Post-Operative Radiation Therapy for Non-Small Cell Lung Cancer Patients With Higher Positive to Examined Lymph Node Ratio is Associated With Improved Overall Survival

Abstract

A recent randomized controlled trial for post-operative radiation therapy (PORT) for non-small cell lung cancer (NSCLC) patients with N2 disease has suggested no clinical benefit. However, data regarding the possible correlation between lymph node disease burden and PORT outcomes is lacking.The National Cancer Database (NCDB) NSCLC participant user file was used to identify patients who received upfront surgical resection and documented pathologic N2 disease. Patients not receiving chemotherapy were excluded. A positive to examined lymph node (PEN) ratio was calculated by dividing the number of positive lymph nodes by the number of examined lymph nodes (range 0 - 1.0). The PEN ratio was then divided into quartiles to compare overall survival (OS) with and without PORT. Cox proportional hazards modeling (CPHM) was used to assess the association between OS and PORT status by quartile group.From 2004 to 2017, 22,354 NSCLC patients received upfront surgery and were found to have pathologic N2 disease. The median number of lymph nodes examined was 11 (Interquartile Range 6, 16). Median OS decreased with increasing PEN ratio: 0-0.16: 58 months, 0.17-0.30: 49 months, 0.31-0.50: 37 months, 0.51-1.0: 29 months, P < 0.001. 10,446 (47%) of this patient population received PORT. The proportion of patients receiving PORT increased by PEN ratio quartile: first quartile 40% versus last quartile 52%, P < 0.001. There was no difference in OS for patients receiving PORT in the first quartile (59 months versus 57 months without PORT, P = 0.3). However, each of the higher quartiles did demonstrate a significant improvement with PORT: 2nd quartile: 51 months versus 47 months, P = 0.01, 3rd quartile: 43 months versus 37 months, P < 0.001, and 4th quartile 33.6 months versus 24 months, P < 0.001. On CPHM, receipt of PORT for patients in the 3rd and 4th quartiles of PEN ratio scores was independently associated with a decreased mortality hazard: 0.88 (0.82 - 0.94), P < 0.001 and 0.79 (0.74, 0.84), P < 0.001, respectively.While a recent prospective clinical trial demonstrated no clinical benefit to PORT in the setting of N2 disease, this analysis shows that there may be a select population of patients that may benefit as the ratio of positive to examined lymph nodes increases. Secondary analyses in prospective trials may help delineate the role of the PEN ratio in treatment selection.