|Title||Next-generation Sequencing of Cerebrospinal Fluid for Clinical Molecular Diagnostics in Pediatric, Adolescent and Young Adult (AYA) Brain Tumor Patients.|
|Publication Type||Journal Article|
|Year of Publication||2022|
|Authors||Miller AM, Szalontay L, Bouvier N, Hill K, Ahmad H, Rafailov J, Lee AJ, M Rodriguez-Sanchez I, Yildirim O, Patel A, Bale TA, Benhamida JK, Benayed R, Arcila ME, Donzelli M, Dunkel IJ, Gilheeney SW, Khakoo Y, Kramer K, Sait SF, Greenfield JP, Souweidane MM, Haque S, Mauguen A, Berger MF, Mellinghoff IK, Karajannis MA|
|Date Published||2022 Feb 11|
BACKGROUND: Safe sampling of CNS tumor tissue for diagnostic purposes may be difficult if not impossible, especially in pediatric patients, and an unmet need exists to develop less invasive diagnostic tests.
METHODS: We report our clinical experience with minimally invasive molecular diagnostics using a clinically validated assay for sequencing of cerebrospinal fluid (CSF) cell-free DNA (cfDNA). All CSF samples were collected as part of clinical care, and results reported to both clinicians and patients/families.
RESULTS: We analyzed 64 CSF samples from 45 pediatric, adolescent and young adult (AYA) patients (pediatric=25; AYA=20) with primary and recurrent brain tumors across 12 histopathological subtypes including high-grade glioma (n=10), medulloblastoma (n=10), pineoblastoma (n=5), low grade glioma (n=4), diffuse leptomeningeal glioneuronal tumor (DLGNT) (n=4), retinoblastoma (n=4), ependymoma (n=3), and other (n=5). Somatic alterations were detected in 30/64 samples (46.9%) and in at least one sample per unique patient in 21/45 patients (46.6%). CSF cfDNA positivity was strongly associated with the presence of disseminated disease at the time of collection (84.6% of samples from patients with disseminated disease were positive). No association was seen between CSF cfDNA positivity and the timing of CSF collection during the patient's disease course.
CONCLUSIONS: We identified three general categories where CSF cfDNA testing provided additional relevant diagnostic, prognostic, and/or therapeutic information, impacting clinical assessment and decision making: 1) diagnosis and/or identification of actionable alterations; 2) monitor response to therapy; and 3) tracking tumor evolution. Our findings support broader implementation of clinical CSF cfDNA testing in this population to improve care.
|Alternate Journal||Neuro Oncol|
|Grant List||P30 CA008748 / CA / NCI NIH HHS / United States|