THE ROLE OF VIBRATIONAL SPECTROSCOPY IN LIQUID BIOPSY OF HIGH-GRADE GLIOMA: A SYSTEMATIC REVIEW

Abstract AIMS In recent years, liquid biopsy has shown potential use in early diagnosis, disease monitoring and prognostica- tion within neuro-oncology. The integration of current liquid biopsy into routine practice remains challenging due to detection of circulating biomarkers. Vibrational spectroscopy (VS) including Raman (RS) and Infrared spectroscopies is an alternative multi-omic technology which detects biomarkers in the form of bio-spectral fin- gerprints. We aim to review the current literature and practice of the use of VS as liquid biopsy tool in patients with high-grade glioma (HGG). METHODS Protocol was registered a priori on PROSPERO (CRD42024611005). Five databases were systematically screened from inception to December 2024 including PubMed, Ovid Embase, Ovid Medline, Web of Science and Clinical- trials.gov. PRISMA reporting guidelines were followed. Data extraction, and risk of bias (using QUADAS-2) were conducted. RESULTS One-hundred and sixty-six articles were identified. Fifty duplicates removed followed by exclusion of 104 arti- cles. Twelve articles published between 2013-2024 were included for data extraction with a cumulative cohort of 827 control vs 2,021 brain tumours (819 were HGG). Nine studies utilises Attenuated Total Reflection-Fourier Transform Infrared Spectroscopy (ATR-FTIR) whilst 3 studies utilises RS. Ten studies utilises serum whilst only 2 studies utilises plasma. Four articles were included in forest plot of sensitivity/specificity for glioblastoma vs control using ATR-FTIR on serum samples (cumulative cohort of 200 HGG vs 167 control). The sensitivity ranges from 87.4%-95.5% whilst the specificity ranges from 80%-100%. The accuracy ranges from 89.9%-96.9%. CONCLUSION This represents the first systematic review to evaluate current evidence on VS for HGG as liquid biopsy tool. All evidence remains largely case-control studies, providing proof-of-concept. Further high-quality studies re- quired to draw robust conclusion on the applicability and to standardise the methodology used. No studies were done to evaluate the potential use of of VS in monitoring disease progression which requires research to elucidate its capability.