoplasm Staging; Nodal clearance; Non-small cell lung cancer; Predictive Value of Tests; Prognosis; Survival Analysis; Treatment Outcome; Nodal clearance; Neoadjuvant chemoradiation; Dose-escalation; Complete response; Lung cancer; Non-small cell lung cancer
• ISSN: 0169-5002; 1872-8332; 1872-8332
• DOI: 10.1016/j.lungcan.2019.02.003

•17% of patients achieved a pathologic complete response (pCR).•37% achieved pathologic nodal clearance (PNC).•Patients who had pCR had superior overall survival compared all patients.•There was no improvement in OS with higher radiation therapy dose. From prospective studies, pathologic nodal clearance (PNC, ypN0) and pathologic complete response (pCR, ypT0N0) 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. 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. 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 + ypN0 cases (p < 0.001). In the subset of non-PNC patients, there was a trend towards higher OS in patients in whom ypT0 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%. 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.