PDTB-27. PRECISION MEDICINE IN PEDIATRIC NEURO-ONCOLOGY

Abstract

Current paradigms utilized in pediatric neuro-oncology as either primary or adjunctive modalities of therapy have failed in enhancing overall survival. Recent studies have shed light on the many facets of genetic instability that drive tumor heterogeneity and evolutionary change within an individual’s tumor that often leads to therapeutic resistance. Chemotherapeutic regimens largely focused on cell cycle inhibition are ineffective and outdated. Faced with dismal outcomes for high grade tumors, the implications for personalized medicine that targets the unique molecular landscape and genetic vulnerabilities of each person’s specific disease becomes paramount. We provide an overview of our institution’s preliminary experience with a patient-specific precision medicine algorithm offered to patients with central nervous system (CNS) tumors. We reviewed the logistics and coordination required for tissue procurement in the operating room to subsequent DNA extraction and whole exome sequencing (WES) culminating with a precision medicine report being generated for each patient. Germline analyses were also performed. Patient WES data is then analyzed for functional relevance using big data portals such as CBIOPORTAL. We report the successful coordination of our precision medicine algorithm for n=30 patients with reports being disseminated to treating neuro-oncology teams. WES data is ultimately presented at the multi-disciplinary precision medicine tumor board on a bi-weekly basis. The reporting mechanism time interval from initial receipt of all materials necessary for WES is roughly 6-8 weeks. Roughly 20% of somatic alterations detected from WES sequencing have yielded molecular targets that may have specificity for FDA approved compounds. We strongly encourage patients to enroll in our precision medicine pathway. The WES platform capture reads for over 20,000 genes and offers a unique data set that may shed light on both known cancer relevant somatic alterations but also functional relevance for less known mutations on a case-specific basis.