Bio

Clinical Focus


  • Bladder Cancer
  • Radiation Oncology
  • Brachytherapy
  • Testicular Cancer
  • Radiotherapy, Image-Guided
  • Prostate Cancer
  • Radiotherapy, Intensity-Modulated
  • Stereotactic Body Radiotherapy
  • Cancer > Radiation Oncology

Academic Appointments


Administrative Appointments


  • Member, Genitourinary Committee, American Board of Radiology (2012 - Present)
  • Chair, Committee for Evidence-Based Brachytherapy, American Brachytherapy Society (2013 - Present)
  • Secretary, American Brachytherapy Society (2010 - 2011)
  • Treasurer, American Brachytherapy Society (2011 - 2013)
  • Vice-Chair, Emerging Technology Committee, American Society for Radiation Oncology (2011 - Present)
  • Editor, Brachytherapy (2013 - Present)
  • Associate Senior Editor, International Journal of Radiation Oncology, Biology, and Physics (2011 - Present)
  • Director, Genitourinary Cancers (2103 - Present)

Honors & Awards


  • RSNA Seed Grant, Radiological Society of North America Roentgen (RSNA) (2008)
  • Travel Grant to attend National Cancer Institute Radiation Research Program, American Society for Radiation Oncology (ASTRO) (2005)
  • Roentgen Resident/Fellow Research Award, Radiological Society of North America Roentgen (RSNA) (2003, 2005)
  • EXCEL Research Scholarship, Department of Physics, Lafayette College (1993)

Boards, Advisory Committees, Professional Organizations


  • Member, American Society of Radiation Oncology (ASTRO) (2001 - Present)
  • Member, American Brachytherapy Society (ABS) (2001 - Present)

Professional Education


  • Internship:St Barnabas Medical Center (2001) NJ
  • Board Certification: Radiation Oncology, American Board of Radiology (2006)
  • Residency:Fox Chase Cancer Center (2005) PA
  • Medical Education:UMDNJ-NJMS (2000) NJ

Community and International Work


  • Radiotherapy – Adjuvant vs Early Salvage

    Partnering Organization(s)

    Independent Data Monitoring Committee

    Ongoing Project

    No

    Opportunities for Student Involvement

    No

Research & Scholarship

Clinical Trials


  • Hormone Therapy, Radiation Therapy, and Steroid 17alpha-monooxygenase TAK-700 in Treating Patients With High-Risk Prostate Cancer Recruiting

    RATIONALE: Androgens can cause the growth of prostate cancer cells. Drugs, such as steroid 17alpha-monooxygenase TAK-700, when used with other hormone therapy, may lessen the amount of androgens made by the body. Radiation therapy uses high energy x rays to kill tumor cells. This may be an effective treatment for prostate cancer when combined with hormone therapy. Studying quality-of-life in patients having cancer treatment may help identify the intermediate- and long-term effects of treatment on patients with prostate cancer. PURPOSE: This randomized phase III trial is studying the use of hormone therapy, including TAK-700, together with radiation therapy in treating patients with prostate cancer.

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  • Prostate Radiation Therapy or Short-Term Androgen Deprivation Therapy and Pelvic Lymph Node Radiation Therapy With or Without Prostate Radiation Therapy in Treating Patients With a Rising Prostate Specific Antigen (PSA) After Surgery for Prostate Cancer Recruiting

    RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as flutamide, bicalutamide, and luteinizing hormone-releasing hormone agonist, may lessen the amount of androgens made by the body. It is not yet known which regimen of radiation therapy with or without androgen-deprivation therapy is more effective for prostate cancer. PURPOSE: This randomized phase III trial is studying prostate radiation therapy to see how well it works compared with short-term androgen deprivation therapy given together with pelvic lymph node radiation therapy with or without prostate radiation therapy in treating patients with a rising PSA after surgery for prostate cancer.

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  • Radiation Therapy With or Without Androgen-Deprivation Therapy in Treating Patients With Prostate Cancer Recruiting

    RATIONALE: Radiation therapy uses high-energy x-rays and other types of radiation to kill tumor cells and shrink tumors. Androgens can cause the growth of prostate cancer cells. Androgen-deprivation therapy may lessen the amount of androgens made by the body. It is not yet known whether radiation therapy is more effective with or without androgen-deprivation therapy in treating patients with prostate cancer. PURPOSE: This randomized phase III trial is studying radiation therapy to see how well it works compared with radiation therapy given together with androgen-deprivation therapy in treating patients with prostate cancer.

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Publications

Journal Articles


  • Randomized trial of hypofractionated external-beam radiotherapy for prostate cancer. Journal of clinical oncology Pollack, A., Walker, G., Horwitz, E. M., Price, R., Feigenberg, S., Konski, A. A., Stoyanova, R., Movsas, B., Greenberg, R. E., Uzzo, R. G., Ma, C., Buyyounouski, M. K. 2013; 31 (31): 3860-3868

    Abstract

    To determine if escalated radiation dose using hypofractionation significantly reduces biochemical and/or clinical disease failure (BCDF) in men treated primarily for prostate cancer.Between June 2002 and May 2006, men with favorable- to high-risk prostate cancer were randomly allocated to receive 76 Gy in 38 fractions at 2.0 Gy per fraction (conventional fractionation intensity-modulated radiation therapy [CIMRT]) versus 70.2 Gy in 26 fractions at 2.7 Gy per fraction (hypofractionated IMRT [HIMRT]); the latter was estimated to be equivalent to 84.4 Gy in 2.0 Gy fractions. High-risk patients received long-term androgen deprivation therapy (ADT), and some intermediate-risk patients received short-term ADT. The primary end point was the cumulative incidence of BCDF. Secondarily, toxicity was assessed.There were 303 assessable patients with a median follow-up of 68.4 months. No significant differences were seen between the treatment arms in terms of the distribution of patients by clinicopathologic or treatment-related (ADT use and length) factors. The 5-year rates of BCDF were 21.4% (95% CI, 14.8% to 28.7%) for CIMRT and 23.3% (95% CI, 16.4% to 31.0%) for HIMRT (P = .745). There were no statistically significant differences in late toxicity between the arms; however, in subgroup analysis, patients with compromised urinary function before enrollment had significantly worse urinary function after HIMRT.The hypofractionation regimen did not result in a significant reduction in BCDF; however, it is delivered in 2.5 fewer weeks. Men with compromised urinary function before treatment may not be ideal candidates for this approach.

    View details for DOI 10.1200/JCO.2013.51.1972

    View details for PubMedID 24101042

  • Transurethral surgery and twice-daily radiation plus paclitaxel-cisplatin or fluorouracil-cisplatin with selective bladder preservation and adjuvant chemotherapy for patients with muscle invasive bladder cancer (RTOG 0233): a randomised multicentre phase 2 trial LANCET ONCOLOGY Mitin, T., Hunt, D., Shipley, W. U., Kaufman, D. S., Uzzo, R., Wu, C., Buyyounouski, M. K., Sandler, H., Zietman, A. L. 2013; 14 (9): 863-872

    Abstract

    We assessed effectiveness, safety, and tolerability of paclitaxel or fluorouracil when added to radiation plus cisplatin followed by adjuvant chemotherapy in a programme of selected bladder preservation for patients with muscle invasive bladder cancer.In our randomised phase 2 trial, we enrolled patients with T2-4a transitional cell carcinoma of the bladder at 24 medical centres in the USA. We randomly allocated patients to receive paclitaxel plus cisplatin (paclitaxel group) or fluorouracil plus cisplatin (fluorouracil group) with twice-daily radiation in random block sizes per site on the basis of clinical T-stage (T2 vs T3-4). Patients and physicians were aware of treatment assignment. All patients had transurethral resection of bladder tumour and twice-daily radiotherapy to 40·3 Gy, along with allocated chemotherapy, followed by cystoscopic and biopsy assessment of response. Patients who had a tumour response with downstaging to T0, Tcis, or Ta received consolidation chemoradiotherapy to 64·3 Gy, with the same chemotherapy regimen as in the induction phase. Patients received adjuvant cisplatin-gemcitabine-paclitaxel after the end of chemoradiotherapy. If, after induction, persistent disease was graded as T1 or worse, we recommended patients undergo cystectomy and adjuvant chemotherapy. We assessed the primary endpoints of rates of treatment completion and toxic effects in all randomly allocated patients. This study is registered with ClinicalTrials.gov, number NCT00055601.Between Dec 13, 2002, and Jan 11, 2008, we enrolled 97 patients, of whom 93 were eligible for analysis. Median follow-up was 5·0 years (IQR 5·0-6·2). Of 46 patients in the paclitaxel group, 45 (98%) completed induction (16 [35%] with grade 3-4 toxicity), 39 (85%) completed induction and consolidation (11 [24%] with grade 3-4 toxicity due to consolidation), and 31 (67%) completed the entire protocol with adjuvant chemotherapy. 34 (85%) of 40 assessable patients in the paclitaxel group had grade 3-4 toxicity during adjuvant chemotherapy. Of 47 patients in the fluorouracil group, 45 (96%) completed induction (nine [19%] with grade 3-4 toxicity), 39 (83%) completed induction and consolidation (12 [26%] had grade 3-4 toxicity due to consolidation), and 25 (53%) completed the entire protocol with adjuvant chemotherapy. 31 (76%) of 41 assessable patients in the fluorouracil group had grade 3-4 toxicity during adjuvant chemotherapy. Five (11%) patients treated with the paclitaxel regimen and three (6%) patients treated with the fluorouracil regimen developed late grade 3-4 radiotherapy toxicities. 11 (24%) patients treated with the paclitaxel regimen and 16 (34%) patients treated with the fluorouracil regimen developed late grade 3-4 toxicities unrelated to radiotherapy. One patient (in the fluorouracil group) died during follow-up. Six (13%) patients in the paclitaxel group and in three (6%) patients in the fluorouracil group discontinued due to treatment-related toxicity.In the absence of phase 3 data, our findings could inform selection of a bladder-sparing trimodality chemotherapy regimen for patients with muscle invasive bladder cancer.US National Cancer Institute.

    View details for DOI 10.1016/S1470-2045(13)70255-9

    View details for Web of Science ID 000323423400043

    View details for PubMedID 23823157

  • Gleason Scoring at a Comprehensive Cancer Center: What's The Difference? JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Townsend, N. C., Ruth, K., Al-Saleem, T., Horwitz, E. M., Sobczak, M., Uzzo, R. G., Viterbo, R., Buyyounouski, M. K. 2013; 11 (7): 812-819

    Abstract

    This study attempted to determine whether the Gleason score (GS) assigned at a comprehensive cancer center better predicts risk of biochemical failure (BF) after prostate radiotherapy compared with the GS of the referring institution (RI). Between 1994 and 2007, 1649 men received radiotherapy for prostate cancer at Fox Chase Cancer Center (FCCC). The Cox proportional hazard regression was used for inferences about the relationship of time to BF and GS. Harrell's C-index (HCI) was used to assess concordance in the Cox regression between predicted and observed events. The discordance rate was 26% for any change in either major or minor Gleason pattern. In the RI GS 2 through 6 group, 79 (8%) patients were upgraded to GS 7. Twenty percent of patients with RI GS 7 were downgraded and 2% were upgraded. In the RI GS 8 through 9 group, 58% were downgraded to GS 6 (12%) or GS 7 (88%). The FCCC GS altered the NCCN risk group assignment in 144 men (9%): 92 (64%) men to lower risk and 52 (36%) to higher risk. FCCC GS was a stronger predictor of BF; the hazard ratios for GS 2 through 6 (ref), 3+4, 4+3, and 8 through 9 were 1.00 (ref), 1.82, 4.14, and 2.92, respectively. In contrast, the hazard ratios for the RI GS were 1.00 (ref), 1.53, 2.44, and 1.76, respectively. FCCC GS (HCI=0.76) had improved performance compared with RI GS (HCI=0.74). Changes in GS were common and the GS assigned by a comprehensive cancer center provided better BF risk stratification and prognostication for patients. Changes in GS may impact treatment recommendations in 9% to 26% of patients.

    View details for Web of Science ID 000321614400007

    View details for PubMedID 23847218

  • Assessment of the American Joint Committee on Cancer Staging (Sixth and Seventh Editions) for Clinically Localized Prostate Cancer Treated With External Beam Radiotherapy and Comparison With the National Comprehensive Cancer Network Risk-Stratification Method CANCER Zaorsky, N. G., Li, T., Devarajan, K., Horwitz, E. M., Buyyounouski, M. K. 2012; 118 (22): 5535-5543

    Abstract

    The objective of this study was to compare the prognostic value of the sixth and seventh editions of the American Joint Cancer Committee (AJCC) Cancer Staging Manual and the risk-stratification model of the National Comprehensive Cancer Network (NCCN).Two-thousand four hundred twenty-nine men who received definitive radiotherapy with or without androgen-deprivation therapy (median follow-up, 74 months) were analyzed.There was a migration of stage II patients to stage I with AJCC seventh edition (stage I increased from 1% to 38%, and stage II decreased from 91% to 55%). One pair-wise comparison (4%) of Kaplan-Meier estimates of biochemical failure, distant metastasis, prostate cancer-specific survival, and overall survival between stages was statistically significant for the AJCC sixth edition. Conversely, 16 of 24 comparisons (67%) were significant for the AJCC seventh edition. With the NCCN risk-stratification model, 9 of 12 comparisons (75%) were significant. Concordance probability estimate (CPE) and standard error (SE) analysis indicated uniform and significant improvement in the predictive power of the AJCC seventh edition versus the sixth edition for all outcomes. CPE ± SE values for the AJCC seventh edition versus the sixth edition were 0.51 ± 0.009 versus 0.59 ± 0.02, respectively, for biochemical failure; 0.54 ± 0.02 versus 0.70 ± 0.05, respectively, for distant metastasis; 0.57 ± 0.009 versus 0.76 ± 0.007, respectively, for prostate cancer-specific survival; and 0.52 ± 0.006 versus 0.57 ± 0.01, respectively, for overall survival. CPE ± SE values for the NCCN model were 0.59 ± 0.02 for biochemical failure, 0.72 ± 0.05 for distant metastasis, 0.80 ± 0.01 for prostate cancer-specific survival, and 0.57 ± 0.01 for overall survival.The current results indicated that the seventh edition of the AJCC Cancer Staging Manual is a major improvement over the sixth edition, because it distributes patients better among the stages and is more prognostic. However, the NCCN model was superior to the AJCC seventh edition and remains the preferred method for risk-based clinical management of prostate cancer with radiotherapy.

    View details for DOI 10.1002/cncr.27597

    View details for Web of Science ID 000310483800010

    View details for PubMedID 22544661

  • Validating the Interval to Biochemical Failure for the Identification of Potentially Lethal Prostate Cancer JOURNAL OF CLINICAL ONCOLOGY Buyyounouski, M. K., Pickles, T., Kestin, L. L., Allison, R., Williams, S. G. 2012; 30 (15): 1857-1863

    Abstract

    To validate the interval to biochemical failure (IBF) as a prognostic factor at the time of biochemical failure for prostate cancer mortality (PCM) following radiotherapy (RT).From a collaborative data set of men with clinically localized prostate cancer treated with RT from four institutions in three countries, we identified 1,722 men with biochemical failure (BF; prostate-specific antigen nadir + 2 ng/mL). The IBF was defined as the time interval from completion of treatment to the date of BF. The primary outcome measure was discriminatory power in the form of the concordance index (c-index).Seventeen percent of men had an IBF ≤ 18 months. Median potential follow-up beyond the time of BF was 67 months. There were 290 deaths from prostate cancer. The IBF was the most discriminating individual prognostic factor overall, with a sensitivity of IBF ≤ 18 months to predict PCM within 10 years of 48.4% (95% CI, 43.3% to 54.1%); the specificity was 86.1% (95% CI, 84.5% to 87.7%), equating to a c-index of 0.611 (95% CI, 0.578 to 0.647). The 5-year cumulative incidence of PCM for IBF more than 18 months versus IBF ≤ 18 months was 9.4% (95% CI, 7.7% to 11.5%) versus 26.3% (95% CI, 21.2% to 31.8%); corresponding 10-year estimates were 26.2% (95% CI, 21.5% to 30.8%) versus 55.9% (95% CI, 48.9% to 63.0%), respectively (P < .001 for both). IBF exhibited minimal change in performance across various follow-up durations.IBF is the single most robust prognostic factor for PCM following RT without androgen deprivation therapy. This external validation demonstrates that patients and clinicians can use this information to make decisions about subsequent treatments.

    View details for DOI 10.1200/JCO.2011.35.1924

    View details for Web of Science ID 000304427600022

    View details for PubMedID 22508816

  • RADIOTHERAPY DOSES OF 80 GY AND HIGHER ARE ASSOCIATED WITH LOWER MORTALITY IN MEN WITH GLEASON SCORE 8 TO 10 PROSTATE CANCER INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Pahlajani, N., Ruth, K. J., Buyyounouski, M. K., Chen, D. Y., Horwitz, E. M., Hanks, G. E., Price, R. A., Pollack, A. 2012; 82 (5): 1949-1956

    Abstract

    Men with Gleason score (GS) 8-10 prostate cancer (PCa) are assumed to have a high risk of micrometastatic disease at presentation. However, local failure is also a major problem. We sought to establish the importance of more aggressive local radiotherapy (RT) to ≥80 Gy.There were 226 men treated consecutively with RT ± ADT from 1988 to 2002 for GS 8-10 PCa. Conventional, three-dimensional conformal or intensity-modulated (IM) RT was used. Radiation dose was divided into three groups: (1) <75 Gy (n = 50); (2) 75-79.9 Gy (n = 60); or (3) ≥80 Gy (n = 116). The endpoints examined included biochemical failure (BF; nadir + 2 definition), distant metastasis (DM), cause-specific mortality, and overall mortality (OM).Median follow-up was 66, 71, and 58 months for Groups 1, 2, and 3. On Fine and Gray's competing risk regression analysis, significant predictors of reduced BF were RT dose ≥80 Gy (p = 0.011) and androgen deprivation therapy duration ≥24 months (p = 0.033). In a similar model of DM, only RT dose ≥80 Gy was significant (p = 0.007). On Cox regression analysis, significant predictors of reduced OM were RT dose ≥80 Gy (p = 0.035) and T category (T3/4 vs. T1, p = 0.041). Dose was not a significant determinant of cause-specific mortality. Results for RT dose were similar in a model with RT dose and ADT duration as continuous variables.The results indicate that RT dose escalation to ≥80 Gy is associated with lower risks of BF, DM, and OM in men with GS 8-10 PCa, independently of androgen deprivation therapy.

