DW-MRI as a biomarker to compare therapeutic outcomes in radiotherapy regimens incorporating temozolomide or gemcitabine in glioblastoma Journal Article
| Authors: | Galbán, S.; Lemasson, B.; Williams, T. M.; Li, F.; Heist, K. A.; Johnson, T. D.; Leopold, J. S.; Chenevert, T. L.; Lawrence, T. S.; Rehemtulla, A.; Mikkelsen, T.; Holland, E. C.; Galbán, C. J.; Ross, B. D. |
| Article Title: | DW-MRI as a biomarker to compare therapeutic outcomes in radiotherapy regimens incorporating temozolomide or gemcitabine in glioblastoma |
| 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. © 2012 Galbán et al. |
| Keywords: | cancer survival; treatment outcome; treatment response; multimodality cancer therapy; nonhuman; gemcitabine; cancer radiotherapy; temozolomide; outcome assessment; brain tumor; brain neoplasms; biological marker; biological markers; mouse; animal; animals; mice; animal tissue; dacarbazine; tumor volume; cell line; animal experiment; animal model; alkylating agent; drug effect; drug screening; pathology; drug screening assays, antitumor; radiation exposure; transgenic mouse; mice, transgenic; disease model; tumor burden; contrast enhancement; glioblastoma; antineoplastic agents, alkylating; drug derivative; neoplasms, experimental; ionizing radiation; clinical effectiveness; experimental neoplasm; kaplan meier method; tumor growth; deoxycytidine; radiosensitizing agent; radiation-sensitizing agents; diffusion weighted imaging; diffusion magnetic resonance imaging; radiosensitization; chemoradiotherapy; kaplan-meier estimate; oncological parameters; physical tolerance; tumor cellularity; tumor diffusion |
| Journal Title: | PLoS ONE |
| Volume: | 7 |
| Issue: | 4 |
| ISSN: | 1932-6203 |
| Publisher: | Public Library of Science |
| Date Published: | 2012-01-01 |
| Start Page: | e35857 |
| Language: | English |
| DOI: | 10.1371/journal.pone.0035857 |
| PROVIDER: | scopus |
| PMCID: | PMC3334987 |
| PUBMED: | 22536446 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 May 2012" - "Source: Scopus" |
