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Peer-reviewedCC BY 4.0Journal of Clinical Medicine

Distant Brain Failure and Subsequent Survival After Gamma Knife Radiosurgery for Breast Cancer Brain Metastases: Prognostic Value of Pretreatment Inflammatory Markers

  1. 1Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China
  2. 2State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China
  3. 3Department of Anesthesiology, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China

Abstract

Background/Objectives: Whether pretreatment inflammatory markers inform both the risk of distant brain failure (DBF) and survival after its occurrence remains unclear in breast cancer brain metastases. We evaluated these associations across the clinical course following Gamma Knife radiosurgery (GKRS). Methods: This retrospective cohort included 91 women undergoing initial GKRS. Four blood-derived inflammatory markers were analyzed separately as standardized log2-transformed variables. Fine–Gray models evaluated first DBF with death as a competing event. Multistate and transition-specific Cox analyses distinguished mortality before and after DBF. Marker comparisons underwent Benjamini–Hochberg false-discovery-rate correction. Results: DBF developed in 57 patients, of whom 36 subsequently died; 16 patients died before DBF. Cumulative DBF incidence reached 41.8% at 12 months and 61.0% at 24 months. A higher pretreatment neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio were associated with first DBF (adjusted subdistribution hazard ratios per standard-deviation increase: 1.52, 95% confidence interval [CI] 1.09–2.10; and 1.38, 95% CI 1.04–1.83, respectively; both q = 0.047). Median survival after DBF was 10.5 months. NLR measured before initial GKRS remained associated with post-DBF mortality after adjustment for age, performance status at DBF, and extracranial disease progression at DBF (hazard ratio, 2.29; 95% CI, 1.45–3.61; q = 0.003). With a time-varying performance-status coefficient, the NLR hazard ratio was 2.75 (95% CI, 1.68–4.51; nominal p < 0.001). No inflammatory marker was significantly associated with mortality before DBF after adjustment for multiple testing. Conclusions: Pretreatment NLR was associated with both first DBF and subsequent mortality, whereas PLR was associated with first DBF. The predominantly HER2-positive cohort (68.1%) limits generalizability. Further validation is needed to establish the predictive and clinical value of these associations.

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BibTeX
@article{diao2026distant,
  title = {{Distant Brain Failure and Subsequent Survival After Gamma Knife Radiosurgery for Breast Cancer Brain Metastases: Prognostic Value of Pretreatment Inflammatory Markers}},
  author = {Sijun Diao and Fujun Liu and Zhongyu Li and Shihong Zhu and Xiyue Lu and Huiyang Luo and Jing Chen},
  journal = {Journal of Clinical Medicine},
  year = {2026},
  month = nov,
  doi = {10.3390/jcm15218701},
  url = {https://www.mdpi.com/2077-0383/15/21/8701},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Distant Brain Failure and Subsequent Survival After Gamma Knife Radiosurgery for Breast Cancer Brain Metastases: Prognostic Value of Pretreatment Inflammatory Markers
AU  - Sijun Diao
AU  - Fujun Liu
AU  - Zhongyu Li
AU  - Shihong Zhu
AU  - Xiyue Lu
AU  - Huiyang Luo
AU  - Jing Chen
PY  - 2026
DA  - 2026/11/07
JO  - Journal of Clinical Medicine
DO  - 10.3390/jcm15218701
UR  - https://www.mdpi.com/2077-0383/15/21/8701
AB  - Background/Objectives: Whether pretreatment inflammatory markers inform both the risk of distant brain failure (DBF) and survival after its occurrence remains unclear in breast cancer brain metastases. We evaluated these associations across the clinical course following Gamma Knife radiosurgery (GKRS). Methods: This retrospective cohort included 91 women undergoing initial GKRS. Four blood-derived inflammatory markers were analyzed separately as standardized log2-transformed variables. Fine–Gray models evaluated first DBF with death as a competing event. Multistate and transition-specific Cox analyses distinguished mortality before and after DBF. Marker comparisons underwent Benjamini–Hochberg false-discovery-rate correction. Results: DBF developed in 57 patients, of whom 36 subsequently died; 16 patients died before DBF. Cumulative DBF incidence reached 41.8% at 12 months and 61.0% at 24 months. A higher pretreatment neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio were associated with first DBF (adjusted subdistribution hazard ratios per standard-deviation increase: 1.52, 95% confidence interval [CI] 1.09–2.10; and 1.38, 95% CI 1.04–1.83, respectively; both q = 0.047). Median survival after DBF was 10.5 months. NLR measured before initial GKRS remained associated with post-DBF mortality after adjustment for age, performance status at DBF, and extracranial disease progression at DBF (hazard ratio, 2.29; 95% CI, 1.45–3.61; q = 0.003). With a time-varying performance-status coefficient, the NLR hazard ratio was 2.75 (95% CI, 1.68–4.51; nominal p < 0.001). No inflammatory marker was significantly associated with mortality before DBF after adjustment for multiple testing. Conclusions: Pretreatment NLR was associated with both first DBF and subsequent mortality, whereas PLR was associated with first DBF. The predominantly HER2-positive cohort (68.1%) limits generalizability. Further validation is needed to establish the predictive and clinical value of these associations.
SN  - 2077-0383
ER  -