Administration of ineffective anticancer therapy is associated with unnecessary toxicity and development of resistant clones. Cancer stem-like cells (CSLCs) resist chemotherapy, thereby causing relapse of the disease. Thus, development of a test that identifies the most effective chemotherapy management offers great promise for individualized anticancer treatments. We have developed an ex vivo chemotherapy sensitivity assay (ChemoID), which measures the sensitivity of CSLCs as well as the bulk of tumor cells to a variety of chemotherapy agents. Two patients, a 21-year old male (patient 1) and a 5-month female (patient 2), affected by anaplastic WHO grade-III ependymoma were screened using the ChemoID assay. Patient 1 was found sensitive to the combination of irinotecan and bevacizumab, which resulted in a prolonged disease progression free period of 18 months. Following recurrence, the combination of various chemotherapy drugs was tested again with the ChemoID assay. We found that benzyl isothiocyanate (BITC) greatly increased the chemosensitivity of the ependymoma cells to the combination of irinotecan and bevacizumab. After patient 1 was treated for two months with irinotecan, bevacizumab and supplements of cruciferous vegetable extracts containing BITC, we observed over 50% tumoral regression in comparison with pre-ChemoID scan as evidenced by MRI. Patient 2 was found resistant to all treatments tested and following 6 cycles of vincristine, carboplatin, cyclophosphamide, etoposide, and cisplatin in various combinations, the tumor of this patient rapidly progressed and proton beam therapy was recommended. As expected animal studies conducted with patient derived xenografts treated with ChemoID screened drugs recapitulated the clinical observation. This assay demonstrates that patients with the same histological stage and grade of cancer may vary considerably in their clinical response, suggesting that ChemoID testing which measures the sensitivity of CSLCs as well as the bulk of tumor cells to a variety of chemotherapy agents could lead to more effective and personalized anticancer treatments in the future.

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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.

e13040 Background: Cancer stem-like cells (CSLCs) 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 individualized anticancer treatments. Methods: We have developed ChemoID, an in vitro chemotherapy assay, designed to predict the sensitivity and resistance of a given patient’s CSLCs and bulk of tumor cells to a variety of chemotherapy agents. Results: A 5-month female (Patient A), and a 21-year old male (Patient B), both affected by anaplastic WHO grade 3 ependymoma were screened using the ChemoID assay. A range of concentrations flanking the clinical doses for vincristine, carboplatin, cyclophosphamide, etoposide, cisplatin, methotrexate, cytosine arabinoside, oxaliplatin, irinotecan, avastin, procarbazine, lomustine, and busulfan were tested. The CSLCs and bulk of tumor ependymoma cells of Patient A were found moderately sensitive (30% cell kill) to only cisplatin and procarbazine, both as single agents and in combination. Following 6 cycles of vincristine, carboplatin, cyclophosphamide, etoposide, and cisplatin in various combinations, Patient A rapidly progressed and proton beam therapy was recommended. The CSLCs and bulk of tumor ependymoma cells of Patient B were found highly sensitive (80% cell kill) to the combination of irinotecan and avastin, which resulted in 18 months free of disease progression. After recurrence, chemotherapies were tested in combination with benzyl-isothiocyanate (BITC), a bioactive natural food component contained in extracts from cruciferous vegetables. BITC greatly increased the chemosensitivity in Patient B to the combination of irinotecan and avastin, resulting in average 90% CSLCs and bulk of tumor ependymoma cell eradication. MRI scan of Patient B showed over 50% tumor regression after two months of treatment with a combination of irinotecan, avastin, and supplements containing BITC. Conclusions: Our findings suggest that no patients are alike in their chemotherapy response. ChemoID assay that measures cell death of CSLCs and bulk of tumor cells from patient biopsies to standard chemotherapy agents in vitro is a feasible approach to personalized anticancer treatments.