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Long-term Outcomes of Stereotactic Body Radiotherapy for Low-Risk and Intermediate-Risk Prostate Cancer. JAMA network open Kishan, A. U., Dang, A., Katz, A. J., Mantz, C. A., Collins, S. P., Aghdam, N., Chu, F., Kaplan, I. D., Appelbaum, L., Fuller, D. B., Meier, R. M., Loblaw, D. A., Cheung, P., Pham, H. T., Shaverdian, N., Jiang, N., Yuan, Y., Bagshaw, H., Prionas, N., Buyyounouski, M. K., Spratt, D. E., Linson, P. W., Hong, R. L., Nickols, N. G., Steinberg, M. L., Kupelian, P. A., King, C. R. 2019; 2 (2): e188006
Abstract

Importance: Stereotactic body radiotherapy harnesses improvements in technology to allow the completion of a course of external beam radiotherapy treatment for prostate cancer in the span of 4 to 5 treatment sessions. Although mounting short-term data support this approach, long-term outcomes have been sparsely reported.Objective: To assess long-term outcomes after stereotactic body radiotherapy for low-risk and intermediate-risk prostate cancer.Design, Setting, and Participants: This cohort study analyzed individual patient data from 2142 men enrolled in 10 single-institution phase 2 trials and 2 multi-institutional phase 2 trials of stereotactic body radiotherapy for low-risk and intermediate-risk prostate cancer between January 1, 2000, and December 31, 2012. Statistical analysis was performed based on follow-up from January 1, 2013, to May 1, 2018.Main Outcomes and Measures: The cumulative incidence of biochemical recurrence was estimated using a competing risk framework. Physician-scored genitourinary and gastrointestinal toxic event outcomes were defined per each individual study, generally by Radiation Therapy Oncology Group or Common Terminology Criteria for Adverse Events scoring systems. After central review, cumulative incidences of late grade 3 or higher toxic events were estimated using a Kaplan-Meier method.Results: A total of 2142 men (mean [SD] age, 67.9 [9.5] years) were eligible for analysis, of whom 1185 (55.3%) had low-risk disease, 692 (32.3%) had favorable intermediate-risk disease, and 265 (12.4%) had unfavorable intermediate-risk disease. The median follow-up period was 6.9 years (interquartile range, 4.9-8.1 years). Seven-year cumulative rates of biochemical recurrence were 4.5% (95% CI, 3.2%-5.8%) for low-risk disease, 8.6% (95% CI, 6.2%-11.0%) for favorable intermediate-risk disease, 14.9% (95% CI, 9.5%-20.2%) for unfavorable intermediate-risk disease, and 10.2% (95% CI, 8.0%-12.5%) for all intermediate-risk disease. The crude incidence of acute grade 3 or higher genitourinary toxic events was 0.60% (n=13) and of gastrointestinal toxic events was 0.09% (n=2), and the 7-year cumulative incidence of late grade 3 or higher genitourinary toxic events was 2.4% (95% CI, 1.8%-3.2%) and of late grade 3 or higher gastrointestinal toxic events was 0.4% (95% CI, 0.2%-0.8%).Conclusions and Relevance: In this study, stereotactic body radiotherapy for low-risk and intermediate-risk disease was associated with low rates of severe toxic events and high rates of biochemical control. These data suggest that stereotactic body radiotherapy is an appropriate definitive treatment modality for low-risk and intermediate-risk prostate cancer.

View details for PubMedID 30735235
Hypofractionated Radiation Therapy for Localized Prostate Cancer: An ASTRO, ASCO, and AUA Evidence-Based Guideline. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Morgan, S. C., Hoffman, K., Loblaw, D. A., Buyyounouski, M. K., Patton, C., Barocas, D., Bentzen, S., Chang, M., Efstathiou, J., Greany, P., Halvorsen, P., Koontz, B. F., Lawton, C., Leyrer, C. M., Lin, D., Ray, M., Sandler, H. 2018: JCO1801097
View details for PubMedID 30307776
NCCN Guidelines Insights: Bladder Cancer, Version 5.2018. Journal of the National Comprehensive Cancer Network : JNCCN Flaig, T. W., Spiess, P. E., Agarwal, N., Bangs, R., Boorjian, S. A., Buyyounouski, M. K., Downs, T. M., Efstathiou, J. A., Friedlander, T., Greenberg, R. E., Guru, K. A., Hahn, N., Herr, H. W., Hoimes, C., Inman, B. A., Jimbo, M., Kader, A. K., Lele, S. M., Meeks, J. J., Michalski, J., Montgomery, J. S., Pagliaro, L. C., Pal, S. K., Patterson, A., Petrylak, D. P., Plimack, E. R., Pohar, K. S., Porter, M. P., Preston, M. A., Sexton, W. J., Siefker-Radtke, A. O., Tward, J., Wile, G., Johnson-Chilla, A., Dwyer, M. A., Gurski, L. A. 2018; 16 (9): 1041?53
Abstract

The NCCN Clinical Practice Guidelines in Oncology for Bladder Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up of patients with bladder cancer. These NCCN Guidelines Insights discuss important updates to the 2018 version of the guidelines, including implications of the 8th edition of the AJCC Cancer Staging Manual on treatment of muscle-invasive bladder cancer and incorporating newly approved immune checkpoint inhibitor therapies into treatment options for patients with locally advanced or metastatic disease.

View details for PubMedID 30181416
Prostate Cancer - Major Changes in the American Joint Committee on Cancer Eighth Edition Cancer Staging Manual CA-A CANCER JOURNAL FOR CLINICIANS Buyyounouski, M. K., Choyke, P. L., McKenney, J. K., Sartor, O., Sandler, H. M., Amin, M. B., Kattan, M. W., Lin, D. W. 2017; 67 (3): 246-253
Abstract

Answer questions and earn CME/CNE The eighth edition of the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) Staging Manual has been updated and improved to ensure the highest degree of clinical relevance and to improve its utility for patient evaluation and clinical research. Major changes include: 1) pathologically organ-confined disease is now considered pT2 and is no longer subclassified by extent of involvement or laterality, 2) tumor grading now includes both the Gleason score (as in the seventh edition criteria) and the grade group (introduced in the eighth edition criteria), 3) prognostic stage group III includes select, organ-confined disease based on prostate-specific antigen and Gleason/grade group status, and 4) 2 statistical prediction models are included in the staging manual. The AJCC will continue to critically analyze emerging prostate cancer biomarkers and tools for their ability to prognosticate and guide treatment decision making with the highest level of accuracy and confidence for patients and physicians. CA Cancer J Clin 2017;67:245-253. � 2017 American Cancer Society.

View details for DOI 10.3322/caac.21391

View details for Web of Science ID 000400939900006
Prostate cancer - major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA: a cancer journal for clinicians Buyyounouski, M. K., Choyke, P. L., McKenney, J. K., Sartor, O., Sandler, H. M., Amin, M. B., Kattan, M. W., Lin, D. W. 2017
Abstract

Answer questions and earn CME/CNE The eighth edition of the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) Staging Manual has been updated and improved to ensure the highest degree of clinical relevance and to improve its utility for patient evaluation and clinical research. Major changes include: 1) pathologically organ-confined disease is now considered pT2 and is no longer subclassified by extent of involvement or laterality, 2) tumor grading now includes both the Gleason score (as in the seventh edition criteria) and the grade group (introduced in the eighth edition criteria), 3) prognostic stage group III includes select, organ-confined disease based on prostate-specific antigen and Gleason/grade group status, and 4) 2 statistical prediction models are included in the staging manual. The AJCC will continue to critically analyze emerging prostate cancer biomarkers and tools for their ability to prognosticate and guide treatment decision making with the highest level of accuracy and confidence for patients and physicians. CA Cancer J Clin 2017;67:245-253. � 2017 American Cancer Society.

View details for DOI 10.3322/caac.21391

View details for PubMedID 28222223
Improving Care With a Portfolio of Physician-Led Cancer Quality Measures at an Academic Center Improving Care With a Portfolio of Physician-Led Cancer Quality Measures at an Academic Center Porter, J. B. 2017; 13 (8): e673-e682
Abstract

Development and implementation of robust reporting processes to systematically provide quality data to care teams in a timely manner is challenging. National cancer quality measures are useful, but the manual data collection required is resource intensive, and reporting is delayed. We designed a largely automated measurement system with our multidisciplinary cancer care programs (CCPs) to identify, measure, and improve quality metrics that were meaningful to the care teams and their patients.Each CCP physician leader collaborated with the cancer quality team to identify metrics, abiding by established guiding principles. Financial incentive was provided to the CCPs if performance at the end of the study period met predetermined targets. Reports were developed and provided to the CCP physician leaders on a monthly or quarterly basis, for dissemination to their CCP teams.A total of 15 distinct quality measures were collected in depth for the first time at this cancer center. Metrics spanned the patient care continuum, from diagnosis through end of life or survivorship care. All metrics improved over the study period, met their targets, and earned a financial incentive for their CCP.Our quality program had three essential elements that led to its success: (1) engaging physicians in choosing the quality measures and prespecifying goals, (2) using automated extraction methods for rapid and timely feedback on improvement and progress toward achieving goals, and (3) offering a financial team-based incentive if prespecified goals were met.

View details for DOI 10.1200/JOP.2017.021139

View details for PubMedCentralID PMC5880618
Prostate-specific antigen kinetics and biochemical control following stereotactic body radiation therapy, high dose rate brachytherapy, and low dose rate brachytherapy: A multi-institutional analysis of 3,502 patients. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology Levin-Epstein, R., Cook, R. R., Wong, J. K., Stock, R. G., Jeffrey Demanes, D., Collins, S. P., Aghdam, N., Suy, S., Mantz, C., Katz, A. J., Nickols, N. G., Miszczyk, L., Napieralska, A., Namysl-Kaletka, A., Prionas, N. D., Bagshaw, H., Buyyounouski, M. K., Cao, M., Mahal, B. A., Shabsovich, D., Dang, A., Yuan, Y., Rettig, M. B., Chang, A. J., Jackson, W. C., Spratt, D. E., Lehrer, E., Zaorsky, N. G., Kupelian, P. A., Steinberg, M. L., Horwitz, E. M., Jiang, N. Y., Kishan, A. U. 2020
Abstract

BACKGROUND AND PURPOSE: Stereotactic body radiation therapy (SBRT), low dose rate brachytherapy (LDR-BT) and high dose rate brachytherapy (HDR-BT) are ablative-intent radiotherapy options for prostate cancer (PCa). These vary considerably in dose delivery, which may impact post-treatment prostate-specific antigen (PSA) patterns and biochemical control. We compared PSA kinetics between SBRT, HDR-BT, and LDR-BT, and assessed their relationships to biochemical recurrence-free survival (BCRFS).METHODS AND MATERIALS: Retrospective PSA data were analyzed for 3,502 men with low-risk (n=2223; 63.5%), favorable intermediate-risk (n=869; 24.8%), and unfavorable intermediate-risk (n=410; 11.7%) PCa treated with SBRT (n=1716; 49.0%), HDR-BT (n=512; 14.6%), or LDR-BT (n=1274; 36.4%) without upfront androgen deprivation therapy at 10 institutions from 1990-2017. We compared nadir PSA (nPSA), time to nPSA, achievement of nPSA <0.2 ng/mL and <0.5 ng/mL, rates of nPSA <0.4 ng/mL at 4 years, and BCRFS.RESULTS: Median follow-up was 72 months. Median nPSA and nPSA <0.2 ng/mL were stratified by risk group (interaction p?0.001). Median nPSA and time to nPSA were 0.2 ng/mL at 44 months after SBRT, 0.1-0.2 ng/mL at 37 months after HDR-BT, and 0.01-0.2 ng/mL at 51 months after LDR-BT (mean log nPSA p?0.009 for LDR-BT vs. SBRT or HDR-BT for low/favorable intermediate-risk). There were no differences in nPSA <0.4 ng/mL at 4 years (p?0.51). BCRFS was similar for all three modalities (p?0.27). Continued PSA decay beyond 4 years was predictive of durable biochemical control.CONCLUSION: LDR-BT led to lower nPSAs with longer continued decay compared to SBRT and HDR-BT, but no differences in BCRFS.

View details for DOI 10.1016/j.radonc.2020.07.014

View details for PubMedID 32663537
Deep learning applications in automatic needle segmentation in ultrasound-guided prostate brachytherapy. Medical physics Wang, F., Xing, L., Bagshaw, H., Buyyounouski, M., Han, B. 2020
Abstract

PURPOSE: High-Dose-Rate (HDR) brachytherapy is one of the most effective ways to treat the prostate cancer, which is the second most common cancer in men worldwide. This treatment delivers highly conformal dose through the transperineal needle implants and is guided by a real time ultrasound (US) imaging system. Currently, the brachytherapy needles in the US images are manually segmented by physicists during the treatment, which is time-consuming and error-prone. In this study, we propose a set of deep learning based algorithms to accurately segment the brachytherapy needles and locate the needle tips from the US images.METHODS: Two deep neural networks are developed to address this problem. First, a modified deep U-Net is used to segment the pixels belonging to the brachytherapy needles from the US images. Second, an additional VGG-16 based deep convolutional network is combined with the segmentation network to predict the locations of the needle tips. The networks are trained and evaluated on a clinical US images dataset with labeled needle trajectories collected in our hospital (Institutional Review Board approval (IRB 41755)).RESULTS: The evaluation results show that our method can accurately extract the trajectories of the needles with a resolution of 0.668 mm and 0.319 mm in x and y direction respectively. 95.4% of the x direction and 99.2% of the y direction have error ? 2 mm. Moreover, The position resolutions of the tips are 0.721 mm, 0.369 mm and 1.877 mm in x, y and z directions respectively, while 94.2%, 98.3% and 67.5% of the data have error ? 2 mm.CONCLUSIONS: This paper proposed a neural network based algorithm to segment the brachytherapy needles from the US images and locate the needle tip. It can be used in the HDR brachytherapy to help improve the efficiency and quality of the treatments.

View details for DOI 10.1002/mp.14328

View details for PubMedID 32542758
NRG Oncology Updated International Consensus Atlas on Pelvic Lymph Node Volumes for Intact and Post-Operative Prostate Cancer. International journal of radiation oncology, biology, physics Hall, W. A., Paulson, E., Davis, B. J., Spratt, D. E., Morgan, T. M., Dearnaley, D., Tree, A. C., Efstathiou, J. A., Harisinghani, M., Jani, A. B., Buyyounouski, M. K., Pisansky, T. M., Tran, P. T., Karnes, R. J., Chen, R. C., Cury, F. L., Michalski, J. M., Rosenthal, S. A., Koontz, B. F., Wong, A. C., Nguyen, P., Hope, T. A., Feng, F., Sandler, H. M., Lawton, C. A. 2020
Abstract

In 2009, the Radiation Therapy Oncology Group (RTOG) genitourinary (GU) members published a consensus atlas for contouring prostate pelvic nodal clinical target volumes (CTV). Data has emerged further informing nodal recurrence patterns. The objective of this study is to provide an updated prostate pelvic nodal consensus atlas.A literature review was performed abstracting data on nodal recurrence patterns. Data was presented to a panel of international experts, including radiation oncologists, radiologists, and urologists. After data review, participants contoured nodal CTVs on three cases: post-operative, intact node positive, and intact node negative. Radiation oncologist contours were analyzed qualitatively using count maps which provided a visual assessment of controversial regions and quantitatively analyzed using Sorensen-Dice similarity coefficients, and Hausdorff distances compared with the 2009 RTOG atlas. Diagnostic radiologists generated a reference table outlining considerations for determining clinical node positivity.Eighteen radiation oncologists' contours (54 CTVs) were included. Two urologists' volumes were examined in a separate analysis. The mean CTV for the post-op case was 302 cc, intact node positive case was 409 cc, and intact node negative case 342 cc. Compared to the original RTOG consensus, the mean Sorensen-Dice similarity coefficient for the post-op case was 0.63 (SD 0.13), intact node positive case was 0.68 (SD 0.13), and intact node negative case 0.66 (SD 0.18). The mean Hausdorff Distance (in cm) for the post-op case was 0.24 (SD 0.13), the intact node positive case was 0.23 (SD 0.09), and intact node negative case 0.33 (SD 0.24). Four regions of CTV controversy were identified and consensus for each of these areas was reached.Discordance with the 2009 RTOG consensus atlas was seen in a group of experienced NRG Oncology and international GU radiation oncologists. To address areas of variability and account for new data, an updated NRG Oncology consensus contour atlas was developed.

