OTHR-09. Cerebrospinal fluid liquid biopsy: initial results following implementation into clinical practice for patients with pediatric embryonal central nervous system tumors

Abstract Liquid biopsy (LB) holds great potential for children with central nervous system (CNS) tumors. Low-pass whole genome sequencing from cerebrospinal fluid (CSF) is now available as a clinical test at our institution. We report on 42 CSF LBs from 17 pediatric patients with embryonal CNS tumors (age range 7 months-19 years), including cytologic, radiologic, and clinical correlates. Histologies included medulloblastoma (n = 13), atypical teratoid rhabdoid tumor (n = 2), CNS neuroblastoma (n = 1), and pineoblastoma (n = 1). Seven patients underwent two or more LBs. CSF was collected by lumbar puncture (n = 23), Ommaya (n = 15), ventriculo-peritoneal shunt (n = 3) and ventriculostomy (n = 1). Circulating tumor DNA (ctDNA) was detected in 28/42 samples (66%); successful detection varied by timepoint: 6/8 (75%) at diagnosis, 13/16 (81%) on-therapy, 2/8 (25%) at end-of-therapy, 2/5 (40%) off-therapy during surveillance, and 5/5 (100%) at radiographic recurrence. Both patients positive at end-of-therapy received salvage. One patient cleared ctDNA and remains in remission off therapy. The other had persistently positive ctDNA and recurred. Overall, 5/28 patients with positive ctDNA (18%) had positive cytology; 14/14 negative LBs were cytology negative. Of patients with positive LBs, 5 had no radiographic disease. Of patients with negative LBs, three patients had radiographic disease (n = 2 with ATRT; n = 1 with copy-neutral medulloblastoma). Compared to primary tumor sequencing 6/20 (30%) LBs detected additional copy number variants. In cases of serial sampling, 8/22 (36%) LBs showed additional copy number alterations over time suggesting tumor evolution, and 7/22 (32%) serial LBs showed resolution of ctDNA, consistent with response to therapy. In one case the diagnosis of radiation-­induced high-grade glioma was made based solely on LB as the patient was not stable for neurosurgery. In our cohort, LB showed a higher sensitivity than CSF cytology, occasionally in the context of negative neuroimaging. It also offered new molecular insights during tumor progression. Optimization will require prospective clinical trials.