Overall Survival of Patients with Early-Stage Non-Small Cell Lung Cancer Treated Daily Versus Non-Daily with Lung Stereotactic Body Radiation Therapy

Abstract

Data is conflicting with regard to the influence of consecutive (daily) treatment on toxicity and even local control in patients with non-small cell lung cancer (NSCLC) treated with lung stereotactic body radiation therapy (SBRT). Small retrospective studies suggest worse toxicity and local control with daily treatment while others have found no difference in outcomes. Large national databases may have sufficient statistical power to discern differences in survival outcomes between these two treatment regimens. We used the National Cancer Database (NCDB) to identify patients with stage I or II NSCLC treated with primary radiation therapy. We included only patients treated in 3-5 fractions with a biologically effective dose (BED) of ≥ 100 Gy. Daily treatment was considered to be treatment within 6 or 7 days for 4- and 5-fraction regimens, respectively, to account for a potential weekend treatment break. Daily treatment was considered to be treatment within 3 days for 3-fraction regimens. We used 1:1 nearest neighbor propensity score matching (caliper 0.1) to balance daily and non-daily cohorts on the basis of age, race, sex, treatment facility type, education, income, insurance status, county population, distance from treatment center, Charlson comorbidity index, tumor laterality, T-stage, histology, radiation dose, and year of diagnosis. Cox regression and Kaplan-Meier analysis were used to assess the association of daily treatment with overall survival. We identified 40,161 patients, 11,168 (27.8%) of which were treated with daily treatments. Daily treatment was associated with a higher proportion of Caucasians (90.6% vs 88.7%, p < 0.001), Charlson comorbidity index of 0-2 (95% vs 93.1%; p < 0.001), treatment at an academic medical center (41.9% vs 39.1%; p < 0.001), and increased distance to treatment facility (12.6 vs 10.8 miles; p < 0.001). There were no significant differences in age or sex. After propensity-score matching, there were 7176, 6402, and 4176 patients treated with 5, 4, and 3 fraction regimens, respectively. There were no significant differences in any of the variables. For 5-fraction regimens, there was no statistically significant difference in overall survival with non-daily vs daily treatment (HR = 1.06; 95% CI 1.00 – 1.13). Non-daily treatment was associated with improved overall survival for 4-fraction (HR = 0.93; 95% CI 0.88 – 0.995; p = 0.033) and 3-fraction (HR = 0.91; 95% CI 0.85 – 0.98; p = 0.018) regimens. We found improved overall survival in patients treated with non-daily fractions when treated with 3- or 4-fraction regimes. We found no significant difference in overall survival in patients treated with 5-fraction regimens. Altering fractionation scheme may be a simple means of improving outcomes in lung SBRT. More data is warranted on the effects of altering fractionation on tumor control outcomes, and these data should be considered to be validated in the context of a prospective randomized trial.