Citations 1
GLIOMA MONITORING VIA LONGITUDINAL INTRACRANIAL CSF CELL-FREE DNA: ONE PATIENT AT A TIME
Riviere-Cazaux, Ms Cecile, Dong, Dr Xiaoxi, Mo, Daojun, Dai, Dr Chao, Campian, Dr Jian, Ruff, Deborah, Eckel-Passow, Dr Jeanette, Kaufmann, Dr Timothy, Kizilbash, Dr Sani, Warrington, D. M., Jenkins, Dr Robert, Du, Doantrang, Jia, Dr Shidong, Burns, Dr Terry, Kizilbash, Sani H. , Kizilbash, Sani H , Dong, Dr Xiaoxi, Dai, Dr Chao, Campian, Jian L , Eckel‐Passow, Jeanette E. , Kaufmann, Dr Timothy, Warrington, Dr Arthur, Jenkins, Dr Robert, Du, Dr Pan, Jia, Dr Shidong, Burns, Dr Terry
Neuro-Oncology | October 15, 2024 | Volume: 26 | Issue: Supplement_7 | Pages: vii2-vii2
Abstract AIMS Methods for disease monitoring in glioma are currently limited. Liquid biopsies are of increasing interest within the field but have been challenging due to the blood-brain barrier. To bypass this challenge, we aimed to assess the technical and clinical feasibility of obtaining intracranial cerebrospinal fluid (CSF) for disease monitoring via cell-free DNA (cfDNA). METHOD Adults with gliomas were recruited for longitudinal intracranial CSF collection via CSF access devices, including Ommaya reservoirs in four patients and an existing VP shunt in one patient. cfDNA was then extracted and analyzed using two sequencing platforms, PredicineCARE for cancer variant profiling and PredicineSCORE for low-pass whole genome sequencing (LP-WGS). This analysis generated genomic aberration profiles and genome wide copy number burden (CNB) score. RESULTS Across five patients, thirty-five CSF samples were obtained (median volume: 3.80 mL; 0.5-5 mL), with 30 samples (85.7%) yielding sufficient cfDNA. Tumor fraction increased by 6.28x and 2.87x in two patients with radiographic disease progression and decreased by 0.08x and 0.04x in another two after chemoradiation. In another patient with pseudoprogression, tumor fraction decreased from 0.26 after resection to unmeasurable levels. Patient specific tumor-associated variant allelic frequencies (VAFs), including TP53, PTEN, and TERT, decreased within individual patients after resection and chemoradiation. In two patients with IDH-mutant gliomas, IDH1 VAF after resection correlated with decreased CSF D-2-hydroxyglutarate (D-2-HG) levels (0.64x and 0.62x, respectively, for the first patient, and 0.01x and 0.07x for the other patient). Both IDH1 VAF and D-2-HG increased in a patient with radiographic progression (2.56x and 9.21x, respectively). CNB decreased below the limit of quantification during treatment and increased above the limit at progression. CONCLUSION Longitudinal CSF cfDNA can feasibly be obtained via CSF access devices in patients with gliomas during their disease course. Further sample collection and analysis are ongoing to determine the thresholds of change indicative of treatment response and progression.