Optimal Timing of SBRT for Treatment of Oligometastatic Disease: A Single Institution Retrospective Analysis.

Abstract

PURPOSE/OBJECTIVE(S)\nThere is mounting evidence that curative-intent stereotactic body radiation therapy (SBRT) may improve overall survival (OS) in patients with oligometastatic disease. However, the optimal sequencing and timing of radiation in this setting remains unclear. Delaying SBRT in favor of upfront systemic therapy can reduce tumor burden whilst allowing for the oligometastatic state to declare itself. However, there is also data to suggest that early upfront SBRT may confer a survival benefit. In this study, we explored the optimal timing of SBRT in the setting of oligometastatic disease.\n\n\nMATERIALS/METHODS\nPatients who were initially diagnosed from 1991-2018 at a single institution and treated with curative intent SBRT to ≤5 extracranial metastatic lesions were included in this study. All primary tumor locations and histologies were included. Chi-squared and Wilcoxon rank-sum tests were used to compare clinical and demographic data. Variables associated with improved OS were examined using univariate and multivariate Cox proportional hazards models.\n\n\nRESULTS\nA total of 70 patients treated with curative intent SBRT in the oligometastatic setting were included. The majority of patients had metachronous disease (n\u202f=\u202f62). Median follow up time, OS, and progression free survival (PFS) were 27.0 months, 33.9 months, and 8.9 months respectively. Median time from diagnosis to treatment with SBRT was 2.7 months. Patients were categorized as those who received concurrent therapy (upfront systemic therapy and SBRT within 3 months of the date of diagnosis, n\u202f=\u202f14), those who received sequential therapy (upfront systemic therapy followed by SBRT outside 3 months of the date of diagnosis, n\u202f=\u202f20), or those who received upfront SBRT (n\u202f=\u202f36). On univariate analysis, a trend between receipt of upfront systemic therapy and improved survival was observed (HR: 0.59, 95% CI: 0.32-1.09, P\u202f=\u202f0.096). Sequential therapy (HR: 2.74, 95% CI: 0.89-8.42, P\u202f=\u202f0.079) and upfront SBRT (HR: 3.30, 95% CI: 1.14-9.54, P\u202f=\u202f0.027) were associated with worse survival compared to concurrent therapy. Higher Karnofsky Performance Score (KPS) (HR:0.96, 95% CI: 0.92-0.99, P\u202f=\u202f0.018) was associated with improved survival. Older age was associated with worse survival (HR:1.02, 95% CI: 1.00-1.05, P\u202f=\u202f0.020). Multivariate Cox analysis included variables with P < 0.1 and showed that sequential therapy (HR: 3.22, 95% CI: 1.01-10.28, P\u202f=\u202f0.049) as well as upfront SBRT (HR: 3.28, 95% CI:1.10-9.76, P\u202f=\u202f0.033) were associated with worse survival compared to upfront systemic therapy and early SBRT.\n\n\nCONCLUSION\nOur results suggest that concurrent systemic therapy and SBRT may be associated with better survival compared to upfront SBRT in the oligometastatic setting. Amongst patients who received upfront systemic therapy, those who received early SBRT performed better than those who delayed SBRT. Given the retrospective nature of our work and small sample size more work will be needed to corroborate our findings.