Alan Pollack, M.D., Ph.D.
Professor and Chair, Department of Radiation Oncology
Description of Research
Dr. Pollack’s research centers on Genitourinary (GU) malignancies with an emphasis on prostate cancer. On the clinical side, Dr. Pollack has been, and continues to be, involved in a number of Phase III trials that have dealt with contemporary radiotherapy questions related to dose, fractionation and the concomitant use of androgen deprivation. He was the principal investigator (PI) on a Phase III trial that compared radiotherapy at 70 Gy to 78 Gy (N=300). The study was completed in 1998 and showed improved freedom from biochemical failure rates at the higher radiation dose (1, 2). This trial has had a major impact on the standard of care for the treatment of prostate cancer with radiotherapy.
Dr. Pollack is the PI on a follow-up Phase III study examining the efficacy of hypofractionation, which completed accrual (N=307) in 2006. A comparison was made between 76 Gy in 2 Gy fractions and 70.2 Gy in 2.7 Gy fractions; the latter hypofractionation scheme was hypothesized to give the equivalent biologically of 84.4 Gy based on data from a number of investigators, suggesting that the &alpha/&beta ratio for prostate cancer is low and that this strategy would result in lower doses biologically to the surrounding normal tissues. There are a number of secondary endpoints involving procurement of quality-of-life data and biosamples (blood and urine), that have been obtained at various time points after the completion of treatment. In addition, pretreatment diagnostic tissue has been analyzed prospectively for a series of biomarkers (described below), and post-treatment biopsies of the prostate have been obtained at two to three years to ensure tumor eradication. These ancillary studies will result in unique data that will supplement the primary endpoint (biochemical failure) results. We are currently analyzing the findings from the hypofractionation trial and have developed a concept for a follow-up study.
Dr. Pollack is also the PI on a national Phase III clinical trial being run by the Radiation Therapy Oncology Group (RTOG 0534), which compares prostate bed RT alone, prostate bed RT+STAD and whole pelvis/prostate bed R+STAD in men with a rising PSA after prostatectomy for prostate cancer.
Biomarker Studies: Pre-treatment diagnostic prostate biopsy tissue has been analyzed for a series of biomarkers related to the apoptotic pathways. The biomarkers analyzed include Ki-67 (3), p53, MDM2 (4), p16, bcl-2/bax (5, 6), Cox-2 (7) and PKA (8). These markers have been analyzed individually in terms of the ability to predict outcome in two RTOG clinical trials (RTOG 86-10 and 92-02) that had tissue available. RTOG 86-10 compared radiotherapy (RT) alone at standard doses to RT alone + short term androgen deprivation (STAD) therapy. RTOG 92-02 compared RT + STAD to RT plus long-term androgen deprivation (LTAD) therapy. The first seven of these markers are being incorporated into a biomarker-based model that also includes pretreatment PSA, Gleason score, T-category and protocol assigned treatment. Four of the biomarkers have proven valuable in addition to the other factors in predicting the 10-year distant metastasis rate. The goal is to validate the model in another patient population with similar features using cases from RTOG 94-13.
Biologic/Small Molecule Targeted Therapy: The overriding goal is to identify agents that sensitize prostate cancer cells to RT, androgen deprivation and the combination of RT+AD; and to bring these agents to clinical trials. Dr. Pollack’s laboratory has studied a number of constructs, such as adenoviral-p53 (9), adenoviral-E2F1 (10), antisense-MDM2 (11-13), antisense-bcl-2 (14) and antisense-PKA type I.
- Principal investigator on a randomized trial that set a new standard for radiotherapy dose escalation for prostate cancer
- Identified biomarkers in the apoptotic pathways that show promise in a novel model of the 10-year risk of distant metastasis
- Developed gene therapy strategies in preclinical models that enhance tumor cell killing in vitro and in vivo to radiation and androgen deprivation
Selected Cancer-Related Publications
- Zhang M, Ho A, Hammond EH, Suzuki Y, Bermudez RS, Lee RJ, Pilepich M, Shipley WU, Sandler H, Khor LY, Pollack A, Chakravarti A. Prognostic Value of Survivin in Locally Advanced Prostate Cancer: Study Based on RTOG 8610. Int J Radiat Oncol Biol Phys 73:1033-42, 2009. Read more »
- Konski A, Movsas B, Konopka M, Ma C, Price R, Pollack A. Developing a radiation error scoring system to monitor quality control events in a radiation oncology department. J Am Coll Radiol 6:45-50, 2009. Read more »
- Pollack A, Bae K, Khor LY, Al-Saleem T, Hammond ME, Venkatesan V, Byhardt RW, Asbell SO, Shipley WU, Sandler HM. The importance of protein kinase A in prostate cancer: relationship to patient outcome in Radiation Therapy Oncology Group trial 92-02. Clin Cancer Res 15:5478-84,2009. Read more »
- Khor LY, Bae K, Paulus R, Al-Saleem T, Hammond ME, Grignon DJ, Che M, Venkatesan V, Byhardt RW, Rotman M, Hanks GE, Sandler HM, Pollack A. MDM2 and Ki-67 Predict for Distant Metastasis and Mortality in Men Treated With Radiotherapy and Androgen Deprivation for Prostate Cancer: RTOG 92-02. J Clin Oncol 27:3177-84, 2009. Read more »
- Michalski JM, Roach M 3rd, Merrick G, Anscher MS, Beyer DC, Lawton CA, Lee WR, Pollack A, Rosenthal SA, Vijayakumar S, Carroll PR. ACR Appropriateness Criteria (R) on External Beam Radiation Therapy Treatment Planning for Clinically Localized Prostate Cancer Expert Panel on Radiation Oncology-Prostate. Int J Radiat Oncol Biol Phys 74:667-672, 2009. Read more »
- Roach M 3rd, Waldman F, Pollack A. Predictive models in external beam radiotherapy for clinically localized prostate cancer. Cancer 115:3112-20, 2009. Read more »
- Abdel-Wahab M, Pollack A. Radiotherapy: encouraging early data for SBRT in prostate cancer. Nat Rev Urol 6:478-9,2009. Read more »
Leader of the Multidisciplinary Research Program: Genitourinary Malignancies Program