View details for DOI 10.1016/j.ijrobp.2020.08.034

View details for PubMedID 32861817
Bladder Cancer, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network : JNCCN Flaig, T. W., Spiess, P. E., Agarwal, N., Bangs, R., Boorjian, S. A., Buyyounouski, M. K., Chang, S., Downs, T. M., Efstathiou, J. A., Friedlander, T., Greenberg, R. E., Guru, K. A., Guzzo, T., Herr, H. W., Hoffman-Censits, J., Hoimes, C., Inman, B. A., Jimbo, M., Kader, A. K., Lele, S. M., Michalski, J., Montgomery, J. S., Nandagopal, L., Pagliaro, L. C., Pal, S. K., Patterson, A., Plimack, E. R., Pohar, K. S., Preston, M. A., Sexton, W. J., Siefker-Radtke, A. O., Tward, J., Wright, J. L., Gurski, L. A., Johnson-Chilla, A. 2020; 18 (3): 329?54
Abstract

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer focuses on the clinical presentation and workup of suspected bladder cancer, treatment of non-muscle-invasive urothelial bladder cancer, and treatment of metastatic urothelial bladder cancer because important updates have recently been made to these sections. Some important updates include recommendations for optimal treatment of non-muscle-invasive bladder cancer in the event of a bacillus Calmette-Gu�rin (BCG) shortage and details about biomarker testing for advanced or metastatic disease. The systemic therapy recommendations for second-line or subsequent therapies have also been revised. Treatment and management of muscle-invasive, nonmetastatic disease is covered in the complete version of the NCCN Guidelines for Bladder Cancer available at NCCN.org. Additional topics covered in the complete version include treatment of nonurothelial histologies and recommendations for nonbladder urinary tract cancers such as upper tract urothelial carcinoma, urothelial carcinoma of the prostate, and primary carcinoma of the urethra.

View details for DOI 10.6004/jnccn.2020.0011

View details for PubMedID 32135513
A Deep Learning Framework for Prostate Localization in Cone Beam CT Guided Radiotherapy. Medical physics Liang, X., Zhao, W., Hristov, D. H., Buyyounouski, M. K., Hancock, S. L., Bagshaw, H., Zhang, Q., Xie, Y., Xing, L. 2020
Abstract

To develop a deep learning-based model for prostate planning target volume (PTV) localization on cone-beam CT (CBCT) to improve the workflow of CBCT-guided patient setup.A two-step task-based residual network (T2 RN) is proposed to automatically identify inherent landmarks in prostate PTV. The input to the T2 RN is the pre-treatment CBCT images of the patient, and the output is the deep learning-identified landmarks in the PTV. To ensure robust PTV localization, the T2 RN model is trained by using over thousand sets of CT images with labeled landmarks, each of the CTs corresponds to a different scenario of patient position and/or anatomy distribution generated by synthetically changing the planning CT (pCT) image. The changes, including translation, rotation, and deformation, represent vast possible clinical situations of anatomy variations during a course of radiation therapy (RT). The trained patient-specific T2 RN model is tested by using 240 CBCTs from six patients. The testing CBCTs consists of 120 original CBCTs and 120 synthetic CBCTs. The synthetic CBCTs are generated by applying rotation/translation transformations to each of the original CBCT.The systematic/random setup errors between the model prediction and the reference are found to be less than 0.25/2.46 mm and 0.14/1.41� in translation and rotation dimensions, respectively. Pearson's correlation coefficient between model prediction and the reference is higher than 0.94 in translation and rotation dimensions. The Bland-Altman plots show good agreement between the two techniques.A novel T2 RN deep learning technique is established to localize the prostate PTV for RT patient setup. Our results show that highly accurate marker-less prostate setup is achievable by leveraging the state-of-the-art deep learning strategy.

View details for DOI 10.1002/mp.14355

View details for PubMedID 32583418
Incorporating imaging information from deep neural network layers into image guided radiation therapy (IGRT). Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology Zhao, W., Han, B., Yang, Y., Buyyounouski, M., Hancock, S. L., Bagshaw, H., Xing, L. 2019; 140: 167?74
Abstract

BACKGROUND AND PURPOSE: To investigate a novel markerless prostate localization strategy using a pre-trained deep learning model to interpret routine projection kilovoltage (kV) X-ray images in image-guided radiation therapy (IGRT).MATERIALS AND METHODS: We developed a personalized region-based convolutional neural network to localize the prostate treatment target without implanted fiducials. To train the deep neural network (DNN), we used the patient's planning computed tomography (pCT) images with pre-delineated prostate target to generate a large amount of synthetic kV projection X-ray images in the geometry of onboard imager (OBI) system. The DNN model was evaluated by retrospectively studying 10 patients who underwent prostate IGRT. Three out of the ten patients who had implanted fiducials and the fiducials' positions in the OBI images acquired for treatment setup were examined to show the potential of the proposed method for prostate IGRT. Statistical analysis using Lin's concordance correlation coefficient was calculated to assess the results along with the difference between the digitally reconstructed radiographs (DRR) derived and DNN predicted locations of the prostate.RESULTS: Differences between the predicted target positions using DNN and their actual positions are (mean?�?standard deviation) 1.58?�?0.43?mm, 1.64?�?0.43?mm, and 1.67?�?0.36?mm in anterior-posterior, lateral, and oblique directions, respectively. Prostate position identified on the OBI kV images is also found to be consistent with that derived from the implanted fiducials.CONCLUSIONS: Highly accurate, markerless prostate localization based on deep learning is achievable. The proposed method is useful for daily patient positioning and real-time target tracking during prostate radiotherapy.

View details for DOI 10.1016/j.radonc.2019.06.027

View details for PubMedID 31302347
Multi-institutional Analysis of Prostate-Specific Antigen Kinetics Following Stereotactic Body Radiotherapy (SBRT). International journal of radiation oncology, biology, physics Jiang, N. Y., Dang, A. T., Yuan, Y., Chu, F., Shabsovich, D., King, C. R., Collins, S. P., Aghdam, N., Suy, S., Mantz, C. A., Miszczyk, L., Napieralska, A., Namysl-Kaletka, A., Bagshaw, H., Prionas, N., Buyyounouski, M. K., Jackson, W. C., Spratt, D. E., Nickols, N. G., Steinberg, M. L., Kupelian, P. A., Kishan, A. U. 2019
Abstract

PURPOSE: Understanding prostate-specific antigen (PSA) kinetics after radiotherapy plays a large role in the management of prostate cancer (PCa) patients. This is particularly true regarding establishing expectations regarding PSA nadir (nPSA) and PSA bounces, which can be disconcerting. As increasingly more patients are being treated with stereotactic body radiotherapy (SBRT) for low- and intermediate-risk PCa, it is imperative to understand the PSA response to SBRT.METHODS&MATERIALS: PSA data from five institutions were retrospectively analyzed for localized PCa patients treated definitively with SBRT alone from 2004 to 2016. Patients received 35-40 Gy in five fractions per institutional standards. Patients who had less than 12 months of PSA data or received androgen deprivation therapy were excluded from this study. Linear and logistic multivariable analysis were performed to identify predictors of nPSA, bounce, and biochemical recurrence, and joint latent class models (JLCM) were developed to identify significant predictors of time to biochemical failure.RESULTS: 1062 patients were included in this study. Median follow-up was 66 months (interquartile range (IQR) 36.4 - 89.9 months). Biochemical failure per the Phoenix criteria occurred in 4% of patients. Median nPSA was 0.2 ng/ml, median time to nPSA was 40 months, 84% of patients had a nPSA <0.5 ng/ml, and 54% of patients had a nPSA <0.2 ng/ml. On multivariable analysis, nPSA was a significant predictor of biochemical failure. Benign PSA bounce was noted in 26% of patients. The median magnitude of PSA bounce was 0.52 ng/ml (IQR 0.3 - 1.0 ng/ml). Median time to PSA bounce was 18.1 months (IQR 12.0 - 31.1 months). On multivariable analysis, age and radiation dose were significantly associated with a lower incidence of bounce. JLCM modeling found that nPSA and radiation dose were significantly associated with longer time to biochemical failure.CONCLUSIONS: In this multi-institutional cohort of patients with long-term follow-up, we found that SBRT led to low nPSAs. In turn, lower nPSAs are associated with reduced incidence of, and longer time to, biochemical failure. Benign PSA bounces occurred in a quarter of patients, as late as several years after treatment. Further studies are needed to directly compare the PSA response of patients who receive SBRT versus other treatment modalities.

View details for DOI 10.1016/j.ijrobp.2019.06.2539

View details for PubMedID 31276777
Incorporating dosimetric features into the prediction of 3D VMAT dose distributions using deep convolutional neural network PHYSICS IN MEDICINE AND BIOLOGY Ma, M., Kovalchuk, N., Buyyounouski, M. K., Xing, L., Yang, Y. 2019; 64 (12)
View details for DOI 10.1088/1361-6560/ab2146

View details for Web of Science ID 000518929400007
Dose Distribution Prediction in Isodose Feature-Preserving Voxelization Domain Using Deep Convolutional Neural Network. Medical physics Ma, M., Buyyounouski, M. K., Vasudevan, V., Xing, L., Yang, Y. 2019
Abstract

PURPOSE: To implement a framework for dose prediction using a deep convolutional neural network (CNN) based on the concept of isodose feature-preserving voxelization (IFPV) in simplifying the representation of the dose distribution.METHODS: The concept of IFPV was introduced for concise representation of a treatment plan. IFPV is a sparse voxelization scheme that partitions the voxels into subgroups according to their geometric, anatomical and dosimetric features. In this study a deep CNN was constructed to build up a dose prediction model in IFPV domain based on 60 volumetric modulated arc therapy (VMAT) treatment plans from a database of previously treated 70 prostate cancer patients. The dose prediction model learns the contour to dose relationship and predicts the dose distribution in IFPV domain given the input contours. Additional 10 independent prostate cases were selected as testing data. DVH comparison, dose difference maps and residual analysis with the sum of absolute residual (SAR) were used to evaluate the performance of the proposed method.RESULTS: The proposed IFPV-based method achieved good prediction performance in terms of DVH comparison and dose difference maps. Statistical results of SARs showed that the IFPV-based method is comparable with voxel-based method even though the number of dose representation points used in the IFPV-based method was substantially reduced. The proposed approach achieved mean SARs of 0.029 � 0.020 and 0.077 �0.030 for bladder and rectum, respectively, compared with mean SARs of 0.039�0.029 and 0.069�0.028 in the conventional voxel-based method.CONCLUSIONS: A novel deep CNN-based dose prediction method in IFPV domain was proposed. The proposed approach has great potential to significantly improve the efficiency of dose prediction and facilitate the treatment planning workflow. This article is protected by copyright. All rights reserved.

View details for DOI 10.1002/mp.13618

View details for PubMedID 31112305
Incorporating dosimetric features into the prediction of 3D VMAT dose distributions using deep convolutional neural network. Physics in medicine and biology Ma, M., Kovalchuk, N., Buyyounouski, M. K., Xing, L., Yang, Y. 2019
Abstract

An accurate prediction of achievable dose distribution on a patient specific basis would greatly improve IMRT/VMAT planning in both efficiency and quality. Recently machine learning techniques have been proposed for IMRT dose prediction based on patient's contour information from planning CT. In these existing prediction models geometric/anatomic features were learned for building the dose prediction models and few features that characterize the dosimetric properties of the patients were utilized. In this study we propose a method to incorporate the dosimetric features in the construction of a more reliable dose prediction model based on the deep convolutional neural network (CNN). In addition to the contour information, the dose distribution from a PTV-only plan (i.e., the plan with the best PTV coverage by sacrificing the OARs sparing) is also employed as the model input to build a deep learning based dose prediction model. A database of 60 volumetric modulated arc therapy (VMAT) plans for the prostate cancer patients was used for training. The trained prediction model was then tested on a cohort of 10 cases. Dose difference maps, DVHs, dosimetric endpoints and statistical analysis of the sum of absolute residuals (SARs) were used to evaluate the proposed method. Our results showed that the mean SARs for the PTV, bladder and rectum using our method were 0.007�0.003, 0.035�0.032 and 0.067�0.037 respectively, lower than the SARs obtained with the contours-based method, indicating the potential of the proposed approach in accurately predicting dose distribution.

View details for PubMedID 31082805
Evaluating Prostate-Specific Antigen (PSA) Nadir and Bounce After Stereotactic Body Radiotherapy (SBRT) in a Multi-Institutional Cohort Jiang, N., Dang, A., Yuan, Y., Chu, F., King, C., Collins, S., Aghdam, N., Suy, S., Miszczyk, L., Mantz, C., Bagshaw, H., Buyyounouski, M., Steinberg, M., Kupelian, P., Kishan, A. ELSEVIER SCIENCE INC. 2019: E17
View details for DOI 10.1016/S0360-3016(19)30440-7

View details for Web of Science ID 000463350600040
Hypofractionated Radiation Therapy for Localized Prostate Cancer: Executive Summary of an ASTRO, ASCO and AUA Evidence-Based Guideline JOURNAL OF UROLOGY Morgan, S. C., Hoffman, K., Loblaw, D., Buyyounouski, M. K., Patton, C., Barocas, D., Bentzen, S., Chang, M., Efstathiou, J., Greany, P., Halvorsen, P., Koontz, B. F., Lawton, C., Leyrer, C., Lin, D., Ray, M., Sandler, H. 2019; 201 (3): 528?34
View details for DOI 10.1097/JU.0000000000000071

View details for Web of Science ID 000475762000038
Hypofractionated Radiation Therapy for Localized Prostate Cancer: Executive Summary of an ASTRO, ASCO and AUA Evidence-Based Guideline. The Journal of urology Morgan, S. C., Hoffman, K., Loblaw, D. A., Buyyounouski, M. K., Patton, C., Barocas, D., Bentzen, S., Chang, M., Efstathiou, J., Greany, P., Halvorsen, P., Koontz, B. F., Lawton, C., Leyrer, C. M., Lin, D., Ray, M., Sandler, H. 2019; 201 (3): 528?34
Abstract

PURPOSE: The aim of this guideline is to present recommendations regarding moderately hypofractionated (240-340 cGy per fraction) and ultrahypofractionated (500 cGy or more per fraction) radiation therapy for localized prostate cancer.METHODS AND MATERIALS: The American Society for Radiation Oncology convened a task force to address 8 key questions on appropriate indications and dose-fractionation for moderately and ultrahypofractionated radiation therapy, as well as technical issues, including normal tissue dose constraints, treatment volumes, and use of image guided and intensity modulated radiation therapy. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and Society-approved tools for grading evidence quality and recommendation strength.RESULTS: Based on high-quality evidence, strong consensus was reached for offering moderate hypofractionation across risk groups to patients choosing external beam radiation therapy. The task force conditionally recommends ultrahypofractionated radiation may be offered for low- and intermediate-risk prostate cancer but strongly encourages treatment of intermediate-risk patients on a clinical trial or multi-institutional registry. For high-risk patients, the task force conditionally recommends against routine use of ultrahypofractionated external beam radiation therapy. With any hypofractionated approach, the task force strongly recommends image guided radiation therapy and avoidance of nonmodulated 3-dimensional conformal techniques.CONCLUSIONS: Hypofractionated radiation therapy provides important potential advantages in cost and convenience for patients, and these recommendations are intended to provide guidance on moderate hypofractionation and ultrahypofractionation for localized prostate cancer. The limits in the current evidentiary base-especially for ultrahypofractionation-highlight the imperative to support large-scale randomized clinical trials and underscore the importance of shared decision making between clinicians and patients.