    View details for DOI 10.1016/j.ijrobp.2011.04.005

    View details for Web of Science ID 000301891300072

    View details for PubMedID 21763081

  • DEVELOPMENT OF RTOG CONSENSUS GUIDELINES FOR THE DEFINITION OF THE CLINICAL TARGET VOLUME FOR POSTOPERATIVE CONFORMAL RADIATION THERAPY FOR PROSTATE CANCER INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Michalski, J. M., Lawton, C., El Naqa, I., Ritter, M., O'Meara, E., Seider, M. J., Lee, W. R., Rosenthal, S. A., Pisansky, T., Catton, C., Valicenti, R. K., Zietman, A. L., Bosch, W. R., Sandler, H., Buyyounouski, M. K., Menard, C. 2010; 76 (2): 361-368

    Abstract

    To define a prostate fossa clinical target volume (PF-CTV) for Radiation Therapy Oncology Group (RTOG) trials using postoperative radiotherapy for prostate cancer.An RTOG-sponsored meeting was held to define an appropriate PF-CTV after radical prostatectomy. Data were presented describing radiographic failure patterns after surgery. Target volumes used in previous trials were reviewed. Using contours independently submitted by 13 radiation oncologists, a statistical imputation method derived a preliminary "consensus" PF-CTV.Starting from the model-derived CTV, consensus was reached for a CT image-based PF-CTV. The PF-CTV should extend superiorly from the level of the caudal vas deferens remnant to >8-12 mm inferior to vesicourethral anastomosis (VUA). Below the superior border of the pubic symphysis, the anterior border extends to the posterior aspect of the pubis and posteriorly to the rectum, where it may be concave at the level of the VUA. At this level, the lateral border extends to the levator ani. Above the pubic symphysis, the anterior border should encompass the posterior 1-2 cm of the bladder wall; posteriorly, it is bounded by the mesorectal fascia. At this level, the lateral border is the sacrorectogenitopubic fascia. Seminal vesicle remnants, if present, should be included in the CTV if there is pathologic evidence of their involvement.Consensus on postoperative PF-CTV for RT after prostatectomy was reached and is available as a CT image atlas on the RTOG website. This will allow uniformity in defining PF-CTV for clinical trials that include postprostatectomy RT.

    View details for DOI 10.1016/j.ijrobp.2009.02.006

    View details for Web of Science ID 000274121500008

    View details for PubMedID 19394158

  • Inflammatory Bowel Disease Is Not an Absolute Contraindication to Definitive Radiation Therapy for Prostate Cancer INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Murphy, C., Ruth, K. J., Buyyounouski, M. K., Heller, S., Weinberg, D., Uzzo, R., Plimack, E., Kutikov, A., Chen, D. Y., Horwitz, E. M. 2013; 87 (2): S356-S356
  • CT-MRI Fusion Uncertainty in Prostate Treatment Planning for Different Image Guidance Techniques INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Chen, X., Xue, J., Chen, L., Buyyounouski, M. K., Horwitz, E. M., Wang, L., Ma, C. 2013; 87 (2): S718-S718
  • Toxicity and Biochemical Failure Following Image-Guided Prostate Intensity Modulated Radiation Therapy: Fiducial Markers Versus Electromagnetic Transponders INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Chang, L., Li, T., Horwitz, E., Chen, D. Y., Viterbo, R., Kutikov, A., Greenberg, R., Buyyounouski, M. K. 2013; 87 (2): S368-S369
  • Improved Outcomes in Men Treated With Adjuvant or Early Salvage Postprostatectomy IMRT or 3DCRT at a Single Institution INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Murphy, C., Uzzo, R. G., Ruth, K. J., Viterbo, R., Plimack, E., Buyyounouski, M. K., Kutikov, A., Chen, D. Y., Greenberg, R. E. 2013; 87 (2): S378-S378
  • Stratifying intermediate-risk patients for radiotherapy NATURE REVIEWS UROLOGY Buyyounouski, M. K. 2013; 10 (8): 438-439
  • Reduction of prostate intrafractional motion from shortening the treatment time PHYSICS IN MEDICINE AND BIOLOGY Li, J. S., Lin, M., Buyyounouski, M. K., Horwitz, E. M., Ma, C. 2013; 58 (14): 4921-4932

    Abstract

    This study aims to quantify the reduction of the intrafractional motion when the prostate intensity modulated radiation therapy (IMRT) treatment time is shortened. Prostate intrafractional motion data recorded by the Calypso system for 105 patients was analyzed. Statistical distributions of the prostate displacements for the regular IMRT treatment and the first 1, 2, 3 and 5 min of the treatment were calculated and used for treatment margin estimation for all the selected patients. The treatment margins estimated for the first 1, 2, 3 and 5 min were compared with those for the regular IMRT treatment to quantify the reduction of the motion. If the treatment can be completed within 5 (3) min, the standard deviation of the prostate displacement could be reduced by up to 45% and the required treatment margins could be reduced to 1.2 (1.1), 0.9 (0.8), 2.2 (1.9), 1.9 (1.5), 1.9 (1.7) and 2.8 (2.4) mm from 1.5, 1.1, 2.8, 3.0, 2.4 and 3.9 mm in the left, right, superior, inferior, anterior and posterior directions, respectively. The same work was also performed for 19 of the 105 patients who exhibited the largest motion with 30% of their treatment time having 3D motion more than 3 mm. For this group of patients, the required margins change to 1.4 (1.2), 0.8 (0.8), 1.8 (1.6), 2.3 (1.8), 1.7 (1.5) and 3.4 (2.8) mm from 1.9, 1.2, 1.7, 3.7, 1.6 and 4.9 mm in the six directions when the treatment time is reduced to 5 (3) min. The intrafractional motion effects on prostate treatment are significantly smaller and the required margins can be therefore reduced when the treatment is shortened.

    View details for DOI 10.1088/0031-9155/58/14/4921

    View details for Web of Science ID 000321243600015

    View details for PubMedID 23798642

  • A Novel Method for Predicting Late Genitourinary Toxicity After Prostate Radiation Therapy and the Need for Age-Based Risk-Adapted Dose Constraints INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Ahmed, A. A., Egleston, B., Alcantara, P., Li, L., Pollack, A., Horwitz, E. M., Buyyounouski, M. K. 2013; 86 (4): 709-715

    Abstract

    There are no well-established normal tissue sparing dose-volume histogram (DVH) criteria that limit the risk of urinary toxicity from prostate radiation therapy (RT). The aim of this study was to determine which criteria predict late toxicity among various DVH parameters when contouring the entire solid bladder and its contents versus the bladder wall. The area under the histogram curve (AUHC) was also analyzed.From 1993 to 2000, 503 men with prostate cancer received 3-dimensional conformal RT (median follow-up time, 71 months). The whole bladder and the bladder wall were contoured in all patients. The primary endpoint was grade ≥2 genitourinary (GU) toxicity occurring ≥3 months after completion of RT. Cox regressions of time to grade ≥2 toxicity were estimated separately for the entire bladder and bladder wall. Concordance probability estimates (CPE) assessed model discriminative ability. Before training the models, an external random test group of 100 men was set aside for testing. Separate analyses were performed based on the mean age (≤ 68 vs >68 years).Age, pretreatment urinary symptoms, mean dose (entire bladder and bladder wall), and AUHC (entire bladder and bladder wall) were significant (P<.05) in multivariable analysis. Overall, bladder wall CPE values were higher than solid bladder values. The AUHC for bladder wall provided the greatest discrimination for late bladder toxicity when compared with alternative DVH points, with CPE values of 0.68 for age ≤68 years and 0.81 for age >68 years.The AUHC method based on bladder wall volumes was superior for predicting late GU toxicity. Age >68 years was associated with late grade ≥2 GU toxicity, which suggests that risk-adapted dose constraints based on age should be explored.

    View details for DOI 10.1016/j.ijrobp.2013.03.020

    View details for Web of Science ID 000320590200026

    View details for PubMedID 23664324

  • Untitled Reply INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Turaka, A., Buyyounouski, M. K., Horwitz, E. M., Movsas, B. 2013; 86 (1): 6-7
  • In reply to Cheung. International journal of radiation oncology, biology, physics Turaka, A., Buyyounouski, M. K., Horwitz, E. M., Movsas, B. 2013; 86 (1): 6-7

    View details for DOI 10.1016/j.ijrobp.2013.01.013

    View details for PubMedID 23582244

  • The impact of dose-escalated radiotherapy plus androgen deprivation for prostate cancer using 2 linked nomograms CANCER Stoyanova, R., Pahlajani, N. H., Egleston, B. L., Buyyounouski, M. K., Chen, D. Y., Horwitz, E. M., Pollack, A. 2013; 119 (5): 1080-1088

    Abstract

    Randomized trials have demonstrated that escalated-dose external-beam radiotherapy (EDRT) is better than standard-dose radiotherapy (SDRT) for patients with prostate cancer and that adding androgen-deprivation therapy (ADT) to SDRT is better than SDRT alone; however, no trials have compared EDRT versus SDRT plus ADT or EDRT versus EDRT plus ADT. The authors designed a model to estimate the results of various doses of radiotherapy (RT) combined with various durations of ADT.From 1989 to 2007, 3215 men consecutively received definitive EDRT with or without ADT. In total, 2012 patients had complete records available for creating the nomogram. The duration of ADT varied for patients who received no RT (n = 1562), ≤6 months of RT (n = 145), from >6 months to <24 months of RT (n = 140), and ≥24 months of RT (n = 165) with a median follow-up of 65.7 months, 66.2 months, 60.1 months, and 63 months, respectively. The model included the following covariates: palpation T-category, biopsy Gleason score, the percentage of tumor cells with a Gleason pattern of 4 or 5, the percentage of tumor tissue, initial pretreatment prostate-specific antigen (PSA) level, ADT duration, and RT dose. Two nomograms, for outcomes with and without ADT, were created from a single competing-risks model. Biochemical failure was defined as a rise in serum PSA of 2 ng/mL over the post-treatment PSA nadir.According to the results from analyzing representative intermediate-risk to high-risk patient parameters, the gains from increasing the RT dose from 70 Gray (Gy) to 80 Gy were far less than the gains from adding ≥3 months of ADT.The nomograms provided unique patient-specific estimates of the effects of various doses and durations of RT and ADT. The results indicated that adding ADT to treatment for intermediate-risk and high-risk prostate cancer is far more beneficial than a modest RT dose escalation.

    View details for DOI 10.1002/cncr.27857

    View details for Web of Science ID 000315214000023

    View details for PubMedID 23096533

  • Prospective Validation of Diagnostic Tumor Tissue Ki-67 as the Most Significant Predictor of Outcome in Men Treated for Prostate Cancer on a Randomized Trial INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Pollack, A., Walker, G., Stoyanova, R., Khor, L., Horwitz, E., Buyyounouski, M. 2012; 84 (3): S25-S26
  • Primary Prostate Radiation Therapy: Where Are We Failing? INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Huang, K. T., Walker, G., Stoyanova, R., SANDLER, K., Horwitz, E., Buyyounouski, M. K., Pollack, A. 2012; 84 (3): S182-S182
  • Determinants of Prostate Biopsy Positivity 2 Years After Radiation Therapy for Men With Prostate Cancer Treated on a Randomized Trial INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Stoyanova, R., Walker, G., SANDLER, K., Khor, L., Horwitz, E., Buyyounouski, M., Pollack, A. 2012; 84 (3): S60-S60
  • Do Testosterone Kinetics After Radiation Therapy (RT) Predict Biochemical Failure (BCF) for Low- and Intermediate-risk Prostate Cancer (CaP)? INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Martin, J. M., Sopka, D. M., Ruth, K. J., Buyyounouski, M. K., Kutikov, A., Sobczak, M. L., Chen, D. Y., Horwitz, E. M. 2012; 84 (3): S185-S186
  • Recursive Partitioning Analysis of Intermediate Risk Prostate Cancer Patients Identifies Subgroup Risk Categories INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Townsend, N. C., Ruth, K., Buyyounouski, M., Kutikov, A., Viterbo, R., Sobczak, M., Horwitz, E. M. 2012; 84 (3): S183-S183
  • A Novel Methodology to Predict Late Urinary Toxicity Following Prostate Radiation Therapy-based on Bladder Wall Dosimetry INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Ahmed, A., Egleston, B., Alcantara, P., Pollack, A., Li, L., Horwitz, E. M., Buyyounouski, M. K. 2012; 84 (3): S418-S419
  • Aspirin and Statin Nonuse Associated With Early Biochemical Failure After Prostate Radiation Therapy INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Zaorsky, N. G., Buyyounouski, M. K., Li, T., Horwitz, E. M. 2012; 84 (1): E13-E17

    Abstract

    To present the largest retrospective series investigating the effect of aspirin and statins, which are hypothesized to have antineoplastic properties, on biochemical failure (nadir plus 2 ng/mL) after prostate radiation therapy (RT).Between 1989 and 2006, 2051 men with clinically localized prostate cancer received definitive RT alone (median dose, 76 Gy). The rates of aspirin use and statin use (defined as any use at the time of RT or during follow-up) were 36% and 34%, respectively. The primary endpoint of the study was an interval to biochemical failure (IBF) of less than 18 months, which has been shown to be the single strongest predictor of distant metastasis, prostate cancer survival, and overall survival after RT. Patient demographic characteristics and tumor staging factors were assessed with regard to associations with the endpoint. Univariate analysis was performed with the χ(2) test for categorical variables and the Wilcoxon test for continuous variables. Multivariable analysis was performed with a multiple logistic regression.The median follow-up was 75 months. Univariate analysis showed that an IBF of less than 18 months was associated with aspirin nonuse (P<.0001), statin nonuse (P<.0001), anticoagulant nonuse (P=.0006), cardiovascular disease (P=.0008), and prostate-specific antigen (continuous) (P=.008) but not with Gleason score, age, RT dose, or T stage. On multivariate analysis, only aspirin nonuse (P=.0012; odds ratio, 2.052 [95% confidence interval, 1.328-3.172]) and statin nonuse (P=.0002; odds ratio, 2.465 [95% confidence interval, 1.529-3.974]) were associated with an IBF of less than 18 months.In patients who received RT for prostate cancer, aspirin or statin nonuse was associated with early biochemical failure, a harbinger of distant metastasis and death. Further study is needed to confirm these findings and to determine the optimal dosing and schedule, as well as the relative benefits and risks, of both therapies in combination with RT.

    View details for DOI 10.1016/j.ijrobp.2012.02.050

    View details for Web of Science ID 000308061900003

    View details for PubMedID 22652109

  • Prostate Bed Motion During Intensity-Modulated Radiotherapy Treatment INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Klayton, T., Price, R., Buyyounouski, M. K., Sobczak, M., Greenberg, R., Li, J., Keller, L., Sopka, D., Kutikov, A., Horwitz, E. M. 2012; 84 (1): 130-136

    Abstract

    Conformal radiation therapy in the postprostatectomy setting requires accurate setup and localization of the prostatic fossa. In this series, we report prostate bed localization and motion characteristics, using data collected from implanted radiofrequency transponders.The Calypso four-dimensional localization system uses three implanted radiofrequency transponders for daily target localization and real-time tracking throughout a course of radiation therapy. We reviewed the localization and tracking reports for 20 patients who received ultrasonography-guided placement of Calypso transponders within the prostate bed prior to a course of intensity-modulated radiation therapy at Fox Chase Cancer Center.At localization, prostate bed displacement relative to bony anatomy exceeded 5 mm in 9% of fractions in the anterior-posterior (A-P) direction and 21% of fractions in the superior-inferior (S-I) direction. The three-dimensional vector length from skin marks to Calypso alignment exceeded 1 cm in 24% of all 652 fractions with available setup data. During treatment, the target exceeded the 5-mm tracking limit for at least 30 sec in 11% of all fractions, generally in the A-P or S-I direction. In the A-P direction, target motion was twice as likely to move posteriorly, toward the rectum, than anteriorly. Fifteen percent of all treatments were interrupted for repositioning, and 70% of patients were repositioned at least once during their treatment course.Set-up errors and motion of the prostatic fossa during radiotherapy are nontrivial, leading to potential undertreatment of target and excess normal tissue toxicity if not taken into account during treatment planning. Localization and real-time tracking of the prostate bed via implanted Calypso transponders can be used to improve the accuracy of plan delivery.

