The Effect of Radiotherapy Dose on Overall Survival and Mediastinal Pathologic Response in Locally Advanced Non-Small Cell Lung Cancer Treated with Neoadjuvant Chemoradiation Followed by Surgical Resection

Abstract

Neoadjuvant chemo-radiation (NACRT) followed by a resection is a standard approach in the treatment of Stage IIIA non-small lung cancer (NSCLC). However, the dose of radiotherapy (RT) in the setting of NARCT is controversial. The purpose of this study is to determine difference in overall survival (OS) or pathologic response based on dose of RT used in NACRT in patients with NSCLC. We queried the National Cancer Database (NCDB) for patients age >18 treated with NACRT followed by at least a lobectomy between 2003-2016 with cT1-4 cN2 M0 NSCLC. Patients were excluded if they received <45 Gy or primary tumor size was unavailable. Low dose RT (LDRT) was defined as 45-54 Gy and high dose RT (HDRT) was >54 Gy. Patients were scored as having mediastinal downstaging (MDS) if they were ypN0-N1 and having a mediastinal pathologic complete response (mpCR) if they were ypN0. Chi square and independent t-test were used to compare variables between treatment groups. OS was analyzed by the Kaplan-Meier method and compared using log rank test. Multivariate analysis was performed using Cox Regression Analysis. 3,056 patients treated with NACRT were identified, 1935 treated with LDRT and 1121 treated with HDRT. Patients treated with LDRT were more likely to be treated at an earlier year of diagnosis, at a non-academic center, and have high grade tumors (see table 1). Patients treated with HDRT were more likely to have tumors >4 cm (see table 1). There was higher use of adjuvant chemotherapy in the LDRT than HDRT (21.3% vs 17.3%, p = 0.006). Other clinical variables including pneumonectomy rates were similar between the groups. There was no difference in median OS between HDRT and LDRT (46.1 months vs 46.6 months, p = 0.820). Factors predicting for worse OS were male sex, age, >60, high grade tumors, and patients receiving pneumonectomy. On multivariate analysis, male sex (HR 1.26, p<0.001), age >60 (HR 1.48, p<0.001), high grade tumors (1.33, p<0.001), and pneumonectomy (HR 1.42, p<0.001) all maintained significance. HDRT did not show improvement in OS on multivariate analysis (HR 0.99, p = 0.812). 2,768 patients had pathologic staging available. Patients treated with HDRT had a higher rate of MDS (70.5% vs 61.3%, p<0.001) and higher rate of mpCR (58.8% vs 48.8%, p<0.001) than those treated with LDRT. Patients who had MDS had an improvement in median OS (56.3 months vs 38.1 months, p<0.001) as did patients with mpCR (59.6 months vs 39.7 months, p<0.001). While >54 Gy RT was associated with approximately a 9% improvement in MDS and mpCR rates in patients treated with NCRT, there was no associated improvement in OS. 45-54 Gy should remain the standard of care in NACRT.Abstract 2221; Table45-54 Gy>54 GyP valueNumber of patients19351121Median Age62610.146Diagnosis after 201143.2%57.9%<0.001Male sex49.4%52.5%0.088Treated at academic center36.8%47.2%<0.001Grade 2+67.5%62.5%0.005Received Adjuvant Chemotherapy21.3%17.3%0.006Pneumonectomy13.4%13.7%0.824 Open table in a new tab