A clinical trial examining the safety of stereotactic body radiotherapy for patients with oligometastases indicated that the modality was safe for patients with multiple metastatic sites.
In the National Cancer Institute (NCI)–funded, phase 1 NRG-BR001 trial (NCT02206334) examining the use of stereotactic body radiotherapy (SBRT) in patients with oligometastases, the treatment modality was found to be safe in patients with 3 or 4 metastatic sites or 2 metastases in close proximity.1
Due to some late grade 3 adverse events (AEs), a need for extended follow-up in patients with long survival times was indicated and research has been expanded into multiple ongoing randomized trials.
“Prior to this trial, little to no evidence was available to support that SBRT is a safe and tolerable treatment option for patients who have multiple metastases. Investigators have hypothesized that SBRT could improve survival outcomes for this patient population; however, it was imperative we determine the safety of this procedure, appropriate dose and scheduling, and how to coordinate across multiple centers the quality assurance of the procedures prior to testing its efficacy,” Steven J. Chmura, MD, PhD, of the Department of Radiation and Cellular Oncology at the University of Chicago Comprehensive Cancer Center and the lead author of the NRG-BR001 manuscript, said in a press release.2 “To ensure safety, this trial used an extensive radiation QA process to test the accuracy of treating moving tumors and was the first NRG trial to require the use of 3D image guidance during treatment for soft tissue tumors.”
The trial was open to accrual from August 4, 2014 through March 20, 2018, to patients with metastatic breast, prostate, or non–small cell lung cancer (NSCLC) who had 3 or 4 metastases or 2 within 5 cm of each other and were amenable to SBRT. Patients had to have controlled primary tumors, an ECOG performance status of 2 or less, and normal organ and marrow function. Brain metastases, severe active comorbid disease, prior palliative radiation to current metastases, and metastatic sites within 3 cm of irradiated organs were exclusion criteria.
In 35 patients evaluable for the primary end point of dose-limiting toxicities (DLTs), no protocol-defined events were observed. When examining all AEs, grade 3 events related to SBRT initiation occurred in 7 patients at approximately 125 to 556 days from treatment initiation.
At a median follow-up of 23.9 months (range, 2.1-26) in 39 evaluable patients, 15 deaths occurred due to metastatic cancer. The median survival had not been reached and the estimated 2-year overall survival was 57% (95% CI, 38%-72%).
That population was made up of 12 patients with breast cancer (34.3%), 10 with NSCLC (28.6%), and 13 with prostate cancer (37.1%). The median number of metastatic sites was 3 per treated patient.
Each metastasis was assigned to 1 of 7 sites of bone/osseous, spinal/paraspinal, peripheral lung, central lung, mediastinal/cervical lymph node, liver, or abdominal-pelvic. Evaluation of DLTs at all locations was based on 6 patients, except for the liver metastatic location which was based on 5.
The protocol-specified SBRT doses were shown to have acceptable short-term toxicity, similar to what is seen with single metastases and primary tumors. Based on these data, the investigators were able to make dose recommendations for each of the sites, which will inform ongoing randomized phase 2/3 trials.
“These are important data from the multicenter study, confirming that complicated stereotactic body radiotherapy to multiple sites is safe and feasible. We eagerly await the results of ongoing, larger randomized trials to demonstrate how effective this is when compared to drug therapy alone for metastatic cancer,” Mitchell Machtay, MD, the Associate Dean for Clinical Cancer Research at the Penn State College of Medicine and the interim Group Chair for NRG Oncology, said in a press release.
1. Chmura S, Winter KA, Robinson C, et al. Evaluation of Safety of Stereotactic Body Radiotherapy for the Treatment of Patients With Multiple Metastases: Findings From the NRG-BR001 Phase 1 Trial. JAMA Oncol. Published online April 22, 2021. doi: 10.1001/jamaoncol.2021.0687
2. NRG Oncology Study Shows Safety of Using Stereotactic Body Radiotherapy to Treat Multiple Metastases. News release. NRG Oncology. April 22, 2021. Accessed April 26, 2021. https://bit.ly/3nnMkPR