The Effect of Biologically Effective Dose and Radiation Treatment Schedule on Overall Survival in Stage I Non-Small Cell Lung Cancer Patients Treated With Stereotactic Body Radiation Therapy

Abstract

To determine the effect of biologically effective dose (BED10) and radiation treatment schedule on overall survival (OS) in patients with early-stage non-small cell lung cancer (NSCLC) undergoing stereotactic body radiation therapy (SBRT). Using data from 65 treatment centers in the United States, we retrospectively reviewed the records of T1-2 N0 NSCLC patients undergoing SBRT alone from 2006 to 2014. Biologically relevant covariates, including dose per fraction, number of fractions, and time between fractions, were used to quantify BED10 and radiation treatment schedule. The linear-quadratic equation was used to calculate BED10 and to generate a dichotomous dose variable of <105Gy versus ≥105Gy BED10. The primary outcome was OS. We used the Kaplan-Meier method, the log-rank test, and Cox proportional hazards regression with propensity score matching to determine whether prescription BED10 was associated with OS. We identified 747 patients who met inclusion criteria. The median BED10 was 132Gy, and 59 (7.7%) had consecutive-day fractions. Median follow-up was 41months, and 452 patients (60.5%) had died by the conclusion of the study. The 581 patients receiving ≥105Gy BED10 had a median survival of 28months, whereas the 166 patients receiving <105Gy BED10 had a median survival of 22months (log-rank, P=.01). Radiation treatment schedule was not a significant predictor of OS on univariable analysis. After adjusting for T stage, sex, tumor histology, and Eastern Cooperative Oncology Group performance status, BED10 ≥105Gy versus <105Gy remained significantly associated with improved OS (hazard ratio 0.78, 95% confidence interval 0.62-0.98, P=.03). Propensity score matching on imbalanced variables within high- and low-dose cohorts confirmed a survival benefit with higher prescription dose. We found that dose escalation to 105Gy BED10 and beyond may improve survival in NSCLC patients treated with SBRT.