    View details for DOI 10.1016/j.ijrobp.2011.11.041

    View details for Web of Science ID 000308061900045

    View details for PubMedID 22330987

  • Stamp Test Delivers Message on Erectile Dysfunction After High-dose Intensity-modulated Radiotherapy for Prostate Cancer UROLOGY Keller, L. M., Buyyounouski, M. K., Sopka, D., Ruth, K., Klayton, T., Pollack, A., Watkins-Bruner, D., Greenberg, R., Price, R., Horwitz, E. M. 2012; 80 (2): 337-342

    Abstract

    To evaluate erectile function after high-dose radiotherapy for prostate cancer using the International Index of Erectile Function, Expanded Prostate Cancer Index Composite, and stamp test.Men with favorable and intermediate-risk prostate cancer were assigned to receive prostate intensity-modulated radiotherapy (IMRT) versus an erectile tissue-sparing IMRT technique in a Phase III randomized, prospective study. The stamp test and International Index of Erectile Function and Expanded Prostate Cancer Index Composite questionnaires were completed at baseline and 6 months, 1 year, and 2 years after IMRT. The Sexual Health Inventory for Men scores were abstracted from the International Index of Erectile Function questionnaire. A partner questionnaire, designated IIEF-P, modeled after the International Index of Erectile Function questionnaire but from the perspective of the partner, was also collected.The data from 94 men who were enrolled in the trial and who had completed ≥1 questionnaire or 1 stamp test were analyzed. The median age of the patient population was 62.5 years. The median radiation dose was 76 Gy (range 74-80). At 6 months and 1 year after high-dose IMRT, a positive stamp result correlated significantly with the median Expanded Prostate Cancer Index Composite sexual summary, sexual function, and bother subscale scores. Additionally, 6 months after IMRT, the stamp test correlated with the median International Index of Erectile Function, International Index of Erectile Function sexual function domain, and Sexual Health Inventory for Men scores. Robust concordance for the International Index of Erectile Function and Sexual Health Inventory for Men scores was appreciated between responding patient and partner pairs.Nocturnal tumescence, as indicated by a positive stamp test, correlated well with established quality of life questionnaires after IMRT. The stamp test should strongly be considered as an objective measure of erectile function in future studies of erectile dysfunction in patients with prostate cancer.

    View details for DOI 10.1016/j.urology.2012.04.048

    View details for Web of Science ID 000307244200036

    View details for PubMedID 22749428

  • Radiotherapy Treatment Planning for Testicular Seminoma INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Wilder, R. B., Buyyounouski, M. K., Efstathiou, J. A., Beard, C. J. 2012; 83 (4): E445-E452

    Abstract

    Virtually all patients with Stage I testicular seminoma are cured regardless of postorchiectomy management. For patients treated with adjuvant radiotherapy, late toxicity is a major concern. However, toxicity may be limited by radiotherapy techniques that minimize radiation exposure of healthy normal tissues. This article is an evidence-based review that provides radiotherapy treatment planning recommendations for testicular seminoma. The minority of Stage I patients who choose adjuvant treatment over surveillance may be considered for (1) para-aortic irradiation to 20 Gy in 10 fractions, or (2) carboplatin chemotherapy consisting of area under the curve, AUC = 7 × 1-2 cycles. Two-dimensional radiotherapy based on bony anatomy is a simple and effective treatment for Stage IIA or IIB testicular seminoma. Centers with expertise in vascular and nodal anatomy may consider use of anteroposterior-posteroanterior fields based on three-dimensional conformal radiotherapy instead. For modified dog-leg fields delivering 20 Gy in 10 fractions, clinical studies support placement of the inferior border at the top of the acetabulum. Clinical and nodal mapping studies support placement of the superior border of all radiotherapy fields at the top of the T12 vertebral body. For Stage IIA and IIB patients, an anteroposterior-posteroanterior boost is then delivered to the adenopathy with a 2-cm margin to the block edge. The boost dose consists of 10 Gy in 5 fractions for Stage IIA and 16 Gy in 8 fractions for Stage IIB. Alternatively, bleomycin, etoposide, and cisplatin chemotherapy for 3 cycles or etoposide and cisplatin chemotherapy for 4 cycles may be delivered to Stage IIA or IIB patients (e.g., if they have a horseshoe kidney, inflammatory bowel disease, or a history of radiotherapy).

    View details for DOI 10.1016/j.ijrobp.2012.01.044

    View details for Web of Science ID 000305423400001

    View details for PubMedID 22436787

  • A survey of current clinical practice in permanent and temporary prostate brachytherapy: 2010 update BRACHYTHERAPY Buyyounouski, M. K., Davis, B. J., Prestidge, B. R., Shanahan, T. G., Stock, R. G., Grimm, P. D., Demanes, D. J., Zaider, M., Horwitz, E. M. 2012; 11 (4): 299-305

    Abstract

    To help establish patterns of care and standards of care of interstitial permanent low-dose-rate (LDR) and temporary high-dose-rate brachytherapy for prostate cancer and to compare the results with a similar 1998 American Brachytherapy Society (ABS) survey.A comprehensive questionnaire intended to survey specific details of current clinical brachytherapy practice was provided to the participants of the seventh ABS Prostate Brachytherapy School. Responses were tabulated and descriptive statistics are reported.Sixty-five brachytherapy practitioners responded to the survey. Eighty-nine percent (89%) of respondents performed LDR and 49% perform high-dose-rate brachytherapy. The median number of years of experience for LDR brachytherapists increased from 5 to 10 years over the course of the 12 years since the preceding survey. Compared with the first ABS, a smaller proportion of respondents received formal brachytherapy residency training (43% vs. 56%) or formal "hands-on" brachytherapy training (15% vs. 63%). There has been a marked decline in the utilization of the Mick applicator (Mick Radio-Nuclear Instruments, Inc., Mount Vernon, NY, USA) (60% vs. 28%) and an increase in the use of stranded seeds (40% vs. 11%). Compliance with postimplant dosimetry was higher in the 2010 survey.This survey does suggest an evolution in the practice of LDR brachytherapy since 1998 and aids in identifying aspects that require further progress or investigation. ABS guidelines and other practice recommendations appear to impact the practice of brachytherapy.

    View details for DOI 10.1016/j.brachy.2011.12.012

    View details for Web of Science ID 000305855300009

    View details for PubMedID 22330104

  • Magnetic Resonance Spectroscopy of the Prostate: A Phantom Study of Metabolite Concentrations MEDICAL PHYSICS Hossain, M., Richardson, T., Buyyounouski, M. K., Schirmer, T., Noeske, R., Chen, L., Ma, C. 2012; 39 (6): 3639-3640
  • How Certain Can the Real-Time Plan Predict the Post Dosimetry for Prostate Seed Implant? MEDICAL PHYSICS Li, J. S., Buyyounouski, M., Horwitz, E., Ma, C. 2012; 39 (6): 3933-3933
  • Effect of Gold Marker Seeds on Magnetic Resonance Spectroscopy of the Prostate INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Hossain, M., Schirmer, T., Richardson, T., Chen, L., Buyyounouski, M. K., Ma, C. M. 2012; 83 (1): 451-458

    Abstract

    Magnetic resonance stereoscopic imaging (MRSI) of the prostate is an emerging technique that may enhance targeting and assessment in radiotherapy. Current practices in radiotherapy invariably involve image guidance. Gold seed fiducial markers are often used to perform daily prostate localization. If MRSI is to be used in targeting prostate cancer and therapy assessment, the impact of gold seeds on MRSI must be investigated. The purpose of this study was to quantify the effects of gold seeds on the quality of MRSI data acquired in phantom experiments.A cylindrical plastic phantom with a spherical cavity 10 centimeters in diameter wss filled with water solution containing choline, creatine, and citrate. A gold seed fiducial marker was put near the center of the phantom mounted on a plastic stem. Spectra were acquired at 1.5 Tesla by use of a clinical MRSI sequence. The ratios of choline + creatine to citrate (CC/Ci) were compared in the presence and absence of gold seeds. Spectra in the vicinity of the gold seed were analyzed.The maximum coefficient of variation of CC/Ci induced by the gold seed was found to be 10% in phantom experiments at 1.5 T.MRSI can be used in prostate radiotherapy in the presence of gold seed markers. Gold seeds cause small effects (in the order of the standard deviation) on the ratio of the metabolite's CC/Ci in the phantom study done on a 1.5-T scanner. It is expected that gold seed markers will have similar negligible effect on spectra from prostate patients. The maximum of 10% of variation in CC/Ci found in the phantom study also sets a limit on the threshold accuracy of CC/Ci values for deciding whether the tissue characterized by a local spectrum is considered malignant and whether it is a candidate for local boost in radiotherapy dose.

    View details for DOI 10.1016/j.ijrobp.2011.06.2001

    View details for Web of Science ID 000302993900084

    View details for PubMedID 22245188

  • Biochemical and clinical experience with real-time intraoperatively planned permanent prostate brachytherapy BRACHYTHERAPY Lubbe, W., Cohen, R., Sharma, N., Ruth, K., Peters, R., Li, J., Buyyounouski, M., Kutikov, A., Chen, D., Uzzo, R., Horwitz, E. 2012; 11 (3): 209-213

    Abstract

    To evaluate patient characteristics and dosimetric parameters that predict biochemical failure (BCF) after real-time planned low-dose-rate prostate brachytherapy.From 1998 to 2008, a low-risk cohort by National Comprehensive Cancer Network criteria of 341 men with a median followup of 41.6 months was analyzed. This cohort had a median age of 65.1 years, prostate volume of 35.8cc, and pretreatment prostate-specific antigen of 5.6ng/mL. Patients had predominately Gleason 6 (95.9%) and T1c (81.3%) disease. About 3.6% of the patients received androgen deprivation therapy. Kaplan-Meier and Cox proportional hazards survival analysis methods were used to analyze predictors of BCF (Phoenix definition).At 72 months, freedom from BCF was 91.1% (95% confidence interval=85.0-94.8). The median D(90) was 145.9Gy, and the median V(100) was 90.3%. Because of infrequent BCF, the following prostate volume groups were examined: 15-<25, 25-<35, 35-<45, and 45+cc. Of all possible predictors, only small prostate volume (15-<25cc group) was significantly associated with BCF (hazard ratio=8.44, 95% confidence interval=1.82-39.14, p=0.007). Using Kaplan-Meier analysis, time to BCF was also significantly increased in the lowest prostate volume 15-<25cc group with 24.1% failing at 48 months compared with 1.6-5.1% among the other groups.Real-time planned low-dose-rate prostate brachytherapy provides excellent biochemical control as a single-agent treatment for low-risk prostate cancer with 91.1% freedom from BCF at 72 months. Only prostate volume less than 25cc was an independent predictor of BCF.

    View details for DOI 10.1016/j.brachy.2011.05.011

    View details for Web of Science ID 000303291600007

    View details for PubMedID 21727033

  • Testicular Cancer Clinical Practice Guidelines in Oncology JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Motzer, R. J., Agarwal, N., Beard, C., Bhayani, S., Bolger, G. B., Buyyounouski, M. K., Carducci, M. A., Chang, S. S., Choueiri, T. K., Gupta, S., Hancock, S. L., Hudes, G. R., Jonasch, E., Kuzel, T. M., Lau, C., Levine, E. G., Lin, D. W., Margolin, K. A., Michaelson, M. D., Olencki, T., Pili, R., Ratliff, T. W., Redman, B. G., Robertson, C. N., Ryan, C. J., Sheinfeld, J., Wang, J., Wilder, R. B. 2012; 10 (4): 502-535

    View details for Web of Science ID 000302445400009

    View details for PubMedID 22491049

  • An evidence based review of proton beam therapy: The report of ASTRO's emerging technology committee RADIOTHERAPY AND ONCOLOGY Allen, A. M., Pawlicki, T., Dong, L., Fourkal, E., Buyyounouski, M., Cengel, K., Plastaras, J., Bucci, M. K., Yock, T. I., Bonilla, L., Price, R., Harris, E. E., Konski, A. A. 2012; 103 (1): 8-11

    Abstract

    Proton beam therapy (PBT) is a novel method for treating malignant disease with radiotherapy. The purpose of this work was to evaluate the state of the science of PBT and arrive at a recommendation for the use of PBT. The emerging technology committee of the American Society of Radiation Oncology (ASTRO) routinely evaluates new modalities in radiotherapy and assesses the published evidence to determine recommendations for the society as a whole. In 2007, a Proton Task Force was assembled to evaluate the state of the art of PBT. This report reflects evidence collected up to November 2009. Data was reviewed for PBT in central nervous system tumors, gastrointestinal malignancies, lung, head and neck, prostate, and pediatric tumors. Current data do not provide sufficient evidence to recommend PBT in lung cancer, head and neck cancer, GI malignancies, and pediatric non-CNS malignancies. In hepatocellular carcinoma and prostate cancer and there is evidence for the efficacy of PBT but no suggestion that it is superior to photon based approaches. In pediatric CNS malignancies PBT appears superior to photon approaches but more data is needed. In large ocular melanomas and chordomas, we believe that there is evidence for a benefit of PBT over photon approaches. PBT is an important new technology in radiotherapy. Current evidence provides a limited indication for PBT. More robust prospective clinical trials are needed to determine the appropriate clinical setting for PBT.

    View details for DOI 10.1016/j.radonc.2012.02.001

    View details for Web of Science ID 000303485600003

    View details for PubMedID 22405807

  • Hypoxic Prostate/Muscle PO2 Ratio Predicts for Outcome in Patients With Localized Prostate Cancer: Long-Term Results INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Turaka, A., Buyyounouski, M. K., Hanlon, A. L., Horwitz, E. M., Greenberg, R. E., Movsas, B. 2012; 82 (3): E433-E439

    Abstract

    To correlate tumor oxygenation status with long-term biochemical outcome after prostate brachytherapy.Custom-made Eppendorf PO(2) microelectrodes were used to obtain PO(2) measurements from the prostate (P), focused on positive biopsy locations, and normal muscle tissue (M), as a control. A total of 11,516 measurements were obtained in 57 men with localized prostate cancer immediately before prostate brachytherapy was given. The Eppendorf histograms provided the median PO(2), mean PO(2), and % <5 mm Hg or <10 mm Hg. Biochemical failure (BF) was defined using both the former American Society of Therapeutic Radiation Oncology (ASTRO) (three consecutive raises) and the current Phoenix (prostate-specific antigen nadir + 2 ng/mL) definitions. A Cox proportional hazards regression model evaluated the influence of hypoxia using the P/M mean PO(2) ratio on BF.With a median follow-up time of 8 years, 12 men had ASTRO BF and 8 had Phoenix BF. On multivariate analysis, P/M PO(2) ratio <0.10 emerged as the only significant predictor of ASTRO BF (p = 0.043). Hormonal therapy (p = 0.015) and P/M PO(2) ratio <0.10 (p = 0.046) emerged as the only independent predictors of the Phoenix BF. Kaplan-Meier freedom from BF for P/M ratio <0.10 vs. ≥0.10 at 8 years for ASTRO BF was 46% vs. 78% (p = 0.03) and for the Phoenix BF was 66% vs. 83% (p = 0.02).Hypoxia in prostate cancer (low mean P/M PO(2) ratio) significantly predicts for poor long-term biochemical outcome, suggesting that novel hypoxic strategies should be investigated.

    View details for DOI 10.1016/j.ijrobp.2011.05.037

    View details for Web of Science ID 000300423500013

    View details for PubMedID 21985947

  • Young age under 60 years is not a contraindication to treatment with definitive dose escalated radiotherapy for prostate cancer RADIOTHERAPY AND ONCOLOGY Klayton, T. L., Ruth, K., Horwitz, E. M., Uzzo, R. G., Kutikov, A., Chen, D. Y., Sobczak, M., Buyyounouski, M. K. 2011; 101 (3): 508-512

    Abstract

    It is widely believed that younger prostate cancer patients are at greater risk of recurrence following radiotherapy (RT).From 1992 to 2007, 2168 (395 age ≤ 60) men received conformal RT alone for prostate cancer at our institution (median dose=76 Gy, range: 72-80). Multivariable analysis (MVA) was used to identify significant predictors for BF and PCSM. Cumulative incidence was estimated using the competing risk method (Fine and Gray) for BF (Phoenix definition) and PCSM to account for the competing risk of death.With a median follow-up of 72.2 months (range: 24.0-205.1), 8-year BF was 27.1% for age ≤ 60 vs. 23.7% for age >60 (p=0.29). Eight-year PCSM was 3.0% for age ≤ 60 vs. 2.0% for age >60 (p=0.52). MVA for BF identified initial PSA [adjusted HR=1.7 (PSA 10-20), 2.6 (PSA >20), p<0.01], Gleason score [adjusted HR=2.1 (G7), 1.9 (G8-10), p<0.01], T-stage [adjusted HR=1.7 (T2b-c), 2.6 (T3-4), p<0.01], and initial androgen deprivation therapy (ADT) [adjusted HR=0.38 (ADT >12 months), p<0.01] as significant, but not age or ADT <12 months. MVA for PCSM identified Gleason score [adjusted HR=3.0 (G8-10), p=0.01] and T-stage [adjusted HR=8.7 (T3-4), p<0.01] as significant, but not age, PSA, or ADT.This is the largest, most mature study of younger men treated with RT for prostate cancer that confirms young age is not prognostic for BF.

