Diagnosis and treatment decision of an IDH-mutant glioma through CSF-based cfDNA sequencing

Classification of tumors of the central nervous system currently requires tumor tissue analysis for histology and molecular markers, according to the 2021 WHO Classification of Tumors of the Central Nervous System. Cerebrospinal fluid (CSF)-based cell-free DNA (cfDNA) sequencing detects these defining molecular alterations and allows for accurate diagnosis and WHO-analogue tumor classification. We hereby report the case of a female patient with an IDH-mutant glioma, TERT promoter mutant, NEC, in whom IDH1 and TERT promoter mutations were identified in CSF after an initially non-informative tissue histology, then confirmed through tissue-based molecular analysis. The patient was initially treated with vorasidenib, an IDH inhibitor, which was then switched to a procarbazine-CCNU chemotherapy due to clinical worsening under initial therapy. CSF-based cfDNA sequencing is a promising tool for minimally invasive diagnosis of tumors of the CNS in situations in which tissue biopsy is challenging or non-informative.