DW-MRI as a biomarker to compare therapeutic outcomes in radiotherapy regimens incorporating temozolomide or gemcitabine in glioblastoma |
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Authors: | Galbán Stefanie Lemasson Benjamin Williams Terence M Li Fei Heist Kevin A Johnson Timothy D Leopold Judith S Chenevert Thomas L Lawrence Theodore S Rehemtulla Alnawaz Mikkelsen Tom Holland Eric C Galbán Craig J Ross Brian D |
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Institution: | Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, United States of America. |
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Abstract: | The effectiveness of the radiosensitizer gemcitabine (GEM) was evaluated in a mouse glioma along with the imaging biomarker diffusion-weighted magnetic resonance imaging (DW-MRI) for early detection of treatment effects. A genetically engineered murine GBM model Ink4a-Arf(-/-) Pten(loxP/loxP)/Ntv-a RCAS/PDGF(+)/Cre(+)] was treated with gemcitabine (GEM), temozolomide (TMZ) +/- ionizing radiation (IR). Therapeutic efficacy was quantified by contrast-enhanced MRI and DW-MRI for growth rate and tumor cellularity, respectively. Mice treated with GEM, TMZ and radiation showed a significant reduction in growth rates as early as three days post-treatment initiation. Both combination treatments (GEM/IR and TMZ/IR) resulted in improved survival over single therapies. Tumor diffusion values increased prior to detectable changes in tumor volume growth rates following administration of therapies. Concomitant GEM/IR and TMZ/IR was active and well tolerated in this GBM model and similarly prolonged median survival of tumor bearing mice. DW-MRI provided early changes to radiosensitization treatment warranting evaluation of this imaging biomarker in clinical trials. |
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