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Stereotactic radiosurgery (SRS) for brainstem metastases (BSM) appears to be safe and effective, and comparable to SRS for non-brainstem brain metastases (BM), according to researchers.

Their systematic review and meta-analysis of retrospective studies involving patients with BSM showed that SRS was associated with high local control, tumor response, and symptom relief, as well as low rates of significant toxic effects.

"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," reported William C. Chen, MD, of the University of California San Francisco, and colleagues in . "Future trials incorporating SRS should consider inclusion of patients with BSM."

"Brainstem metastases are challenging to manage given the lack of surgical management options and concern with treatment with systemic therapy alone, given the critical location and risk of neurologic symptomatology in the setting of disease progression," Rupesh R. Kotecha, MD, chief of radiosurgery and director of the CNS Metastasis program at Miami Cancer Institute of Baptist Health South Florida, told MedPage Today.

Considering risk-to-benefit ratio and choosing the appropriate stereotactic radiotherapy technique "requires a careful balance between dose and fractionation selection to optimize local control but also keep the risk of radiation necrosis low," added Kotecha, who was not involved in the study.

Chen and colleagues pointed out that SRS has been effective in treating patients with non-brainstem BM and does not cause the neurological damage seen with whole-brain radiotherapy. However, most prospective trials of SRS among patients with BM have excluded those with BSM.

Consequently, the efficacy and safety of SRS for BSM is incompletely understood, the authors suggested. Therefore, they performed a quantitative meta-analysis of SRS for BSM to estimate pooled measures of efficacy and safety in the context of prospective trials of SRS or molecular therapy for BM.

The meta-analysis included 32 retrospective studies of 1,446 patients who underwent SRS for BSM from 1999 to 2019. These studies included at least 10 patients each and reported one or more outcomes (1- and 2-year local control and overall survival, objective response and symptom response rates, neurological death rate, and grade 3-5 toxic effects).

Chen and team found that the 1-year local control rate was 86% in 1,410 patients across 31 studies, the objective response rate was 59% in 642 patients across 17 studies, and the rate of symptom improvement was 55% in 323 patients across 13 studies.

"These results compared favorably to trials of targeted or immunotherapy for BM, which had a wide objective response rate range from 17% to 56%," they observed.

The authors also found that the 1-year overall survival rate was 33% in 1,254 patients across 27 studies, while the 2-year overall survival rate was 13% in 959 patients across 22 studies. Death attributed to BSM progression occurred in 2.7% of patients across 19 studies, while the rate of neurologic death was 24%, which was on par with patients with BM who were treated on prospective trials.

In 1,421 patients across 31 studies, 56% experienced symptomatic toxic effects of any grade after SRS for BSM, while 2.4% experienced toxic effects of grade 3-5.

In comparing these results with published prospective trials of SRS for BM, Chen and colleagues found that pooled rates of neurologic death between BSM studies and the BM trials were similar (22% vs 24%). "Moreover, local control (86% vs 81%) and rates of grade 3 to 5 toxic effects (2.4% vs 5.1%) among BSM studies compared favorably with prospective BM trials despite the lower SRS doses used to treat BSM," they reported.

These results support the inclusion of these patients in ongoing clinical trials, said Kotecha. "Moreover, the authors also demonstrate favorable outcomes in these patients compared to outcomes of patients with brain metastasis treated with systemic therapy alone and overall support the role of radiotherapy. Patient-level data with prospective reporting of outcomes will be important to understand the impact of tumor histology, molecular profile, size, volume, location, and impact of systemic therapy to provide clarity on optimal dose/fractionation principles."

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