Safety of Stereotactic Body Radiotherapy (SBRT/SABR) for Oligometastatic Solid Tumors With Multiple Metastases: NRG-BR001 Phase 1 Trial Findings

Abstract

Importance: Stereotactic body radiotherapy (SBRT), also termed stereotactic ablative radiotherapy (SABR), for oligometastatic cancer is hypothesized to improve survival and is increasingly used in clinical practice. However, limited evidence supports the safe use of SBRT to treat patients with multiple metastatic lesions. Objective: To determine the safety of SBRT dose schedules for patients with 3 to 4 metastases or with 2 metastases located in close proximity to each other. Design, Setting, and Participants: This phase 1 NRG-BR001 trial opened on August 4, 2014, and closed to accrual on March 20, 2018. Metastases in 7 anatomic locations were eligible: bone/osseous (BO), spinal/paraspinal (SP), peripheral lung (PL), central lung (CL), abdominal-pelvic (AP), mediastinal/cervical lymph node (MC), and liver (L). Up to 6 patients could be enrolled for each anatomic site. The study was conducted in a consortium of North American academic and community practice cancer centers participating in NRG Oncology trials. Patients with breast cancer, prostate cancer, or non-small cell lung cancer and either 3 to 4 metastases or 2 metastases in close proximity (≤5 cm) that were amenable to SBRT were eligible. Statistical analyses were performed from December 31, 2017, to September 19, 2019. Interventions: Starting SBRT dose schedules were 50 Gy in 5 fractions for CL and MC metastases, 45 Gy in 3 fractions for PL, AP, and L metastases, and 30 Gy in 3 fractions for BO and SP metastases. Main Outcomes and Measures: The primary end point was dose-limiting toxicity (DLT), defined using Common Terminology Criteria for Adverse Events, version 4.0, as protocol-specified grade 3 to 5 adverse events (AEs) that were definitely or probably related to SBRT within 180 days after treatment. Dose levels were considered safe if DLTs occurred in no more than 1 of 6 patients per anatomic location; otherwise, the dose for that location would be de-escalated. Results: Overall, 42 patients enrolled, 39 were eligible, and 35 were evaluable for DLT (mean [SD] age, 63.1 [14.2] years; 20 men [57.1%]; 30 White patients [85.7%]). Twelve patients (34.3%) had breast cancer, 10 (28.6%) had non-small cell lung cancer, and 13 (37.1%) had prostate cancer; the median number of metastases treated per patient was 3. Median survival was not reached. No protocol-defined DLTs were observed. In assessment of all AEs, 8 grade 3 AEs considered most likely related to protocol therapy occurred in 7 patients approximately 125 to 556 days after SBRT initiation. Conclusions and Relevance: This phase 1 trial demonstrated the safety of SBRT/SABR for oligometastatic patients with 3 to 4 metastases or 2 metastases in close proximity. No treatment-related deaths occurred. Late grade 3 AEs indicate the need for extended follow-up in long-surviving patients with oligometastatic disease. SBRT treatment for multiple metastases has been expanded into ongoing randomized phase 2/3 National Cancer Institute-sponsored trials, including NRG-BR002 and NRG-LU002. Trial Registration: ClinicalTrials.gov Identifier: NCT02206334.