? This is a renewal of a very successful project in which we have demonstrated that 3D MRSI data provided valuable information prostate cancer patients receiving External Beam Radiation Therapy (EBRT) and Brachytherapy. For patients that were scanned prior to therapy, we observed that the degree and spatial extent of elevated choline, reduced citrate and reduced polyamine correlated with pathologic tumor volume and grade, and that these parameters predicted short-term (_<1yr) response to therapy. For patients that were followed after therapy, we demonstrated that it was possible to detect the presence of biopsy proven prostate cancer after therapy based on elevated choline to creatine ratios and that """"""""metabolic atrophy"""""""" occurred earlier than reductions in PSA. Of particular interest were the differences in the time course of changes in metabolite levels that we observed for EBRT versus Brachytherapy. The motivation for this project is to obtain longer follow-up and to study a larger patient population that is stratified for both risk and type of treatment. These are important issues because treatment failure normally occurs 3 to 10 years after radiation therapy and because there is considerable variability in the time course of response to therapy. This renewal will be a prospective MRI/MRSI study of patients prior to and serially after EBRT and Brachytherapy (HDR and PPI) in order to determine the prognostic value of the degree and spatial extent of the metabolic abnormalities. It will also test the hypotheses that; """"""""metabolic atrophy"""""""" and elevated choline-to-creatine are early predictors of therapeutic outcome and that there are radiation dose dependent differences in the time course of metabolic response for EBRT versus Brachytherapy. Finally, ex-vivo HRMAS spectroscopy will be applied to biopsy samples of patients with biochemical failure to better define the metabolic profile of residual/recurrent cancer and its relationship with cellular proliferation and apoptosis. This is a translational project intended to provide new biochemical information about prostate cancer before and after radiation therapy and to aid in the translation of this technology into clinical practice. ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA079980-10
Application #
7459719
Study Section
Diagnostic Radiology Study Section (RNM)
Program Officer
Deye, James
Project Start
1999-02-05
Project End
2010-06-30
Budget Start
2008-07-01
Budget End
2010-06-30
Support Year
10
Fiscal Year
2008
Total Cost
$294,482
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
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Westphalen, Antonio C; Coakley, Fergus V; Roach 3rd, Mack et al. (2010) Locally recurrent prostate cancer after external beam radiation therapy: diagnostic performance of 1.5-T endorectal MR imaging and MR spectroscopic imaging for detection. Radiology 256:485-92
Joseph, Tim; McKenna, David A; Westphalen, Antonio C et al. (2009) Pretreatment endorectal magnetic resonance imaging and magnetic resonance spectroscopic imaging features of prostate cancer as predictors of response to external beam radiotherapy. Int J Radiat Oncol Biol Phys 73:665-71
Westphalen, Antonio C; Kurhanewicz, John; Cunha, Rui M G et al. (2009) T2-Weighted endorectal magnetic resonance imaging of prostate cancer after external beam radiation therapy. Int Braz J Urol 35:171-80; discussion 181-2
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Kim, Yongbok; Hsu, I-Chow J; Lessard, Etienne et al. (2008) Class solution in inverse planned HDR prostate brachytherapy for dose escalation of DIL defined by combined MRI/MRSI. Radiother Oncol 88:148-55
Kurhanewicz, John; Vigneron, Daniel B (2008) Advances in MR spectroscopy of the prostate. Magn Reson Imaging Clin N Am 16:697-710, ix-x
Westphalen, Antonio C; Coakley, Fergus V; Qayyum, Aliya et al. (2008) Peripheral zone prostate cancer: accuracy of different interpretative approaches with MR and MR spectroscopic imaging. Radiology 246:177-84
Noworolski, Susan Moyher; Vigneron, Daniel B; Chen, Albert P et al. (2008) Dynamic contrast-enhanced MRI and MR diffusion imaging to distinguish between glandular and stromal prostatic tissues. Magn Reson Imaging 26:1071-80
Hom, Jeffrey J; Coakley, Fergus V; Simko, Jeffry P et al. (2007) High-grade prostatic intraepithelial neoplasia in patients with prostate cancer: MR and MR spectroscopic imaging features--initial experience. Radiology 242:483-9

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