Increasing Radiation Therapy Dose Is Associated With Improved Survival in Patients Undergoing Stereotactic Body Radiation Therapy for Stage I Non-Small-Cell Lung Cancer

Purpose: To determine the comparative effectiveness of different stereotactic body radiation therapy (SBRT) dosing regimens for early-stage nonesmall-cell lung cancer, using a large national database, focusing on the relative impact of dose as a function of tumor stage. Methods and Materials: The study included patients in the National Cancer Database from 2003 to 2006 with T1-T2N0M0 inoperable lung cancer (n=498). The biologically effective dose (BED) was calculated according to the linear quadratic formula using an alpha/beta ratio of 10. High versus lower-dose (HD vs LD) SBRT was defined as a calculated BED above or below 150 Gy. Overall survival was estimated using Kaplan-Meier methods and Cox proportional hazard regression. Results: The 5 most common dose fractionation schemes (percentage of cohort) used were 20 Gy x 3 (34%), 12 Gy x 4 (16%), 18 Gy x 3 (10%), 15 Gy x 3 (10%), and 16 Gy x 3 (4%). The median calculated BED was 150 Gy (interquartile range 106-166 Gy). The 3-year overall survival (OS) for patients who received HD versus LD was 55% versus 46% (log-rank P=. 03). On subset analysis of the T1 cohort there was no association between calculated BED and 3-year OS (61% vs 60% with HD vs LD, P=. 9). Among the T2 cohort, patients receiving HD experienced superior 3-year OS (37% vs 24%, P=. 01). On multivariable analysis, factors independently prognostic for mortality were female gender (hazard ratio [HR] 0.76, P=. 01), T2 tumor (HR 1.99, P=. 0001), and HD (HR 0.68, P=. 001). Conclusions: This comparative effectiveness analysis of SBRT dose for patients with stage I nonesmall-cell lung cancer suggests that higher doses (> 150 Gy BED) are associated with a significant survival benefit in patients with T2 tumors. (C) 2015 Elsevier Inc.