View details for PubMedID 30759696
Prostate cancer classification with multiparametric MRI transfer learning model MEDICAL PHYSICS Yuan, Y., Qin, W., Buyyounouski, M., Ibragimov, B., Hancock, S., Han, B., Xing, L. 2019; 46 (2): 756?65
View details for DOI 10.1002/mp.13367

View details for Web of Science ID 000459616200032
Dosimetric features-driven machine learning model for DVH prediction in VMAT treatment planning MEDICAL PHYSICS Ma, M., Kovalchuk, N., Buyyounouski, M. K., Xing, L., Yang, Y. 2019; 46 (2): 857?67
View details for DOI 10.1002/mp.13334

View details for Web of Science ID 000459616200041
Long-term Outcomes of Stereotactic Body Radiotherapy for Low-Risk and Intermediate-Risk Prostate Cancer JAMA NETWORK OPEN Kishan, A. U., Dang, A., Katz, A. J., Mantz, C. A., Collins, S. P., Aghdam, N., Chu, F., Kaplan, I. D., Appelbaum, L., Fuller, D. B., Meier, R. M., Loblaw, D., Cheung, P., Pham, H. T., Shaverdian, N., Jiang, N., Yuan, Y., Bagshaw, H., Prionas, N., Buyyounouski, M. K., Spratt, D. E., Linson, P. W., Hong, R. L., Nickols, N. G., Steinberg, M. L., Kupelian, P. A., King, C. R. 2019; 2 (2)
View details for DOI 10.1001/jamanetworkopen.2018.8006

View details for Web of Science ID 000465423800030
Results from a Phase 1 Study of Sodium Selenite in Combination with Palliative Radiation Therapy in Patients with Metastatic Cancer. Translational oncology Knox, S. J., Jayachandran, P., Keeling, C. A., Stevens, K. J., Sandhu, N., Stamps-DeAnda, S. L., Savic, R., Shura, L., Buyyounouski, M. K., Grimes, K. 2019; 12 (11): 1525?31
Abstract

In preclinical studies, selenite had single agent activity and radiosensitized tumors in vivo. Here we report results from a Phase 1 trial in 15 patients with metastatic cancer treated with selenite (5.5 to 49.5 mg) orally as a single dose 2 hours before each radiation therapy (RT) treatment. Patients received RT regimens that were standard of care. The primary objective of the study was to assess the safety of this combination therapy. Secondary objectives included measurement of pharmacokinetics (PK) and evaluation of efficacy. Endpoints included assessment of PK, toxicity, tumor response, and pain before and after treatment. The half-life of selenite was 18.5 hours. There were no adverse events attributable to selenite until the 33 mg dose level, at which the primary toxicities were grade 1 GI side effects. One patient treated with 49.5 mg had grade 2 GI toxicity. Although this was not a DLT, it was felt that the highest acceptable dose in this patient population was 33 mg. Most patients had stabilization of disease within the RT fields, with some demonstrating objective evidence of tumor regression. Most patients had a marked improvement in pain and seven out of nine patients with prostate cancer had a decrease in PSA ranging from 11-78%. Doses up to 33 mg selenite were well tolerated in combination with RT. A randomized, well controlled study is needed at the 33 mg dose level to determine if selenite results in clinically meaningful improvements in the response to palliative RT.

View details for DOI 10.1016/j.tranon.2019.08.006

View details for PubMedID 31454725
PROSTATE SEGMENTATION WITH ENCODER -DECODER DENSELY CONNECT CONVOLUTIONAL NETWORK (ED-DENSENET) Yuan, Y., Qin, W., Guo, X., Buyyounouski, M., Hancock, S., Hai, B., Xing, L., IEEE IEEE. 2019: 434?37
View details for Web of Science ID 000485040000095
Prostate Cancer Classification with Multi-parametric MRI Transfer Learning Model. Medical physics Yuan, Y., Qin, W., Buyyounouski, M., Ibragimov, B., Hancock, S., Han, B., Xing, L. 2018
Abstract

PURPOSE: Prostate cancer classification has significantly impact on the prognosis and treatment planning of patients. Currently, the classifying is based on the Gleason score analysis of biopsied tissues, which is neither accurate nor risk-free. This study aims to learn discriminative features for prostate images and assist physicians to classify prostate cancer automatically.METHODS: We develop a novel multi-parametric magnetic resonance transfer learning (MPTL) method to automatically stage prostate cancer. We first establish a deep convolutional neural network with three branch architectures, which transfer pre-trained model to compute features from multi-parametric MRI images (mp-MRI) : T2w transaxial, T2w sagittal and apparent diffusion coefficient (ADC). The learned features are concatenated to represent information of mp-MRI sequences. A new image similarity constraint is then proposed to enable the distribution of the features within the same category in a narrow angle region. With the joint constraints of softmax loss and image similarity loss in the fine-tuning process, the MPTL can provide descriptive features with intraclass compactness and interclass separability.RESULTS: Two cohorts: 132 cases from our institutional review board approved patient database and 112 cases from the PROSTATEx-2 Challenge are utilized to evaluate the robustness and effectiveness of the proposed MPTL model. Our model achieved high accuracy of prostate cancer classification (accuracy of 86.92%). Moreover, the comparison results demonstrate that our method outperforms both hand-crafted feature based methods and existing deep learning models in prostate cancer classification with higher accuracy.CONCLUSION: The experiment results showed that the proposed method can learn discriminative features for prostate images and classify the cancer accurately. Our MPTL model could be further applied in the clinical practice to provide valuable information for cancer treatment and precision medicine. This article is protected by copyright. All rights reserved.

View details for PubMedID 30597561
Dosimetric Features-Driven Machine Learning Model for DVHs Prediction in VMAT Treatment Planning. Medical physics Ma, M., Kovalchuk, N., Buyyounouski, M. K., Xing, L., Yang, Y. 2018
Abstract

PURPOSE: Few features characterizing the dosimetric properties of the patients are included in currently available dose-volume histogram (DVH) prediction models, making it intractable to build a correlative relationship between the input and output parameters. Here we use PTV-only treatment plans of the patients (i.e., the achievable dose distribution in the absence of organs-at-risks (OARs) constraints) to estimate the potentially achievable quality of treatment plans and establish a machine learning-based DVH prediction framework with the use of the dosimetric metric as model input parameters.METHODS: A support vector regression (SVR) approach was used as the backbone of our machine learning model. A database containing volumetric modulated arc therapy (VMAT) plans of 63 prostate cancer patients were used. For each patient, the PTV-only plan was generated first. A correlative relationship between the OAR DVH of the PTV-only plan (model input) and the corresponding DVH of the clinical treatment plan (CTP) (model output) was then established with the 53 training cases. The prediction model was tested by the validation cohort of 10 cases.RESULTS: For the training cohort, the checks of dosimetric endpoints (DEs) indicated that 52 out of 53 plans (98%) were within 10% error bound for bladder, and 45 out of 53 plans (85%) were within 10% error bound for rectum. In the validation tests, 92% and 96% of the DEs were within the 10% error bounds for bladder and rectum respectively, and 8 out of 10 validation plans (80%) were within 10% error bound for both bladder and rectum. The sum of absolute residuals (SAR) achieved mean 0.034 � 0.028 and 0.046 � 0.021 for the bladder and rectum, respectively.CONCLUSIONS: A novel dosimetric features-driven machine learning model with the use of PTV-only plan has been established for DVH prediction. The framework is capable of efficiently generating best achievable DVHs for VMAT planning. This article is protected by copyright. All rights reserved.

View details for PubMedID 30536442
Hypofractionated Radiation Therapy for Localized Prostate Cancer: An ASTRO, ASCO, and AUA Evidence-Based Guideline JOURNAL OF CLINICAL ONCOLOGY Morgan, S. C., Hoffman, K., Loblaw, D., Buyyounouski, M. K., Patton, C., Barocas, D., Bentzen, S., Chang, M., Efstathiou, J., Greany, P., Halvorsen, P., Koontz, B. F., Lawton, C., Leyrer, C., Lin, D., Ray, M., Sandler, H. 2018; 36 (34): 3411-+
View details for DOI 10.1200/JCO.18.01097

View details for Web of Science ID 000452256500009
Hypofractionated Radiation Therapy for Localized Prostate Cancer: Executive Summary of an ASTRO, ASCO, and AUA Evidence-Based Guideline PRACTICAL RADIATION ONCOLOGY Morgan, S. C., Hoffman, K., Loblaw, D., Buyyounouski, M. K., Patton, C., Barocas, D., Bentzen, S., Chang, M., Efstathiou, J., Greany, P., Halvorsen, P., Koontz, B. F., Lawton, C., Leyrer, C., Lin, D., Ray, M., Sandler, H. 2018; 8 (6): 354?60
View details for DOI 10.1016/j.prro.2018.08.002

View details for Web of Science ID 000448881600005
Hypofractionated Radiation Therapy for Localized Prostate Cancer: Executive Summary of an ASTRO, ASCO, and AUA Evidence-Based Guideline. Practical radiation oncology Morgan, S. C., Hoffman, K., Loblaw, D. A., Buyyounouski, M. K., Patton, C., Barocas, D., Bentzen, S., Chang, M., Efstathiou, J., Greany, P., Halvorsen, P., Koontz, B. F., Lawton, C., Leyrer, C. M., Lin, D., Ray, M., Sandler, H. 2018; 8 (6): 354?60
Abstract

PURPOSE: The aim of this guideline is to present recommendations regarding moderately hypofractionated (240-340 cGy per fraction) and ultrahypofractionated (500 cGy or more per fraction) radiation therapy for localized prostate cancer.METHODS AND MATERIALS: The American Society for Radiation Oncology convened a task force to address 8 key questions on appropriate indications and dose-fractionation for moderately and ultrahypofractionated radiation therapy, as well as technical issues, including normal tissue dose constraints, treatment volumes, and use of image guided and intensity modulated radiation therapy. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and Society-approved tools for grading evidence quality and recommendation strength.RESULTS: Based on high-quality evidence, strong consensus was reached for offering moderate hypofractionation across risk groups to patients choosing external beam radiation therapy. The task force conditionally recommends ultrahypofractionated radiation may be offered for low- and intermediate-risk prostate cancer but strongly encourages treatment of intermediate-risk patients on a clinical trial or multi-institutional registry. For high-risk patients, the task force conditionally recommends against routine use of ultrahypofractionated external beam radiation therapy. With any hypofractionated approach, the task force strongly recommends image guided radiation therapy and avoidance of nonmodulated 3-dimensional conformal techniques.CONCLUSIONS: Hypofractionated radiation therapy provides important potential advantages in cost and convenience for patients, and these recommendations are intended to provide guidance on moderate hypofractionation and ultrahypofractionation for localized prostate cancer. The limits in the current evidentiary base-especially for ultrahypofractionation-highlight the imperative to support large-scale randomized clinical trials and underscore the importance of shared decision making between clinicians and patients.

View details for PubMedID 30322661
Hypofractionated Radiation Therapy for Localized Prostate Cancer: An ASTRO, ASCO, and AUA Evidence-Based Guideline. The Journal of urology Morgan, S. C., Hoffman, K., Loblaw, D. A., Buyyounouski, M. K., Patton, C., Barocas, D., Bentzen, S., Chang, M., Efstathiou, J., Greany, P., Halvorsen, P., Koontz, B. F., Lawton, C., Leyrer, C. M., Lin, D., Ray, M., Sandler, H. 2018
Abstract

PURPOSE: The aim of this guideline is to present recommendations regarding moderately hypofractionated (240-340 cGy per fraction) and ultrahypofractionated (500 cGy or more per fraction) radiation therapy for localized prostate cancer.METHODS AND MATERIALS: The American Society for Radiation Oncology convened a task force to address 8 key questions on appropriate indications and dose-fractionation for moderately and ultrahypofractionated radiation therapy, as well as technical issues, including normal tissue dose constraints, treatment volumes, and use of image guided and intensity modulated radiation therapy. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and Society-approved tools for grading evidence quality and recommendation strength.RESULTS: Based on high-quality evidence, strong consensus was reached for offering moderate hypofractionation across risk groups to patients choosing external beam radiation therapy. The task force conditionally recommends ultrahypofractionated radiation may be offered for low- and intermediate-risk prostate cancer but strongly encourages treatment of intermediate-risk patients on a clinical trial or multi-institutional registry. For high-risk patients, the task force conditionally recommends against routine use of ultrahypofractionated external beam radiation therapy. With any hypofractionated approach, the task force strongly recommends image guided radiation therapy and avoidance of nonmodulated 3-dimensional conformal techniques.CONCLUSIONS: Hypofractionated radiation therapy provides important potential advantages in cost and convenience for patients, and these recommendations are intended to provide guidance on moderate hypofractionation and ultrahypofractionation for localized prostate cancer. The limits in the current evidentiary base-especially for ultrahypofractionation-highlight the imperative to support large-scale randomized clinical trials and underscore the importance of shared decision making between clinicians and patients.

