Higher biologically effective dose is associated with improved survival in patients with squamous cell carcinoma of the lung treated with stereotactic body radiation therapy

Abstract

Background: Multiple studies have suggested that patients with early-stage SCC of the lung treated with SBRT are more susceptible to local failure compared to other NSCLC histologies. It is unknown if higher BED leads to improved outcomes in this patient population. We evaluated the effect of "high" BED versus "low" BED SBRT on overall survival (OS) in SCC and non-SCC NSCLC patients.

Methods: The National Cancer Database was used to identify patients with cT1-2N0M0 NSCLC diagnosed between 2006-2016 treated with 3-5 fraction SBRT. Patients were grouped by BED_high (>150 Gy) and BED_low (≤132 Gy). Univariate and multivariable analysis using Kaplan-Meier and Cox proportional hazards regression modeling were performed. Propensity-score matched analysis with inverse probability of treatment (IPTW) weighting was used to account for selection bias.

Results: We identified 4,717 eligible SCC patients and 8,807 eligible non-SCC NSCLC patients. In SCC patients, BED_high was associated with improved OS in both univariate and 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 BED_low group. In contrast, BED_high was not associated with improved OS compared to BED_low 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% and 53%, respectively.

Conclusions: Our analysis suggests that in patients with early-stage NSCLC, SBRT regimens with 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.

Keywords: Biological equivalent dose; Dose-response relationship; Population-based analysis; Squamous cell carcinoma of the lung.