Timing of systemic therapy relative to stereotactic radiosurgery for brain metastases: a real-world cohort study
- 1Department of Radiation Oncology, Sharett Institute of Oncology, Hebrew University Medical Center, Jerusalem, Israel
- 2Department of Military Medicine and “Tzamert”, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, 9112002 Israel
- 3Faculty of Medicine, Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Hebrew University of Jerusalem, Jerusalem, Israel
Abstract
Purpose: Combining stereotactic radiosurgery (SRS) with systemic therapy is increasingly common for brain metastases, yet real-world evidence on immunotherapy timing relative to SRS remains limited. We evaluated the association of immunotherapy and its timing with survival, intracranial control and toxicity, with exploratory analyses of chemotherapy and targeted therapy.
Methods: We retrospectively analyzed 155 patients with 556 brain metastases treated with SRS at a single tertiary center (January 2021–February 2025). Patient-level associations of systemic therapy, overall and by timing (before, concurrent with or after SRS), with overall survival, 1-year local, distant intracranial and systemic progression, toxicity and radionecrosis were assessed using Kaplan–Meier, Cox and logistic regression analyses, with false discovery rate correction for immunotherapy timing.
Results: Median follow-up was 18.8 months. Immunotherapy (n = 88) was not associated with overall survival (adjusted HR 0.79, 95% CI 0.46–1.35), intracranial progression or toxicity, and no timing window remained significant after correction (all q ≥ 0.53). In exploratory analyses, targeted therapy was associated with longer survival (adjusted HR 0.45, 95% CI 0.26–0.79) and with more frequent radionecrosis (13.2% vs. 3.5%; p = 0.034), the latter not robust to sensitivity analysis. A higher number of treated metastases was independently associated with local (aOR 1.15, 95% CI 1.02–1.30) and distant intracranial progression (aOR 1.45, 95% CI 1.24–1.71).
Conclusion: In this single-institution real-world cohort, immunotherapy and its timing relative to SRS were not associated with survival, intracranial control or toxicity. Exploratory associations of targeted therapy with survival and radionecrosis are hypothesis-generating and warrant prospective, histology-specific validation.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s11060-026-05857-0.
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BibTeX
@article{ptascinsky2026timing,
title = {{Timing of systemic therapy relative to stereotactic radiosurgery for brain metastases: a real-world cohort study}},
author = {Mijal Ptascinsky and Antoni Skripai and Yair Hillman and Marc Wygoda and Aron Popovtzer and Tal Falick Michaeli},
journal = {Journal of Neuro-Oncology},
year = {2026},
month = nov,
doi = {10.1007/s11060-026-05857-0},
url = {https://doi.org/10.1007/s11060-026-05857-0},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Timing of systemic therapy relative to stereotactic radiosurgery for brain metastases: a real-world cohort study
AU - Mijal Ptascinsky
AU - Antoni Skripai
AU - Yair Hillman
AU - Marc Wygoda
AU - Aron Popovtzer
AU - Tal Falick Michaeli
PY - 2026
DA - 2026/11/03
JO - Journal of Neuro-Oncology
DO - 10.1007/s11060-026-05857-0
UR - https://doi.org/10.1007/s11060-026-05857-0
AB - Purpose: Combining stereotactic radiosurgery (SRS) with systemic therapy is increasingly common for brain metastases, yet real-world evidence on immunotherapy timing relative to SRS remains limited. We evaluated the association of immunotherapy and its timing with survival, intracranial control and toxicity, with exploratory analyses of chemotherapy and targeted therapy. Methods: We retrospectively analyzed 155 patients with 556 brain metastases treated with SRS at a single tertiary center (January 2021–February 2025). Patient-level associations of systemic therapy, overall and by timing (before, concurrent with or after SRS), with overall survival, 1-year local, distant intracranial and systemic progression, toxicity and radionecrosis were assessed using Kaplan–Meier, Cox and logistic regression analyses, with false discovery rate correction for immunotherapy timing. Results: Median follow-up was 18.8 months. Immunotherapy (n = 88) was not associated with overall survival (adjusted HR 0.79, 95% CI 0.46–1.35), intracranial progression or toxicity, and no timing window remained significant after correction (all q ≥ 0.53). In exploratory analyses, targeted therapy was associated with longer survival (adjusted HR 0.45, 95% CI 0.26–0.79) and with more frequent radionecrosis (13.2% vs. 3.5%; p = 0.034), the latter not robust to sensitivity analysis. A higher number of treated metastases was independently associated with local (aOR 1.15, 95% CI 1.02–1.30) and distant intracranial progression (aOR 1.45, 95% CI 1.24–1.71). Conclusion: In this single-institution real-world cohort, immunotherapy and its timing relative to SRS were not associated with survival, intracranial control or toxicity. Exploratory associations of targeted therapy with survival and radionecrosis are hypothesis-generating and warrant prospective, histology-specific validation. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s11060-026-05857-0.
SN - 0167-594X
SN - 1573-7373
ER -