View details for PubMedID 30316897
NCCN Guidelines (R) Insights Bladder Cancer, Version 5.2018 Featured Updates to the NCCN Guidelines JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Flaig, T. W., Spiess, P. E., Agarwal, N., Bangs, R., Boorjian, S. A., Buyyounouski, M. K., Downs, T. M., Efstathiou, J. A., Friedlander, T., Greenberg, R. E., Guru, K. A., Noah Hahn, Herr, H. W., Hoimes, C., Inman, B. A., Jimbo, M., Kader, A., Lele, S. M., Meeks, J. J., Michalski, J., Montgomery, J. S., Pagliaro, L. C., Pal, S. K., Patterson, A., Petrylak, D. P., Plimack, E. R., Pohar, K. S., Porter, M. P., Preston, M. A., Sexton, W. J., Siefker-Radtke, A. O., Tward, J., Wile, G., Johnson-Chilla, A., Dwyer, M. A., Gurski, L. A. 2018; 16 (9): 1041?53
View details for DOI 10.6004/jnccn.2018.0072

View details for Web of Science ID 000443581300004
Radiation therapy for prostate cancer TRANSLATIONAL ANDROLOGY AND UROLOGY Buyyounouski, M. K. 2018; 7 (3): 295?96
View details for DOI 10.21037/tau.2018.05.11

View details for Web of Science ID 000436539400001
Long-term outcomes of stereotactic body radiotherapy for low- and intermediate-risk prostate adenocarcinoma: A multi-institutional consortium study. Kishan, A., Katz, A. J., Mantz, C., Chu, F., Appelbaum, L., Loblaw, A., Cheung, P., Kaplan, I. D., Fuller, D. B., Pham, H. T., Meier, R., Buyyounouski, M. K., Shaverdian, N., Dang, A., Yuan, Y., Bagshaw, H., Prionas, N., Kupelian, P., Steinberg, M. L., King, C. R. AMER SOC CLINICAL ONCOLOGY. 2018
View details for DOI 10.1200/JCO.2018.36.6_suppl.84

View details for Web of Science ID 000436179500080
Radiation therapy for prostate cancer. Translational andrology and urology Buyyounouski, M. K. 2018; 7 (3): 295?96
View details for PubMedID 30050790
Bladder Cancer, Version 5.2017 JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Spiess, P. E., Agarwal, N., Bangs, R., Boorjian, S. A., Buyyounouski, M. K., Clark, P. E., Downs, T. M., Efstathiou, J. A., Flaig, T. W., Friedlander, T., Greenberg, R. E., Guru, K. A., Noah Hahn, Herr, H. W., Hoimes, C., Inman, B. A., Jimbo, M., Kader, A., Lele, S. M., Meeks, J. J., Michalski, J., Montgomery, J. S., Pagliaro, L. C., Pal, S. K., Patterson, A., Plimack, E. R., Pohar, K. S., Porter, M. P., Preston, M. A., Sexton, W. J., Siefker-Radtke, A. O., Sonpavde, G., Tward, J., Wile, G., Dwyer, M. A., Gurski, L. A. 2017; 15 (10): 1240?67
Abstract

This selection from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Bladder Cancer focuses on systemic therapy for muscle-invasive urothelial bladder cancer, as substantial revisions were made in the 2017 updates, such as new recommendations for nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab. The complete version of the NCCN Guidelines for Bladder Cancer addresses additional aspects of the management of bladder cancer, including non-muscle-invasive urothelial bladder cancer and nonurothelial histologies, as well as staging, evaluation, and follow-up.

View details for DOI 10.6004/jnccn.2017.0156

View details for Web of Science ID 000412320900010

View details for PubMedID 28982750
Peering over the chasm: Diffusion of prostate radiation therapy hypofractionation PRACTICAL RADIATION ONCOLOGY Buyyounouski, M. K. 2017; 7 (4): 279?80
View details for DOI 10.1016/j.prro.2017.03.012

View details for Web of Science ID 000416330300017

View details for PubMedID 28501507
What More Can Be Learned From the ASCENDE-RT Trial? INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Hamstra, D. A., Krauss, D., Buyyounouski, M. K. 2017; 98 (2): 481?82
View details for PubMedID 28463168
Robust Estimation of Electron Density From Anatomic Magnetic Resonance Imaging of the Brain Using a Unifying Multi-Atlas Approach. International journal of radiation oncology, biology, physics Ren, S., Hara, W., Wang, L., Buyyounouski, M. K., Le, Q., Xing, L., Li, R. 2017; 97 (4): 849-857
Abstract

To�develop a reliable method to estimate electron density based on anatomic magnetic resonance imaging (MRI) of the brain.We proposed a unifying multi-atlas approach for electron density estimation based on standard T1- and T2-weighted MRI. First, a composite atlas was constructed through a voxelwise matching process using multiple atlases, with the goal of mitigating effects of inherent anatomic variations between patients. Next we computed for each voxel 2 kinds of conditional probabilities: (1) electron density given its image intensity on T1- and T2-weighted MR images; and (2) electron density given its spatial location in a reference anatomy, obtained by deformable image registration. These were combined into a unifying posterior probability density function using the Bayesian formalism, which provided the optimal estimates for electron density. We evaluated the method on 10 patients using leave-one-patient-out cross-validation. Receiver operating characteristic analyses�for detecting different tissue types were performed.The proposed method significantly reduced the errors in electron density estimation, with a mean absolute Hounsfield unit error of 119, compared with 140 and 144 (P<.0001) using conventional T1-weighted intensity and geometry-based approaches, respectively. For detection of bony anatomy, the proposed method achieved an 89% area under the curve, 86% sensitivity, 88% specificity, and 90% accuracy, which improved upon intensity and geometry-based approaches (area under the curve: 79% and 80%, respectively).The proposed multi-atlas approach provides robust electron density estimation and bone detection based on anatomic MRI. If validated on a larger population, our work could enable the use of MRI as a primary modality for radiation treatment planning.

View details for DOI 10.1016/j.ijrobp.2016.11.053

View details for PubMedID 28244422
Improving care with portfolio of physician-led cancer quality measures at an academic center Porter, J., Smith, A., Winget, M., Rosenthal, E., Seshadri, S., Vetteth, Y., Kiamanesh, E. F., Badwe, A., Advani, R. H., Buyyounouski, M. K., Coutre, S., Dorigo, O., Ganjoo, K. N., Johnston, L. J., Recht, L., Shrager, J. B., Skinner, E. C., Swetter, S. M., Visser, B. C., Blayney, D. W. AMER SOC CLINICAL ONCOLOGY. 2017
View details for Web of Science ID 000443301600049
Prospective Validation of Diagnostic Tumor Biomarkers in Men Treated With Radiotherapy for Prostate Cancer JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE Pollack, A., Kwon, D., Walker, G., Khor, L. Y., Horwitz, E. M., Buyyounouski, M. K., Stoyanova, R. 2017; 109 (2)
Abstract

In prior retrospective studies, we assessed a number of prostate tumor tissue biomarkers that were associated independently with the clinical outcome of men treated with radiotherapy (RT) � androgen deprivation therapy (ADT). In this report, the associations of selected biomarkers with biochemical or clinical disease failure (BCDF) were prospectively evaluated in men with T1-T3 prostate cancer on a randomized hypofractionation trial.Biomarkers were analyzed in 263 of 303 men randomly assigned to standard vs moderate hypofractionation. Median follow-up was 65.9 months. Archival tissue was analyzed for Ki-67 (n?=?231), MDM2 (n?=?209), p16 (n?=?195), Cox-2 (n?=?126), p53 (n?=?206), bcl2 (n?=?223), bax (n?=?210), and PKA (n?=?160). The base model for multivariable Fine-Gray regression analysis included treatment assignment and risk groups. All statistical tests were two-sided.Each biomarker was tested one at a time relative to the base model and selected for inclusion in multivariable analysis. Ki-67 (hazard ratio [HR] = 2.31, 95% confidence interval [CI] = 1.19 to 4.48, P = .01) and bcl2&bax (HR?=?2.19, 95% CI?=?1.08 to 4.46, P = .03) were statistically significantly related to higher BCDF and were independently statistically significant when considered jointly (Ki-67: HR?=?2.26, 95% CI?=?1.12 to 4.58, P = .02; bcl2&bax: HR?=?2.14, 95% CI?=?1.03 to 4.41, P = .04). At 2.5 years postradiotherapy, the C-index of Ki-67 was 73.2%, while for the base model was only 46.2%; Ki-67 was the most statistically significant when tested without bcl2&bax.In this prospective multiple biomarker analysis in men with prostate cancer treated with RT�ADT, both Ki-67 and bcl2&bax were independently related to early BCDF; however, Ki-67 alone is indicated to be the most clinically meaningful by C-index analysis and is universally available.

View details for DOI 10.1093/jnci/djw232

View details for Web of Science ID 000396774100009

View details for PubMedID 28376214
NCCN Guidelines (R) Insights Bladder Cancer, Version 2.2016 Featured Updates to the NCCN Guidelines JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Clark, P. E., Spiess, P. E., Agarwal, N., Bangs, R., Boorjian, S. A., Buyyounouski, M. K., Efstathiou, J. A., Flaig, T. W., Friedlander, T., Greenberg, R. E., Guru, K. A., Hahn, N., Herr, H. W., Holmes, C., Inman, B. A., Kader, A. K., Kibel, A. S., Kuzel, T. M., Lele, S. M., Meeks, J. J., Michalski, J., Montgomery, J. S., Pagliaro, L. C., Pal, S. K., Patterson, A., Petrylak, D., Plimack, E. R., Pohar, K. S., Porter, M. P., Sexton, W. J., Siefker-Radtke, A. O., Sonpavde, G., Tward, J., Wile, G., Dwyer, M. A., Smith, C. 2016; 14 (10): 1213-1224
Abstract

These NCCN Guidelines Insights discuss the major recent updates to the NCCN Guidelines for Bladder Cancer based on the review of the evidence in conjunction with the expert opinion of the panel. Recent updates include (1) refining the recommendation of intravesical bacillus Calmette-Gu�rin, (2) strengthening the recommendations for perioperative systemic chemotherapy, and (3) incorporating immunotherapy into second-line therapy for locally advanced or metastatic disease. These NCCN Guidelines Insights further discuss factors that affect integration of these recommendations into clinical practice.

View details for Web of Science ID 000385057100003
NCCN Guidelines Insights: Bladder Cancer, Version 2.2016. Journal of the National Comprehensive Cancer Network Clark, P. E., Spiess, P. E., Agarwal, N., Bangs, R., Boorjian, S. A., Buyyounouski, M. K., Efstathiou, J. A., Flaig, T. W., Friedlander, T., Greenberg, R. E., Guru, K. A., Hahn, N., Herr, H. W., Hoimes, C., Inman, B. A., Kader, A. K., Kibel, A. S., Kuzel, T. M., Lele, S. M., Meeks, J. J., Michalski, J., Montgomery, J. S., Pagliaro, L. C., Pal, S. K., Patterson, A., Petrylak, D., Plimack, E. R., Pohar, K. S., Porter, M. P., Sexton, W. J., Siefker-Radtke, A. O., Sonpavde, G., Tward, J., Wile, G., Dwyer, M. A., Smith, C. 2016; 14 (10): 1213-1224
Abstract

These NCCN Guidelines Insights discuss the major recent updates to the NCCN Guidelines for Bladder Cancer based on the review of the evidence in conjunction with the expert opinion of the panel. Recent updates include (1) refining the recommendation of intravesical bacillus Calmette-Gu�rin, (2) strengthening the recommendations for perioperative systemic chemotherapy, and (3) incorporating immunotherapy into second-line therapy for locally advanced or metastatic disease. These NCCN Guidelines Insights further discuss factors that affect integration of these recommendations into clinical practice.

View details for PubMedID 27697976
Electronic Release of Pathology and Radiology Results to Patients: Opinions and Experiences of Oncologists. Journal of oncology practice / American Society of Clinical Oncology Winget, M., Haji-Sheikhi, F., Brown-Johnson, C., Rosenthal, E. L., Sharp, C., Buyyounouski, M. K., Asch, S. M. 2016; 12 (8): e792-9
Abstract

There is an emerging standard to provide patients rapid electronic access to elements of their medical records. Although surveys of patients generally support it, this practice is controversial among oncologists, because few empiric data are available for scenarios of potentially life-threatening conditions like cancer. We report the views of oncologists about patient electronic access to radiology and pathology results that could potentially indicate disease progression.Four months before oncologists were surveyed, final results of radiology/pathology reports were routinely made available to patients online through a secure portal after a 7-day, hold to provide clinicians time to review and communicate results with the patients. Mixed methods were used to assess physician attitudes and experiences toward this change.One hundred twenty-nine oncologists were surveyed, and 82 (64%) responded. A small majority (54%) responded that the release of reports was somewhat or very beneficial for patients who received normal radiology/pathology results before discussion with a physician, but 87% said it was somewhat or very harmful for patients to receive abnormal results before discussion. Forty-nine percent reported that release of reports had a somewhat or very negative impact on communication with their patients.Almost half of oncologists reported that sharing digital radiology and pathology records had a negative impact on their communication with patients. Patient surveys in similar cancer populations would complement the physician perspective. Efforts are needed to improve consensus among oncologists and patients on how to best communicate such results in a timely fashion.

View details for DOI 10.1200/JOP.2016.011098

View details for PubMedID 27382001
Overall Survival in Patients with Localized Prostate Cancer in the US Veterans Health Administration: Is PIVOT Generalizable? EUROPEAN UROLOGY Barbosa, P. V., Thomas, I., Srinivas, S., Buyyounouski, M. K., Chung, B. I., Chertow, G. M., Asch, S. M., Wagner, T. H., Brooks, J. D., Leppert, J. T. 2016; 70 (2): 227-230
Abstract

A better understanding of overall survival among patients with clinically localized prostate cancer (PCa) in the US Veterans Health Administration (VHA) is critical to inform PCa treatment decisions, especially in light of data from the Prostate Intervention Versus Observation Trial (PIVOT). We sought to describe patterns of survival for all patients with clinically localized PCa treated by the VHA. We created an analytic cohort of 35 954 patients with clinically localized PCa diagnosed from 1995 to 2001, approximating the PIVOT inclusion criteria (age of diagnosis ?75 yr and clinical stage T2 or lower). Mean patient age was 65.9 yr, and median follow-up was 161 mo. Overall, 22.5% of patients were treated with surgery, 16.6% were treated with radiotherapy, and 23.1% were treated with androgen deprivation. Median survival of the entire cohort was 14 yr (25th, 75th percentiles, range: 7.9-20 yr). Among patients who received treatment with curative intent, median survival was 17.9 yr following surgery and 12.9 yr following radiotherapy. One-third of patients died within 10 yr of diagnosis compared with nearly half of the participants in PIVOT. This finding sounds a note of caution when generalizing the mortality data from PIVOT to VHA patients and those in the community.More than one-third of patients diagnosed with clinically localized prostate cancer treated through the US Veterans Health Administration from 1995 to 2001 died within 10 yr of their diagnosis. Caution should be used when generalizing the estimates of competing mortality data from PIVOT.

View details for DOI 10.1016/j.eururo.2016.02.037

View details for PubMedID 26948397
SBRT and HDR brachytherapy produce lower PSA nadirs and different PSA decay patterns than conventionally fractionated IMRT in patients with low- or intermediate-risk prostate cancer. Practical radiation oncology Kishan, A. U., Wang, P., Upadhyaya, S. K., Hauswald, H., Demanes, D. J., Nickols, N. G., Kamrava, M., Sadeghi, A., Kupelian, P. A., Steinberg, M. L., Prionas, N. D., Buyyounouski, M. K., King, C. R. 2016; 6 (4): 268-275
Abstract

To compare patterns of prostate-specific antigen (PSA) response following stereotactic body radiation therapy (SBRT), high-dose-rate (HDR) brachytherapy, and conventionally fractionated intensity modulated radiation therapy (IMRT) in patients with low- or intermediate-risk prostate cancer (CaP).Eligible study patients included 439 patients with low- or intermediate-risk prostate cancer who were treated with radiation therapy (RT) alone between 2003 and 2013, remained free of biochemical recurrence, and had at least 2 PSA values within the first year following RT. Of these, 130 were treated with SBRT, 220 with HDR brachytherapy, and 89 with IMRT. Multivariate regression analysis was used to compare PSA nadirs (nPSA), time to nPSA, and PSA bounce parameters among the 3 modalities. Indicator variable analysis was used to develop empirical models of PSA decay using the treatment modalities as indicator variables.Significantly more patients treated with SBRT or HDR brachytherapy achieved raw nPSAs of <0.5 ng/mL compared with patients treated with IMRT (76.2% and 75.9% vs 44.9%, respectively; P < .0001 for SBRT or HDR brachytherapy vs IMRT). On multivariate analysis, nPSA was significantly lower with SBRT and HDR compared with IMRT (P < .0001). Time to nPSA and bounce parameters was not significantly different among IMRT, SBRT, and HDR. Overall, SBRT and HDR brachytherapy caused significantly larger PSA decay rates (P < .001). When truncating follow-up at 1000 days, the corresponding decay rates were larger for all 3 modalities, with no significant differences between them.Stereotactic body radiation therapy and HDR brachytherapy produce lower nPSAs than IMRT. Within 1000 days of follow-up, the modalities produce similar rates of PSA decay; subsequently, decay continues (albeit at a slower pace) after SBRT and HDR brachytherapy but plateaus with IMRT. Because nPSA is a validated predictor of long-term outcome, these data not only suggest a distinct radiobiological effect with SBRT and HDR brachytherapy, but also predict for clinical outcomes that might equal or surpass those of IMRT.

