Effect of Adjuvant Chemotherapy After SBRT for Node Negative, Non-Metastatic Non-Small Cell Lung Cancer

Abstract

Administration of adjuvant chemotherapy (ACT) after surgical resection of a tumor ≥4cm is standard of care based on studies demonstrating improved overall survival. No such standard exists for tumors ≥ 4cm treated with stereotactic body radiation therapy (SBRT), and thus, administration of ACT remains variable across institutions. Using the National Cancer Database (NCDB), we aim to analyze overall survival (OS) in patients who undergo SBRT followed by ACT for localized non-small cell lung cancer (NSCLC). Additionally, we seek to identify predictors for receipt of ACT.Patients with node negative, non-metastatic NSCLC treated with definitive SBRT between 2004-2017 were identified from the NCDB. Patients were grouped into tumor size < 4cm or ≥4cm, and by use of ACT within 30 days of SBRT. Demographics were described by treatment. Logistic regression was used to assess the association between tumor size and treatment, adjusting for age, gender, race and comorbidities. Overall survival was calculated from date of end of radiation to date of death or last follow up. Multivariable Cox proportional regression was used to investigate the association between tumor size, treatment type, and OS, adjusting for the factors above.Of the 17441 patients identified meeting the inclusion criteria, 195 received ACT after SBRT (1.1%). Forty-nine percent of these patients were male, and 91% were white. The median age of patients who received ACT was 69. Twenty-six percent of the patients who received ACT had tumors ≥ 4cm (n = 51). There was a significant difference in hazard of death; patients with tumors ≥ 4cm without ACT (n = 1310) had worse OS as compared to those with tumors < 4cm without ACT (n = 15936) (HR 1.45; 95% CI 1.34-1.56, P < 0.0001). This difference became non-significant when comparing ≥4cm with ACT versus < 4cm without ACT (HR 1.17; P = 0.40). On pairwise comparison, there was no difference in hazard of death when comparing tumors ≥ 4cm with ACT versus ≥4cm without ACT (HR 0.81; P = 0.26). On multivariate analysis, tumor size ≥ 4cm was a significant predictor for receipt of ACT (OR 5.08; 95% CI 3.64-7.07, P < 0.0001). Older patients (OR 0.93 per 10yr increase; 95% CI 0.92-0.95, P < 0.0001) and those with comorbidities (OR 0.73 any vs no comorbidities; 95% CI 0.54-0.97, P = 0.032) were less likely to receive ACT. Notably, there was no difference between sex and race, white versus non-white, in administration of ACT.Patients with tumors ≥4cm treated with SBRT without ACT have decreased OS as compared to those with tumors < 4cm who are similarly treated without ACT. This survival decrement disappears when comparing tumors ≥4cm with ACT to tumors < 4cm without ACT suggesting a benefit to ACT. While there was no difference in OS between patients with tumors ≥4cm with or without ACT, this could be due to the small number of patients with tumors ≥4cm who received ACT. These findings identify a need to further study the roll of systemic therapy after SBRT.