In the phase I NRG-BR001 trial reported in JAMA Oncology, Chmura et al found that stereotactic body radiotherapy (SBRT) could be used safely to treat multiple metastases in patients with breast, lung, and prostate cancers.
Study Details
The trial was conducted within a consortium of North American academic and community practice cancer centers participating in NRG Oncology trials. Between August 2014 and March 2018, the trial enrolled a total of 39 eligible patients with three to four metastases or two metastases in close proximity (≤ 5 cm) amenable to SBRT.
Starting radiotherapy doses to the seven anatomic sites with metastases included in the study were:
- 50 Gy in 5 fractions for central lung and mediastinal/cervical lymph nodes
- 45 Gy in 3 fractions for peripheral lung, abdominal-pelvic sites, and liver
- 30 Gy in 3 fractions for bone/osseous sites and spinal/paraspinal sites.
Among 35 patients evaluable for dose-limiting toxicity, 12 had breast cancer, 10 had non–small cell lung cancer (NSCLC), and 13 had prostate cancer. The primary endpoint was dose-limiting toxicity defined as specific grade 3 to 5 adverse events related to SBRT within 180 days of treatment. Dose levels were considered safe if dose-limiting toxicity were observed in one or fewer of six patients per location, with the dose at that location being reduced if dose-limiting toxicities were observed in more than one patient.
Key Findings
A median of three metastases were treated per patient.
This phase I trial demonstrated the safety of SBRT for patients with three to four metastases or two metastases in close proximity. There were no treatment-related deaths. Late grade 3 adverse events demonstrate the need for extended follow-up in long-surviving patients with oligometastatic disease.— Chmura et al
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No protocol-specified dose-limiting toxicities were observed at any of the seven metastatic locations, with the initial starting dose for each location thus being considered the recommended SBRT dose for each metastatic site.
A total of 50 grade 3 to 4 adverse events were observed in 18 patients; and a total of 18 grade 3 to 4 adverse events in 9 patients were considered at least possibly related to treatment. Six of the 18 adverse events occurred within 180 days of treatment, with 12 occurring after 180 days. None of the adverse events met the defined criteria for dose-limiting toxicity. The 18-month and 2-year cumulative incidences of late grade 3 to 4 treatment-related adverse events were 17% and 20%.
Among all 39 eligible patients, with a median follow-up of 23.9 months (range = 2.1–26 months) among surviving patients, 15 patients had died, including 5 (38%) of 13 with breast cancer, 6 (46%) of 13 with NSCLC, and 4 (30%) of 13 with prostate cancer; all deaths were due to metastatic disease. Median overall survival was not reached, with an estimated 2-year rate of 57%.
The investigators concluded, “This phase I trial demonstrated the safety of SBRT for patients with three to four metastases or two metastases in close proximity. There were no treatment-related deaths. Late grade 3 adverse events demonstrate the need for extended follow-up in long-surviving patients with oligometastatic disease. Treatment with SBRT for multiple metastases has been expanded into multiple ongoing randomized phase II/III National Cancer Institute–sponsored trials (NRG-BR002, NRG-LU002).”
Steven J. Chmura, MD, PhD, of the Department of Radiation and Cellular Oncology, University of Chicago, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by grants from the National Cancer Institute. For full disclosures of the study authors, visit jamanetwork.com.