    View details for DOI 10.1016/j.radonc.2011.07.022

    View details for Web of Science ID 000298894700028

    View details for PubMedID 21889222

  • Long-Term Survival After Radical Prostatectomy Versus External-Beam Radiotherapy for Patients With High-Risk Prostate Cancer CANCER Boorjian, S. A., Karnes, R. J., Viterbo, R., Rangel, L. J., Bergstralh, E. J., Horwitz, E. M., Blute, M. L., Buyyounouski, M. K. 2011; 117 (13): 2883-2891

    Abstract

    The long-term survival of patients with high-risk prostate cancer was compared after radical prostatectomy (RRP) and after external beam radiation therapy (EBRT) with or without adjuvant androgen-deprivation therapy (ADT).In total, 1238 patients underwent RRP, and 609 patients received with EBRT (344 received EBRT plus ADT, and 265 received EBRT alone) between 1988 and 2004 who had a pretreatment prostate-specific antigen (PSA) level ≥ 20 ng/mL, a biopsy Gleason score between 8 and 10, or clinical tumor classification ≥ T3. The median follow-up was 10.2 years, 6.0 years, and 7.2 years after RRP, EBRT plus ADT, and EBRT alone, respectively. The impact of treatment modality on systemic progression, cancer-specific survival, and overall survival was evaluated using multivariate Cox proportional hazard regression analysis and a competing risk-regression model.The 10-year cancer-specific survival rate was 92%, 92%, and 88% after RRP, EBRT plus ADT, and EBRT alone, respectively (P = .06). After adjustment for case mix, no significant differences in the risks of systemic progression (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.51-1.18; P = .23) or prostate cancer death (HR, 1.14; 95% CI, 0.68-1.91; P = .61) were observed between patients who received EBRT plus ADT and patients who underwent RRP. The risk of all-cause mortality, however, was greater after EBRT plus ADT than after RRP (HR, 1.60; 95% CI, 1.25-2.05; P = .0002).RRP alone and EBRT plus ADT provided similar long-term cancer control for patients with high-risk prostate cancer. The authors concluded that continued investigation into the differing impact of treatments on quality-of-life and noncancer mortality will be necessary to determine the optimal management approach for these patients.

    View details for DOI 10.1002/cncr.25900

    View details for Web of Science ID 000292056200010

    View details for PubMedID 21692049

  • INTENSITY-MODULATED RADIOTHERAPY REDUCES GASTROINTESTINAL TOXICITY IN PATIENTS TREATED WITH ANDROGEN DEPRIVATION THERAPY FOR PROSTATE CANCER INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Sharma, N. K., Li, T., Chen, D. Y., Pollack, A., Horwitz, E. M., Buyyounouski, M. K. 2011; 80 (2): 437-444

    Abstract

    Androgen deprivation therapy (AD) has been shown to increase late Grade 2 or greater rectal toxicity when used concurrently with three-dimensional conformal radiotherapy (3D-CRT). Intensity-modulated radiotherapy (IMRT) has the potential to reduce toxicity by limiting the radiation dose received by the bowel and bladder. The present study compared the genitourinary and gastrointestinal (GI) toxicity in men treated with 3D-CRT+AD vs. IMRT+AD.Between July 1992 and July 2004, 293 men underwent 3D-CRT (n = 170) or IMRT (n = 123) with concurrent AD (<6 months, n = 123; ≥6 months, n = 170). The median radiation dose was 76 Gy for 3D-CRT (International Commission on Radiation Units and Measurements) and 76 Gy for IMRT (95% to the planning target volume). Toxicity was assessed by a patient symptom questionnaire that was completed at each visit and recorded using a Fox Chase Modified Late Effects Normal Tissue Task radiation morbidity scale.The mean follow-up was 86 months (standard deviation, 29.3) for the 3D-CRT group and 40 months (standard deviation, 9.7) for the IMRT group. Acute GI toxicity (odds ratio, 4; 95% confidence interval, 1.6-11.7; p = .005) was significantly greater with 3D-CRT than with IMRT and was independent of the AD duration (i.e., <6 vs. ≥6 months). The interval to the development of late GI toxicity was significantly longer in the IMRT group. The 5-year Kaplan-Meier estimate for Grade 2 or greater GI toxicity was 20% for 3D-CRT and 8% for IMRT (p = .01). On multivariate analysis, Grade 2 or greater late GI toxicity (hazard ratio, 2.1; 95% confidence interval, 1.1-4.3; p = .04) was more prevalent in the 3D-CRT patients.Compared with 3D-CRT, IMRT significantly decreased the acute and late GI toxicity in patients treated with AD.

    View details for DOI 10.1016/j.ijrobp.2010.02.040

    View details for Web of Science ID 000290837100018

    View details for PubMedID 21050673

  • PREDICTORS OF ANDROGEN DEPRIVATION THERAPY EFFICACY COMBINED WITH PROSTATIC IRRADIATION: THE CENTRAL ROLE OF TUMOR STAGE AND RADIATION DOSE INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Williams, S., Buyyounouski, M., Kestin, L., Duchesne, G., Pickles, T. 2011; 79 (3): 724-731

    Abstract

    To evaluate the response of clinically localized prostate cancer to various durations of planned androgen deprivation therapy (ADT) and to investigate subgroups predicting response.Data of 3,666 prostate cancer patients treated with either combined ADT and external beam radiotherapy (EBRT) or EBRT alone at four institutions were examined. ADT consisted of neoadjuvant, concurrent, or adjuvant ADT or combinations of these regimens. The primary endpoint was time to biochemical failure (nadir plus 2 ng/ml), assessed from the end of therapy. Factors predictive for the need for ADT were examined with interaction analyses.The impact of increasing ADT duration was nonlinear with, on average, 6 months of adjuvant ADT resulting in a reduction of the risk of biochemical failure by 38% (95% confidence interval [CI], 29%-46%), while 12, 24, and 36 months of ADT resulted in a 58% (95% CI, 47%-67%), 66% (95% CI, 55%-75%), and 66% (95% CI, 51%-77%) relative failure reduction, respectively. Patients with higher T stage cancers and those treated with lower radiation doses had a significantly greater benefit for increasing ADT duration (interaction, p=0.016 and p=0.007, respectively). Pretreatment prostate-specific antigen values, Gleason score, age, and risk group did not modify the response to ADT.The known ADT efficacy derived from randomized studies can be generalized to patients with different features, and individual predictions of potential benefit from ADT use and duration may be calculated to aid patient and physician decision making. Tumor stage and radiation dose variations were related to significantly different ADT duration effects. The validity of these predictive factors requires prospective evaluation.

    View details for DOI 10.1016/j.ijrobp.2009.11.044

    View details for Web of Science ID 000287382400012

    View details for PubMedID 20472361

  • The Impact of Gleason Scoring at a Comprehensive Cancer Center on the Ability to Predict Recurrence After Radiotherapy for Prostate Cancer INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Townsend, N. C., Ruth, K., Al-Saleem, T., Horwitz, E. M., Sobczak, M., Uzzo, R. G., Viterbo, R., Buyyounouski, M. K. 2011; 81 (2): S409-S410
  • A Nomogram Predicting 5-year Probability of Cause Specific Survival from Biochemical Failure following Radiotherapy INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Buyyounouski, M. K., Kestin, L., Duchesne, G., Pickles, T., Allison, R., Williams, S. 2011; 81 (2): S389-S389
  • Aspirin Use Reduces the Risk of Biochemical Failure and Distant Metastases Following Post-Prostatectomy Radiotherapy INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Cohen, R. J., Li, T., Horwitz, E. M., Peter, R., Uzzo, R. G., Viterbo, R., Buyyounouski, M. K. 2011; 81 (2): S391-S392
  • A Family History of Prostate Cancer is not Associated with Poorer Outcomes following Radiotherapy INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Bagshaw, H. P., Ruth, K., Horwitz, E. M., Chen, D., Buyyounouski, M. K. 2011; 81 (2): S211-S211
  • VMAT Reduces Moderate to High Integral Dose When Compared to Conventional IMRT for Treatment of Prostate Cancer INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Lubbe, W. J., Price, R., Ruth, K., Cherian, G., Kutikov, A., Chen, D., Uzzo, R., Buyyounouski, M., Ma, C., Horwitz, E. 2011; 81 (2): S446-S446
  • Identification of a Single Nucleotide Polymorphism Related to Late Toxicity in a Randomized Hypofractionation Trial for Prostate Cancer INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Oh, J., Deasy, J., Stoyanova, R., Saleh, Z., Buyyounouski, M., Wong, H. P., Apte, A. P., Price, R. A., Hu, J., Pollack, A. 2011; 81 (2): S156-S157
  • Potential Treatment Margin Reduction for Prostate Treatment with RapidArc and VMAT INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Li, J., Buyyounouski, M. K., Lin, M., Horwitz, E. M., Ma, C. 2011; 81 (2): S391-S391
  • Five Year Results of a Randomized External Beam Radiotherapy Hypofractionation Trial for Prostate Cancer INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Pollack, A., Walker, G., Buyyounouski, M., Horwitz, E., Price, R., Feigenberg, S., Konski, A., Stoyanova, R., Ma, C. 2011; 81 (2): S1-S1
  • Genetic Polymorphisms of DNA Repair and Inflammatory Responses as Determinants of Late Toxicity in Prostate Cancer Patients Who Received Radiotherapy in a Randomized Trial INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Hu, J. J., Stoyanova, R., Deasy, J. O., Chung, R., Martin, E., Buyyounouski, M. K., Allen, G. O., Pollack, A. 2011; 81 (2): S109-S110
  • Prostate Bed Motion during Intensity Modulated Radiotherapy Treatment INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Klayton, T. L., Price, R., Buyyounouski, M. K., Sobczak, M., Greenberg, R. E., Li, J., Kutikov, A., Horwitz, E. M. 2011; 81 (2): S101-S101
  • Treatment-related Side Effects And Quality Of Life Among Prostate Cancer Patients Treated With Conventional versus Hypofractionated Intensity Mediated Radiotherapy: A Phase III Hypofractionation Trial INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Jean-Pierre, P., Stoyanova, R., Penedo, F., Antoni, M., Abramowitz, M., Buyyounouski, M., Pollack, A. 2011; 81 (2): S667-S667
  • Implantation of electromagnetic transponders following radical prostatectomy for delivery of IMRT CANADIAN JOURNAL OF UROLOGY Canter, D., Greenberg, R. E., Horwitz, E. M., Kutikov, A., Li, J., Long, C., Buyyounouski, M., Boorjian, S. A. 2010; 17 (5): 5365-5369

    Abstract

    Radiation therapy (RT) after radical prostatectomy (RP) has been associated with a survival benefit in both the adjuvant and salvage setting. Nevertheless, optimal targeting of the prostate bed following surgery remains challenging. The Calypso 4D Localization System (Calypso Medical Technologies, Seattle, WA, USA) is a target positioning device that continuously monitors the location of three implantable electromagnetic transponders. We describe our technique of ultrasound-guided placement of these transponders into the prostate bed for adjuvant and salvage RT.Seventeen patients presenting to Fox Chase Cancer Center for postoperative RT underwent transrectal ultrasound-guided placement of Calypso beacons. The three transponders were placed approximately 1 cm apart in a triangular fashion around the vesico-urethral anastomosis and in the retrovesicular tissue.All patients were successfully implanted without periprocedural complications. Appropriate beacon position was confirmed by CT scan performed at the time of RT simulation. Intensity-modulated radiation therapy was delivered at a dose of 68 Gy (range 64-68). Treatment was well-tolerated with no Grade 3 or 4 toxicities. Grade > 2 enteritis was not observed, and there were no cases of rectal bleeding. Genitourinary toxicity was noted in 10 patients and consisted of Grade 1 and 2 frequency and dysuria. No patient developed gross hematuria or urinary retention. All patients (9/9) with at least 6 months of follow up after treatment had an undetectable PSA.The placement of Calypso transponders for adjuvant/salvage RT is a safe and efficacious method for treatment targeting with an acceptable acute toxicity profile.

    View details for Web of Science ID 000283634000005

    View details for PubMedID 20974028

  • STEREOTACTIC BODY RADIOTHERAPY FOR EARLY-STAGE NON-SMALL-CELL LUNG CANCER: REPORT OF THE ASTRO EMERGING TECHNOLOGY COMMITTEE INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Buyyounouski, M. K., Balter, P., Lewis, B., D'Ambrosio, D. J., Dilling, T. J., Miller, R. C., Schefter, T., Tome, W., Harris, E. E., Price, R. A., Konski, A. A., Wallner, P. E. 2010; 78 (1): 3-10

    View details for DOI 10.1016/j.ijrobp.2010.04.010

    View details for Web of Science ID 000281304600002

    View details for PubMedID 20643514

  • Androgen Deprivation Therapy in High-Risk Prostate Cancer ONCOLOGY-NEW YORK Buyyounouski, M. K. 2010; 24 (9): 806-809

    View details for Web of Science ID 000293340500003

    View details for PubMedID 20923033

  • RADIOTHERAPY PSA nadir predicts long-term mortality NATURE REVIEWS CLINICAL ONCOLOGY Buyyounouski, M. K. 2010; 7 (4): 188-190

    Abstract

    The effect of PSA level on distant metastases and cause-specific mortality was assessed in a recent study, and showed a nadir PSA level 1.5 ng/ml within 2 years of radiotherapy treatment predicts distant metastases and death from prostate cancer.

    View details for DOI 10.1038/nrclinonc.2010.33

    View details for Web of Science ID 000276152300007

    View details for PubMedID 20354541

  • STEREOTACTIC BODY RADIOTHERAPY FOR PRIMARY MANAGEMENT OF EARLY-STAGE, LOW- TO INTERMEDIATE-RISK PROSTATE CANCER: REPORT OF THE AMERICAN SOCIETY FOR THERAPEUTIC RADIOLOGY AND ONCOLOGY EMERGING TECHNOLOGY COMMITTEE INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Buyyounouski, M. K., Price, R. A., Harris, E. E., Miller, R., Tome, W., Schefter, T., Parsai, E. I., Konski, A. A., Wallner, P. E. 2010; 76 (5): 1297-1304

    View details for DOI 10.1016/j.ijrobp.2009.09.078

    View details for Web of Science ID 000276675300006

    View details for PubMedID 20338473

  • An intraoperative real-time sleeved seed technique for permanent prostate brachytherapy BRACHYTHERAPY Sharma, N. K., Cohen, R. J., Eade, T. N., Buyyounouski, M. K., Uzzo, R. G., Li, J., Crawford, K., Chen, D. Y., McNeeley, S., Horwitz, E. M. 2010; 9 (2): 126-130

    Abstract

    To describe a novel technique that integrates customized sleeved seed production to reduce seed migration using preloaded needles with real-time intraoperative dosimetric planning for patients treated with iodine-125 (I-125) permanent prostate seed implants.Customized seed-spacer sequences were calculated for patients in real time based on an intraoperative transrectal ultrasound-guided volume study. Using a Fox Chase Cancer Center modified Best Iodine-125 seed loader (Best Medical, Springfield, VA), the seeds and spacers were inserted into a hollow suture material (sleeve) and then loaded into the implant needles. Needles were placed sequentially under transrectal ultrasound guidance with sagittal plane visualization of the dropped sleeved seeds.This technique was successfully implemented allowing intraoperative planning to be combined with real-time sleeved seed production.The use of sleeves for seeds combined with real-time intraoperative planning allowed for the intraoperative customization of implants with the practical advantages of linked seeds.

    View details for DOI 10.1016/j.brachy.2009.08.004

    View details for Web of Science ID 000277012000005

    View details for PubMedID 19850534

  • Evaluation of the Prostate Cancer Prevention Trial Risk calculator in a high-risk screening population BJU INTERNATIONAL Kaplan, D. J., Boorjian, S. A., Ruth, K., Egleston, B. L., Chen, D. Y., Viterbo, R., Uzzo, R. G., Buyyounouski, M. K., Raysor, S., Giri, V. N. 2010; 105 (3): 334-337

    Abstract

    Study Type - Diagnostic (exploratory cohort) Level of Evidence 2b.To evaluate the Prostate Cancer Prevention Trial (PCPT) risk calculator in a screening cohort of young, racially diverse, high-risk men with a low baseline prostate-specific antigen (PSA) level and enrolled in the Prostate Cancer Risk Assessment Program (PRAP). The PCPT calculator provides an assessment of prostate cancer risk based on age, PSA level, race, previous biopsy, and family history.Eligibility for PRAP includes men aged 35-69 years who are African-American, have a family history of prostate cancer, or have a known BRCA1/2 mutation. PCPT risk scores were determined for PRAP participants, and were compared to observed prostate cancer rates.In all, 624 participants were evaluated, including 382 (61.2%) African-American men and 242 (38.7%) men with a family history of prostate cancer; the median (range) age was 49.0 (34.0-69.0) years and the median PSA level 0.9 (0.1-27.2) ng/mL. The PCPT risk score correlated with prostate cancer diagnosis, as the median baseline risk score in patients diagnosed with prostate cancer was 31.3%, vs 14.2% in patients not diagnosed with prostate cancer (P < 0.001). The PCPT calculator similarly stratified the risk of diagnosis of Gleason score > or =7 disease, as the median risk score was 36.2% in patients diagnosed with Gleason > or =7 prostate cancer vs 15.2% in all other participants (P < 0.001).The PCPT risk calculator score was found to stratify prostate cancer risk in a cohort of young, primarily African-American men with a low baseline PSA level. These results support further evaluation of this predictive tool for assessing the risk of prostate cancer in high-risk men.