View details for DOI 10.1016/j.prro.2015.11.002

View details for PubMedID 26850649
Oncologists' opinions and experiences with electronic release of radiology and pathology results to patients. Winget, M., Sheikhi, F., Rosenthal, E., Sharp, C., Buyyounouski, M. K., Asch, S. AMER SOC CLINICAL ONCOLOGY. 2016
View details for DOI 10.1200/jco.2016.34.7_suppl.162

View details for Web of Science ID 000378109900158
Interval to biochemical failure is prognostic for distant metastases after salvage radiation therapy for prostate cancer JOURNAL OF RADIATION ONCOLOGY Zaorsky, N., Li, T., Turaka, A., Chen, D. T., Horwitz, E. M., Buyyounouski, M. K. 2016; 5 (1): 79?85
View details for DOI 10.1007/s13566-015-0208-5

View details for Web of Science ID 000379662900010
Comparison of testicular dose delivered by intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) in patients with prostate cancer. Medical dosimetry Martin, J. M., Handorf, E. A., Price, R. A., Cherian, G., Buyyounouski, M. K., Chen, D. Y., Kutikov, A., Johnson, M. E., Ma, C. C., Horwitz, E. M. 2015; 40 (3): 186-189
Abstract

A small decrease in testosterone level has been documented after prostate irradiation, possibly owing to the incidental dose to the testes. Testicular doses from prostate external beam radiation plans with either intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT) were calculated to investigate any difference. Testicles were contoured for 16 patients being treated for localized prostate cancer. For each patient, 2 plans were created: 1 with IMRT and 1 with VMAT. No specific attempt was made to reduce testicular dose. Minimum, maximum, and mean doses to the testicles were recorded for each plan. Of the 16 patients, 4 received a total dose of 7800cGy to the prostate alone, 7 received 8000cGy to the prostate alone, and 5 received 8000cGy to the prostate and pelvic lymph nodes. The mean (range) of testicular dose with an IMRT plan was 54.7cGy (21.1 to 91.9) and 59.0cGy (25.1 to 93.4) with a VMAT plan. In 12 cases, the mean VMAT dose was higher than the mean IMRT dose, with a mean difference of 4.3cGy (p = 0.019). There was a small but statistically significant increase in mean testicular dose delivered by VMAT compared with IMRT. Despite this, it unlikely that there is a clinically meaningful difference in testicular doses from either modality.

View details for DOI 10.1016/j.meddos.2014.11.003

View details for PubMedID 25595491

View details for PubMedCentralID PMC4500753
Comparison of testicular dose delivered by intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) in patients with prostate cancer MEDICAL DOSIMETRY Martin, J. M., Handorf, E. A., Price, R. A., Cherian, G., Buyyounouski, M. K., Chen, D. Y., Kutikov, A., Johnson, M. E., Ma, C. C., Horwitz, E. M. 2015; 40 (3): 186-189
Abstract

A small decrease in testosterone level has been documented after prostate irradiation, possibly owing to the incidental dose to the testes. Testicular doses from prostate external beam radiation plans with either intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT) were calculated to investigate any difference. Testicles were contoured for 16 patients being treated for localized prostate cancer. For each patient, 2 plans were created: 1 with IMRT and 1 with VMAT. No specific attempt was made to reduce testicular dose. Minimum, maximum, and mean doses to the testicles were recorded for each plan. Of the 16 patients, 4 received a total dose of 7800cGy to the prostate alone, 7 received 8000cGy to the prostate alone, and 5 received 8000cGy to the prostate and pelvic lymph nodes. The mean (range) of testicular dose with an IMRT plan was 54.7cGy (21.1 to 91.9) and 59.0cGy (25.1 to 93.4) with a VMAT plan. In 12 cases, the mean VMAT dose was higher than the mean IMRT dose, with a mean difference of 4.3cGy (p = 0.019). There was a small but statistically significant increase in mean testicular dose delivered by VMAT compared with IMRT. Despite this, it unlikely that there is a clinically meaningful difference in testicular doses from either modality.

View details for DOI 10.1016/j.meddos.2014.11.003

View details for Web of Science ID 000359449400003

View details for PubMedID 25595491

View details for PubMedCentralID PMC4500753
Development and preliminary testing of PROGRESS: a Web-based education program for prostate cancer survivors transitioning from active treatment JOURNAL OF CANCER SURVIVORSHIP Miller, S. M., Hudson, S. V., Hui, S. A., Diefenbach, M. A., Fleisher, L., Raivitch, S., Belton, T., Roy, G., Njoku, A., Scarpato, J., Viterbo, R., Buyyounouski, M., Denlinger, C., Miyamoto, C., Reese, A., Baman, J. 2015; 9 (3): 541-553
Abstract

This formative research study describes the development and preliminary evaluation of a theory-guided, online multimedia psycho-educational program (PROGRESS) designed to facilitate adaptive coping among prostate cancer patients transitioning from treatment into long-term survivorship.Guided by the Cognitive-Social Health Information Processing Model (C-SHIP) and using health communications best practices, we conducted a two-phase, qualitative formative research study with early stage prostate cancer patients (n?=?29) to inform the Web program development. Phase 1 included individual (n?=?5) and group (n?=?12) interviews to help determine intervention content and interface. Phase 2 employed iterative user/usability testing (n?=?12) to finalize the intervention. Interview data were independently coded and collectively analyzed to achieve consensus.Survivors expressed interest in action-oriented content on (1) managing treatment side effects, (2) handling body image and comorbidities related to overweight/obesity, (3) coping with emotional and communication issues, (4) tips to reduce disruptions of daily living activities, and (5) health skills training tools. Patients also desired the use of realistic and diverse survivor images.Incorporation of an established theoretical framework, application of multimedia intervention development best practices, and an evidence-based approach to content and format resulted in a psycho-educational tool that comprehensively addresses survivors' needs in a tailored fashion.The results suggest that an interactive Web-based multimedia program is useful for survivors if it covers the key topics of symptom control, emotional well-being, and coping skills training; this tool has the potential to be disseminated and implemented as an adjunct to routine clinical care.

View details for DOI 10.1007/s11764-015-0431-5

View details for Web of Science ID 000359745900018

View details for PubMedID 25697335

View details for PubMedCentralID PMC4537811
Aspirin use decreases the risk of prostate cancer recurrence after post-prostatectomy radiotherapy JOURNAL OF RADIATION ONCOLOGY Zaorsky, N., Li, T., Cohen, R. J., Horwitz, E. M., Uzzo, R. G., Viterbo, R., Buyyounouski, M. K. 2015; 4 (2): 193?201
View details for DOI 10.1007/s13566-015-0197-4

View details for Web of Science ID 000218775200011
Evaluating toxicity from definitive radiation therapy for prostate cancer in men with inflammatory bowel disease: Patient selection and dosimetric parameters with modern treatment techniques. Practical radiation oncology Murphy, C. T., Heller, S., Ruth, K., Buyyounouski, M. K., Weinberg, D., Uzzo, R. G., Plimack, E., Kutikov, A., Chen, D. Y., Horwitz, E. M. 2015; 5 (3): e215-22
Abstract

Inflammatory bowel disease (IBD) is considered a contraindication to abdominopelvic radiation therapy (RT). We examined our experience in men with IBD who were treated with definitive RT for prostate cancer.We queried our institutional database for patients with a diagnosis of ulcerative colitis, Crohn disease, or IBD not otherwise specified. Endpoints were: acute and late ?grade 2 (G2) GI toxicity and IBD flare after RT. Outcomes were compared with controls using propensity scoring matched 3 to 1. We matched controls to the IBD cohort according to: RT technique, RT dose, risk group, hormone use, treatment year, and age. We determined predictors of acute outcomes using the Fisher exact test and time to outcomes using the log-rank test.Between 1990 and 2010, 84 men were included. Sixty-three men served as matched controls and 21 with IBD: 13 ulcerative colitis, 7 Crohn disease, and 1 IBD not otherwise specified. For men with IBD, median age was 69 years, and median follow-up was 49 months. Median flare-free interval before RT was 10 years. Seven were taking IBD medications during RT. There was no difference in acute or late gastrointestinal (GI) toxicity in the IBD group versus controls. Among IBD patients, IBD medication use was the only predictor of acute ?G2 GI toxicity: 57.1% with medication versus7.7% without (49.4% absolute difference, 95% confidence interval [CI] 10.0%-88.9%, P = .03). The 5-year risk of late GI toxicity in men with IBD versus controls was not statistically significant (hazard ratio = 1.19, 95%CI 0.28-5.01, P = .83). The crude incidence of late ?G2 GI toxicity was 10%.Acute GI toxicity appears to be exacerbated in patients on concomitant medical therapy for IBD. Overall, late GI toxicity was relatively low and not significantly different between patients with IBD versus no IBD. However, the small sample size limits the interpretation of our estimates and the wide confidence intervals indicate these patients warrant careful selection.

View details for DOI 10.1016/j.prro.2014.09.004

View details for PubMedID 25424586
Post-radiotherapy prostate biopsies reveal heightened apex positivity relative to other prostate regions sampled RADIOTHERAPY AND ONCOLOGY Huang, K. T., Stoyanova, R., Walker, G., Sandler, K., Studenski, M. T., Dogan, N., Al-Saleem, T., Buyyounouski, M. K., Horwitz, E. M., Pollack, A. 2015; 115 (1): 101-106
Abstract

Prostate biopsy positivity after radiotherapy (RT) is a significant determinant of eventual biochemical failure. We mapped pre- and post-treatment tumor locations to determine if residual disease is location-dependent.There were 303 patients treated on a randomized hypofractionation trial. Of these, 125 underwent prostate biopsy 2-years post-RT. Biopsy cores were mapped to a sextant template, and 86 patients with both pre-/post-treatment systematic sextant biopsies were analyzed.The pretreatment distribution of positive biopsy cores was not significantly related to prostate region (base, mid, apex; p=0.723). Whereas all regions post-RT had reduced positive biopsies, the base was reduced to the greatest degree and the apex the least (p=0.045). In 38 patients who had a positive post-treatment biopsy, there was change in the rate of apical positivity before and after treatment (76 vs. 71%; p=0.774), while significant reductions were seen in the mid and base.In our experience, persistence of prostate tumor cells after RT increases going from the base to apex. MRI was used in planning and image guidance was performed daily during treatment, so geographic miss of the apex is unlikely. Nonetheless, the pattern observed suggests that attention to apex dosimetry is a priority.

View details for DOI 10.1016/j.radonc.2015.03.006

View details for Web of Science ID 000356736300019

View details for PubMedID 25963053
The Case for Prostate Brachytherapy in the Affordable Care Act Era INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Durkee, B. Y., Buyyounouski, M. K. 2015; 91 (3): 465?67
View details for PubMedID 25680591
Radiobiological Modeling and the Study of Hypofractionated Radiotherapy for Prostate Cancer EUROPEAN UROLOGY Buyyounouski, M. K. 2014; 66 (6): 1031?32
View details for PubMedID 25130566
Salvage low-dose-rate I-125 partial prostate brachytherapy after dose-escalated external beam radiotherapy JOURNAL OF CONTEMPORARY BRACHYTHERAPY Chang, L., Buyyounouski, M. K. 2014; 6 (3): 304-310
Abstract

To report outcomes on 5 patients treated with salvage partial low-dose-rate (LDR) 125-iodine ((125)I) permanent prostate seed brachytherapy (BT) for biopsy-proven locally persistent prostate cancer, following failure of dose-escalated external beam radiotherapy (EBRT).A retrospective review of the Fox Chase Cancer Center prostate cancer database identified five patients treated with salvage partial LDR (125)I seed implant for locally persistent disease following dose-escalated EBRT to 76-84 Gy in 2 Gy per fraction equivalent. All patients had post-EBRT biopsies confirming unilateral locally persistent prostate cancer. Pre-treatment, EBRT and BT details, as well as post-treatment characteristics were documented and assessed.The median follow-up post-implant was 41 months. All five patients exhibited low acute genitourinary and gastrointestinal toxicities. Increased erectile dysfunction was noted in three patients. There were no biochemical failures following salvage LDR (125)I seed BT to date, with a median post-salvage PSA of 0.4 ng/mL.In carefully selected patients with local persistence of disease, partial LDR (125)I permanent prostate seed implant appears to be a feasible option for salvage local therapy with an acceptable toxicity profile. Further study is needed to determine long-term results of this approach.

View details for DOI 10.5114/jcb.2014.45134

View details for Web of Science ID 000344200000011

View details for PubMedID 25337135

View details for PubMedCentralID PMC4200181
Reply to m.j. Brenner et Al and I.R. Vogelius et Al. 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. 2014; 32 (17): 1853-1854
View details for DOI 10.1200/JCO.2013.54.7729

View details for PubMedID 24778402
Tadalafil for Prevention of Erectile Dysfunction After Radiotherapy for Prostate Cancer The Radiation Therapy Oncology Group [0831] Randomized Clinical Trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Pisansky, T. M., Pugh, S. L., Greenberg, R. E., Pervez, N., Reed, D. R., Rosenthal, S. A., Mowat, R. B., Raben, A., Buyyounouski, M. K., Kachnic, L. A., Bruner, D. W. 2014; 311 (13): 1300-1307
Abstract

Tadalafil is used to treat erectile dysfunction after prostate cancer treatment, but its role as a preventive agent is undefined.To determine primarily whether tadalafil preserved erectile function in men treated with radiotherapy for prostate cancer, and secondarily to determine whether participant- or partner-reported overall sexual function and sexual and marital satisfaction were affected.Stratified, placebo-controlled, double-blind, parallel-group study with 1:1 randomization at 76 community-based and tertiary medical sites in the United States and Canada. Two hundred forty-two participants with intact erectile function scheduled to receive radiotherapy for prostate cancer were recruited between November 2009 and February 2012 with follow-up through March 2013.One hundred twenty-one participants were assigned 5 mg of tadalafil daily and 121 were assigned placebo for 24 weeks starting with external radiotherapy (63%) or brachytherapy (37%). Participant-reported International Index of Erectile Function response before radiotherapy and at weeks 2 and 4, between weeks 20 and 24, between weeks 28 and 30, and 1 year thereafter. Participants and partners could respond also to the Sexual Adjustment Questionnaire and to the Locke Marital Adjustment Test before radiotherapy, between weeks 20 and 24 and weeks 28 and 30, and at 1 year.Primary outcome was off-drug spontaneous erectile function 28 to 30 weeks after radiotherapy started. Secondary end points were spontaneous erection at 1 year; overall sexual function and satisfaction; marital adjustment; and partner-reported satisfaction and marital adjustment at 28 to 30 weeks and 1 year, predictors of tadalafil response; and adverse events.Among 221 evaluable participants, 80 (79%; 95% CI, 70%-88%) assigned to receive tadalafil retained erectile function between weeks 28 and 30 compared with 61 (74%; 95% CI, 63%-85%) assigned to receive placebo (P?=?.49); an absolute difference of 5% (95% CI, -9% to 19%). A significant difference was also not observed at 1 year (72%; 95% CI, 60%-84% vs 71%; 95% CI, 59%-84%; P?=?.93). Tadalafil was not associated with significantly improved overall sexual function or satisfaction; a significant difference was not observed in any domain subscale. Partners of men assigned tadalafil noted no significant effect on sexual satisfaction, and marital adjustment was not significantly improved in participants or partners.Among men undergoing radiotherapy for prostate cancer, daily use of tadalafil compared with placebo did not result in improved erectile function. These findings do not support daily use of tadalafil to prevent erectile dysfunction in these patients.clinicaltrials.gov Identifier: NCT00931528.

