Population Based Phase II Trial of Stereotactic Ablative Radiotherapy (SABR): Overall Survival Results of the SABR-5 Trial

Abstract

<h3>Purpose/Objective(s)</h3> Despite increasing utilization of stereotactic ablative radiotherapy (SABR), there is a lack of large population-based outcomes data. This study was designed to examine, as the primary end point, side effects and quality of life, which were reported elsewhere. This analysis focuses on overall survival as a secondary endpoint. <h3>Materials/Methods</h3> From November 2016 to July 2020, 401 patients across 6 regional cancer centers in British Columbia, Canada were screened for eligibility in this single arm, phase II trial of SABR in patients with 5 or fewer oligometastatic or oligo-progressive lesions. During this time period, such patients were eligible for SABR only on trial. Of those screened, 385 patients were enrolled, with 381 completing SABR. This analysis was by intention to treat. <h3>Results</h3> The median follow up was 26.7 months (range 0-57 months). 68% of the patients were male, the mean age was 68 years old (SD 11 years, range 30-97 years). Median Charlson Comorbidity Index (CCI) was 9 (range 6-15). 60% had ECOG 0, 36% ECOG 1, and 4% ECOG 2. Prostate cancer was the most common histology (32%), followed by colorectal (16%), breast (11%), lung (9%), renal (9%), and others (22%). SABR was given to 1 site in 69% of patients, 2 sites for 22%, 3 sites for 7%, and 4-5 sites for 3%. The most common sites treated with SABR were lung (35%), non-spine bone (25%), spine (16%), lymph node (14%), liver (5%), adrenal (3%), and others (3%). 20% had synchronous disease, and 16% had oligoprogressive disease. Median survival was not reached. At 2 years, the overall survival was 79.8% (75.5-84.1%), and at 4 years, 58.0% (49.6-66.4%). In univariate analysis, age (p=0.023), ECOG (p<0.001), decline in ECOG 6 months before SABR (p=0.001), systemic therapy use after SABR (p=0.001), histology (p<0.001), Synchronous disease (p=0.050), and disease-free interval > 18 months (p<0.001) were significant predictors for overall survival. CCI (p=0.054), gender, oligometastatic disease, and number of lesions treated with SABR were not significant. Multi-variate analysis showed histology (Breast, ref; Lung, HR 9.91 (2.21-44.48), p=0.003; Colorectal, HR 5.09 (1.12-23.09), p=0.035; Renal, HR 5.20 (1.09-24.82), p=0.039; Prostate, p>0.05; Others HR 8.97 (2.07-38.77), p=0.003), ECOG (ECOG 1 vs 0, HR 1.69 (1.10-2.60), p=0.017; ECOG 2 vs 0, HR 3.00 (1.24-7.24), p=0.015), synchronous disease (HR 0.48 (0.27-0.85), p=0.012), and disease-free interval >18 months (HR 2.36 (1.52-3.66), p<0.001) predicted overall survival. Sensitivity analysis of only the patients who completed SABR showed similar results. Analyzing oligometastatic disease only, synchronous disease was not a significant predictor in univariate and multivariate analysis. <h3>Conclusion</h3> The 2 years overall survival (80%) was similar to another population-based study in the UK by Chalkidou et al. We recommend continuing to stratify by favorable histology, performance status, and disease-free interval in ongoing randomized phase III trials on the efficacy of SABR.