SABR ‘Quite Safe’ for Treating Oligometastases

A new population-based phase 2 trial suggests stereotactic ablative body radiotherapy (SABR) for oligometastases has acceptable rates of toxicity and could eventually become a standard of care.

Investigators found a low rate of high-grade toxic effects, with a cumulative incidence of grade 3 to 5 toxic effects of less than 5%, suggesting SABR is safe for treating oligometastases.

The authors, who published their findings in JAMA Oncology, write that this is the most comprehensive analysis of SABR toxic effects in the setting of oligometastatic disease. The results are reassuring news following the publication of the landmark SABR-COMET trial, which raised concerns regarding high-grade toxic effects with SABR. In the current study, the rates of grade 2, 3, 4, and 5 toxicity were 14.2%, 4.3%, 0%, and 0.3%, respectively.

“This study shows that SABR is quite safe, and has relatively lower rates of toxicity compared to invasive procedures,” said the study’s corresponding author, Robert A. Olson, MD, MSc, of the University of British Columbia in Vancouver, where he is Associate Head of Research in the Department of Surgery and head of the Division of Radiation Oncology and Developmental Radiotherapeutics. “It is important to do studies that are population-based to get accurate estimates of toxicity, as population-based studies reduce the bias that is often seen in highly selected series where only the fittest patients are included.”

The non-randomized clinical trial included 381 patients with oligometastatic or oligoprogressive disease. It was designed to capture toxic effects prospectively as the primary endpoint (ClinicalTrials.gov Identifier: NCT02933242). All of the patients were treated at 6 cancers centers in British Columbia from November 2016 to July 2020.

Patients with brain metastases only and no other site of disease were excluded from the trial. All the patients had systemic therapy discontinued for at least 2 weeks before and 1 week after treatment with SABR. Imaging requirements to enter the trial included brain computed tomography (CT) or magnetic resonance imaging (MRI) for tumor sites with propensity for brain metastasis, positron emission tomography (PET), CT in evidence-based indications, or CT of the neck/chest/abdomen/pelvis and a bone scan if no PET-CT was performed. An MRI of the spine was an additional requirement for patients with vertebral or para spinal metastases.

The cohort included 122 women (32%) and 259 men (68%). The mean age was 68 years (range 30 to 97 years).The median follow-up was 25 months. Of these, 123 patients (32%) had prostate cancer, 63 (19%) had colorectal cancer, 42 (11%) had breast cancer, and 33 (9%) had lung cancer. Of the cohort, 263 patients (69%) had one SABR-treated site, 82 (22%) had 2 treated sites, and 36 (10%) had 3 or more treated sites. Among the 263 patients with a single metastasis treated with SABR, 214 (81%) had oligometastatic disease and 49 (19%) had oligoprogressive disease.

The most common sites of SABR were lung (34%), non-spine bone (25%), spine (16%), lymph nodes (14%), liver (5%), and adrenal (3%). Kaplan-Meier analysis showed that the cumulative incidence of grade 2 or higher toxic effects associated with SABR at year 2 was 8%. It was 4% for grade 3 or higher.

“We found that the rate of grade 3-5 toxicities was less than 5% in our population-based cohort, suggesting SABR is relatively safe, within a well-coordinated program with peer review of plans and prioritizing organs at risk over tumor coverage,” Dr Olson said. “We were surprised that treating upper abdominal metastases was associated with a higher rate of toxicity than other sites.”

The rates of grade 2 or higher toxic effects were 18.6%, which was significantly lower than previously published for SABR-COMET, which demonstrated a rate of 29%. These results suggest that SABR treatment for oligometastases has acceptable rates of toxic effects and further clinical evaluation is warranted. “SABR for oligometastases can be given safely,” Dr Olson said. “This supports the ongoing accrual to phase 3 trials, and we hypothesize that SABR for oligometastases will become the standard of care for a few metastases in the next 5 years.”

David Palma, MD, MS, PhD, a radiation oncologist at the London Health Sciences Centre in London, Ontario, and a clinician-scientist with the Ontario Institute for Cancer Research in Toronto, said the latest investigation is an excellent study that will greatly advance the use of SABR for oligometastases. Using a population-based approach that included all patients treated with SABR in British Columbia, it was possible to reduce the risk of any selection bias and also ensure that outcomes are well-recorded, Dr Palma said.

“Their grade 3-5 toxicity rate of less than 5% is very low, and the overall risk of grade 5 toxicity was about 1 in 300,” Dr Palma said. “This compares very favorably with toxicity rates after other ablative approaches like surgery or thermal ablation. In the original SABR-COMET trial we saw higher rates of grade 5 toxicity, and based on the SABR-5 trial and others, it appears those high toxicity rates could have been due to chance, due to the relatively small size of the SABR-COMET trial.”

The next step is to test the benefits of SABR for oligometastases in phase 3 trials. The SABR-COMET-3 and SABR-COMET-10 trials are underway, along with other histology-specific trials.

Chad Tang, MD, an associate professor of radiation oncology at The University of Texas MD Anderson Cancer Center in Houston, said the current study is valuable because it establishes the safety of definitive multi-site SBRT for oligometastatic disease. “It demonstrated low grade 3-5 toxicities across a province-wide study, and the findings were not surprising,” Dr Tang said. “If multi-site SBRT is to be offered as standard of care before the publication of large phase 3 randomized trials, it is important to establish that this practice is, at a minimum, safe. This study, combined with other large single arm studies assessing safety, provides reassurance.”

Reference

Olson R, Jiang W, Liu M, et al. Treatment with stereotactic ablative radiotherapy for up to 5 oligometastases in patients with cancer. JAMA Oncol. doi:10.1001/jamaoncol.2022.4394 Published online September 29, 2022.

This article originally appeared on Renal and Urology News