Outcomes of Patients With Melanoma Brain Metastases Treated With Ipilimumab and Nivolumab With or Without Upfront Comprehensive Stereotactic Radiosurgery

Authors

Troy J Kleber
Denái R Milton
Subhiksha Srinivasan
Bikash Panthi
Warren Floyd
Eric A Goethe
Michael A Davies
Hussein A Tawbi
Isabella C Glitza Oliva
Diana Kaya
Jing Li
Todd A Swanson
Subha Perni
Martin C Tom
Chenyang Wang
Sujit Prabhu
Jeffrey S Weinberg
Ian E McCutcheon
Caroline Chung
Sherise D Ferguson
Thomas H Beckham

Language

English

Publication Date

1-1-2026

Journal

Neuro-Oncology Advances

DOI

10.1093/noajnl/vdaf276

PMID

41664820

PMCID

PMC12883207

PubMedCentral® Posted Date

1-7-2026

PubMedCentral® Full Text Version

Post-print

Abstract

Background: The efficacy of ipilimumab and nivolumab (ipi/nivo) for melanoma brain metastases (MBMs) has been previously reported, leading to uncertainty regarding the optimal role of comprehensive stereotactic radiosurgery (cSRS). We therefore conducted a single-institution retrospective study to compare outcomes of upfront versus deferred cSRS for MBM treated with ipi/nivo.

Methods: We identified patients who started ipi/nivo for newly diagnosed MBMs between 2018 and 2023, with or without upfront cSRS. Patients with >15 MBMs, leptomeningeal disease, or whole-brain radiotherapy at baseline were excluded. Outcomes were compared using multivariable regression and reported as adjusted hazard ratios (aHRs) with 95% CIs.

Results: Of the 132 patients identified, 52.3% received upfront cSRS and 47.7% did not. Patients who received upfront cSRS had larger maximum MBMs (median 2.3 vs 0.7 cm; P < .001), more symptomatic MBMs (59.4% vs 11.1%; P < .001), higher rates of upfront craniotomy (47.8% vs 7.9%; P < .001), and fewer BRAF V600 mutations (34.8% vs 54.0%; P = .035). Upfront cSRS was not associated with longer overall survival (median 47.0 mo vs not reached; aHR = 1.01 [95% CI, 0.60-1.68]; P = .98) but was associated with reduced incidence of intracranial progression (median 37.6 vs 5.5 mo; aHR = 0.40 [95% CI, 0.25-0.64]; P < .001).

Conclusions: In this retrospective study, upfront cSRS was more often used in patients with higher-risk MBM and was associated with improved intracranial control, although no significant survival benefit was observed. These findings suggest that starting ipi/nivo alone may be reasonable for lower-risk MBM, but prospective studies are needed to guide optimal integration of cSRS.

Keywords

brain metastasis, checkpoint inhibitor, immunotherapy, melanoma, stereotactic radiosurgery

Published Open-Access

yes

Recommended Citation

Kleber, Troy J; Milton, Denái R; Srinivasan, Subhiksha; et al., "Outcomes of Patients With Melanoma Brain Metastases Treated With Ipilimumab and Nivolumab With or Without Upfront Comprehensive Stereotactic Radiosurgery" (2026). Faculty, Staff and Student Publications. 5518.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5518