Assessing the Benefit of Higher Biologically Effective Dose in Patients With Squamous Cell Carcinoma of the Lung Treated With Stereotactic Body Radiation Therapy

Abstract

Multiple studies have suggested that patients with early-stage squamous cell carcinoma (SCC) of the lung treated with stereotactic body radiation therapy (SBRT) are more susceptible to local failure when compared to other non-small cell lung cancer (NSCLC) histologies. It is unknown if higher biological equivalent dose (BED) leads to improved outcomes in this patient population. We used the National Cancer Database (NCDB) to compare overall survival (OS) between patients with SCC and non-SCC NSCLC treated with "high" or "low" BED SBRT.The NCDB was used to identify patients with cT1-2N0M0 NSCLC diagnosed between 2006-2016 and treated with 3-5 fraction SBRT. Patients were grouped by BEDhigh (> 150 Gy) and BEDlow (≤132 Gy). OS was estimated by Kaplan-Meier analysis. Correlation between BED and OS was tested with univariate and doubly-robust multivariable Cox regression analysis (MVA). The MVA included age, sex, Charlson-Deyo score, tumor grade, clinical T stage, and BED group. Propensity-score matched analysis with inverse probability of treatment (IPTW) weighting was used to minimize selection bias.We identified 4,717 eligible SCC patients and 8,807 eligible non-SCC NSCLC patients. For the matched SCC cohorts, BEDhigh was associated with improved OS in both univariate and doubly robust multivariate analysis (MVA HR 0.84 95% CI 0.76-0.92, P < 0.001), with estimated IPTW-adjusted 3-year OS of 49% compared to 41% for the BEDlow group. In contrast, BEDhigh was not associated with improved OS compared to BEDlow for non-SCC NSCLC patients (MVA HR 0.94 95% CI 0.86-1.04, P = 0.23), with estimated IPTW-adjusted 3-year OS of 54% compared to 53% for the BEDlow group.Our analysis suggests that in patients with early-stage NSCLC, SBRT regimens employing the use of BED > 150 Gy may confer a survival benefit in patients with SCC histology. Histology-based dose modification should be considered, and prospective validation may be warranted.