An International Multi-Institutional Pooled Analysis of 1033 Extra-Cranial Oligometastatic Patients Treated with Definitive Stereotactic Body Radiotherapy (SBRT)

Abstract

To report progression survival outcomes and toxicities in 1033 patients with extracranial oligometastatic (OM) sites ablated with stereotactic body radiotherapy (SBRT). An international retrospective study was initiated amongst six centers of consecutive patients with 5 or fewer extracranial OM treated with definitive SBRT. Overall survival (OS), progression-free-survival (PFS) and freedom from widespread progression (F-WSP, >6 metastases and/or malignant effusion(s)) rates were determined using the Kaplan-Meier method from the date of SBRT. 1033 patients comprised of 46% lung and colorectal, treated with 1412 SBRT courses in patients with 58% and 24% had solitary or 2 OM respectively. 36% of patients had systemic therapy for metastatic disease prior to SBRT, 22% had a non-SBRT metastases-directed ablative local therapy, 73% presented with metachronous OM and 95% treated with SBRT to all OM sites at the time of presentation. Median follow-up and OS were 24 months (range, 0.3 -105) and 44 months (confidence interval (CI) - 39.2-48.8), respectively. Median PFS and F-WSP were 12.9(CI -11.6-14.2) and 37.7 months (CI-31.4-42.3), respectively. The 1, 3, and 5-year OS, PFS, and F-WSP rates 84.1%, 69.6% and 35.2%, 52.1%, 30.8%, and 14.8%, 74.8%, 61.1%, and 39.4%. On 1st progression, 342 recurred with OM disease (oligoprogression) and 230 (21.3%) were subsequently treated with further ablative therapies to all known metastatic sites, while 55 patients with oligoprogression were managed with a change of systemic therapy. 143 developed a recurrence of a treated metastatic site. Within the 446 patients who developed wide spread progression (WSP), the median time to develop WSP was short, 10.8 months with 220 (49.3%) of the 446 who developed WSP at 1st progression. Of the 328 who did not develop a recurrence, only 67 were censored due to death without disease leaving 261 (25.3%) patients without any known disease recurrence. There were 66 (6.4) grade 3 or greater acute/late toxicities, including 1(0.1%) grade 5 event. We confirm in the largest series of extra-cranial OM ablated with SBRT the favorable long-term OS and but modest PFS. An oligoprogression pattern of failure is observed where a substantial cohort can undergo further SBRT for disease control. Although further follow up is needed, there appears to be a small but significant cohort with prolonged disease-free survival.