DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

MRI-Derived Cellularity Index as a Potential Noninvasive Imaging Biomarker of Prostate Cancer

Principal Investigator: KAROW, DAVID
Institution Receiving Award: CALIFORNIA, UNIVERSITY OF, SAN DIEGO
Program: PCRP
Proposal Number: PC120532
Award Number: W81XWH-13-1-0391
Funding Mechanism: Idea Development Award-New Investigator Option
Partnering Awards:
Award Amount: $348,750.00


PUBLIC ABSTRACT

Recently, enhanced imaging techniques have been utilized to identify glioblastoma multiforme (GBM) brain tumors. The output from these techniques has been termed the tumor "cellularity" index (CI) and provides significantly greater accuracy in distinguishing brain tumor from normal tissue than traditional imaging measures. The CI tumor signal was noted to be 10-fold greater than conventional imaging measures.

Increasing Gleason score correlates with loss of normal gland formation, loss of peripheral gland tubular structure, and increased cellularity. Therefore, we make the following hypothesis: CI will correlate with higher tumor grade based on Gleason score and will provide significantly greater accuracy in discriminating aggressive tumor from benign and indolent lesions when compared to current imaging techniques.

Based on its prior ability to discriminate between brain tumors and adjacent normal tissue with high accuracy and high signal to noise, we hypothesize that the CI will perform similarly in prostate tissue. We propose a non-invasive (without endorectal coil or IV contrast), rapid imaging test based on these procedures. Our goal in this proposal is to test whether that objective is feasible.

Impact: (1) Potentially permit a low-cost, accurate, rapid (15 minutes) non-invasive screening test. (2) We imagine a yearly screening test similar to a mammogram, whereby a patient would undergo a brief, noninvasive imaging test yielding accurate noninvasive information about a person's likelihood of cancer. (3) Our proposed techniques could be used to appropriately triage men to active surveillance, US/MR targeted biopsies and/or focal therapy while minimizing overtreatment and associated complications such as impotence and incontinence. (4) An imaging biomarker with a strong signal such as the one proposed may be translated into guidance of targeted biopsies and targeted therapies. A recent study showed that targeted therapy using MR-guidance achieved the trifecta of a disease free phenotype at 1 year without incontinence or impotence in 90% of their examined patients. These procedures could make such interventions more focal and complication-free. (5) These techniques could also prove relevant for the early detection of other solid organs tumors.

Ultimately, this proposed imaging test could be used to screen all males above a certain age who are at risk for prostate cancer. The benefit of a rapid, non-invasive imaging screening test is as follows: Early detection of prostate cancer with more options for conservative management including watchful waiting or more aggressive therapy including prostatectomy and regional treatment. If successful, this study will validate the feasibility of such a test; future studies will need to determine the precise efficacy in large populations.