View details for DOI 10.1001/jama.2014.2626

View details for Web of Science ID 000333645400013

View details for PubMedID 24691606
Does family history of prostate cancer affect outcomes following radiotherapy? Radiotherapy and oncology Bagshaw, H., Ruth, K., Horwitz, E. M., Chen, D. Y., Buyyounouski, M. K. 2014; 110 (2): 229-234
Abstract

To examine family history (FH) as a prognostic factor following radiotherapy (RT).Between 1989 and 2007, 1711 men with clinically localized prostate cancer and complete family history who had received RT (median RT dose=74Gy) without androgen deprivation therapy were analyzed. FH was defined as any prostate cancer in a first degree relative. For the biochemical failure (BF) outcome, this sample size has 85% power to detect a hazard ratio of 1.56 for positive versus negative FH.With a median follow-up of 71 months, there was no significant difference in the distribution of Gleason score (GS) or prostate specific antigen (PSA) based on FH. A positive FH was not an independent predictor of BF, distant metastasis (DM), prostate cancer specific mortality (PCSM), or overall mortality (OM) in Cox proportional multivariable analysis. On further analysis in a Cox proportional multivariable analysis, men with two or more first degree relatives with prostate cancer had a significantly higher likelihood of BF and DM than those with no FH, although there was no difference in PCSM or OM. Men with a positive FH (23%) were more likely to be younger, have a lower PSA, and non-palpable disease. There was no interaction between a positive FH and neither race nor treatment era (pre-PSA vs. PSA era).A positive FH is not a prognostic factor following RT and should not alter standard treatment recommendations. Patients with two or more first degree relatives with prostate cancer had a higher likelihood of BF and DM, but there was no effect on survival. There was no interaction between a positive FH and African American race or treatment era. A positive FH was however, associated with more favorable PSA values and T-stage that may be the result of earlier screening.

View details for DOI 10.1016/j.radonc.2013.11.014

View details for PubMedID 24560758
Toxicity analysis of lymph node irradiation for prostate cancer patients treated with IMRT Johnson, M. E., Li, T., Kutikov, A., Buyyounouski, M. K., Sobczak, M. L., Viterbo, R., Horwitz, E. M. AMER SOC CLINICAL ONCOLOGY. 2014
View details for DOI 10.1200/jco.2014.32.4_suppl.41

View details for Web of Science ID 000335318100044
A novel biomarker panel examining response to adjuvant pancreatic cancer therapy in RTOG 9704 Heestand, G. M., Murphy, J., Moughan, J., Regine, W., Luo, J., Graber, M., Kunz, P. L., Fisher, G. A., Guha, C., Lin, B., Mowat, R. B., Gaur, R., Buyyounouski, M. K., Chen, Y., Chang, D., Koong, A. AMER SOC CLINICAL ONCOLOGY. 2014
View details for DOI 10.1200/jco.2014.32.3_suppl.176

View details for Web of Science ID 000333682100180
Examining the evidence in pursuit of the highest possible brachytherapy standards BRACHYTHERAPY Buyyounouski, M. K., Viswanathan, A. N., Prestidge, B. R., Amer Brachytherapy Soc Comm Eviden 2014; 13 (1): 15?16
View details for PubMedID 24055009
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

View details for PubMedCentralID PMC3805927
Inflammatory Bowel Disease Is Not an Absolute Contraindication to Definitive Radiation Therapy for Prostate Cancer 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Murphy, C., Ruth, K. J., Buyyounouski, M. K., Heller, S., Weinberg, D., Uzzo, R., Plimack, E., Kutikov, A., Chen, D. Y., Horwitz, E. M. ELSEVIER SCIENCE INC. 2013: S356?S356
View details for Web of Science ID 000324503601315
Toxicity and Biochemical Failure Following Image-Guided Prostate Intensity Modulated Radiation Therapy: Fiducial Markers Versus Electromagnetic Transponders 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Chang, L., Li, T., Horwitz, E., Chen, D. Y., Viterbo, R., Kutikov, A., Greenberg, R., Buyyounouski, M. K. ELSEVIER SCIENCE INC. 2013: S368?S369
View details for Web of Science ID 000324503601346
Improved Outcomes in Men Treated With Adjuvant or Early Salvage Postprostatectomy IMRT or 3DCRT at a Single Institution 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Murphy, C., Uzzo, R. G., Ruth, K. J., Viterbo, R., Plimack, E., Buyyounouski, M. K., Kutikov, A., Chen, D. Y., Greenberg, R. E. ELSEVIER SCIENCE INC. 2013: S378?S378
View details for Web of Science ID 000324503601370
CT-MRI Fusion Uncertainty in Prostate Treatment Planning for Different Image Guidance Techniques 55th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Chen, X., Xue, J., Chen, L., Buyyounouski, M. K., Horwitz, E. M., Wang, L., Ma, C. ELSEVIER SCIENCE INC. 2013: S718?S718
View details for Web of Science ID 000324503602544
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
Stratifying intermediate-risk patients for radiotherapy NATURE REVIEWS UROLOGY Buyyounouski, M. K. 2013; 10 (8): 438-439
View details for DOI 10.1038/nrurol.2013.142

View details for Web of Science ID 000323033500003
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

View details for PubMedCentralID PMC3860375
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
Preliminary results of RTOG 0831, a randomized, double-blinded, placebo-controlled trial of tadalafil in the prevention of erectile dysfunction in patients treated with radiotherapy for prostate cancer Bruner, D., Pugh, S. L., Pisansky, T., Greenberg, R., Pervez, N., Reed, D. R., Rosenthal, S. A., Mowat, R. B., Raben, A., Buyyounouski, M. K., Kachnic, L. A. AMER SOC CLINICAL ONCOLOGY. 2013
View details for Web of Science ID 000335419603008
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
Untitled Reply 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 Web of Science ID 000317345700005
Seminal Vesicle Target Delineation for Intermediate-Risk Prostate Cancer IMRT. Practical radiation oncology Johnson, M. E., Ruth, K., Buyyounouski, M. K., Horwitz, E. M. 2013; 3 (2): S31-2
View details for DOI 10.1016/j.prro.2013.01.108

View details for PubMedID 24674548
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
Use of biopsy detail to identify subgroup risk in high-risk patients with prostate cancer Townsend, N. C., Buyyounouski, M. K., Ruth, K. J., Kutikov, A., Viterbo, R., Sobczak, M., White, T., Horwitz, E. M. AMER SOC CLINICAL ONCOLOGY. 2013
View details for DOI 10.1200/jco.2013.31.6_suppl.169

View details for Web of Science ID 000333679600170
Prostate cancer: stratifying intermediate-risk patients for radiotherapy. Nature reviews. Urology Buyyounouski, M. K. 2013; 10 (8): 438?39
View details for PubMedID 23797340
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

View details for PubMedCentralID PMC3410044
Do Testosterone Kinetics After Radiation Therapy (RT) Predict Biochemical Failure (BCF) for Low- and Intermediate-risk Prostate Cancer (CaP)? Best in Physics Session at the 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Martin, J. M., Sopka, D. M., Ruth, K. J., Buyyounouski, M. K., Kutikov, A., Sobczak, M. L., Chen, D. Y., Horwitz, E. M. ELSEVIER SCIENCE INC. 2012: S185?S186
View details for Web of Science ID 000310542900462
Primary Prostate Radiation Therapy: Where Are We Failing? Best in Physics Session at the 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Huang, K. T., Walker, G., Stoyanova, R., SANDLER, K., Horwitz, E., Buyyounouski, M. K., Pollack, A. ELSEVIER SCIENCE INC. 2012: S182?S182
View details for Web of Science ID 000310542900454
Determinants of Prostate Biopsy Positivity 2 Years After Radiation Therapy for Men With Prostate Cancer Treated on a Randomized Trial Best in Physics Session at the 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Stoyanova, R., Walker, G., SANDLER, K., Khor, L., Horwitz, E., Buyyounouski, M., Pollack, A. ELSEVIER SCIENCE INC. 2012: S60?S60
View details for Web of Science ID 000310542900150
Recursive Partitioning Analysis of Intermediate Risk Prostate Cancer Patients Identifies Subgroup Risk Categories Best in Physics Session at the 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Townsend, N. C., Ruth, K., Buyyounouski, M., Kutikov, A., Viterbo, R., Sobczak, M., Horwitz, E. M. ELSEVIER SCIENCE INC. 2012: S183?S183
View details for Web of Science ID 000310542900456
A Novel Methodology to Predict Late Urinary Toxicity Following Prostate Radiation Therapy-based on Bladder Wall Dosimetry Best in Physics Session at the 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Ahmed, A., Egleston, B., Alcantara, P., Pollack, A., Li, L., Horwitz, E. M., Buyyounouski, M. K. ELSEVIER SCIENCE INC. 2012: S418?S419
View details for Web of Science ID 000310542901249
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 Best in Physics Session at the 54th Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Pollack, A., Walker, G., Stoyanova, R., Khor, L., Horwitz, E., Buyyounouski, M. ELSEVIER SCIENCE INC. 2012: S25?S26
View details for Web of Science ID 000310542900066
Aspirin and Statin Nonuse Associated With Early Biochemical Failure After Prostate Radiation Therapy 93rd Annual Meeting of the American-Radium-Society Zaorsky, N. G., Buyyounouski, M. K., Li, T., Horwitz, E. M. ELSEVIER SCIENCE INC. 2012: 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 ?(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

View details for PubMedCentralID PMC3423546
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

View details for PubMedCentralID PMC3285397
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

View details for PubMedCentralID PMC3461589
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 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) Hossain, M., Richardson, T., Buyyounouski, M. K., Schirmer, T., Noeske, R., Chen, L., Ma, C. AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS. 2012: 3639?40
View details for Web of Science ID 000308905804181
How Certain Can the Real-Time Plan Predict the Post Dosimetry for Prostate Seed Implant? 54th Annual Meeting and Exhibition of the American-Association-of-Physicists-in-Medicine (AAPM) Li, J. S., Buyyounouski, M., Horwitz, E., Ma, C. AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS. 2012: 3933?33
View details for Web of Science ID 000308905805512
Validating the Interval to Biochemical Failure for the Identification of Potentially Lethal Prostate Cancer 51st Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Buyyounouski, M. K., Pickles, T., Kestin, L. L., Allison, R., Williams, S. G. AMER SOC CLINICAL ONCOLOGY. 2012: 1857?63
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
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
RTOG 0320:A phase Ill trial comparing whole brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) alone versus WBRT with temozolomide (TMZ) or erlotinib for non-small cell lung cancer (NSCLC) and 1-3 brain metastases Sperduto, P. W., Wang, M., Robins, H., Schell, M. C., Werner-Wasik, M., Komaki, R. U., Souhami, L., Buyyounouski, M. K., Khuntia, D., Demas, W. F., Shah, S. A., Nedzi, L. A., Perry, G. A., Suh, J. H., Mehta, M. P. AMER ASSOC CANCER RESEARCH. 2012
View details for DOI 10.1158/1538-7445.AM2012-736

View details for Web of Science ID 000209701601464
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
Continuous localization technologies for radiotherapy delivery: Report of the American Society for Radiation Oncology Emerging Technology Committee PRACTICAL RADIATION ONCOLOGY D'Ambrosio, D. J., Bayouth, J., Chetty, I. J., Buyyounouski, M. K., Price, R. A., Correa, C. R., Dilling, T. J., Franklin, G. E., Xia, P., Harris, E. R., Konski, A. 2012; 2 (2): 145?50
View details for DOI 10.1016/j.prro.2011.10.005

View details for Web of Science ID 000422319100008
Continuous localization technologies for radiotherapy delivery: Report of the American Society for Radiation Oncology Emerging Technology Committee. Practical radiation oncology D'Ambrosio, D. J., Bayouth, J., Chetty, I. J., Buyyounouski, M. K., Price, R. A., Correa, C. R., Dilling, T. J., Franklin, G. E., Xia, P., Harris, E. E., Konski, A. 2012; 2 (2): 145-150
View details for DOI 10.1016/j.prro.2011.10.005

View details for PubMedID 24175000

View details for PubMedCentralID PMC3808750
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
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

View details for PubMedCentralID PMC3827957
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
Assessment of the American Joint Committee on Cancer (6th and 7th editions) for clinically localized prostate cancer and comparison to the National Comprehensive Cancer Network risk stratification method Buyyounouski, M. K., Zaorsky, N. G., Li, T., Devarajan, K., Horwitz, E. M. AMER SOC CLINICAL ONCOLOGY. 2012
View details for DOI 10.1200/jco.2012.30.5_suppl.23

View details for Web of Science ID 000208892400025
Androgen deprivation therapy toxicity and management for men receiving radiation therapy. Prostate cancer Johnson, M. E., Buyyounouski, M. K. 2012; 2012: 580306-?
Abstract

Androgen deprivation therapy is commonly used in combination with radiotherapy as part of the definitive treatment for men with clinically localized and locally advanced prostate cancer. Androgen deprivation has been associated with a wide range of iatrogenic effects impacting a variety of body systems including metabolic, musculoskeletal, cardiovascular, neurocognitive, and sexual. This review aims to provide the radiation oncology community with the knowledge to monitor and manage androgen deprivation therapy toxicity in an effort to provide the highest level of care for patients and to minimize the iatrogenic effects of androgen deprivation as much as possible.

