ChemoID assay for anaplastic spinal ependymoma.

Abstract

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.