    View details for DOI 10.1111/j.1464-410X.2009.08793.x

    View details for Web of Science ID 000273656600009

    View details for PubMedID 19709072

  • Young Age under 60 is not a Contraindication to Treatment with Definitive High Dose External Beam Radiation Therapy Prostate Cancer INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Klayton, T. L., Ruth, K., Horwitz, E. M., Uzzo, R. G., Kuritzky, N. K., Chen, D. Y., Buyyounouski, M. K. 2010; 78 (3): S334-S334
  • Intermediate-risk Prostate Cancer Treated with High Dose Radiotherapy Alone or in Combination with Androgen Deprivation Therapy: The Fox Chase Experience INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Sopka, D. M., Li, T., Horwitz, E. M., Chen, D. Y., Buyyounouski, M. K. 2010; 78 (3): S351-S352
  • Low Pretreatment PET SUV Predicts for Increased Local Failure following Stereotactic Body Radiation Therapy for Lung Cancer INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Husain, Z. A., Sharma, N. K., Hanlon, A. L., Buyyounouski, M. K., Mirmiran, A., Dhople, A. A., Turaka, A., Yu, M., Chen, W., Feigenberg, S. J. 2010; 78 (3): S525-S525
  • The Stamp Test Delivers the Message on Erectile Dysfunction following High Dose IMRT INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Keller, L. M., Ruth, K., Horwitz, E. M., Pollack, A., Watkins-Bruner, D., Konski, A., Greenberg, R., Price, R., Buyyounouski, M. K. 2010; 78 (3): S596-S597
  • Preliminary Results of RTOG 0233: A Phase II Randomized Trial for Muscle-invading Bladder Cancer Treated by Transurethral Resection and Radiotherapy Comparing Two Forms of Concurrent Induction Chemotherapy INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Zietman, A. L., HUNT, D., Kaufman, D. S., Uzzo, R., Wu, C., Buyyounouski, M. K., Sandler, H., Shipley, W. U. 2010; 78 (3): S31-S32
  • A Practical Strategy to Correct Prostate Rotation Reported by a 4D Localization System INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Li, J., Jin, L., Horwitz, E. M., Buyyounouski, M. K., Price, R. A., Ma, C. 2010; 78 (3): S701-S702
  • Interval to Biochemical Failure is Highly Prognostic for Distant Metastases and Mortality after Salvage Radiation Therapy INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Buyyounouski, M. K., Li, T., Turaka, A., Chen, D. Y., Horwitz, E. M. 2010; 78 (3): S348-S348
  • Conventional versus Hypofractionated IMRT: Results of Late GI and GU Toxicity and Quality of Life from a Phase III Trial INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Turaka, A., Zhu, F., Buyyounouski, M. K., Horwitz, E. M., Watkins-Bruner, D., Konski, A. A., Pollack, A. 2010; 78 (3): S67-S67
  • The Role of Adjuvant and Salvage Post-Prostatectomy IMRT or 3DCRT: The Fox Chase Experience INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Horwitz, E. M., Sharma, N. K., Ruth, K., Silverman, J. S., Buyyounouski, M. K., Chen, D. Y., Greenberg, R. E., Uzzo, R. G. 2010; 78 (3): S333-S334
  • GAINS FROM REAL-TIME TRACKING OF PROSTATE MOTION DURING EXTERNAL BEAM RADIATION THERAPY INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Li, J. S., Jin, L., Pollack, A., Horwitz, E. M., Buyyounouski, M. K., Price, R. A., Ma, C. 2009; 75 (5): 1613-1620

    Abstract

    To study the gains from real-time tracking of prostate motion and threshold-based intervention and the feasibility of margin reduction for external beam radiation therapy of prostate cancer.Prostate intrafractional motion data from 775 randomly selected treatment fractions (105 prostate patients) were analyzed. Statistical distributions of prostate intrafractional displacement from baseline were used for treatment margin calculation together with other geometrical uncertainties for all patients and a subset of 7 patient who exhibited the largest intrafractional motion. Compared with treatment without any intrafractional intervention, potential reductions in treatment margins were evaluated for treatments with 5-mm and 3-mm threshold-based intervention and four-dimensional (4D) treatments with and without prostate rotation correction.The percentage of time of prostate displacement from the baseline by 3 mm and 5 mm in any direction was 13.4% and 1.8%, respectively, for the general patient population. The ratios were 41% and 15% for the 7 selected patients. Reductions in the posterior margin were 0.2, 0.5, 1.3, and 3.1 mm from the original 7.7 mm, respectively, for 5-mm and 3-mm threshold-based treatments and 4D treatments with and without prostate rotation correction for all patients. They were 1.3, 1.9, 3.1 and 4.9 mm from the original 9.5 mm, corresponding to the 7 selected patients. The treatment margin reductions in other directions were even smaller.Real-time motion tracking and threshold-based intrafractional intervention may play a significant roll in treatment margin reduction for a small fraction of patients but not for the general patient population. Four-dimensional treatments with prostate rotation correction can reduce the treatment margin more significantly.

    View details for DOI 10.1016/j.ijrobp.2009.05.022

    View details for Web of Science ID 000272341800046

    View details for PubMedID 19836164

  • Androgen Deprivation Therapy and Prostate Cancer Duration JOURNAL OF CLINICAL ONCOLOGY Williams, S. G., Pickles, T., Buyyounouski, M. K. 2009; 27 (34): E228-E228

    View details for DOI 10.1200/JCO.2009.24.4137

    View details for Web of Science ID 000272177500042

    View details for PubMedID 19884533

  • Optimal PET response following stereotactic body radiotherapy (SBRT) for non-small cell lung cancer (NSCLC) is closely related to the pre-SBRT maximum standard uptake value JOURNAL OF THORACIC ONCOLOGY Feigenberg, S. J., Sharma, N., Yu Jian Q, J. Q., Lally, B., Borghaei, H., Mehra, R., Simon, G., Scott, W., Buyyounouski, M., Unger, M., Movsas, B. 2009; 4 (9): S734-S734
  • Final report of a phase I Dose Escalation Trial of Stereotactic Body Radiotherapy (SBRT) for lung tumors JOURNAL OF THORACIC ONCOLOGY Feigenberg, S. J., Sharma, N., Yu, J. Q., Buyyounouski, M., Borghaei, H., Scott, W., Simon, G., Unger, M., Movsas, B. 2009; 4 (9): S943-S943
  • Surveillance for Stage I Seminoma: Better the Devil You Know Than the Devil You Don't? The Lawrentschuk/Fleshner Article Reviewed ONCOLOGY-NEW YORK Buyyounouski, M. K. 2009; 23 (9): 762-764

    View details for Web of Science ID 000208017300003

    View details for PubMedID 19777760

  • RTOG GU RADIATION ONCOLOGY SPECIALISTS REACH CONSENSUS ON PELVIC LYMPH NODE VOLUMES FOR HIGH-RISK PROSTATE CANCER INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Lawton, C. A., Michalski, J., El-Naqa, I., Buyyounouski, M. K., Lee, W. R., Menard, C., O'Meara, E., Rosenthal, S. A., Ritter, M., Seider, M. 2009; 74 (2): 383-387

    Abstract

    Radiation therapy to the pelvic lymph nodes in high-risk prostate cancer is required on several Radiation Therapy Oncology Group (RTOG) clinical trials. Based on a prior lymph node contouring project, we have shown significant disagreement in the definition of pelvic lymph node volumes among genitourinary radiation oncology specialists involved in developing and executing current RTOG trials.A consensus meeting was held on October 3, 2007, to reach agreement on pelvic lymph node volumes. Data were presented to address the lymph node drainage of the prostate. Extensive discussion ensued to develop clinical target volume (CTV) pelvic lymph node consensus.Consensus was obtained resulting in computed tomography image-based pelvic lymph node CTVs. Based on this consensus, the pelvic lymph node volumes to be irradiated include: distal common iliac, presacral lymph nodes (S(1)-S(3)), external iliac lymph nodes, internal iliac lymph nodes, and obturator lymph nodes. Lymph node CTVs include the vessels (artery and vein) and a 7-mm radial margin being careful to "carve out" bowel, bladder, bone, and muscle. Volumes begin at the L5/S1 interspace and end at the superior aspect of the pubic bone. Consensus on dose-volume histogram constraints for OARs was also attained.Consensus on pelvic lymph node CTVs for radiation therapy to address high-risk prostate cancer was attained and is available as web-based computed tomography images as well as a descriptive format through the RTOG. This will allow for uniformity in evaluating the benefit and risk of such treatment.

    View details for DOI 10.1016/j.ijrobp.2008.08.002

    View details for Web of Science ID 000266057900009

    View details for PubMedID 18947938

  • Dosimetric comparison of stereotactic body radiotherapy using 4D CT and multiphase CT images for treatment planning of lung cancer: Evaluation of the impact on daily dose coverage RADIOTHERAPY AND ONCOLOGY Wang, L., Hayes, S., Paskalev, K., Jin, L., Buyyounouski, M. K., Ma, C. C., Feigenberg, S. 2009; 91 (3): 314-324

    Abstract

    To investigate the dosimetric impact of using 4D CT and multiphase (helical) CT images for treatment planning target definition and the daily target coverage in hypofractionated stereotactic body radiotherapy (SBRT) of lung cancer.For 10 consecutive patients treated with SBRT, a set of 4D CT images and three sets of multiphase helical CT scans, taken during free-breathing, end-inspiration and end-expiration breath-hold, were obtained. Three separate planning target volumes (PTVs) were created from these image sets. A PTV(4D) was created from the maximum intensity projection (MIP) reconstructed 4D images by adding a 3mm margin to the internal target volume (ITV). A PTV(3CT) was created by generating ITV from gross target volumes (GTVs) contoured from the three multiphase images. Finally, a third conventional PTV (denoted PTV(conv)) was created by adding 5mm in the axial direction and 10mm in the longitudinal direction to the GTV (in this work, GTV=CTV=clinical target volume) generated from free-breathing helical CT scans. Treatment planning was performed based on PTV(4D) (denoted as Plan-1), and the plan was adopted for PTV(3CT) and PTV(conv) to form Plan-2 and Plan-3, respectively, by superimposing "Plan-1" onto the helical free-breathing CT data set using modified beam apertures that conformed to either PTV(3CT) or PTV(conv). We first studied the impact of PTV design on treatment planning by evaluating the dosimetry of the three PTVs under the three plans, respectively. Then we examined the effect of the PTV designs on the daily target coverage by utilizing pre-treatment localization CT (CT-on-rails) images for daily GTV contouring and dose recalculation. The changes in the dose parameters of D(95) and D(99) (the dose received by 95% and 99% of the target volume, respectively), and the V(p) (the volume receiving the prescription dose) of the daily GTVs were compared under the three plans before and after setup error correction.For all 10 patients, we found that the PTV(4D) consistently resulted in the smallest volumes compared with the other PTV's (p=0.005). In general, the plans generated based PTV(3CT) could provide reasonably good coverage for PTV(4D), while the reverse can only achieve 90% of the planned values for PTV(3CT). The coverage of both PTV(4D) and PTV(3CT) in Plan-3 generally reserves the original planned values in terms of D(95), D(99), and V(p,) with the average ratios of 0.996, 0.977, and 0.977, respectively, for PTV(3CT), and 1.025, 1.025, and 1.0, respectively, for PTV(4D). However, it increased the dose significantly to normal lung tissue. Additionally, the plans generated using the PTV(4D) presented an equivalent daily target coverage compared to the plans generated using the PTV(3CT) (p=0.953) and PTV(conv) (p=0.773) after setup error correction. Consequently, this minimized the dose to the surrounding normal lung.Compared to the conventional approach using helical images for target definition, 4D CT and multiphase 3D CT have the advantage to provide patient-specific tumor motion information, based on which such designed PTVs could ensure daily target coverage. 4D CT-based treatment planning further reduces the amount of normal lung being irradiated while still providing a good target coverage when image guidance is used.

    View details for DOI 10.1016/j.radonc.2008.11.018

    View details for Web of Science ID 000266749200007

    View details for PubMedID 19111362

  • Correlation of hypoxic prostate/muscle p(O2) (P/M P-O2) ratio and biochemical failure in patients with localized prostate cancer: Long-term results JOURNAL OF CLINICAL ONCOLOGY Turaka, A., Buyyounouski, M. K., Hanlon, A. L., Horwitz, E. M., Greenberg, R. E., Movsas, B. 2009; 27 (15)
  • Residual Prostate Cancer After Radiotherapy: A Study of Radical Cystoprostatectomy Specimens Editorial Comment JOURNAL OF UROLOGY Kaplan, D. J., Crispen, P. L., Greenberg, R. E., Chen, D. Y., Viterbo, R., Buyyounouski, M. K., Horwitz, E. M., Uzzo, R. G. 2009; 181 (5): 2111-2112
  • Race, Genetic West African Ancestry, and Prostate Cancer Prediction by Prostate-Specific Antigen in Prospectively Screened High-Risk Men CANCER PREVENTION RESEARCH Giri, V. N., Egleston, B., Ruth, K., Uzzo, R. G., Chen, D. Y., Buyyounouski, M., Raysor, S., Hooker, S., Torres, J. B., Ramike, T., Mastalski, K., Kim, T. Y., Kittles, R. 2009; 2 (3): 244-250

    Abstract

    "Race-specific" prostate-specific antigen (PSA) needs evaluation in men at high risk for prostate cancer for optimizing early detection. Baseline PSA and longitudinal prediction for prostate cancer were examined by self-reported race and genetic West African (WA) ancestry in the Prostate Cancer Risk Assessment Program, a prospective high-risk cohort. Eligibility criteria were age 35 to 69 years, family history of prostate cancer, African American race, or BRCA1/2 mutations. Biopsies were done at low PSA values (<4.0 ng/mL). WA ancestry was discerned by genotyping 100 ancestry informative markers. Cox proportional hazards models evaluated baseline PSA, self-reported race, and genetic WA ancestry. Cox models were used for 3-year predictions for prostate cancer. Six hundred forty-six men (63% African American) were analyzed. Individual WA ancestry estimates varied widely among self-reported African American men. Race-specific differences in baseline PSA were not found by self-reported race or genetic WA ancestry. Among men with > or =1 follow-up visit (405 total, 54% African American), 3-year prediction for prostate cancer with a PSA of 1.5 to 4.0 ng/mL was higher in African American men with age in the model (P = 0.025) compared with European American men. Hazard ratios of PSA for prostate cancer were also higher by self-reported race (1.59 for African American versus 1.32 for European American, P = 0.04). There was a trend for increasing prediction for prostate cancer with increasing genetic WA ancestry. "Race-specific" PSA may need to be redefined as higher prediction for prostate cancer at any given PSA in African American men. Large-scale studies are needed to confirm if genetic WA ancestry explains these findings to make progress in personalizing prostate cancer early detection.

    View details for DOI 10.1158/1940-6207.CAPR-08-0150

    View details for Web of Science ID 000264294600009

    View details for PubMedID 19240249

  • Initial PSA (iPSA) and Radiation Dose Predict for an Undetectable PSA following 3DCRT or IMRT for Low-intermediate Risk Prostate Cancer INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Sharma, N. K., Ruth, K. J., Boorjian, S. A., Uzzo, R. G., Buyyounouski, M. K., Horwitz, E. M. 2009; 75 (3): S313-S313
  • Defining Biochemical Failure following Salvage Radiotherapy INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Lubbe, W. J., Ruth, K., Devarajan, K., Horwitz, E. M., Boorjian, S., Buyyounouski, M. K. 2009; 75 (3): S330-S330
  • A Potential Outcomes Framework to Determine Whether Age and Medical Co-morbidities Predict Who is Harmed by Combined Androgen Deprivation Therapy INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Silverman, J. S., Egleston, B., Horwitz, E. M., Chen, D. Y., Buyyounouski, M. K. 2009; 75 (3): S326-S326
  • Is MRI-based Week Three Post-implant Dosimetry Necessary following LDR Prostate Brachytherapy? INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Cohen, R. J., Sharma, N. K., Ruth, K., Buyyounouski, M. K., Li, J., Crawford, K., Feigenberg, S. J., Chen, D. Y., Uzzo, R. G., Horwitz, E. M. 2009; 75 (3): S298-S298
  • Validating the Interval to Biochemical Failure for the Identification of Potentially Lethal Prostate Cancer INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Buyyounouski, M. K., Pickles, T., Kestin, L., Allison, R., Williams, S. G. 2009; 75 (3): S103-S104
  • Undetectable Post-treatment PSA following 3DCRT or IMRT Alone for Patients with Low or Intermediate Risk Prostate Cancer is an Independent Predictor of Biochemical and Clinical Outcome INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Horwitz, E. M., Ruth, K. J., Sharma, N. K., Chen, D. Y., Buyyounouski, M. K., Uzzo, R. G. 2009; 75 (3): S301-S301
  • Hypofractionation for Prostate Cancer: Interim Results of a Randomized Trial INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Pollack, A., Li, T., Buyyounouski, M., Horwitz, E., Price, R., Feigenberg, S., Konski, A., Greenberg, R., Uzzo, R., Ma, C. 2009; 75 (3): S81-S82
  • DOES TREATMENT DURATION AFFECT OUTCOME AFTER RADIOTHERAPY FOR PROSTATE CANCER? INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS D'Ambrosio, D. J., Li, T., Horwitz, E. M., Chen, D. Y., Pollack, A., Buyyounouski, M. K. 2008; 72 (5): 1402-1407

    Abstract

    The protraction of external beam radiotherapy (RT) time is detrimental in several disease sites. In prostate cancer, the overall treatment time can be considerable, as can the potential for treatment breaks. We evaluated the effect of elapsed treatment time on outcome after RT for prostate cancer.Between April 1989 and November 2004, 1,796 men with prostate cancer were treated with RT alone. The nontreatment day ratio (NTDR) was defined as the number of nontreatment days divided by the total elapsed days of RT. This ratio was used to account for the relationship between treatment duration and total RT dose. Men were stratified into low risk (n = 789), intermediate risk (n = 798), and high risk (n = 209) using a single-factor model.The 10-year freedom from biochemical failure (FFBF) rate was 68% for a NTDR <33% vs. 58% for NTDR >/=33% (p = 0.02; BF was defined as a prostate-specific antigen nadir + 2 ng/mL). In the low-risk group, the 10-year FFBF rate was 82% for NTDR <33% vs. 57% for NTDR >/=33% (p = 0.0019). The NTDR was independently predictive for FFBF (p = 0.03), in addition to T stage (p = 0.005) and initial prostate-specific antigen level (p < 0.0001) on multivariate analysis, including Gleason score and radiation dose. The NTDR was not a significant predictor of FFBF when examined in the intermediate-risk group, high-risk group, or all risk groups combined.A proportionally longer treatment duration was identified as an adverse factor in low-risk patients. Treatment breaks resulting in a NTDR of >/=33% (e.g., four or more breaks during a 40-fraction treatment, 5 d/wk) should be avoided.

