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Stereotactic body radiotherapy (SBRT) proved safe for treating cancer patients with multiple metastases, according to a phase I trial.

In the NRG-BR001 trial, standard doses of SBRT were safe in 35 patients with oligometastatic breast, prostate, and non-small cell lung cancer (NSCLC) with a median of three or four metastases, or two within proximity to each other, reported Steve Chmura, MD, PhD, of University of Chicago Medicine, and colleagues.

Also, there were no protocol-defined dose-limiting toxicities in these patients at 180 days after the initiation of therapy, they stated in .

However, the authors noted that a number of patients experienced late grade 3 adverse events (AEs), most likely related to the protocol therapy, which demonstrated the need for long-term follow-up with these patients.

The use of SBRT can improve survival in cancer patients with multiple metastases, Chmura's group explained. While practitioners are increasingly using SBRT to treat patients with multiple metastases, they pointed out that little evidence supports its safe use for these patients.

"Existing data include mostly treatment of 1 or 2 metastases separated widely from each other and use of differing radiation doses, toxicity reporting, image guidance, and normal tissue constraints," they wrote. "Given the critical need, NRG Oncology NRG-BR001 trial sought to determine the safety of delivering curative-intent SBRT to patients with 3 to 4 metastases or 2 metastases within close proximity to each other."

Patients were considered eligible for the study if they had metastatic breast, prostate, or NSCLC, and either three or four metastases, or two within 5 cm of each other that were otherwise considered amenable to SBRT.

Each metastasis was assigned to one of seven metastatic locations -- bone/osseous, spinal/paraspinal, peripheral lung, central lung, mediastinal/cervical lymph node, liver, or abdominal-pelvic -- based on the potential for toxicity.

The radiation dose specified for the protocol was based on either phase II data for single metastases or expert consensus if the data were unavailable. The starting dose was 50 Gy in five fractions for central lung and mediastinal/cervical lymph nodes; 45 Gy in three fractions for peripheral lung, abdominal-pelvic, and liver locations; and 30 Gy in three fractions for bone/osseous and spinal/paraspinal sites.

The primary outcome of the study was dose-limiting toxicity (DLT), defined as specific AEs of grades 3 to 5 related to SBRT within 180 days of treatment. Dose levels were considered to be safe if DLTs were seen in no more than one of six patients per metastatic location.

Of 42 patients registered for the trial, 35 were evaluable, 12 (34.3%) of whom had breast cancer, 10 NSCLC (28.6%), and 13 (37.1%) prostate cancer. There were a median of three metastases per treated patient, with two-thirds having three to four metastases.

DLT analysis were based on six evaluable patients in all of the metastatic locations save the liver (five evaluable patients). The authors reported there were no protocol-specified DLTs in any of the seven metastatic locations within 180 days of the initiation of treatment.

There were 50 grade 3 or 4 AEs reported in 18 patients, and eight were determined to be mechanistically related to the protocol therapy. Of those eight, six (including bone pain, pulmonary fibrosis, bronchial fistula, bronchial stenosis, spinal fracture, and humeral fracture) were reported in six patients more than 180 days after the start of treatment. There were no treatment-related deaths, according to the authors.

Considering the number of late AEs reported in this trial, they suggested patients should be monitored closely for late toxic effects.

"Given the potential for ablative radiotherapy to improve outcomes of patients with oligometastatic cancer, the finding that SBRT is safe when delivered to 3 to 4 metastases or 2 metastases in close proximity to one another is important, and serves as the foundation for ongoing randomized trials," wrote Chmura and colleagues. They noted that these include studies such as the phase II/III NCI-sponsored trial.

In an , Charles R. Thomas Jr., MD, of Oregon Health Sciences University in Portland, noted that since NRG-BR001 was launched in 2014, numerous systemic agents have been approved for the treatment of breast, lung, and prostate cancer, which means more patients are living long enough to exhibit radiation-induced normal tissue toxicity.

"Because these toxic effects, particularly bone fractions and pulmonary toxicity, can compromise daily quality of life, we strongly believe that clinicians must be sure to caution patients about the specific normal tissue toxicity profile that can occur depending on the anatomic site that is to be targeted with SBRT," Thomas observed.

Still, the trial provides evidence to guide patient care, and a framework for future clinical trials for patients with oligometastatic disease, he added.

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