CEREBROSPINAL FLUID LIQUID BIOPSY FOR MOLECULAR MONITORING OF GLIOMA: FROM CELL-FREE DNA DETECTION TO LONGITUDINAL MINIMAL RESIDUAL DISEASE ASSESSMENT

Abstract

Background. In adult diffuse gliomas across diagnosis, postoperative surveillance, and suspected progression, neurosurgical decisions remain difficult because MRI cannot consistently distinguish viable tumor from treatment-related change, and repeated tissue biopsy is invasive, spatially limited, and unsuitable for frequent longitudinal monitoring.

Materials and methods. A structured narrative review is proposed using clinical trials, prospective cohorts, diagnostic-accuracy studies, systematic reviews, and relevant technical investigations. Evidence is organized by biological plausibility, technical performance, patient selection, safety, clinical effectiveness, reproducibility, and implementation. A prospective comparative study is specified for adults with molecularly characterized diffuse glioma undergoing lumbar puncture, ventricular access, or clinically indicated CSF sampling, with MRI surveillance and conventional clinical assessment without CSF molecular monitoring as the reference strategy.

Results. The synthesis addresses five domains: analytical validity, sampling route and preanalytics, diagnostic and prognostic utility, minimal residual disease, clinical decision integration. The proposed primary endpoint is diagnostic accuracy for molecular progression before conventional radiographic progression; secondary endpoints include lead time, tissue–CSF concordance, assay failure rate, prognostic value, detection by sampling route, impact on treatment decisions, and procedure-related complications. Originality derives from linking technical accuracy to patient-centered outcomes, explicitly modeling uncertainty, and requiring external validation.

Conclusion. Standardized endpoints support reliable clinical comparison. Independent adjudication strengthens causal interpretation. Longitudinal follow-up clarifies therapeutic durability. Equity analysis supports responsible implementation. Transparent reporting improves scientific reproducibility. Patient safety remains the central priority. Rigorous independent prospective multicenter external validation remains essential.