STEM-21. CLINICAL RELEVANCE OF CANCER STEM CELL CYTOTOXICITY ASSAY IN GUIDING TREATMENT FOR GLIOBLASTOMA

Abstract

Abstract BACKGROUND. The prognosis of glioblastoma (GBM) treated with standard-of-care regimens remains very poor with a median time to recurrence of 7-9 months, and a median survival of 15-18 months. GBMs contain a small, but resilient population of cancer stem cells (CSCs) that contribute to tumor initiation, maintenance, and therapy resistance. For these reasons, its is extremely important to determine the sensitivity of CSCs to chemotherapeutic agents, with the intent of identifying more effective treatment protocols which would then translate into improved clinical survival. METHODS. We have used a novel CLIA and CAP-accredited Cancer Stem Cell Cytotoxicity Assay (ChemoID) to guide treatment for 55 Grade III and Grade IV glioma patients with the most efficacious chemotherapy treatments from a panel of FDA approved drugs or their combinations. Patients were evaluated by MRI scans and response was assessed according to RANO criteria. RESULTS: We report here a prospective clinical investigation using the ChemoID assay to measure the sensitivity and resistance of CSCs and bulk of tumor cells cultured from 55 GBM clinical specimens challenged with several chemotherapy agents, which were also correlated to the clinical response of the treated patients, independently of other biomarkers. The median recurrence time was 15 months for patients with a sensitive (>40% cell kill) CSCs test versus only 6 months for patients with a resistant CSCs test. CONCLUSIONS. The data suggests that GBM patients treated with CSC Cytotoxicity Assay-guided responsive drugs have delayed time to recurrence and the assay has the potential to help tailor chemotherapy choices to improve clinical outcomes.