Stereotactic Radiosurgery Safe and Effective for Brainstem Metastases

Matthew Fowler

The results from a retrospective trial that found stereotactic radiosurgery produced comparable results for both brainstem metastases and nonbrainstem brain metastases suggest both groups of patients should be eligible for stereotactic radiosurgery clinical trials.

Stereotactic radiosurgery (SRS) was safe and effective for brainstem metastases (BSM) with comparable results to that of SRS for nonbrainstem brain metastases (BM), according to data published in JAMA Oncology.

Patients who underwent SRS for BSM rarely died from BSM progression according to this research, with the included cohort experiencing symptomatic improvement from the procedure.

These results, specifically the safety and efficacy data, suggest that patients with BSM should be eligible for clinical trials focusing on SRS. More, SRS should be considered at the time of BM-targeted therapy clinical trial enrollment.

“Results of this systematic review and meta-analysis demonstrate that SRS for BSM has been associated with effectiveness, safety, and improved symptoms,” wrote the investigators. “Additionally, BSM size, prior [whole-brain radiotherapy], and histology results may be associated with treatment-related toxic effects.”

A total of 1446 patients with 1590 BSM treated with SRS from 32 retrospective studies published between 1999 and 2019 were included in the investigation.

For 1410 patients across 31 studies, the rate of local control at 1 year was 86% (95% CI, 83%-88%; I2 = 38%). More, the objective response rate (ORR) for 642 patients across 17 studies was 59% (95% CI, 47%-71%; I2 = 88%), with symptom improvement at 55% (95% CI, 47%-63%; I2 = 41%) for 323 patients across 13 studies.

Nineteen deaths from BSM progression out of 703 patients who underwent SRS across 19 studies were observed (2.7%). The neurologic death rate of 24% in patients with BSM is equal to that of the neurologic death rate for patients with BM treated on prospective trials (95% CI, 19%-31%; I2 = 62%).

Looking at the safety profile, the observed rate of treatment-related grade 3 or greater toxic effects for 1421 patients across 31 studies was 2.4% (95% CI, 1.5%-3.7%; I2 = 33%).

“Given the risks of acute morbidity or death from BSM growth in the context of the efficacy and safety of SRS for BSM, future trials of targeted therapy or immunotherapy for BM should consider including patients with BSM after treatment with SRS,” wrote the investigators.

The primary end points of this research included the local control and overall survival rates at 1- and 2-years, objective response rate, symptom response rate, neurological death rate, and rate of grade 3 or greater toxic effects.

The large sample size and substantial number of studies included are a strength of the results from this study. More, low-to-moderate heterogeneity across and the partially independent report corroborating findings act as strengths of the data.

As for limitations, the investigative team acknowledged that they were unable to account for patient-level confounders and competing risks. More, the data regarding the safety and efficacy of SRS in combination with systemic therapy for BSM were limited because only 2 studies analyzed the prevalence of concurrent molecular/immune therapy.

“Patients with BSM are unlikely to experience severe toxic effects after SRS and have similar rates of neurologic death compared with patients with BM treated with SRS on prospective trials,” wrote the investigators. “Future trials incorporating SRS should consider inclusion of patients with BSM.”

Reference

Chen WC, Baal UH, Baal JD, et al. Efficacy and Safety of Stereotactic Radiosurgery for Brainstem Metastases: A Systematic Review and Meta-analysis. JAMA Oncol. May 13, 2021. doi:10.1001/jamaoncol.2021.1262