    View details for DOI 10.1016/j.ijrobp.2008.03.011

    View details for Web of Science ID 000261214600020

    View details for PubMedID 18472368

  • Residual prostate cancer after radiotherapy: A study of radical cystoprostatectomy specimens UROLOGY Kaplan, D. J., Crispen, P. L., Greenberg, R. E., Chen, D. Y., Viterbo, R., Buyyounouski, M. K., Horwitz, E. M., Uzzo, R. G. 2008; 72 (3): 654-658

    Abstract

    The incidence of histologic prostate cancer (CaP) after definitive radiation therapy (RT) for localized disease is rarely quantitated. We investigated the relationship between prostate-specific antigen (PSA) and histologically residual CaP after definitive RT in patients undergoing radical cystoprostatectomy (RCP) for unrelated indications.We reviewed our prostate cancer database to identify patients undergoing RCP who previously received definitive RT for localized CaP. Pre-radiation variables examined include PSA, Gleason score, radiation modality, and dose. Post-radiation variables reviewed include PSA, time to RCP, the presence of histologically proven prostate cancer, and Gleason score.We identified 21 patients who underwent RCP at a median of 60 months after RT for localized CaP. Pre-radiation Gleason scores were low (6 or less) to intermediate risk (3+4) in 82% (14 of 17), intermediate (4+3) to high (8 or greater) in 18% (3 of 17), and unavailable in 4 patients. Median pre-radiation PSA was 9 ng/mL. Median PSA before RCP in all patients was 0.8 ng/mL. A total of 52% (11 of 21) of patients demonstrated active CaP in the RCP specimen. Although 89% (16 of 18) of patients met the Phoenix definition of biochemical freedom from disease, 50% (8 of 16) of these patients had histologically residual CaP at the time of RCP. Median PSA was not significantly different between patients with and without active CaP.Histologic evidence of CaP was noted in 50% of patients demonstrating biochemical freedom from disease at the time of RCP. Although the biological significance of active CaP in this select population is uncertain, our findings demonstrate the limitations of PSA in monitoring CaP disease activity after definitive RT.

    View details for DOI 10.1016/j.urology.2007.11.020

    View details for Web of Science ID 000259853800056

    View details for PubMedID 18289645

  • Comment on dose escalation and biochemical failure in prostate cancer: In regard to Kuban et al. (Int J Radiat Oncol Biol Phys 2008;70 : 67-74) - In reply to Drs. Schultz and Kagan INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Pollack, A., Eade, T. M., Horwitz, E. M., Buyyounouski, M. K., Hanks, G. E. 2008; 71 (4): 1288-1289
  • A comparison of acute and chronic toxicity for men with low-risk prostate cancer treated with intensity-modulated radiation therapy or I-125 permanent implant INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Eade, T. N., Horwitz, E. M., Ruth, K., Buyyounouski, M. K., D'Ambrosio, D. J., Feigenberg, S. J., Chen, D. Y., Pollack, A. 2008; 71 (2): 338-345

    Abstract

    To compare the toxicity and biochemical outcomes of intensity-modulated radiation therapy (IMRT) and (125)I transperineal permanent prostate seed implant ((125)I) for patients with low-risk prostate cancer.Between 1998 and 2004, a total of 374 low-risk patients (prostate-specific antigen < 10 ng/ml, T1c-T2b, Gleason score of 6 or less, and no neoadjuvant hormones) were treated at Fox Chase Cancer Center (216 IMRT and 158 (125)I patients). Median follow-up was 43 months for IMRT and 48 months for (125)I. The IMRT prescription dose ranged from 74-78 Gy, and (125)I prescription was 145 Gy. Acute and late gastrointestinal (GI) and genitourinary (GU) toxicity was recorded by using a modified Radiation Therapy Oncology Group scale. Freedom from biochemical failure was defined by using the Phoenix definition (prostate-specific antigen nadir + 2.0 ng/ml).Patients treated by using IMRT were more likely to be older and have a higher baseline American Urological Association symptom index score, history of previous transurethral resection of the prostate, and larger prostate volumes. On multivariate analysis, IMRT was an independent predictor of lower acute and late Grade 2 or higher GU toxicity and late Grade 2 or higher GI toxicity. Three-year actuarial estimates of late Grade 2 or higher toxicity were 2.4% for GI and 3.5% for GU by using IMRT compared with 7.7% for GI and 19.2% for GU for (125)I, respectively. Four-year actuarial estimates of freedom from biochemical failure were 99.5% for IMRT and 93.5% for (125)I (p = 0.09).The IMRT and (125)I produce similar outcomes, although IMRT appears to have less acute and late toxicity.

    View details for DOI 10.1016/j.ijrobp.2007.10.019

    View details for Web of Science ID 000255971100005

    View details for PubMedID 18207665

  • Does transurethral resection of prostate (TURP) affect outcome in patients who subsequently develop prostate cancer? UROLOGY D'Ambrosio, D. J., Ruth, K., Horwitz, E. M., Chen, D. Y., Pollack, A., Buyyounouski, M. K. 2008; 71 (5): 938-941

    Abstract

    Pretreatment prostate specific antigen (PSA) is a strong predictor of prostate cancer outcome after radiotherapy and is a key parameter in pretreatment risk assessment. Because PSA is secreted from both benign and malignant tissue, a prior transurethral resection of prostate (TURP) may lower pretreatment PSA levels out of proportion to the extent of cancer. The purpose of this study was to determine whether a history of TURP is associated with increased biochemical failure (BF) after definitive radiotherapy for prostate cancer.From April 1989 to October 2001, 1135 men with low to intermediate risk T1c-2NX/0M0 (2002 AJCC) prostate cancer with a pretreatment PSA less than 20 ng/mL received three-dimensional conformal radiotherapy (median dose, 76 Gy) without androgen deprivation. The median pretreatment PSA was 7.4 ng/mL (range, 0.4 to 19.9). There were 126 men with a prior history of TURP. The Cox proportional hazards model was used for univariate and multivariate analyses for BF (nadir + 2 ng/mL definition).On multivariable analysis, Gleason score (GS), PSA, and T-stage were significant predictors of BF in a model containing TURP and dose. A history of TURP was not a significant independent predictor of BF on subgroup analysis. There was a trend toward significance for the subgroup of GS less than 7 (P = 0.12).A history of prior TURP does not affect outcome after RT for prostate cancer in low to intermediate risk patients.

    View details for DOI 10.1016/j.urology.2007.09.049

    View details for Web of Science ID 000255992000053

    View details for PubMedID 18279939

  • Influence of local tumor control on distant metastases and cancer related mortality after external, beam radiotherapy for prostate cancer - Editorial comment JOURNAL OF UROLOGY Buyyounouski, M. K. 2008; 179 (4): 1373-1373
  • How can men destined for biochemical failure after androgen deprivation and radiotherapy be identified earlier? INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS D'Ambrosio, D. J., Ruth, K., Horwitz, E. M., Uzzo, R. G., Pollack, A., Buyyounouski, M. K. 2008; 70 (5): 1487-1491

    Abstract

    The significance of prostate-specific antigen (PSA) increases during the recovery of androgen after androgen deprivation therapy (ADT) and radiotherapy for prostate cancer is not well understood. This study sought to determine whether the initial PSA increase from undetectable after completion of all treatment predicts for eventual biochemical failure (BF).Between July 1992 and March 2004, 163 men with a Gleason score of 8-10 or initial PSA level >20 ng/mL, or Stage T3 prostate cancer were treated with radiotherapy (median dose, 76 Gy) and ADT and achieved an undetectable PSA level. The first detectable PSA level after the cessation of ADT was defined as the PSA sentinel rise (SR). A PSA-SR of >0.25, >0.5, >0.75, and >1.0 ng/mL was studied as predictors of BF (nadir plus 2 ng/mL). Cox proportional hazards models were used for univariate and multivariate analyses for BF adjusting for pretreatment differences in Gleason score, stage, PSA level (continuous), dose (continuous), and ADT duration (<12 vs. > or = 12 months).Of the 163 men, 41 had BF after therapy. The median time to BF was 25 months (range, 4-96). The 5-year BF rate stratified by a PSA-SR of < or = 0.25 vs. >0.25 ng/mL was 28% vs. 43% (p = 0.02), < or = 0.5 vs. >0.5 ng/mL was 30% vs. 56% (p = 0.0003), < or = 0.75 vs. >0.75 ng/mL was 29% vs. 66% (p < 0.0001), and < or = 1.0 vs. >1.0 ng/mL was 29% vs. 75% (p < 0.0001). All four PSA-SRs were independently predictive of BF on multivariate analysis.The PSA-SR predicts for BF. A PSA-SR of >0.5 ng/mL can be used for early identification of men at greater risk of BF.

    View details for DOI 10.1016/j.ijrobp.2007.08.057

    View details for Web of Science ID 000254660800030

    View details for PubMedID 18164854

  • Percentage of biopsy cores positive for malignancy and biochemical failure following prostate cancer radiotherapy in 3,264 men: Statistical significance without predictive performance INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Williams, S. G., Buyyounouski, M. K., Pickles, T., Kestin, L., Martinez, A., Hanlon, A. L., Duchesne, G. M. 2008; 70 (4): 1169-1175

    Abstract

    To define and incorporate the impact of the percentage of positive biopsy cores (PPC) into a predictive model of prostate cancer radiotherapy biochemical outcome.The data of 3264 men with clinically localized prostate cancer treated with external beam radiotherapy at four institutions were retrospectively analyzed. Standard prognostic and treatment factors plus the number of biopsy cores collected and the number positive for malignancy by transrectal ultrasound-guided biopsy were available. The primary endpoint was biochemical failure (bF, Phoenix definition). Multivariate proportional hazards analyses were performed and expressed as a nomogram and the model's predictive ability assessed using the concordance index (c-index).The cohort consisted of 21% low-, 51% intermediate-, and 28% high-risk cancer patients, and 30% had androgen deprivation with radiotherapy. The median PPC was 50% (interquartile range [IQR] 29-67%), and median follow-up was 51 months (IQR 29-71 months). Percentage of positive biopsy cores displayed an independent association with the risk of bF (p=0.01), as did age, prostate-specific antigen value, Gleason score, clinical stage, androgen deprivation duration, and radiotherapy dose (p<0.001 for all). Including PPC increased the c-index from 0.72 to 0.73 in the overall model. The influence of PPC varied significantly with radiotherapy dose and clinical stage (p=0.02 for both interactions), with doses<66 Gy and palpable tumors showing the strongest relationship between PPC and bF. Intermediate-risk patients were poorly discriminated regardless of PPC inclusion (c-index 0.65 for both models).Outcome models incorporating PPC show only minor additional ability to predict biochemical failure beyond those containing standard prognostic factors.

    View details for DOI 10.1016/j.ijrobp.2007.08.021

    View details for Web of Science ID 000253942900028

    View details for PubMedID 17967518

  • Commentary on dose escalation and biochemical failure in prostate cancer: In regard to Eade et al. (Int J Radiat Oncol Biol Phys 2007;68 : 682-689) - In reply INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Pollack, A., Eade, T. N., Hanlon, A. L., Horwitz, E. M., Buyyounouski, M. K., Hanks, G. E. 2008; 70 (2): 645-646
  • Predicting local persistence of intermediate and high-risk prostate cancer using percentage of adenocarcinoma in pretreatment biopsy tissue INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Buyyounouski, M. K., Li, T., Al-Saleem, T., Horwitz, E., Konski, A., Feigenberg, S., Uzzo, R., Greenberg, R., Pollack, A. 2008; 72 (1): S321-S322
  • Interval to biochemical failure highly prognostic for distant metastasis and prostate cancer-specific mortality after radiotherapy INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Buyyounouski, M. K., Hanlon, A. L., Horwitz, E. M., Pollack, A. 2008; 70 (1): 59-66

    Abstract

    Few biochemical parameters have been related to mortality. The present study examined the clinical utility of the interval to biochemical failure (IBF) as a prognostic factor for distant metastasis (DM) and prostate cancer-specific mortality (PCSM) after radiotherapy.The study group consisted of 211 T1c-T3Nx-N0M0 patients who had experienced BF among 1,174 men treated with three-dimensional conformal radiotherapy alone. Biochemical failure was defined as a post-treatment prostate-specific antigen (PSA) level of at, or greater than, the PSA nadir plus 2 ng/mL. Cox proportional hazards modeling was used to identify independent predictors of DM and PCSM on multivariate analysis.An IBF of <18 months was independently predictive for DM (p = 0.008), as was a Gleason score of 7-10 (p = 0.0005), PSA nadir >or=2 ng/mL (p = 0.04), and decreasing radiation dose (p = 0.02) on multivariate analysis, including increasing pretreatment PSA level, PSA nadir >or=2.5 ng/mL, PSA doubling time of <3 months, and Stage T3 disease. An IBF of <18 months was the only predictor of PCSM (p = 0.0003) in the same model. The actuarial 5-year DM rate for an IBF of <18 vs. >or=18 months was 52% vs. 20% (p < 0.0001), and the actuarial PCSM rate was 36% vs. 6%, respectively (p = 0.0001).The IBF is an important descriptor of the PSA kinetics after radiotherapy to identify men at high risk of clinical failure and death. A IBF of <18 months could aid in selecting men for early, aggressive salvage therapy or participation in a clinical trial.

    View details for DOI 10.1016/j.ijrobp.2007.05.047

    View details for Web of Science ID 000251867700008

    View details for PubMedID 17919840

  • Low morbidity and excellent local control using image guided stereotactic body radiotherapy (IGSBRT) for lung tumors INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Sharma, N. K., Ruth, K., Konski, A. A., Buyyounouski, M. K., Nicolaou, N., Lally, B. E., Yu, J. Q., Langer, C. J., Movsas, B., Feigenberg, S. J. 2008; 72 (1): S454-S454
  • Gains from real-time prostate motion monitoring during external beam radiation therapy INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Li, J., Jin, L., Horwitz, E., Buyyounouski, M., Pollack, A., Johnston, S., Price, R., Ma, C. 2008; 72 (1): S287-S288
  • The optimum duration of combination androgen deprivation therapy (ADT) with prostate cancer radiotherapy: Determining the duration-benefit relationship from multi-institutional analysis INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Pickles, T., Williams, S. G., Buyyounouski, M. K., Kestin, L. L., Duchesne, G. M. 2008; 72 (1): S73-S73
  • The phoenix definition of biochemical failure predicts for overall survival in patients with prostate cancer CANCER Abramowitz, M. C., Li, T., Buyyounouski, M. K., Ross, E., Uzzo, R. G., Pollack, A., Horwitz, E. M. 2008; 112 (1): 55-60

    Abstract

    The American Society for Therapeutic Radiology and Oncology (ASTRO) definition of biochemical failure (BF) incorporates backdating, resulting in an artificial flattening of Kaplan-Meier curves and overly favorable estimates when follow-up is short. The nadir + 2 ng/mL (Nadir + 2; Phoenix) definition reduces these artifacts. The objective of the current study was to compare ASTRO and Phoenix BF estimates as determinants of distant metastasis (DM), cause-specific mortality (CSM), and overall mortality (OM).A total of 1831 patients with T1-4N0M0 prostate cancer were treated with external beam radiotherapy (RT) using conventional or three-dimensional conformal methods to at least 60 grays (Gy). The median follow-up was 71 months and the median RT dose was 72 Gy (range, 60-79 Gy). Cox regression models incorporating BF as a time-dependent covariate were used for both univariate and multivariate analyses. Other covariates included in the analyses were T classification, Gleason score, neoadjuvant/adjuvant androgen deprivation, age, RT dose, and pretreatment prostate-specific antigen.BF was observed in 389 men (21%) using the Phoenix definition and 460 men (25%) using the ASTRO definition. DM was observed in 84 patients (5%), 48 patients (3%) patients died of prostate cancer, and 404 patients (22%) died of any cause. The Phoenix definition of BF was found to be a significant predictor of DM, CSM, and OM, after controlling for other significant covariates. The ASTRO definition was found to be associated with CSM and DM, but not OM.The Phoenix definition of BF is a more robust determinant of patient outcome compared with the ASTRO definition. The correlation with mortality, including OM, and the independence of this correlation from the use of neoadjuvant/adjuvant androgen deprivation, supports the use of Nadir + 2 in prostate cancer clinical trials of RT with or without androgen deprivation.