View details for DOI 10.1155/2012/580306

View details for PubMedID 23326671

View details for PubMedCentralID PMC3544287
Androgen Deprivation Therapy Toxicity and Management for Men Receiving Radiation Therapy PROSTATE CANCER Johnson, M. E., Buyyounouski, M. K. 2012
View details for DOI 10.1155/2012/580306

View details for Web of Science ID 000214688000015
Young age under 60 years is not a contraindication to treatment with definitive dose escalated radiotherapy for prostate cancer 52nd Annual Meeting of the American-Society-for-Therapeutic-Radiation-Oncology (ASTRO) Klayton, T. L., Ruth, K., Horwitz, E. M., Uzzo, R. G., Kutikov, A., Chen, D. Y., Sobczak, M., Buyyounouski, M. K. ELSEVIER IRELAND LTD. 2011: 508?12
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

View details for PubMedCentralID PMC3225561
Prostate-specific antigen doubling time predicts the development of distant metastases for patients who fail 3-dimensional conformal radiotherapy or intensity modulated radiation therapy using the Phoenix definition PRACTICAL RADIATION ONCOLOGY Klayton, T. L., Ruth, K., Buyyounouski, M. K., Uzzo, R. G., Wong, Y., Chen, D. T., Sobczak, M., Peter, R., Horwitz, E. M. 2011; 1 (4): 235?42
View details for DOI 10.1016/j.prro.2011.02.003

View details for Web of Science ID 000422308200006
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

View details for PubMedCentralID PMC3139725
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
PSA Doubling Time Predicts for the Development of Distant Metastases for Patients Who Fail 3DCRT Or IMRT Using the Phoenix Definition. Practical radiation oncology Klayton, T. L., Ruth, K., Buyyounouski, M. K., Uzzo, R. G., Wong, Y., Chen, D. Y., Sobczak, M., Peter, R., Horwitz, E. M. 2011; 1 (4): 235-242
Abstract

PURPOSE: PSA doubling time (PSADT) is commonly used as an indication for salvage androgen deprivation therapy (ADT) for PSA failure following RT. Previously, we had shown that PSADT of <12 months is an important predictor of distant metastasis following 3DCRT using the ASTRO definition of BF. We sought to determine if this approach is still valid using the Phoenix definition. METHODS: Eligible patients included 432 men with T1-3N0M0 prostate cancer who demonstrated PSA failure after completing definitive 3DCRT or IMRT from 1989-2005. Endpoints included freedom from distant metastasis (FDM), cause-specific survival (CSS) and overall survival (OS). PSADT was stratified by 0-6, 6-12, 12-18, 18-24, and >24 months. The median follow-up was 95 months (6-207 months). RESULTS: The 7 year FDM, CSS, and OS rates for the entire group were 73%, 77% and 52%, respectively. 7 year FDM was 50% for PSADT <6 months vs. 83% for PSADT >6 months (p=0.0001). 7 year CSS was 61% for PSADT <6 and 85% for PSADT >6 (p=0.0001). 7 year OS was 47% for PSADT <6 and 53% for PSADT >6 (p=0.04). The proportion of men with BF receiving salvage ADT with a PSADT <6 months was 59%, 6-12 was 45%, 12-18 was 42%, 18-24 was 36%, >24 was 28%. ADT was associated with improved 7 year CSS (68% vs. 46%, p=0.015). Of the 314 men with PSADT >6 months, 124 received ADT and 190 were observed. With a median follow-up of 38 months from BF, there was no demonstrable benefit to ADT in the 7 year CSS (87% vs. 79%, respectively; p=0.758). Independent predictors of FDM were PSADT (p<0.0001), GS (p=0.011), and the use of initial ADT (p=0.005). CONCLUSION: PSADT remains a significant predictor of clinical failure and CSS for men treated with 3DCRT or IMRT who fail according to the Phoenix definition. Immediate use of ADT in patients with PSADT <6 months is significantly associated with improved CSS, although the benefit is less apparent in patients with longer PSADT. These results further refine the role of PSADT in predicting which patients may benefit from salvage ADT and those who may be observed expectantly.

View details for PubMedID 22025934
A Nomogram Predicting 5-year Probability of Cause Specific Survival from Biochemical Failure following Radiotherapy Buyyounouski, M. K., Kestin, L., Duchesne, G., Pickles, T., Allison, R., Williams, S. ELSEVIER SCIENCE INC. 2011: S389?S389
View details for Web of Science ID 000296411700803
Aspirin Use Reduces the Risk of Biochemical Failure and Distant Metastases Following Post-Prostatectomy Radiotherapy Cohen, R. J., Li, T., Horwitz, E. M., Peter, R., Uzzo, R. G., Viterbo, R., Buyyounouski, M. K. ELSEVIER SCIENCE INC. 2011: S391?S392
View details for Web of Science ID 000296411700809
A Family History of Prostate Cancer is not Associated with Poorer Outcomes following Radiotherapy Bagshaw, H. P., Ruth, K., Horwitz, E. M., Chen, D., Buyyounouski, M. K. ELSEVIER SCIENCE INC. 2011: S211?S211
View details for Web of Science ID 000296411700427
Identification of a Single Nucleotide Polymorphism Related to Late Toxicity in a Randomized Hypofractionation Trial for Prostate Cancer Oh, J., Deasy, J., Stoyanova, R., Saleh, Z., Buyyounouski, M., Wong, H. P., Apte, A. P., Price, R. A., Hu, J., Pollack, A. ELSEVIER SCIENCE INC. 2011: S156?S157
View details for Web of Science ID 000296411700314
Potential Treatment Margin Reduction for Prostate Treatment with RapidArc and VMAT Li, J., Buyyounouski, M. K., Lin, M., Horwitz, E. M., Ma, C. ELSEVIER SCIENCE INC. 2011: S391?S391
View details for Web of Science ID 000296411700808
Five Year Results of a Randomized External Beam Radiotherapy Hypofractionation Trial for Prostate Cancer Pollack, A., Walker, G., Buyyounouski, M., Horwitz, E., Price, R., Feigenberg, S., Konski, A., Stoyanova, R., Ma, C. ELSEVIER SCIENCE INC. 2011: S1?S1
View details for Web of Science ID 000296411700002
VMAT Reduces Moderate to High Integral Dose When Compared to Conventional IMRT for Treatment of Prostate Cancer Lubbe, W. J., Price, R., Ruth, K., Cherian, G., Kutikov, A., Chen, D., Uzzo, R., Buyyounouski, M., Ma, C., Horwitz, E. ELSEVIER SCIENCE INC. 2011: S446?S446
View details for Web of Science ID 000296411700920
Genetic Polymorphisms of DNA Repair and Inflammatory Responses as Determinants of Late Toxicity in Prostate Cancer Patients Who Received Radiotherapy in a Randomized Trial Hu, J. J., Stoyanova, R., Deasy, J. O., Chung, R., Martin, E., Buyyounouski, M. K., Allen, G. O., Pollack, A. ELSEVIER SCIENCE INC. 2011: S109?S110
View details for Web of Science ID 000296411700218
Prostate Bed Motion during Intensity Modulated Radiotherapy Treatment Klayton, T. L., Price, R., Buyyounouski, M. K., Sobczak, M., Greenberg, R. E., Li, J., Kutikov, A., Horwitz, E. M. ELSEVIER SCIENCE INC. 2011: S101?S101
View details for Web of Science ID 000296411700202
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 Jean-Pierre, P., Stoyanova, R., Penedo, F., Antoni, M., Abramowitz, M., Buyyounouski, M., Pollack, A. ELSEVIER SCIENCE INC. 2011: S667?S667
View details for Web of Science ID 000296411701453
The Impact of Gleason Scoring at a Comprehensive Cancer Center on the Ability to Predict Recurrence After Radiotherapy for Prostate Cancer Townsend, N. C., Ruth, K., Al-Saleem, T., Horwitz, E. M., Sobczak, M., Uzzo, R. G., Viterbo, R., Buyyounouski, M. K. ELSEVIER SCIENCE INC. 2011: S409?S410
View details for Web of Science ID 000296411700844
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

View details for PubMedCentralID PMC2809782
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

View details for PubMedCentralID PMC2847420
Intermediate-risk Prostate Cancer Treated with High Dose Radiotherapy Alone or in Combination with Androgen Deprivation Therapy: The Fox Chase Experience 52nd Annual Meeting of the American-Society-for-Therapeutic-Radiation-Oncology (ASTRO) Sopka, D. M., Li, T., Horwitz, E. M., Chen, D. Y., Buyyounouski, M. K. ELSEVIER SCIENCE INC. 2010: S351?S352
View details for Web of Science ID 000288775700764
Low Pretreatment PET SUV Predicts for Increased Local Failure following Stereotactic Body Radiation Therapy for Lung Cancer 52nd Annual Meeting of the American-Society-for-Therapeutic-Radiation-Oncology (ASTRO) 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. ELSEVIER SCIENCE INC. 2010: S525?S525
View details for Web of Science ID 000288775701216
The Stamp Test Delivers the Message on Erectile Dysfunction following High Dose IMRT 52nd Annual Meeting of the American-Society-for-Therapeutic-Radiation-Oncology (ASTRO) Keller, L. M., Ruth, K., Horwitz, E. M., Pollack, A., Watkins-Bruner, D., Konski, A., Greenberg, R., Price, R., Buyyounouski, M. K. ELSEVIER SCIENCE INC. 2010: S596?S597
View details for Web of Science ID 000288775701376
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 52nd Annual Meeting of the American-Society-for-Therapeutic-Radiation-Oncology (ASTRO) Zietman, A. L., HUNT, D., Kaufman, D. S., Uzzo, R., Wu, C., Buyyounouski, M. K., Sandler, H., Shipley, W. U. ELSEVIER SCIENCE INC. 2010: S31?S32
View details for Web of Science ID 000288775700068
A Practical Strategy to Correct Prostate Rotation Reported by a 4D Localization System 52nd Annual Meeting of the American-Society-for-Therapeutic-Radiation-Oncology (ASTRO) Li, J., Jin, L., Horwitz, E. M., Buyyounouski, M. K., Price, R. A., Ma, C. ELSEVIER SCIENCE INC. 2010: S701?S702
View details for Web of Science ID 000288775701605
Interval to Biochemical Failure is Highly Prognostic for Distant Metastases and Mortality after Salvage Radiation Therapy 52nd Annual Meeting of the American-Society-for-Therapeutic-Radiation-Oncology (ASTRO) Buyyounouski, M. K., Li, T., Turaka, A., Chen, D. Y., Horwitz, E. M. ELSEVIER SCIENCE INC. 2010: S348?S348
View details for Web of Science ID 000288775700756
Conventional versus Hypofractionated IMRT: Results of Late GI and GU Toxicity and Quality of Life from a Phase III Trial 52nd Annual Meeting of the American-Society-for-Therapeutic-Radiation-Oncology (ASTRO) Turaka, A., Zhu, F., Buyyounouski, M. K., Horwitz, E. M., Watkins-Bruner, D., Konski, A. A., Pollack, A. ELSEVIER SCIENCE INC. 2010: S67?S67
View details for Web of Science ID 000288775700143
The Role of Adjuvant and Salvage Post-Prostatectomy IMRT or 3DCRT: The Fox Chase Experience 52nd Annual Meeting of the American-Society-for-Therapeutic-Radiation-Oncology (ASTRO) Horwitz, E. M., Sharma, N. K., Ruth, K., Silverman, J. S., Buyyounouski, M. K., Chen, D. Y., Greenberg, R. E., Uzzo, R. G. ELSEVIER SCIENCE INC. 2010: S333?S334
View details for Web of Science ID 000288775700725
Young Age under 60 is not a Contraindication to Treatment with Definitive High Dose External Beam Radiation Therapy Prostate Cancer 52nd Annual Meeting of the American-Society-for-Therapeutic-Radiation-Oncology (ASTRO) Klayton, T. L., Ruth, K., Horwitz, E. M., Uzzo, R. G., Kuritzky, N. K., Chen, D. Y., Buyyounouski, M. K. ELSEVIER SCIENCE INC. 2010: S334?S334
View details for Web of Science ID 000288775700726
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
Lung cancer presents as Addisonian crisis secondary to a solitary pituitary metastasis JOURNAL OF RADIOTHERAPY IN PRACTICE Turaka, A., Parsons, R. B., Buyyounouski, M. K. 2009; 8 (4): 229?32
View details for DOI 10.1017/S1460396909990082

View details for Web of Science ID 000212250400007
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
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 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. LIPPINCOTT WILLIAMS & WILKINS. 2009: S734?S734
View details for Web of Science ID 000269496002263
Final report of a phase I Dose Escalation Trial of Stereotactic Body Radiotherapy (SBRT) for lung tumors Feigenberg, S. J., Sharma, N., Yu, J. Q., Buyyounouski, M., Borghaei, H., Scott, W., Simon, G., Unger, M., Movsas, B. LIPPINCOTT WILLIAMS & WILKINS. 2009: S943?S943
View details for Web of Science ID 000269496002730
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
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
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

View details for PubMedCentralID PMC2905150
Correlation of hypoxic prostate/muscle p(O2) (P/M P-O2) ratio and biochemical failure in patients with localized prostate cancer: Long-term results 45th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) Turaka, A., Buyyounouski, M. K., Hanlon, A. L., Horwitz, E. M., Greenberg, R. E., Movsas, B. AMER SOC CLINICAL ONCOLOGY. 2009
View details for Web of Science ID 000276606604009
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
View details for Web of Science ID 000265074800045
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

View details for PubMedCentralID PMC2652509
Initial PSA (iPSA) and Radiation Dose Predict for an Undetectable PSA following 3DCRT or IMRT for Low-intermediate Risk Prostate Cancer 51st Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Sharma, N. K., Ruth, K. J., Boorjian, S. A., Uzzo, R. G., Buyyounouski, M. K., Horwitz, E. M. ELSEVIER SCIENCE INC. 2009: S313?S313
View details for Web of Science ID 000270573601161
Is MRI-based Week Three Post-implant Dosimetry Necessary following LDR Prostate Brachytherapy? 51st Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) 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. ELSEVIER SCIENCE INC. 2009: S298?S298
View details for Web of Science ID 000270573601129
Defining Biochemical Failure following Salvage Radiotherapy 51st Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Lubbe, W. J., Ruth, K., Devarajan, K., Horwitz, E. M., Boorjian, S., Buyyounouski, M. K. ELSEVIER SCIENCE INC. 2009: S330?S330
View details for Web of Science ID 000270573601198
A Potential Outcomes Framework to Determine Whether Age and Medical Co-morbidities Predict Who is Harmed by Combined Androgen Deprivation Therapy 51st Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Silverman, J. S., Egleston, B., Horwitz, E. M., Chen, D. Y., Buyyounouski, M. K. ELSEVIER SCIENCE INC. 2009: S326?S326
View details for Web of Science ID 000270573601190
Validating the Interval to Biochemical Failure for the Identification of Potentially Lethal Prostate Cancer 51st Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Buyyounouski, M. K., Pickles, T., Kestin, L., Allison, R., Williams, S. G. ELSEVIER SCIENCE INC. 2009: S103?S104
View details for Web of Science ID 000270573600221
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 51st Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Horwitz, E. M., Ruth, K. J., Sharma, N. K., Chen, D. Y., Buyyounouski, M. K., Uzzo, R. G. ELSEVIER SCIENCE INC. 2009: S301?S301
View details for Web of Science ID 000270573601135
Hypofractionation for Prostate Cancer: Interim Results of a Randomized Trial 51st Annual Meeting of the American-Society-for-Radiation-Oncology (ASTRO) Pollack, A., Li, T., Buyyounouski, M., Horwitz, E., Price, R., Feigenberg, S., Konski, A., Greenberg, R., Uzzo, R., Ma, C. ELSEVIER SCIENCE INC. 2009: S81?S82
View details for Web of Science ID 000270573600173
DOES TREATMENT DURATION AFFECT OUTCOME AFTER RADIOTHERAPY FOR PROSTATE CANCER? 49th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) D'Ambrosio, D. J., Li, T., Horwitz, E. M., Chen, D. Y., Pollack, A., Buyyounouski, M. K. ELSEVIER SCIENCE INC. 2008: 1402?7
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

View details for PubMedCentralID PMC2763099
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

View details for PubMedCentralID PMC2660570
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
View details for DOI 10.1016/j.ijrobp.2008.03.025

View details for Web of Science ID 000257299200045
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 48th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) Eade, T. N., Horwitz, E. M., Ruth, K., Buyyounouski, M. K., D'Ambrosio, D. J., Feigenberg, S. J., Chen, D. Y., Pollack, A. ELSEVIER SCIENCE INC. 2008: 338?45
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

View details for PubMedCentralID PMC2763097
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
View details for Web of Science ID 000254175000046
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

View details for PubMedCentralID PMC2763093
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
View details for DOI 10.1016/j.ijrobp.2007.08.002

