Serial H3K27M cell-free tumor DNA (cf-tDNA) tracking predicts ONC201 treatment response and progression in diffuse midline glioma
Cantor E, Wierzbicki K, Tarapore RS, Ravi K, Thomas C, Cartaxo R, Yadav VN, Ravindran R, Bruzek AK, Wadden J, John V, Babila CM, Cummings JR, Kawakibi AR, Ji S, Ramos J, Paul A, Walling D, Leonard M, Robertson P, Franson A, Mody R, Garton HJL, Venneti S, Odia Y, Kline C, Vitanza NA, Khatua S, Mueller S, Allen JE, Gardner SL, Koschmann C.
Neuro-Oncology, Aug 2022, Vol 24(8), pp 1366-1374. doi:10.1093/neuonc/noac030
In plain English
By repeatedly sampling spinal fluid during treatment, the team tracked a tumor's DNA over time. Falling levels matched patients doing better — and helped tell true tumor growth apart from harmless, treatment-related swelling.
For scientists
First demonstrated feasibility of serial CSF collection for cf-tDNA tracking in a multi-site Phase 1 trial of ONC201 in H3K27M-mutant diffuse midline glioma. Change in H3K27M variant allele fraction over time correlated with progression-free survival, enabling differentiation of pseudo-progression from true tumor progression.