    View details for DOI 10.1002/cncr.23139

    View details for Web of Science ID 000251994400008

    View details for PubMedID 17968996

  • Androgen deprivation therapy plus hypofractionated prostate radiotherapy-are we castrating the radiobiological advantage? INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Williams, S. G., Pickles, T., Kestin, L., Buyyounouski, M., Martinez, A., Demanes, J., Taylor, J. M., Duchesne, G. 2008; 72 (1): S73-S74
  • Radiation therapy for high risk prostate cancer: Do patients 70 years or older benefit from combined androgen deprivation therapy? INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Silverman, J. S., Ruth, K., Horwitz, E. M., Pollack, A., Chen, D. Y., Buyyounouski, M. K. 2008; 72 (1): S75-S76
  • Estimating gains in biochemical outcome from various durations of androgen deprivation in patients treated with dose escalated radiotherapy for prostate cancer using two nomograms INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Pahlajani, N. H., Egleston, B. L., Buyyounouski, M. K., Chen, D. Y., Horwitz, E., Pollack, A. 2008; 72 (1): S54-S54
  • PSA doubling time predicts for the development of distant metastases for patients who fail 3DCRT or IMRT using the Phoenix definition INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Horwitz, E. M., Ruth, K., Uzzo, R. G., Buyyounouski, M. K., Wong, Y., Chen, D. Y., Pollack, A. 2008; 72 (1): S135-S136
  • Prostate cancer risk assessment program: A 10-year update of cancer detection JOURNAL OF UROLOGY Giri, V. N., Beebe-Dimmer, J., Buyyounouski, M., Konski, A., Feigenberg, S. J., Uzzo, R. G., Hanks, G., Godwin, A. K., Chen, D. Y., Gordon, R., Cescon, T., Raysor, S., Watkins-Bruner, D. 2007; 178 (5): 1920-1924

    Abstract

    Guidelines for screening men at high risk for prostate cancer remain under investigation. We report our 10-year cancer detection data from the Prostate Cancer Risk Assessment Program, a longitudinal screening program for men at high risk.Men between ages 35 and 69 years with a family history of prostate cancer, any black man regardless of family history or any patient with a known mutation in the BRCA 1 gene are eligible for the Prostate Cancer Risk Assessment Program and undergo longitudinal followup. Cancer detection, prostate cancer features and the predictive value of screening parameters were determined based on Prostate Cancer Risk Assessment Program biopsy criteria.A total of 609 men were accrued to the Prostate Cancer Risk Assessment Program as of the end of June 2006, of whom 61.2% were black. Of all participants 19% underwent prostate biopsies. The prostate cancer incidence was 9.0%, more than 90% of prostate cancers were Gleason score 6 or higher and 22% were Gleason score 7 or higher. The majority were organ confined. Of men diagnosed with prostate cancer 20% had a prostate specific antigen of less than 2.5 ng/ml and a free prostate specific antigen of less than 25% with a normal digital rectal examination.Our results support aggressive screening measures for men at high risk for prostate cancer. The majority of cancers detected were at a prostate specific antigen of less than 4.0 ng/ml with a fifth diagnosed at a prostate specific antigen of below 2.5 ng/ml. These cancers were intermediate to high grade and organ confined, indicating a greater likelihood of cure following local therapy in these men.

    View details for DOI 10.1016/j.juro.2007.07.010

    View details for Web of Science ID 000250187000020

    View details for PubMedID 17868726

  • Timing of biochemical failure and distant metastatic disease for low-, intermediate-, and high-risk prostate cancer after radiotherapy CANCER Morgan, P. B., Hanlon, A. L., Horwitz, E. M., Buyyounouski, M. K., Uzzo, R. G., Pollack, A. 2007; 110 (1): 68-80

    Abstract

    The relation of prostate cancer risk-group stratification and the timing of biochemical failure (BF) and distant metastasis (DM) is not well defined. The authors hypothesized that early failures due to subclinical micrometastasis at presentation could be differentiated from late failures due to local persistence.A total of 1833 men with clinically localized prostate cancer treated with 3D-conformal radiotherapy with or without short-term androgen deprivation were retrospectively analyzed. By using American Society for Therapeutic Radiology and Oncology (ASTRO) and Phoenix (Nadir+2) definitions (developed at the ASTRO-RTOG [Radiation Therapy Oncology Group] consensus meeting, Phoenix, Arizona, January 21, 2005), the interval hazard rates of BF and DM were determined for men with low-risk, intermediate-risk, and high-risk disease.Median follow-up was 67 months. Multivariate analysis showed that increasing risk group was independently associated with higher ASTRO BF (P < .0001) and Nadir+2 BF (P < .0001). The preponderance (87%) of ASTRO BF occurred 4 years. The hazard of Nadir+2 BF persisted in Years 8-12 in all risk groups. The interval hazard function for DM appeared to be biphasic (early peak followed by a drop and late increase) for intermediate-risk and high-risk patients, but no distinct early wave was evident for low-risk patients.Because of backdating, ASTRO BF underestimates late BF. Local persistence of disease is suggested by delayed Nadir+2 BF and subsequent late DM in every risk group. The paucity of early DM among those with low-risk tumors supports the hypothesis that occult micrometastases contributed to the early wave.

    View details for DOI 10.1002/cncr22755

    View details for Web of Science ID 000247384200009

    View details for PubMedID 17520705

  • What dose of external-beam radiation is high enough for prostate cancer? INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Eade, T. N., Hanlon, A. L., Horwitz, E. M., Buyyounouski, M. K., Hanks, G. E., Pollack, A. 2007; 68 (3): 682-689

    Abstract

    To quantify the radiotherapy dose-response of prostate cancer, adjusted for prognostic factors in a mature cohort of men treated relatively uniformly at a single institution.The study cohort consisted of 1,530 men treated with three-dimensional conformal external-beam radiotherapy between 1989 and 2002. Patients were divided into four isocenter dose groups: <70 Gy (n = 43), 70-74.9 Gy (n = 552), 75-79.9 Gy (n = 568), and > or =80 Gy (n = 367). The primary endpoints were freedom from biochemical failure (FFBF), defined by American Society for Therapeutic Radiology and Oncology (ASTRO) and Phoenix (nadir + 2.0 ng/mL) criteria, and freedom from distant metastases (FFDM). Multivariate analyses were performed and adjusted Kaplan-Meier estimates were calculated. Logit regression dose-response functions were determined at 5 and 8 years for FFBF and at 5 and 10 years for FFDM.Radiotherapy dose was significant in multivariate analyses for FFBF (ASTRO and Phoenix) and FFDM. Adjusted 5-year estimates of ASTRO FFBF for the four dose groups were 60%, 68%, 76%, and 84%. Adjusted 5-year Phoenix FFBFs for the four dose groups were 70%, 81%, 83%, and 89%. Adjusted 5-year and 10-year estimates of FFDM for the four dose groups were 96% and 93%, 97% and 93%, 99% and 95%, and 98% and 96%. Dose-response functions showed an increasing benefit for doses > or =80 Gy.Doses of > or =80 Gy are recommended for most men with prostate cancer. The ASTRO definition of biochemical failure does not accurately estimate the effects of radiotherapy at 5 years because of backdating, compared to the Phoenix definition, which is less sensitive to follow-up and more reproducible over time.

    View details for DOI 10.1016/j.ijrobp.2007.01.008

    View details for Web of Science ID 000247284600007

    View details for PubMedID 17398026

  • Daily localization for prostate bed patients based on surgical clips MEDICAL PHYSICS Paskalev, K., Horwitz, E., Price, R., Feigenberg, S., Buyyounouski, M., Chen, Y., Konski, A., Silverman, I., Ma, C., Pollack, A. 2007; 34 (6): 2381-2382
  • Dosimetric comparison of 4D and 3 multi-phase CT imaging for stereotactic body radiation therapy (SBRT) planning in lung cancer MEDICAL PHYSICS Wang, L., Jin, L., Hayes, S., Paskalev, K., Buyyounouski, M., Feigenberg, S. 2007; 34 (6): 2384-2384
  • Surface smoothing of a tubular structure using a non-shrinking algorithm MEDICAL PHYSICS Chen, Y., Paskalev, K., Horwitz, E., Price, R., Buyyounouski, M., Ma, C., Pollack, A. 2007; 34 (6): 2637-2637
  • Do stranded seeds improve the quality of permanent prostate seed implant? MEDICAL PHYSICS Li, J., Horwitz, E., Buyyounouski, M., McNeeley, S., Crawford, K., Ma, C. 2007; 34 (6): 2330-2330
  • Role of radiotherapy in ductal (endometrioid) carcinoma of the prostate CANCER Eade, T. N., Al-Saleem, T., Horwitz, E. M., Buyyounouski, M. K., Chen, D. Y., Pollack, A. 2007; 109 (10): 2011-2015

    Abstract

    Ductal carcinoma of the prostate is a rare variant of prostate cancer that presents most commonly with obstructive urinary symptoms or hematuria. This case series of 6 patients is the first to report the outcome of ductal carcinoma treated with external beam radiotherapy.A retrospective review was performed of patients treated between 1980 and 2006 at Fox Chase Cancer Center, Philadelphia, Penn. Six patients were identified with ductal carcinoma.Five of the 6 patients were treated definitively and the sixth patient was treated at recurrence 3 years after a radical prostatectomy. Patient ages ranged from 66-80 years and the initial prostate-specific antigen (iPSA) ranged from 1.69-100.3 ng/mL. Three patients had a mixed acinar and ductal carcinoma, 2 with a Gleason score (GS) of 8 and 1 with a GS of 7. Of the patients treated definitively, 4 had clinical stage T2A-T2C and 1 had clinical stage T1B. Definitive radiotherapy was delivered to the prostate with doses between 72 Gy and 78 Gy. Pelvic lymph nodes were treated in all patients. One patient was treated postradical prostatectomy to the prostate bed to a dose of 60 Gy. Adjuvant androgen deprivation was given in 5 of the patients. Two of the patients died from metastatic disease at 1.4 and 7.1 years after treatment. The remaining 4 patients remain alive between 3.2 and 4.8 years from treatment, with 3 patients biochemically without evidence of disease. No patients have developed a local recurrence.Ductal carcinoma of the prostate may be treated effectively with external beam radiotherapy. Aggressive management is indicated, even with low-volume metastatic disease.

    View details for DOI 10.1002/cncr22644

    View details for Web of Science ID 000246252800012

    View details for PubMedID 17420979

  • Radiation dose and late failures in prostate cancer INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Morgan, P. B., Hanlon, A. L., Horwitz, E. M., Buyyounouski, M. K., Uzzo, R. G., Pollack, A. 2007; 67 (4): 1074-1081

    Abstract

    To quantify the impact of radiation dose escalation on the timing of biochemical failure (BF) and distant metastasis (DM) for prostate cancer treated with radiotherapy (RT) alone.The data from 667 men with clinically localized intermediate- and high-risk prostate cancer treated with three-dimensional conformal RT alone were retrospectively analyzed. The interval hazard rates of DM and BF, using the American Society for Therapeutic Radiology and Oncology (ASTRO) and Phoenix (nadir + 2) definitions, were determined. The median follow-up was 77 months.Multivariate analysis showed that increasing radiation dose was independently associated with decreased ASTRO BF (p < 0.0001), nadir + 2 BF (p = 0.001), and DM (p = 0.006). The preponderance (85%) of ASTRO BF occurred at < or =4 years after RT, and nadir + 2 BF was more evenly spread throughout Years 1-10, with 55% of BF in < or =4 years. Radiation dose escalation caused a shift in the BF from earlier to later years. The interval hazard function for DM appeared to be biphasic (early and late peaks) overall and for the <74-Gy group. In patients receiving > or =74 Gy, a reduction occurred in the risk of DM in the early and late waves, although the late wave appeared reduced to a greater degree.The ASTRO definition of BF systematically underestimated late BF because of backdating. Radiation dose escalation diminished and delayed BF; the delay suggested that local persistence may still be present in some patients. For DM, a greater radiation dose reduced the early and late waves, suggesting that persistence of local disease contributed to both.

    View details for DOI 10.1016/j.ijrobp.2006.10.023

    View details for Web of Science ID 000245021100016

    View details for PubMedID 17197131

  • The proportion of prostate biopsy tissue with Gleason pattern 4 or 5 predicts for biochemical and clinical outcome after radiotherapy for prostate cancer INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS D'Ambrosio, D. J., Hanlon, A. L., Al-Saleem, T., Feigenberg, S. J., Horwitz, E. M., Uzzo, R. G., Pollack, A., Buyyounouski, M. K. 2007; 67 (4): 1082-1087

    Abstract

    To investigate the prognostic utility of the proportion of prostate biopsy tissue containing Gleason pattern 4 or 5 (GP4/5) after definitive radiotherapy (RT) for prostate cancer.A total of 568 patients with T1c-3 Nx/0 prostate cancer who received three-dimensional conformal RT alone between May 1989 and August 2001 were studied. There were 161 men with Gleason score 7-10 disease. The GP4/5 was defined as the percentage of biopsy tissue containing Gleason pattern 4 or 5. A Cox proportional hazards model was used for univariate and multivariate analyses (MVA) for biochemical failure (BF) (American Society of Therapeutic Radiology and Oncology definition) and distant metastasis (DM). A recursive partitioning analysis was done using the results of the MVA to identify a cutpoint for GP4/5.The median follow-up was 46 (range, 13-114) months and median RT dose was 76 (range, 65-82) Gy. On MVA, increasing initial prostate-specific antigen (p = 0.0248) decreasing RT dose (continuous, p = 0.0022), T stage (T1/2 vs. T3), (p = 0.0136) and GP4/5 (continuous, p < 0.0001) were significant predictors of BF in a model also containing GS. GP4/5 was the only significant predictor of DM in the same model (p < 0.0001).The GP4/5 in prostate biopsy specimens is a predictor of BF and DM after RT independent of Gleason score. This parameter should be reported by the pathologist when reviewing prostatic biopsy specimens.

    View details for DOI 10.1016/j.ijrobp.2006.09.050

    View details for Web of Science ID 000245021100017

    View details for PubMedID 17241749

  • FDG PET response by 3 months following stereotactic body radiotherapy for non-small cell lung cancer may be an early surrogate of local failure INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Feigenberg, S., Yu, J. Q., Eade, T. N., Buyyounouski, M., Wang, L., Langer, C., Scott, W., Konski, A., Movsas, B. 2007; 69 (3): S479-S480
  • Prostate-specific antigen nadir within 12 months of prostate cancer radiotherapy predicts metastasis and death CANCER Alcantara, P., Hanlon, A., Buyyounouski, M. K., Horwitz, E. M., Pollack, A. 2007; 109 (1): 41-47

    Abstract

    The nadir prostate-specific antigen (PSA) at 1 year (nPSA12) was investigated as an early estimate of biochemical and clinical outcome after radiotherapy (RT) alone for localized prostate cancer.METHODS.From May 1989 to November 1999, 1000 men received 3D conformal RT alone (median, 76 Gy) with minimum and median follow-up periods of 26 and 58 months, respectively, from the end of treatment. The calculation of PSA doubling time (PSADT) was possible in 657 patients. Multivariate analyses (MVAs) via Cox proportional hazards regression were used to determine the association of nPSA12 to biochemical failure (BF; ASTRO definition), distant metastasis (DM), cause-specific mortality (CSM), and overall mortality (OM). Dichotomization of nPSA12 was optimized by evaluating the sequential model likelihood ratio and P-values.RESULTS.In MVA, nPSA12 as a continuous variable was independent of RT dose, T-stage, Gleason score, pretreatment initial PSA, age, and PSADT in predicting for BF, DM, CSM, and OM. Dichotomized nPSA12 (2 versus >2 ng/mL) was independently related to DM and CSM. Kaplan-Meier 10-year DM rates for nPSA12 2 versus >2 ng/mL were 4% versus 19% (P<.0001).CONCLUSIONS.nPSA12 is a strong independent predictor of outcome after RT alone for prostate cancer and should be useful in identifying patients at high risk for progression to metastasis and death.

