Abstract 2061: Extended adjuvant temozolomide improves survival in a glioblastoma mouse model

Abstract

Abstract Glioblastoma (GBM) represents the most aggressive malignant primary brain tumor. Temozolomide (TMZ) is a standard of care for newly diagnosed GBM patients in conjunction with ionizing radiation (IR) or as an adjuvant agent. Yet the prognosis of GBM remains devastating with a median survival of 14 months. We investigated whether extended TMZ treatment cycles would provide survival benefit for GBM patients. To recapitulate the genomic and pathological heterogeneity found in GBM patients, we utilized patient derived xenograft (PDX) mouse models. We demonstrated that the combination of TMZ and IR prevents tumor progression, but tumors ultimately recur and lead to death. Overall survival was prolonged when adjuvant TMZ treatment was administered with minimal toxicity. Additionally, development of resistance to TMZ and IR was often correlated with an increase in levels of MGMT protein, irrespective of the promoter methylation status. Moreover, we demonstrate the utility of a voxel-based MRI biomarker, the functional diffusion map (fDM), as an imaging surrogate to detect spatially varying changes in tumor response, as well as a more sensitive predictor of overall response versus whole-volume tumor measurements. The fDM biomarker was also useful as an early predictor of impeding resistance to TMZ and IR. In summary, we demonstrate that prolonged TMZ treatment should be considered for the treatment of GBM patients. Furthermore, MRI based imaging allows early prediction of therapy response as well as impeding resistance. Citation Format: Hanxiao Wang, Wajd Al-Holou, Kevin Heist, Craig J. Galbán, Ana C. deCarvalho, Tom Mikkelsen, Brian D. Ross, Alnawaz Rehemtulla. Extended adjuvant temozolomide improves survival in a glioblastoma mouse model. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2061. doi:10.1158/1538-7445.AM2014-2061