脳幹グリオーマにおけるイソクエン酸デヒドロゲナーゼ1/2変異の非侵襲的同定

A subset of brainstem gliomas harbor an isocitrate dehydrogenase 1/2 (IDH1/2) mutation, which has important prognostic and treatment implications. We evaluated the radiographic features and the sensitivity of magnetic resonance spectroscopy (MRS) and cerebrospinal fluid cell-free DNA (CSF cfDNA) sequencing at detecting IDH1/2 mutations in a cohort of these tumors.

We identified IDH-mutant brainstem gliomas by retrospective chart review. IDH1/2 mutation was established by biopsy, CSF cfDNA sequencing, and/or the presence of a 2-hydroxyglutarate (2HG) peak by 3-Tesla MRS.

Twenty-one patients with IDH-mutant brainstem gliomas were identified, 57% male with a median age of 26 (6-59) years. All tumors involved the pons and/or abutted the brachium pontis. Although 18 (86%) of 21 were nonenhancing, only one of 21 demonstrated T2-FLAIR mismatch. An IDH1/2 mutation was identified by biopsy in 17 and by CSF cfDNA sequencing in three; in the final patient, an IDH1/2 mutation was inferred by the presence of a 2HG peak. The sensitivity of MRS at identifying 2HG in patients with confirmed IDH1/2 mutations was 64.3% (95% CI, 35.1 to 87.2), which increased to 85.7% (95% CI, 42.1 to 99.6) when the study was performed before treatment. The 2HG peak was absent in all four patients with a repeat MRS after completion of radiation. IDH1/2 mutation was identified in four of seven patients who underwent sequencing of CSF cfDNA. In this cohort, median progression-free survival and overall survival were 57.6 and 90.4 months, respectively. An objective response to radiotherapy was observed in 76%.

IDH-mutant brainstem gliomas have a characteristic clinical and radiographic phenotype. MRS is more sensitive than CSF cfDNA sequencing for noninvasively identifying the presence of an IDH1/2 mutation when performed before radiotherapy.