Research Abstract
My research is focused on two levels. At the basic science level, I have independent funding to support work in two laboratories. One lab is investigating the effect that benign prostatic epithelial and stromal cells have on the growth of juxtaposed malignant prostatic epithelial cells. This work aims to explain an improved PSA failure survival that I noted in prostate cancer patients managed with RT or surgery who also had moderate benign prostatic hypertrophy. The second lab is dedicated to the synthesis of prostate specific antigen cleavable pro-drugs whose target is the androgen independent metastatic prostate cancer cell.
On the clinical research level, I am the principal investigator of a national phase II prospective trial which will determine ability of endorectal coil MRI to assess androgen responsiveness and outcome (cause-specific and overall survival) after external beam radiation therapy and androgen suppression therapy for prostate cancer. I am also the principal investigator of a phase III prospective randomized trial evaluating the impact on survival (cause-specific and overall) from the addition of androgen suppression therapy to external beam radiation therapy for localized prostate cancer. I have developed a staging system for clinically localized prostate cancer from retrospective data analysis of radiation and surgically managed patients and with others I am prospectively attempting to validate it. Other retrospective studies that I am leading include identification of the optimal patients for interstitial prostate brachytherapy, external beam plus interstitial prostate brachytherapy, and androgen suppression plus external beam and interstitial prostate brachytherapy. These studies will be the basis for patient selection for prospective trials assessing the relative efficacy of these treatments on cause-specific and overall survival.
I have developed a new way of delivering interstitial radiation therapy for select patients with prostate cancer. Using the magnetic resonance image guided system at the Brigham and Women's Hospital, dose distributions that optimize dose to the prostate while minimizing dose to normal surrounding and indwelling structures have been achieved through the use of real time imaging and dosimetry. Ongoing research projects include (i) outcomes testing (cancer control - PSA, cause specific and overall survival and quality of life [GI, GU, sexual] - using a prospectively validated instrument), (ii) dose escalation studies in the intra-prostatic endorectal coil MR signal abnormality consistent with tumor, and a prospective randomized trial comparing the results of MR and ultrasound guided brachytherapy for select patients with prostate cancer. Other planned applications of this MR image guided device include interstitial implantation for locally advanced cancers of the female gynecological tract.
Currently I have created an interdisciplinary team whose goals are first, to define the molecular markers that characterize the key steps involved in the pathogenesis of prostate cancer so that these events can become targets for experimental therapeutics. The second goal is to develop a molecular imaging methodology by combining endorectal coil MRI and optical imaging in conjunction with uniquely designed photosensitive contrast agents that are the substrates for the specific gene products of interest.