    View details for DOI 10.1002/cncr.22341

    View details for Web of Science ID 000243199400005

    View details for PubMedID 17133416

  • A matched pair comparison of intensity modulated radiotherapy and three-dimensional conformal radiotherapy for prostate cancer: Toxicity and outcomes INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Morgan, P. B., Ruth, K., Horwitz, E. M., Buyyounouski, M. K., Uzzo, R. G., Pollack, A. 2007; 69 (3): S319-S319
  • Intensity modulated radiation therapy reduces gastrointestinal morbidity in patients treated with androgen deprivation therapy for prostate cancer INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Sharma, N. K., Li, T., Horwitz, E. M., Pollack, A., Buyyounouski, M. K. 2007; 69 (3): S10-S10
  • Does total treatment duration affect outcome in prostate cancer treated with radiotherapy? INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS D'Ambrosio, D. J., Horwitz, T. L., Chen, D., Pollack, A., Buyyounouski, M. K. 2007; 69 (3): S176-S176
  • A comparison of sexual function following radiotherapy for prostate cancer: Results of a prospective, randomized trial of hypofractionated intensity modulated radiotherapy INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Buyyounouski, M. K., Li, T., Watkins-Bruner, D., Horwitz, E. M., Pollack, A. 2007; 69 (3): S7-S8
  • Effect of target smoothness on treatment planning for prostate IMRT INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Chen, Y., Paskalev, K., Horwitz, E., Price, R., Buyyounouski, M., Ma, C., Pollack, A. 2007; 69 (3): S649-S649
  • Impact of pelvic nodal irradiation with intensity-modulated radiotherapy on treatment of prostate cancer INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Price, R. A., Hannoun-Levi, J., Horvvitz, E., Buyyounouski, M., Ruth, K. J., Ma, C., Pollack, A. 2006; 66 (2): 583-592

    Abstract

    The aim of this study was to evaluate the feasibility of treating the pelvic lymphatic regions during prostate intensity-modulated radiotherapy (IMRT) with respect to our routine acceptance criteria.A series of 10 previously treated prostate patients were randomly selected and the pelvic lymphatic regions delineated on the fused magnetic resonance/computed tomography data sets. A targeting progression was formed from the prostate and proximal seminal vesicles only to the inclusion of all pelvic lymphatic regions and presacral region resulting in 5 planning scenarios of increasing geometric difficulty. IMRT plans were generated for each stage for two accelerator manufacturers. Dose volume histogram data were analyzed with respect to dose to the planning target volumes, rectum, bladder, bowel, and normal tissue. Analysis was performed for the number of segments required, monitor units, "hot spots," and treatment time.Both rectal endpoints were met for all targets. Bladder endpoints were not met and the bowel endpoint was met in 40% of cases with the inclusion of the extended and presacral lymphatics. A significant difference was found in the number of segments and monitor units with targeting progression and between accelerators, with the smaller beamlets yielding poorer results. Treatment times between the 2 linacs did not exhibit a clinically significant difference when compared.Many issues should be considered with pelvic lymphatic irradiation during IMRT delivery for prostate cancer including dose per fraction, normal structure dose/volume limits, planning target volumes generation, localization, treatment time, and increased radiation leakage. We would suggest that, at a minimum, the endpoints used in this work be evaluated before beginning IMRT pelvic nodal irradiation.

    View details for DOI 10.1016/j.ijrobp.2006.05.033

    View details for Web of Science ID 000240699500040

    View details for PubMedID 16966000

  • Daily changes in seminal vesicle location during treatment of prostate carcinoma MEDICAL PHYSICS McNeeley, S., Paskalev, K., Buyyounouski, M., Ma, C. 2006; 33 (6): 2030-2030
  • Dosimetry and preliminary acute toxicity in the first 100 men treated for prostate cancer on a randomized hypofractionation dose escalation trial INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Pollack, A., Hanlon, A. L., Horwitz, E. M., Feigenberg, S. J., Konski, A. A., Movsas, B., Greenberg, R. E., Uzzo, R. G., Ma, C. M., McNeeley, S. W., Buyyounouski, M. K., Price, R. A. 2006; 64 (2): 518-526

    Abstract

    The alpha/beta ratio for prostate cancer is postulated to be between 1 and 3, giving rise to the hypothesis that there may be a therapeutic advantage to hypofractionation. The dosimetry and acute toxicity are described in the first 100 men enrolled in a randomized trial.The trial compares 76 Gy in 38 fractions (Arm I) to 70.2 Gy in 26 fractions (Arm II) using intensity modulated radiotherapy. The planning target volume (PTV) margins in Arms I and II were 5 mm and 3 mm posteriorly and 8 mm and 7 mm in all other dimensions. The PTV D95% was at least the prescription dose.The mean PTV doses for Arms I and II were 81.1 and 73.8 Gy. There were no differences in overall maximum acute gastrointestinal (GI) or genitourinary (GU) toxicity acutely. However, there was a slight but significant increase in Arm II GI toxicity during Weeks 2, 3, and 4. In multivariate analyses, only the combined rectal DVH parameter of V65 Gy/V50 Gy was significant for GI toxicity and the bladder volume for GU toxicity.Hypofractionation at 2.7 Gy per fraction to 70.2 Gy was well tolerated acutely using the planning conditions described.

    View details for DOI 10.1016/j.ijrobp.2005.07.970

    View details for Web of Science ID 000234883300025

    View details for PubMedID 16242256

  • CT-based daily localization of prostate patients: Anatomy vs. implanted markers INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Paskalev, K., Feigenberg, S., McNeeley, S., Horwitz, E., Price, R., Konski, A., Buyyounouski, M., Ma, C., Alan, P. 2006; 66 (3): S621-S621
  • Increasing radiotherapy dose for prostate cancer reduces a late wave of distant metastasis INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Morgan, P. B., Hanlon, A. L., Horwitz, E. M., Buyyounouski, M. K., Uzzo, R. G., Pollack, A. 2006; 66 (3): S9-S10
  • The prostate specific antigen velocity is unaltered by radiotherapy alone when 2 ng/mL per year or greater: Distant metastasis are the cause INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Buyyounouski, M. K., Hanlon, A. L., Horwitz, E. M., Pollack, A. 2006; 66 (3): S206-S207
  • Intensity modulated radiation therapy for prostate cancer: Preliminary results on treatment morbidity compared to 3-D conformal radiation therapy INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Kirichenko, A. V., Ruth, K., Horwitz, E. M., Buyyounouski, M. K., Feigenberg, S. J., Chen, D. Y., Pollack, A. 2006; 66 (3): S326-S326
  • Comparison of outcomes in low risk prostate cancer: I-125 seed brachytherapy vs. intensity modulated radiotherapy INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Eade, T. N., Ruth, K., D'Ambrosio, D. J., Feigenberg, S. J., Buyyounouski, M. K., Uzzo, R. G., Pollack, A., Horwitz, E. M. 2006; 66 (3): S60-S61
  • Smoking and its relationship to GU and GI toxicity in prostate cancer patients treated with radiation INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Pahlajani, N. H., Ruth, K., Horwitz, E. M., Buyyounouski, M. B., Chen, D. Y., Pollack, A. 2006; 66 (3): S317-S317
  • Adjusted radiotherapy dose response curves following treatment for prostate cancer: Biochemical failure and distant metastasis INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Hanlon, A. L., Horwitz, E. M., Buyyounouski, M. K., Pollack, A. 2006; 66 (3): S346-S347
  • Prostate specific antigen kinetics in men treated with radiotherapy and androgen deprivation INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS D'Ambrosio, D. J., Ruth, K., Buyyounouski, M. K., Horwitz, E. M., Uzzo, R. G., Pollack, A. 2006; 66 (3): S334-S334
  • The nadir+2 definition of biochemical failure predicts for overall survival INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Abramowitz, M. C., Li, T., Ross, E., Buyyounouski, M., Uzzo, R. G., Pollack, A., Horwitz, E. M. 2006; 66 (3): S207-S208
  • Defining biochemical failure after radiotherapy with and without androgen deprivation for prostate cancer INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Buyyounouski, M. K., Hanlon, A. L., Eisenberg, D. F., Horwitz, E. M., Feigenberg, S. J., Uzzo, R. G., Pollack, A. 2005; 63 (5): 1455-1462

    Abstract

    To compare several characteristics of alternative definitions of biochemical failure (BF) in men with extended follow-up after radiotherapy (RT) with or with androgen deprivation therapy (ADT) for prostate cancer.From December 1, 1991, to April 30, 1998, 688 men with Stage T1c-T3NX-N0M0 prostate cancer received RT alone (n = 586) or RT plus ADT (n = 102) with a minimal follow-up of 4 years and five or more "ADT-free" posttreatment prostate-specific antigen levels. BF was defined by three methods: (1) the ASTRO definition (three consecutive rises in prostate-specific antigen level); (2) a modified American Society for Therapeutic Radiology Oncology (ASTRO) definition requiring two additional consecutive rises when a decline immediately subsequent to three consecutive rises occurred; and (3) the "Houston" or nadir plus 2-ng/mL definition (a rise of at least 2 ng/mL greater than the nadir). The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were determined for each using clinical progression as the endpoint. Furthermore, the misclassification rates for a steadily rising prostate-specific antigen level, ability to satisfy the proportional hazards (RT with or without ADT), effects of short follow-up, and intervals to the diagnosis of BF were compared.The misclassification rate for BF using the nadir plus 2-ng/mL definition was 2% for RT alone and 0% for RT plus ADT compared with 0% and 0% for the modified ASTRO definition, and 5% and 23% for the ASTRO definition, respectively. The hazard rates for RT alone and RT plus ADT were proportional only for the nadir plus 2 ng/mL definition and seemingly unaffected by the length of follow-up. For RT with or without ADT, the nadir plus 2 ng/mL definition was the most specific (RT, 80% vs. RT plus ADT, 75%) with the greatest positive predictive value (RT, 36% vs. RT plus ADT, 25%) and overall accuracy (RT, 81% vs. RT plus ADT, 77%). A greater proportion of BF was diagnosed in the first 2 years of follow-up with the nadir plus 2 ng/mL definition compared with the ASTRO definition (13% vs. 5%, p = 0.0138, chi-square test).The nadir plus 2 ng/mL definition was the best predictor of sustained, true, biochemical, and clinical failure, and was not affected by the use of ADT or follow-up length.

    View details for DOI 10.1016/j.ijrobp.2005.05.053

    View details for Web of Science ID 000233477300025

    View details for PubMedID 16169682

  • Biochemical failure and the temporal kinetics of prostate-specific antigen after radiation therapy with androgen deprivation INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Buyyounouski, M. K., Hanlon, A. L., Horwitz, E. M., Uzzo, R. G., Pollack, A. 2005; 61 (5): 1291-1298

    Abstract

    The accuracy of the American Society of Therapeutic Radiation Oncology consensus definition of biochemical failure (BF) after radiation therapy (RT) and androgen deprivation (AD) has been questioned, because posttreatment prostate-specific antigen (PSA) levels typically rise after release from AD, and misclassification of BF may be made. The temporal kinetics of posttreatment PSA levels was examined to define the error in the classification of BF.Between December 1, 1991 and April 30, 1998, 688 men with T1c-T3 NX/0 M0 prostate cancer received three-dimensional conformal RT alone (n = 586) or in combination with either short-term (STAD: 3 to 12 months, n = 82) or long-term (LTAD: 12 to 36 months, n = 20) AD. Follow-up, calculated from the end of all treatment, was >/=48 months. The mean posttreatment PSA was calculated in 3-month intervals.The median posttreatment clinical follow-up period was 76 months (range, 48-152 months). The posttreatment PSA values from the end of all treatment for the RT+STAD-BF group showed an initial period of rise followed by a period of decline at 30 months and then a continued rise again. The decline in the mean posttreatment PSA is explained in part by stabilization in PSA level after 3 consecutive rises. Nonbiochemical failures (NBF) after RT+STAD had a relatively constant mean PSA over time of approximately 0.5 ng/mL. Unlike the RT+STAD-NBF profile, the RT+LTAD-NBF profile rose continuously and steadily to a level approaching 1 ng/mL. The RT+LTAD-BF profile rose continuously but at a slower rate over time. Nine RT+STAD-NBF patients (22%) and 2 RT+LTAD-BF (29%) patients experienced 3 consecutive rises followed by a subsequent decline and stabilization of PSA compared to 10 RT-BF patients (5%). Redistributing these misclassified patients to their respective NBF groups changed the mean posttreatment PSA profiles as follows: The RT+LTAD-BF profile rose constantly and steadily with a doubling time of approximately 16 months, and the RT+LAD-NF initially rose to a value of approximately 0.5 ng/mL, then at 36 months began to decline.The temporal kinetics of posttreatment PSA after RT+AD and RT alone are different. The American Society of Therapeutic Radiation Oncology definition for biochemical failure overestimates BF in 20-30% after RT+AD compared to 5% after RT alone.

    View details for DOI 10.1016/j.ijrobp.2004.08.034

    View details for Web of Science ID 000228101400002

    View details for PubMedID 15817330

  • In regard to Selek et al. erectile dysfunction and radiation dose to penile base structures: a lack of correlation. IJROBP 2004;59:1039-1046. International journal of radiation oncology, biology, physics Buyyounouski, M. K., Hanlon, A. L., Price, R. A., Horwitz, E. M., Feigenberg, S. J., Pollack, A. 2004; 60 (5): 1664-1665

    View details for PubMedID 15590205

  • The radiation doses to erectile tissues defined with magnetic resonance imaging after intensity-modulated radiation therapy or iodine-125 brachytherapy INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Buyyounouski, M. K., Horwitz, E. M., Uzzo, R. G., Price, R. A., McNeeley, S. W., Azizi, D., Hanlon, A. L., Milestone, B. N., Pollack, A. 2004; 59 (5): 1383-1391

    Abstract

    To report penile bulb (PB) and corporal bodies (CB) doses during intensity-modulated radiation therapy (IMRT) and permanent (125)I prostate implant alone (BT) for favorable, early stage, clinically localized prostate cancer using computed tomography (CT) and magnetic resonance imaging (MRI) to provide a basis for comparison as the initial report of a comprehensive project to develop erectile tissues sparing techniques.Prostate, PB and CB volumes were defined by a fused CT/MRI simulation study performed before treatment in 29 IMRT patients and verification study performed 30 days postimplant in 15 BT patients. The median prescribed prostate dose for the IMRT and BT groups was 74 Gy and 145 Gy, respectively. Dose volume histograms (DVHs) were generated to determine the dose characteristics for the PB, CB, and prostate for each patient. D(90), V(100), and V(50) were used, where D(i) was defined as the dose that covers i% of the prostate volume and V(i) is the fractional volume of the prostate that receives i% of the prescribed dose. The Wilcoxon rank sum test was used to evaluate significance between the groups.The median PB D(90), V(100), and V(50) values were 17.5 Gy, 0%, and 31.9% for the IMRT group; and 52.5 Gy, 21.5%, and 89.7% for the BT group. The median CB D(90), V(100), and V(50) values were 7.3 Gy, 0%, and 0.9% for the IMRT group; and 26.9 Gy, 2.4%, and 20.1% for the BT group. The differences between the IMRT vs. BT V(100) values, but not V(50), were statistically significant for the PB (p = 0.001) and CB (p = 0.001).Radiation dose to the PB and CB is low with IMRT or BT. Magnetic resonance imaging is superior to CT for the imaging of erectile tissues. Intensity-modulated radiation therapy may offer further reductions in the doses received by the PB and CB; however, at what cost to prostate coverage and normal tissue sparing will be the subject of a follow-up study.

    View details for DOI 10.1016/j.ijrobp.2004.01.042

    View details for Web of Science ID 000222932800016

    View details for PubMedID 15275723

  • Intensity-modulated radiotherapy with MRI simulation to reduce doses received by erectile tissue during prostate cancer treatment INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Buyyounouski, M. K., Horwitz, E. M., Price, R. A., Hanlon, A. L., Uzzo, R. G., Pollack, A. 2004; 58 (3): 743-749

    Abstract

    The radiation doses received by erectile tissue may contribute to erectile dysfunction after treatment of prostate cancer. This is the first description of the ability to limit the dose received by the penile bulb (PB) and corporal bodies (CB) using intensity-modulated radiotherapy (IMRT).Twenty-three patients with palpation Stage T1c-T2bN0M0 prostate cancer received IMRT alone. The dose prescribed to the planning target volume was 74-78 Gy. All patients underwent CT and MRI simulation to define the target and normal structures. Three plans with identical beam arrangements and energy were generated for each patient, with varying dose constraints for the PB and CB: no dose constraint, intermediate-dose constraint (20 Gy and 15 Gy, respectively) and low-dose constraint (15 Gy and 7 Gy, respectively). All plans were normalized, such that 95% of the planning target volume received at least 100% of the prescribed dose. For each plan, the ability to meet prostate dose homogeneity criteria (PHC; prostate maximal dose /=50% without significantly compromising the PHC, RTC, or treatment duration. A Phase III randomized trial has been designed to test the clinical significance of the erectile tissue-sparing technique described here.

    View details for DOI 10.1016/S0360-3016(03)01617-1

    View details for Web of Science ID 000188934600013

    View details for PubMedID 14967429

  • Re: improved clinical staging system combining biopsy laterality and TNM stage for men with T1c and T2 prostate cancer: results from the search database. journal of urology Buyyounouski, M. K., Horwitz, E. M., Hanlon, A. L., Uzzo, R. G., Pollack, A. 2004; 171 (3): 1246-1247

    View details for PubMedID 14767321

  • Positive prostate biopsy laterality and implications for staging UROLOGY Buyyounouski, M. K., Horwitz, E. M., Hanlon, A. L., Uzzo, R. G., Hanks, G. E., Pollack, A. 2003; 62 (2): 298-303

    Abstract

    To examine the effect of including positive prostate biopsy information in palpation staging (2002 system) and the influence of this information on freedom from biochemical failure (bNED). Prostate biopsy laterality status (unilateral versus bilateral positive) is part of clinical staging using American Joint Commission on Cancer criteria, but is rarely used.From April 1, 1989 to September 30, 1999, 1038 patients with palpable T1-T3Nx-0M0 prostate cancer were treated with three-dimensional conformal radiotherapy alone. Kaplan-Meier bNED curves were compared using the log-rank test. The Cox proportional hazards regression model of bNED was used for multivariate analysis.The median follow-up was 46 months. The proportion of patients with bilateral positive biopsies by palpation category T1c was 24%, by T2a was 17%, by T2b was 26%, by T2c was 65%, and by T3 was 53%. No statistically significant difference was noted in bNED on the basis of biopsy laterality status for the palpation T stages T1c, T2a, T2b, or T3. A statistically significant difference in the 5-year bNED in the T2c stage was found; those with unilateral positive biopsies fared worse (46% versus 74%, respectively, P = 0.04).Inclusion of positive biopsy laterality status into clinical staging causes stage migration without reflecting a change in outcome and should not be used.

    View details for DOI 10.1016/S0090-4295(03)00334-0

    View details for Web of Science ID 000184557200021

    View details for PubMedID 12893339

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