Abstract

e13544 Background: We have developed a drug response assay (ChemoID) that identifies effective chemotherapy against cancer stem cells (CSCs) vs. bulk of tumor cells from of a panel of potential treatments. A prospective study was conducted evaluating the use of the CSC drug response assay in glioblastoma patients treated with standard-of-care. Methods: 41 glioblastoma patients were enrolled in an IRB-approved protocol. Patients were all treated with standard-of-care TMZ plus radiation with or without maximal surgery. Patients were prospectively monitored for tumor response, time to recurrence, progression-free survival (PFS), and overall survival (OS). Results: For every 5% increase in in-vitro CSC cell kill by TMZ, 12-month patient response (non-recurrence of cancer) increased 2-fold, OR=2.2 (p=0.016). Similar associations with the bulk tumor test were seen, OR=2.75 (p=0.07) for each 5% bulk tumor cell kill by TMZ. Combining CSC and bulk tumor assay results in a single model yielded a statistically supported CSC association, OR=2.36 (p=0.036) but a much attenuated remaining bulk tumor association, OR=1.46 (p=0.472). Areas under the curve (AUC) and [sensitivity/specificity] at optimal outpoints (>40% CSC cell kill and >55% bulk tumor cell kill) were AUC=0.989 [Sens=100/Spec=97], 0.972 [100/89] and 0.989 [100/97] for the CSC only, bulk tumor only, and combined models, respectively. Risk categorization of patients was improved by 11% when using the CSC test in conjunction with the bulk test (risk reclassification non-event NRI and overall NRI = 0.111, p=0.030). Median recurrence time was 20 months for patients with a positive (>40% cell kill) CSC test versus only 3 months with a negative CSC test, whereas median recurrence time was 13 months versus 4 months for patients with a positive (>55% cell kill) bulk test versus negative. Similar favorable results for the CSC test were observed for PFS and OS. Results across 14 potential other treatments indicated that 34/41 (83%) and 27/41 (66%) potentially more optimal alternative therapies may have been chosen using CSC results and Bulk results, respectively. Conclusions: The ChemoID assay has the potential to increase the accuracy of bulk tumor assays.

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