Abstract
INTRODUCTION: Glioblastoma Multiforme (GBM) is the most common and lethal primary adult brain tumor, with significant variability in therapeutic response due to its underlying molecular and pathological heterogeneity. This study investigated the prognostic and predictive value of an established explant assay of surgical specimens of gliomas in response to the clinically relevant chemotherapy temozolomide (TMZ). METHODS: One hundred and thirty-eight patients with pathologically-verified gliomas and ongoing follow-up of clinical outcomes were included in the study. Tumor specimens at the time of resection were plated onto a collagen matrix with and without TMZ. Using video microscopy, the migratory distance of the cells was quantified over 5 days. RESULTS: One hundred and eleven viable explant assays were collected in glioma patients including 65 GBMs, 19 anaplastic, 13 grade II and 14 recurrent high grade glioma. GBMs showed increased invasiveness compared to anaplastic and grade II gliomas on the assay. Glioma patients whose tumors showed a greater invasive distance on the assay had reduced overall survival. Inhibition of invasion by 20% by TMZ on the explant assay predicted the time to recurrence after TMZ treatment and the overall survival of GBM patients. CONCLUSION: This study demonstrates that an explant assay of surgical specimens of gliomas, by reproducing the in vivo environment, can predict overall survival of gliomas patients and response to temozolomide. Investigations are ongoing to determine whether response on the assay is of predictive value beyond genetic markers including MGMT and IDH1.
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