Intraoperative Perilesional CS Cytology Predicts Intracranial and Leptomeningeal Progression of Brain Metastases
Ruju Talati1, Richard Song1, Anika Khandekar1, Osaama Khan1, Vinai Gondi2
1Neurosurgery, 2Radiation Oncology, Northwestern Medicine
Objective:
To analyze the cohort of patients where the resection cavity fluid was collected pre-resection and analyze those findings to gauge potential for new biomarkers, targets, or treatment for brain metastasis.
To scan and search for potential patterns and predictors of outcome and response to treatment in order to potentially alter pre- and post-operative management for these patients.
Background:
Brain metastases frequently recur after surgery and radiotherapy, and a subset of patients develop leptomeningeal disease, which carries a poor prognosis. Current surveillance relies on MRI imaging and no validated intraoperative analyses exist to identify dissemination risk. In this study, intraoperative perilesional cerebrospinal fluid cytology was investigated for its potential to predict intracranial and leptomeningeal progression in patients without radiographic evidence of LMD.
Design/Methods:
Fifty-nine patients who underwent brain metastasis resection between 2022 and 2025 had perilesional CSF collected immediately before and after tumor removal for cytologic analysis. Clinical and radiographic data were evaluated using Fine–Gray competing-risks regression adjusted for age, sex, tumor burden, and perioperative radiotherapy. Malignant cells were identified in 23 patients (38.9%).
Results:
CSF positivity independently predicted shorter time to intracranial progression (sHR = 3.27, 95% CI 1.17–5.12, p = 0.028) and to LMD progression (sHR = 4.21, 95% CI 1.36–7.83, p = 0.008). At 24 months, the cumulative incidence of intracranial progression was 86.1% in CSF-positive versus 28.4% in CSF-negative patients, with the perilesional CSF positivity conferring the highest risk. Breast and gastrointestinal primaries showed the greatest frequency of CSF positivity.
Conclusions:
Presence of tumor cells in perilesional CSF is most commonly associated with primary breast cancer and associated with intracranial metastatic progression and risk of LMD. CSF positivity was the only independent predictor of progression.
Future directions can characterize molecular makeup of peritumoral CSF liquid biopsies, validate findings in larger multi-institutional cohorts, and explore integration into pre- and post-operative management strategies.
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