Abstract 19
Category: Clinical Science
At the end of the session, participants will be able to:
- Appreciate the clinical utility of liquid biopsy for the diagnosis and monitoring of brain tumour patients
COI Disclosure:
I have a relationship with a for-profit and/or a not-for-profit organization to disclose.
Name of for-profit or not-for-profit organization(s) : Servier Canada
Description of relationship(s) : Honorarium
Presenter
Dr. Cynthia Hawkins obtained her MD/PhD from Western University. She completed her residency training in neuropathology at the University of Toronto, including a post-doctoral fellowship at the University of Zurich. Dr. Hawkins is a Neuropathologist and the Head of the Division of Pathology and Medical Director of Translational Molecular Pathology at the Hospital for Sick Children (SickKids). She is also a Senior Scientist at the SickKids Research Institute, a Professor of Laboratory Medicine and Pathobiology at The University of Toronto and holds a Garron Family Chair in Childhood Cancer Research and is a Fellow of the Canadian Academy of Health Sciences. Her research interests include molecular pathogenesis and therapeutics for pediatric glioma and clinical implementation of novel diagnostic, prognostic and therapeutic markers for pediatric brain tumors.
Yoshiko Nakano1, Robert Siddaway2, Liana Nobre3, Ian Burns4, Mansuba Rana2, Richard Yuditskiy2, Cyril Li2, Julie Bennett1, Anthony Liu1, Uri Tabori1, Cynthia Hawkins2
1 Division of Haematology/Oncology, The Hospital for Sick Children
2 Department of Paediatric Laboratory Medicine, The Hospital for Sick Children
3 Department of Paediatrics, University of Alberta
4 Department of Paediatrics, The Hospital for Sick Children
Target Audience:
Pathologists, Residents, Medical Students, Other – Write In (Required): Scientists
CanMEDS:
Medical Expert (the integrating role), Health Advocate, Scholar
Liquid biopsy for CNS tumours
Abstract
Introduction
Liquid biopsy (LB) is an emerging diagnostic tool for detecting tumor-specific alterations in body fluids that has many potential advantages including: identifying tumors with higher sensitivity and specificity than imaging; replacing invasive surgical biopsy; and monitoring tumor evolution by serial assessments. We investigated the feasibility and utility of cerebrospinal fluid (CSF)-based LB for patients with CNS tumors.
Methods
475 CSF samples were collected from patients with known or putative CNS tumors. To detect circulating tumor DNA (ctDNA), cell-free DNA was extracted and panel sequencing and/or low-pass whole genome sequencing were performed.
Results
At diagnosis/baseline assessment, ctDNA was detected in 78% of high-grade gliomas, 44% of low-grade gliomas, 55% of medulloblastomas and 93% of germ cell tumor cases. In patients with non-biopsied CNS lesions, ctDNA was diagnostic in 14 patients including for glioma, neuroblastoma and leukemia. Furthermore, in seven recurrent medulloblastoma cases where primary tumor copy number profiles were available, new copy number variants suggestive of tumor evolution/new subclones were seen. In patients for whom serial sampling was performed during and/or after completion of therapy, ctDNA clearance was observed in response to therapy. However, persistent ctDNA was observed in some patients despite imaging showing no residual tumor, highlighting the potential utility of ctDNA as a molecular-based measurable residual disease assessment for better risk stratification.
Conclusion
These findings pave the way for the clinical use of LB in CNS tumors and provide proof of concept for future incorporation of LB into clinical trials.