P17.56 A 3-DIMENSIONAL MATRIX ASSAY TO HELP PREDICT TREATMENT RESPONSE TO TEMOZOLOMIDE IN PATIENTS WITH GLIOBASTOMA: UPDATE OF RESULTS AND SUBGROUP ANALYSIS OF PATIENTS UNDERGOING MGMT TESTING

INTRODUCTION: Usual treatment for glioblastoma is surgical resection, if possible, followed by radiotherapy with adjuvant chemotherapy using temozolomide. However a significant number of patients have a short response to temozolomide and subsequently a poorer prognosis. We investigated the possibility that surgical specimens obtained at the time of surgery might provide valuable information regarding sensitivity to chemotherapies, including temozolomide. In order to do this we used a 3-dimensional matrix assay that mimics brain. We analyzed a subgroup of these patients for O-6-methylguanine-DNA methyltransferase (MGMT) status and correlated this with the response of tumor tissue in the assay to temozolomide. METHODS: Records for patients treated for newly diagnosed or recurrent glioblastoma were analyzed. All patients had undergone surgical resection and tumor specimens at time of surgery were available for culture in a 3-dimensional matrix assay and observed for growth and invasion. Drug effects on mean invasion and growth were expressed as a ratio relative to control conditions. Length of survival was compared between temozolomide treated patients whose screening results had predicted a positive or negative response to temozolomide. The MGMT status of a subgroup of these patients was analyzed and correlated with the response of tumor tissue in the assay to temozolomide. RESULTS: Fifty-eight patients with glioblastoma were assessed. Each patient's tumor displayed a unique invasion and response profile. We looked in particular at the correlation between the outcome of a patient with glioblastoma treated with temozolomide and the response of that patient's tumor tissue to temozolomide in the 3-dimensional assay. Mean survival time for patients whose tumors were not significantly sensitive to temozolomide in the assay was 181.7 +/- 43 days. Mean survival time for patients whose tumors were significantly sensitive to temozolomide in the assay was 290.0 +/- 33 days. Twelve patients underwent MGMT testing. In 10 of the 12 patients there was a correlation between tumor response in the assay and MGMT status. CONCLUSION: The 3-dimensional assay may help predict glioblastoma patients who will show a treatment response to temozolomide. There appears to be a positive correlation between the response profiles in the assay to the MGMT status of the patient's tumor.