DEPARTMENT OF DEFENSE - CONGRESSIONALLY DIRECTED MEDICAL RESEARCH PROGRAMS

Magnetic Resonance Spectroscopy: An Objective Technique for the Quantification of Prostate Cancer Pathologies

Principal Investigator: CHENG, LEO L
Institution Receiving Award: MASSACHUSETTS GENERAL HOSPITAL
Program: PCRP
Proposal Number: PC030840
Award Number: W81XWH-04-1-0190
Funding Mechanism: Idea Development Award
Partnering Awards:
Award Amount: $648,750.00


PUBLIC ABSTRACT

Due to recent public awareness campaigns and improved detection procedures, particularly in screening examinations and prostate specific antigen (PSA) tests, prostate cancer has become the most commonly diagnosed cancer in American males, especially among African American males. At present, it is the second leading cause of cancer death among men, although most frequently (more than 70%) tumors are diagnosed as moderately malignant with Gleason scores (GS) of 5, 6, and 7 in a 2 to 10 scale. This broad group of tumors follows two distinct courses: one life-threatening if untreated, the other indolent for the duration of a patient's life. Unfortunately, currently available pathological techniques primarily evaluate structural changes in prostate tissue cells and cannot determine the aggressive potential of a tumor. As a result, many patients whose tumors likely present no threat to life endure radical local treatments (prostatectomy and radiation therapy) and attendant risks, such as incontinence and/or impotence, with a subsequently compromised quality of life, while other patients whose tumors are life-threatening may risk death with delayed treatment. This gap in knowledge poses an intolerable dilemma. It is imperative to find a means of predicting tumor aggressiveness to assist clinicians in determining prognosis and appropriate treatment options for individual prostate cancer patients.

In response to the limits of current pathological evaluation, we here propose to use a specialized magnetic resonance spectroscopy (MRS) technique, namely HRMAS 1HMRS, as a diagnostic modality. This method is nondestructive and sensitive to the subtle, cellular changes in metabolism that are known to accompany tumor development and progression and likely to precede visible cellular architectural changes and hence may identify tumor biological behavior invisible with pathology. The HRMAS 1HMRS technique makes use of unaltered tissue specimens. It is rapid (less than 20 minutes), not labor-intensive, independent of the skill and experience of the observer, and objective. Analysis is carried out within a magnetic field and pulsed with radio frequency (RF) current. The chemical metabolites in tissue respond to the energy pulses, resulting in a frequency spectrum, with different chemical metabolites absorbing energy at distinct frequencies.

In this study, we plan to quantify prostate cancer with both HRMAS 1HMRS and histopathology in order to define metabolic markers that can distinguish cancer from normal tissue, as well as provide biological distinctions among the less understood GS 5, 6, and 7 tumors. We expect to recruit 180-200 tumor cases in the study, among them 80-100 surgical samples will be obtained from African American patients. Since the project will work with tissue specimens that have already been surgically removed, there will be no additional risks to the study participants. By working closely with currently accepted pathology criteria, at the end of this proposed project, we will establish the basis for a new, improved grading system for GS 5, 6, and 7 tumors based on metabolic profiles obtained by HRMAS 1HMRS, as well as test the sensitivity of this new grading system in reflecting the high disease occurrence among African Americans. Our goal is to develop this tool for easy use in the prostate cancer clinic to help determine the most appropriate strategy for protecting both life and quality of life for individual patients.