The objective of this project is to integrate metabolic and physiologic MR imaging data into the clinical management of patients with newly diagnosed glioblastoma multiforme (GBM) who are being treated with combined radiation, chemo and antiangiogenic therapy. Our current studies have provided strong evidence that Magnetic Resonance Spectroscopic Imaging (MRSI), Perfusion Weighted imaging (PWI) and Diffusion Weighted Imaging (DWI) produce information concerning the biological behavior of such lesions that is likely to be valuable for clinical decision making. We propose to explore the impact of these imaging methods with respect to quantifying changes in imaging parameters and assessing therapeutic response in patients treated with concurrent Enzastaurin, Temozolomide and Radiation Therapy (ETRT), a therapeutic strategy that combines cytotoxic and antiangiogenic approaches. The first area that is of interest is to validate the biological interpretation of selected imaging variables presumed to be representative surrogates for tumor extent, heterogeneity, and therapeutic responsiveness, as well as prognostic significance with respect to survival. The second area of interest is in evaluating imaging characteristics prior to ETRT and their short and longer term changes that occur as a result of ETRT in order to quantify and assess treatment response. Previous studies have not utilized state of the art metabolic and physiologic imaging methods to select patients, to identify microscopic disease and heterogeneity or to evaluate response to therapy. We believe that it is critical to determine whether this approach is feasible and to obtain evidence that would help in deciding how to best integrate such information into future clinical trials.
Specific Aim 1 will provide direct correlation between specific in vivo imaging and tissue characteristics by immunohistochemical and ex vivo NMR spectroscopy of image guided surgical samples from patients with newly diagnosed GBM. This will establish the link between in vivo and ex vivo MR parameters and biological behavior as defined by molecular morphology.
Specific Aim 2 will analyze the characteristics of GBM in patients who are participating in an institutional Phase II clinical trial of ETRT. It will examine the relationship between pre-ETRT MR parameters and subsequent imaging changes at multiple time points up to 6 months after completion of RT. While the focus of this proposal is on one specific clinical trial, the knowledge that will be gained has broad implications for selecting and designing many other types of antiangiogenic and molecularly targeted therapies and is likely to enhance the non-invasive imaging based interpretation of treatment response, change the definition of tumor burden in patients with GBM as well as improve patient selection for future clinical trials.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA127612-04
Application #
8020016
Study Section
Cancer Biomarkers Study Section (CBSS)
Program Officer
Henderson, Lori A
Project Start
2008-04-28
Project End
2013-01-31
Budget Start
2011-02-01
Budget End
2012-01-31
Support Year
4
Fiscal Year
2011
Total Cost
$382,605
Indirect Cost
Name
University of California San Francisco
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Lupo, Janine M; Molinaro, Annette M; Essock-Burns, Emma et al. (2016) The effects of anti-angiogenic therapy on the formation of radiation-induced microbleeds in normal brain tissue of patients with glioma. Neuro Oncol 18:87-95
Akassoglou, Katerina; Agalliu, Dritan; Chang, Christopher J et al. (2016) Neurovascular and Immuno-Imaging: From Mechanisms to Therapies. Proceedings of the Inaugural Symposium. Front Neurosci 10:46
Nelson, Sarah J; Li, Yan; Lupo, Janine M et al. (2016) Serial analysis of 3D H-1 MRSI for patients with newly diagnosed GBM treated with combination therapy that includes bevacizumab. J Neurooncol 130:171-179
Wen, Qiuting; Jalilian, Laleh; Lupo, Janine M et al. (2015) Comparison of ADC metrics and their association with outcome for patients with newly diagnosed glioblastoma being treated with radiation therapy, temozolomide, erlotinib and bevacizumab. J Neurooncol 121:331-9
Li, Yan; Park, Ilwoo; Nelson, Sarah J (2015) Imaging tumor metabolism using in vivo magnetic resonance spectroscopy. Cancer J 21:123-8
Li, Yan; Larson, Peder; Chen, Albert P et al. (2015) Short-echo three-dimensional H-1 MR spectroscopic imaging of patients with glioma at 7 Tesla for characterization of differences in metabolite levels. J Magn Reson Imaging 41:1332-41
Elkhaled, Adam; Jalbert, Llewellyn; Constantin, Alexandra et al. (2014) Characterization of metabolites in infiltrating gliomas using ex vivo ¹H high-resolution magic angle spinning spectroscopy. NMR Biomed 27:578-93
Lupo, Janine M; Nelson, Sarah J (2014) Advanced magnetic resonance imaging methods for planning and monitoring radiation therapy in patients with high-grade glioma. Semin Radiat Oncol 24:248-58
Essock-Burns, Emma; Phillips, Joanna J; Molinaro, Annette M et al. (2013) Comparison of DSC-MRI post-processing techniques in predicting microvascular histopathology in patients newly diagnosed with GBM. J Magn Reson Imaging 38:388-400
Ozhinsky, Eugene; Vigneron, Daniel B; Chang, Susan M et al. (2013) Automated prescription of oblique brain 3D magnetic resonance spectroscopic imaging. Magn Reson Med 69:920-30

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