Chemopredictive assay for patients with primary brain tumors.

Abstract

2089 Background: Cancer stem-like cells (CSLCs) in primary brain tumors can resist certain chemotherapies, thereby causing relapse of the disease. Thus, development of a test that identifies the most effective chemotherapy management offers great promise for personalized anticancer treatments. Methods: We have developed an ex vivo ChemoID assay designed to predict the sensitivity and resistance of CSLCs and bulk of tumor cells of a given patient's solid tumor to a variety of chemotherapy agents by measuring the percentage of cell death. In a retrospective study of five patients with malignancies of the central nervous system, we assessed the correlation between the results of the ChemoID assay and clinical response. Two anaplastic WHO grade-III ependymomas, two IDH-1 negative WHO grade 4 glioblastomas, and one medulloblastoma were tested. Tumors were classified as responsive (50-100% cell kill), intermediately responsive (30-50% cell kill), and nonresponsive (0-30% cell kill) to chemotherapy. Treatment selection was blinded to assay results. MRI and CT scan determined response to therapy. Results: The ChemoID assay performed on the tumor bulk produced a correct prediction in 4 out of 5 cases (p = 0.4, Fisher's Exact Test; PPV = 75%, NPV = 100%) when compared to the drugs received. The same assay performed on the CSLCs produced a correct prediction in all 5 cases (p = 0.1, Fisher's Exact Test; PPV=NPV=100%). Conclusions: An assay such as ChemoID that measures cell death of CSLCs and bulk of tumor cells appears to be beneficial in selecting specific standard chemotherapy agents ex vivo for patients with malignancies of the central nervous system.

Treatment of unmethylated MGMT-promoter recurrent glioblastoma with cancer stem cell assay-guided chemotherapy and the impact on patients’ healthcare costs

“…Details regarding the CSCs cytotoxicity assay (ChemoID) procedure have been described previously. 11–15 In brief, recurrent GBM participants underwent surgical resection of the recurrent tumor and fresh tissue biopsy samples were collected in the operating room under sterile conditions and divided into 2 parts. One part of the biopsy was sent overnight via FedEx clinical pack in a sterile vial containing a transportation medium to the clinical-pathology laboratory at Cabell Huntington Hospital in West Virginia under physician order to perform the ChemoID assay under Clinical Laboratory Improvement Amendments (CLIA)-certified and College of American Pathologists.…”