A Histologic Basis for the Efficacy of SBRT to the lung

Stereotactic body radiation therapy (SBRT) is the standard of care for medically inoperable patients with early-stage NSCLC. However, NSCLC is composed of several histological subtypes and the impact of this heterogeneity on SBRT treatments has yet to be established.

We analyzed 740 patients with early-stage NSCLC treated definitively with SBRT from 2003 through 2015. We calculated cumulative incidence curves using the competing risk method and identified predictors of local failure using Fine and Gray regression.

Overall, 72 patients had a local failure, with a cumulative incidence of local failure at 3 years of 11.8%. On univariate analysis, squamous histological subtype, younger age, fewer medical comorbidities, higher body mass index, higher positron emission tomography standardized uptake value, central tumors, and lower radiation dose were associated with an increased risk for local failure. On multivariable analysis, squamous histological subtype (hazard ratio = 2.4 p = 0.008) was the strongest predictor of local failure. Patients with squamous cancers fail SBRT at a significantly higher rate than do those with adenocarcinomas or NSCLC not otherwise specified, with 3-year cumulative rates of local failure of 18.9% (95% confidence interval [CI]: 12.7-25.1), 8.7% (95% CI: 4.6-12.8), and 4.1% (95% CI: 0-9.6), respectively.

Our results demonstrate an increased rate of local failure in patients with squamous cell carcinoma. Standard approaches for radiotherapy that demonstrate efficacy for a population may not achieve optimal results for individual patients. Establishing the differential dose effect of SBRT across histological groups is likely to improve efficacy and inform ongoing and future studies that aim to expand indications for SBRT.