Stereotactic Body Radiotherapy (SBRT) With Biologically Equivalent Dose > 150 Gy is Associated With Improved Local Control in Patients With Squamous but not Non-Squamous Cell Carcinoma of the Lung: A Multi-Institutional Analysis

Abstract

<h3>Purpose/Objective(s)</h3> Recent studies suggest improved local control (LC) of early-stage non-small cell lung cancer (NSCLC) treated with SBRT regimens with biologically equivalent dose (BED₁₀) > 150 Gy. It is unclear if this association is histology dependent. Multiple groups have shown lower LC rates after SBRT for squamous cell carcinoma (SCC), compared to non-SCC NSCLC. We compared LC between BED_low and BED_high SBRT schemes, stratified by histology. <h3>Materials/Methods</h3> As part of an IRB approved collaborative, we retrospectively analyzed 684 patients with cT1-2, cN0, cM0 NSCLC, treated with definitive SBRT to a minimum BED of 100 Gy at five international centers. Patients were grouped into SCC and non-SCC, then divided into BED_high (BED₁₀ ≥150 Gy) or BED_low (BED10 < 150 Gy) based on prescription dose, and propensity-score matched for age, sex, smoking history, performance status, T-stage, tumor grade and location, mediastinal staging, and receipt of chemotherapy. LC was estimated by Kaplan-Meier. Univariate (UVA) and multivariable analyses (MVA) were used to correlate BED with clinical outcomes. We also compared BED groups based on dose to planning and gross target volumes (PTVmean, GTVmean) to account for plan heterogeneity among institutions. <h3>Results</h3> Of 684 eligible tumors, 457 were non-SCC and 227 SCC. Median follow-up was 30 months. Of non-SCC patients, 262 (57%) were BED_low and 195 (43%) BED_high. Of SCC patients, 144 (63%) were BED_low and 83 (37%) BED_high. BED_high SBRT included those treated with 54 Gy in 3 fractions (54/3). BED_low included 60/5, 50/5, 48/4, or 60/8. Baseline characteristics, including T-stage and max tumor dimension, were similar between BED groups after matching. MVA including T-stage, tumor grade, and tumor location, showed BED_low regimens were associated with higher rates of local failure for SCC (HR 9.8, 95% CI 1.9-25.1, <b>P</b> = 0.007), but not for non-SCC (HR 1.2, 95% CI 0.6-2.5, <b>P</b> = 0.6). Three-year LC rates for BED_low and BED_high were 70% and 97%, respectively for SCC, and 91% and 92%, respectively, for non-SCC. Similarly, there were higher rates of failure with BED_low PTVmean (3 yr LC 94 vs 69%, MVA HR 6.4, 95% CI 1.9-22.2, <b>P</b> = 0.003) and BED_low GTVmean (3 yr LC 87 vs 68%, MVA HR 7.6, 95% CI 2.7-21.6, <i>P</i> = 0.001) in SCC patients. In non-SCC patients, LC was similar between BED groups for PTVmean (3 yr LC 92% vs 93%, MVA HR 1.1, 95% CI 0.5-2.8, <b>P</b> = 0.8) and GTVmean (3 yr LC 94 vs 90%, MVA HR 0.8, 95% CI 0.3-2.6, <b>P</b> = 0.8). There was a trend of worse survival in BED_low SCC patients (MVA HR 1.3, 95% CI 0.9-1.9, <b>P</b> = 0.1), but survival was similar in non-SCC patients (MVA HR 1.02, 95% CI 0.8-1.3, <b>P</b> = 0.9). There were no differences in regional recurrence or distant metastases between BED groups in either histology. <h3>Conclusion</h3> This multi-institutional analysis shows improved LC in early-stage SCC NSCLC treated with SBRT regimens with BED₁₀ > 150 Gy. No difference was observed in LC between BED groups for non-SCC patients. Our results suggest BED_high SBRT should be strongly considered for early-stage non-central SCC NSCLC.