Stereotactic Radiotherapy for Oligometastatic and Oligoprogressive Solid Tumors: Who Benefits?

Abstract

Recent prospective studies suggest a survival benefit to surgery or stereotactic ablative radiotherapy (SABR) for oligometastatic (OM) solid tumors. SABR is also increasingly used for oligoprogressive (OP) disease, wherein limited metastatic sites progress on otherwise effective systemic therapy. However, data to define specific benefitting patient subgroups are lacking. We retrospectively analyzed outcomes following SABR for OM and OP solid tumors to identify promising patient subgroups for future prospective studies. We retrospectively analyzed all patients treated at a single institution with SABR for OM and OP solid tumors between March 2007-Sept 2018. OP was defined as limited metastatic progression while on otherwise effective systemic therapy, and OM was defined as limited metastases in which all metastatic sites were addressed with radiation and/or surgery. For OP patients, the line of systemic therapy at progression was documented. Disease free survival (DFS) and overall survival (OS) were calculated using the Kaplan-Meier method. The log-rank method was used to compare outcomes between groups. Toxicity was graded using CTCAE v 5.0. 78 patients completing 89 courses of SABR were identified, 57 targeting OM tumors and 32 targeting OP tumors. Median age was 64 years (range: 27-95) and median follow up was 25.4 months (range: 1.2-79.7). Histologic subtypes include NSCLC (20), colorectal (n = 15), breast (n = 10), sarcoma (n = 9), melanoma (n = 6), prostate (n = 5), renal cell (n = 5), and other (n = 22). SABR was delivered to a median of 50 Gy (range: 16-60 Gy) over 5 fractions (range: 2-5) to a median of one tumor (range:1-6). Among oligoprogressive cases, systemic therapy at OP included chemotherapy (n = 12), targeted therapy (n = 13), immunotherapy (n = 4), and endocrine therapy (n = 3). Metastatic targets included lung (n = 47), liver (n = 17), bone (n = 18), and other (n = 7). Two-year OS was 71% for OM and 80% for OP patients, and 2-year PFS was 26% for OM and 21% for OP patients. Three-year PFS for the entire cohort was 20%. Ten patients had sustained PFS beyond 3 years (5 OM and 5 OP), including patients with NSCLC (n = 2), melanoma (n = 2), colon (n = 2), sarcoma, kidney, breast, and skin. Patients with long-term PFS predominantly underwent SABR to lung metastases (n = 7). No significant predictors of PFS or were identified. Grade 3+ toxicity included grade 3 pneumonitis (n = 1) and grade 5 bowel perforation (n = 1). OM and OP solid tumor patients have excellent outcomes, with 20% 3-year PFS in this cohort with limited toxicity. However, predictors of long-term disease control remain elusive. In our cohort, select patients with a range of solid tumor types and prior therapies had extended disease control. Well-designed, prospective studies in focused tumor settings are necessary to better define which patients will benefit from aggressive local therapies.