What question did this study set out to answer?

This analysis aims to evaluate the survival benefit of adding stereotactic radiosurgery (SRS) to dual immune checkpoint blockade (N+I) in melanoma brain metastases.

May 29, 2026

Survival outcomes of adding stereotactic radiosurgery to dual immune checkpoint blockade in melanoma brain metastases: A systematic review and meta-analysis.

Key Points

This analysis aims to evaluate the survival benefit of adding stereotactic radiosurgery (SRS) to dual immune checkpoint blockade (N+I) in melanoma brain metastases.
Conducted a systematic review and meta-analysis following PRISMA guidelines.
Included 13 studies (10 observational, 3 randomized) from 2,972 records, totaling 2,055 patients.
Utilized random-effects models to pool hazard ratios (HRs) and risk ratios (RRs) for overall and progression-free survival.
N+I + SRS improved overall survival (OS) compared to N+I alone (HR = 0.56; 95% CI, 0.44–0.71; p<0.00001).
Two-year OS for N+I + SRS was higher (RR = 1.35; 95% CI, 1.17-1.55; p<0.0001) compared to 48% for N+I alone.
High lactate dehydrogenase (LDH) levels (>2× upper limit) seen in 37% of patients were linked to worse survival outcomes.

Abstract

9550 Background: Melanoma brain metastases (MBM) carry a poor prognosis and remain understudied in prospective trials. Dual immune checkpoint blockade (ICB) with nivolumab plus ipilimumab (N+I) achieves durable intracranial responses; stereotactic radiosurgery (SRS) is sometimes added but its survival benefit is unclear. Despite the increasing real-world use of SRS in combination with dual ICB, no prior meta-analysis has compared survival outcomes of N+I + SRS versus N+I alone. Methods: A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines.PubMed, Embase, Scopus, and Web of Science were searched for randomized controlled trials (RCTs) and observational/real-world (ORW) studies published from January 2015 to July 1, 2025. Primary outcomes were overall survival (OS) and progression-free survival (PFS).Secondary outcomes included radiologic responses rates assessed by RECIST 1.1 and prognostic biomarkers. Random-effects models were used to pool risk ratios (RRs) and hazard ratios (HRs) with 95%confidence intervals (CIs). Analyses were performed in RevMan and R. Results: From 2,972 records, a total of thirteen studies included (ten ORW studies and three RCTs) met our inclusion criteria, including 2,055 patients. Median age was 57.2 years and 64.28% were male. N+I + SRS significantly improved OS compared with N+I alone (HR = 0.56; 95% CI, 0.44–0.71; p2× upper limit of normal) was observed in 37% of patients (95% CI, 20–58) and was associated with inferior survival outcomes. Conclusions: In patients with MBM, the addition of stereotactic radiosurgery with dual immune checkpoint blockade is associated with significant overall survival advantage compared with N+I alone. This first meta-analysis defines the incremental survival benefit of adding SRS to contemporary dual immunotherapy N+I integrating long-term survival outcomes, radiologic response, and prognostic biomarkers. These findings support N+I as the systemic backbone for MBM management and support SRS integration for appropriately selected patients. Prospective trials are warranted to optimize sequencing,timing, and patient selection.

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Cite This Study

Ortíz et al. (Thu,) studied this question.

synapsesocial.com/papers/6a192eb9fab5b468c4417ed6 https://doi.org/https://doi.org/10.1200/jco.2026.44.16_suppl.9550

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