View details for Web of Science ID 000252521700045
Predicting local persistence of intermediate and high-risk prostate cancer using percentage of adenocarcinoma in pretreatment biopsy tissue 50th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) Buyyounouski, M. K., Li, T., Al-Saleem, T., Horwitz, E., Konski, A., Feigenberg, S., Uzzo, R., Greenberg, R., Pollack, A. ELSEVIER SCIENCE INC. 2008: S321?S322
View details for Web of Science ID 000258805301194
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 50th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) 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. ELSEVIER SCIENCE INC. 2008: S454?S454
View details for Web of Science ID 000258805301490
Gains from real-time prostate motion monitoring during external beam radiation therapy 50th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) Li, J., Jin, L., Horwitz, E., Buyyounouski, M., Pollack, A., Johnston, S., Price, R., Ma, C. ELSEVIER SCIENCE INC. 2008: S287?S288
View details for Web of Science ID 000258805301119
The optimum duration of combination androgen deprivation therapy (ADT) with prostate cancer radiotherapy: Determining the duration-benefit relationship from multi-institutional analysis 50th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) Pickles, T., Williams, S. G., Buyyounouski, M. K., Kestin, L. L., Duchesne, G. M. ELSEVIER SCIENCE INC. 2008: S73?S73
View details for Web of Science ID 000258805300164
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? 50th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) Williams, S. G., Pickles, T., Kestin, L., Buyyounouski, M., Martinez, A., Demanes, J., Taylor, J. M., Duchesne, G. ELSEVIER SCIENCE INC. 2008: S73?S74
View details for Web of Science ID 000258805300165
Radiation therapy for high risk prostate cancer: Do patients 70 years or older benefit from combined androgen deprivation therapy? 50th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) Silverman, J. S., Ruth, K., Horwitz, E. M., Pollack, A., Chen, D. Y., Buyyounouski, M. K. ELSEVIER SCIENCE INC. 2008: S75?S76
View details for Web of Science ID 000258805300169
Estimating gains in biochemical outcome from various durations of androgen deprivation in patients treated with dose escalated radiotherapy for prostate cancer using two nomograms 50th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) Pahlajani, N. H., Egleston, B. L., Buyyounouski, M. K., Chen, D. Y., Horwitz, E., Pollack, A. ELSEVIER SCIENCE INC. 2008: S54?S54
View details for Web of Science ID 000258805300121
PSA doubling time predicts for the development of distant metastases for patients who fail 3DCRT or IMRT using the Phoenix definition 50th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) Horwitz, E. M., Ruth, K., Uzzo, R. G., Buyyounouski, M. K., Wong, Y., Chen, D. Y., Pollack, A. ELSEVIER SCIENCE INC. 2008: S135?S136
View details for Web of Science ID 000258805300302
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
Intensity Modulated Radiation Therapy 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. 2007; 69 (3): S10-?
Abstract

PURPOSE: Androgen deprivation therapy (AD) has been shown to increase late ? grade 2 rectal toxicity when used concurrently with three-dimensional conformal radiotherapy (3DCRT). Intensity modulated radiotherapy (IMRT) has the potential to reduce toxicity by limiting the radiation dose received by the bowel and bladder. This study compares both genitourinary (GU) and gastrointestinal (GI) toxicity in men treated with 3DCRT+AD versus IMRT+AD. METHODS AND MATERIALS: From July 1992 to July 2004, 293 men received 3DCRT (n=170) or IMRT (n=123) with concurrent AD (< 6 months, n=123; ? 6 months, n =170). Median RT doses were 76 Gy for 3DCRT (ICRU) and 76 Gy for IMRT (95% to the PTV). Toxicity was assessed by a patient symptom questionnaire assessing toxicity completed at each visit and recorded using a modified late effects normal tissue task force radiation morbidity scale (LENT). RESULTS: Mean follow-up was 86 months (SD=29.3) for the 3DCRT group and 40 months (SD=9.7) for the IMRT group. Acute GI toxicity (OR=4, 95% CI: 1.6-11.7, p=0.005) was significantly higher with 3DCRT than with IMRT and was independent of AD duration (i.e. <6 vs. ?6 months). Time to development of late GI toxicity was significantly longer in the IMRT group. The 5-year Kaplan-Meier estimates for ? grade 2 GI toxicity were 20% for 3DCRT versus 8% for IMRT (p=0.01). On MVA, ? grade 2 late GI toxicity (HR=2.1, 95% CI: 1.1-4.3, p=0.04) was more prevalent in 3DCRT patients. CONCLUSIONS: Compared to 3DCRT, IMRT significantly decreased acute and late GI toxicity in patients treated with AD.

View details for PubMedID 20664712
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

View details for PubMedCentralID PMC1950742
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

View details for PubMedCentralID PMC2770596
Daily localization for prostate bed patients based on surgical clips 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine Paskalev, K., Horwitz, E., Price, R., Feigenberg, S., Buyyounouski, M., Chen, Y., Konski, A., Silverman, I., Ma, C., Pollack, A. AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS. 2007: 2381?82
View details for Web of Science ID 000247479600279
Dosimetric comparison of 4D and 3 multi-phase CT imaging for stereotactic body radiation therapy (SBRT) planning in lung cancer 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine Wang, L., Jin, L., Hayes, S., Paskalev, K., Buyyounouski, M., Feigenberg, S. AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS. 2007: 2384?84
View details for Web of Science ID 000247479600290
Surface smoothing of a tubular structure using a non-shrinking algorithm 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine Chen, Y., Paskalev, K., Horwitz, E., Price, R., Buyyounouski, M., Ma, C., Pollack, A. AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS. 2007: 2637?37
View details for Web of Science ID 000247479601312
Do stranded seeds improve the quality of permanent prostate seed implant? 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine Li, J., Horwitz, E., Buyyounouski, M., McNeeley, S., Crawford, K., Ma, C. AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS. 2007: 2330?30
View details for Web of Science ID 000247479600061
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

View details for PubMedCentralID PMC1950740
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

View details for PubMedCentralID PMC1892585
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 49th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) Feigenberg, S., Yu, J. Q., Eade, T. N., Buyyounouski, M., Wang, L., Langer, C., Scott, W., Konski, A., Movsas, B. ELSEVIER SCIENCE INC. 2007: S479?S480
View details for Web of Science ID 000249950201189
Prostate-specific antigen nadir within 12 months of prostate cancer radiotherapy predicts metastasis and death 40th Annual Meeting of the American-Society-of-Clinical-Oncology Alcantara, P., Hanlon, A., Buyyounouski, M. K., Horwitz, E. M., Pollack, A. JOHN WILEY & SONS INC. 2007: 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

View details for PubMedCentralID PMC1892752
A matched pair comparison of intensity modulated radiotherapy and three-dimensional conformal radiotherapy for prostate cancer: Toxicity and outcomes 49th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) Morgan, P. B., Ruth, K., Horwitz, E. M., Buyyounouski, M. K., Uzzo, R. G., Pollack, A. ELSEVIER SCIENCE INC. 2007: S319?S319
View details for Web of Science ID 000249950200571
Intensity modulated radiation therapy reduces gastrointestinal morbidity in patients treated with androgen deprivation therapy for prostate cancer 49th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) Sharma, N. K., Li, T., Horwitz, E. M., Pollack, A., Buyyounouski, M. K. ELSEVIER SCIENCE INC. 2007: S10?S10
Abstract

PURPOSE: Androgen deprivation therapy (AD) has been shown to increase late ? grade 2 rectal toxicity when used concurrently with three-dimensional conformal radiotherapy (3DCRT). Intensity modulated radiotherapy (IMRT) has the potential to reduce toxicity by limiting the radiation dose received by the bowel and bladder. This study compares both genitourinary (GU) and gastrointestinal (GI) toxicity in men treated with 3DCRT+AD versus IMRT+AD. METHODS AND MATERIALS: From July 1992 to July 2004, 293 men received 3DCRT (n=170) or IMRT (n=123) with concurrent AD (< 6 months, n=123; ? 6 months, n =170). Median RT doses were 76 Gy for 3DCRT (ICRU) and 76 Gy for IMRT (95% to the PTV). Toxicity was assessed by a patient symptom questionnaire assessing toxicity completed at each visit and recorded using a modified late effects normal tissue task force radiation morbidity scale (LENT). RESULTS: Mean follow-up was 86 months (SD=29.3) for the 3DCRT group and 40 months (SD=9.7) for the IMRT group. Acute GI toxicity (OR=4, 95% CI: 1.6-11.7, p=0.005) was significantly higher with 3DCRT than with IMRT and was independent of AD duration (i.e. <6 vs. ?6 months). Time to development of late GI toxicity was significantly longer in the IMRT group. The 5-year Kaplan-Meier estimates for ? grade 2 GI toxicity were 20% for 3DCRT versus 8% for IMRT (p=0.01). On MVA, ? grade 2 late GI toxicity (HR=2.1, 95% CI: 1.1-4.3, p=0.04) was more prevalent in 3DCRT patients. CONCLUSIONS: Compared to 3DCRT, IMRT significantly decreased acute and late GI toxicity in patients treated with AD.

View details for Web of Science ID 000249950200018

View details for PubMedCentralID PMC2909627
A comparison of sexual function following radiotherapy for prostate cancer: Results of a prospective, randomized trial of hypofractionated intensity modulated radiotherapy 49th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) Buyyounouski, M. K., Li, T., Watkins-Bruner, D., Horwitz, E. M., Pollack, A. ELSEVIER SCIENCE INC. 2007: S7?S8
View details for Web of Science ID 000249950200014
Does total treatment duration affect outcome in prostate cancer treated with radiotherapy? 49th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) D'Ambrosio, D. J., Horwitz, T. L., Chen, D., Pollack, A., Buyyounouski, M. K. ELSEVIER SCIENCE INC. 2007: S176?S176
View details for Web of Science ID 000249950200312
Effect of target smoothness on treatment planning for prostate IMRT 49th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) Chen, Y., Paskalev, K., Horwitz, E., Price, R., Buyyounouski, M., Ma, C., Pollack, A. ELSEVIER SCIENCE INC. 2007: S649?S649
View details for Web of Science ID 000249950201492
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 48th Annual Meeting of the American-Association-of-Physicists-in-Medicine McNeeley, S., Paskalev, K., Buyyounouski, M., Ma, C. AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS. 2006: 2030?30
View details for Web of Science ID 000238688500243
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

View details for PubMedCentralID PMC1892754
CT-based daily localization of prostate patients: Anatomy vs. implanted markers 48th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) Paskalev, K., Feigenberg, S., McNeeley, S., Horwitz, E., Price, R., Konski, A., Buyyounouski, M., Ma, C., Alan, P. ELSEVIER SCIENCE INC. 2006: S621?S621
View details for Web of Science ID 000241221602249
The nadir+2 definition of biochemical failure predicts for overall survival 48th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) Abramowitz, M. C., Li, T., Ross, E., Buyyounouski, M., Uzzo, R. G., Pollack, A., Horwitz, E. M. ELSEVIER SCIENCE INC. 2006: S207?S208
View details for Web of Science ID 000241221600348
Prostate specific antigen kinetics in men treated with radiotherapy and androgen deprivation 48th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) D'Ambrosio, D. J., Ruth, K., Buyyounouski, M. K., Horwitz, E. M., Uzzo, R. G., Pollack, A. ELSEVIER SCIENCE INC. 2006: S334?S334
View details for Web of Science ID 000241221601170
Adjusted radiotherapy dose response curves following treatment for prostate cancer: Biochemical failure and distant metastasis 48th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) Hanlon, A. L., Horwitz, E. M., Buyyounouski, M. K., Pollack, A. ELSEVIER SCIENCE INC. 2006: S346?S347
View details for Web of Science ID 000241221601190
Smoking and its relationship to GU and GI toxicity in prostate cancer patients treated with radiation 48th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) Pahlajani, N. H., Ruth, K., Horwitz, E. M., Buyyounouski, M. B., Chen, D. Y., Pollack, A. ELSEVIER SCIENCE INC. 2006: S317?S317
View details for Web of Science ID 000241221601140
The prostate specific antigen velocity is unaltered by radiotherapy alone when 2 ng/mL per year or greater: Distant metastasis are the cause 48th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) Buyyounouski, M. K., Hanlon, A. L., Horwitz, E. M., Pollack, A. ELSEVIER SCIENCE INC. 2006: S206?S207
View details for Web of Science ID 000241221600347
Comparison of outcomes in low risk prostate cancer: I-125 seed brachytherapy vs. intensity modulated radiotherapy 48th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) Eade, T. N., Ruth, K., D'Ambrosio, D. J., Feigenberg, S. J., Buyyounouski, M. K., Uzzo, R. G., Pollack, A., Horwitz, E. M. ELSEVIER SCIENCE INC. 2006: S60?S61
View details for Web of Science ID 000241221600102
Intensity modulated radiation therapy for prostate cancer: Preliminary results on treatment morbidity compared to 3-D conformal radiation therapy 48th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) Kirichenko, A. V., Ruth, K., Horwitz, E. M., Buyyounouski, M. K., Feigenberg, S. J., Chen, D. Y., Pollack, A. ELSEVIER SCIENCE INC. 2006: S326?S326
View details for Web of Science ID 000241221601155
Increasing radiotherapy dose for prostate cancer reduces a late wave of distant metastasis 48th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) Morgan, P. B., Hanlon, A. L., Horwitz, E. M., Buyyounouski, M. K., Uzzo, R. G., Pollack, A. ELSEVIER SCIENCE INC. 2006: S9?S10
View details for Web of Science ID 000241221600022
Defining biochemical failure after radiotherapy with and without androgen deprivation for prostate cancer 86th Annual Meeting of the American-Radium-Society Buyyounouski, M. K., Hanlon, A. L., Eisenberg, D. F., Horwitz, E. M., Feigenberg, S. J., Uzzo, R. G., Pollack, A. ELSEVIER SCIENCE INC. 2005: 1455?62
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 45th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) Buyyounouski, M. K., Hanlon, A. L., Horwitz, E. M., Uzzo, R. G., Pollack, A. ELSEVIER SCIENCE INC. 2005: 1291?98
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 PubMedID 15817330
FDG PET imaging of signet-ring cell adenocarcinoma of the stomach CLINICAL NUCLEAR MEDICINE Buyyounouski, M. K., Klump, W. J., Konski, A., Wu, H., Adler, L. P. 2005; 30 (2): 118?19
View details for PubMedID 15647683
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 85th Annual Meeting of the American-Radium-Society 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. ELSEVIER SCIENCE INC. 2004: 1383?91
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 85th Annual Meeting of the American-Radium-Society Buyyounouski, M. K., Horwitz, E. M., Price, R. A., Hanlon, A. L., Uzzo, R. G., Pollack, A. ELSEVIER SCIENCE INC. 2004: 743?49
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 44th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology Buyyounouski, M. K., Horwitz, E. M., Hanlon, A. L., Uzzo, R. G., Hanks, G. E., Pollack, A. ELSEVIER SCIENCE INC. 2003: 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
Prostate cancer gene therapy and the role of radiation CANCER TREATMENT REVIEWS Kaminski, J. M., Nguyen, K., Buyyounouski, M., Pollack, A. 2002; 28 (1): 49-64
Abstract

Even though prostate cancer is detected earlier than in the pre-PSA era, prostate cancer is the second leading cause of cancer mortality in the American male. Prostate cancer therapy is not ideal, especially for high-risk localized and metastatic cancer; therefore, investigators have sought new therapeutic modalities such as angiogenesis inhibitors, inhibitors of the cell signaling pathway, vaccines, and gene therapy. Gene therapy has emerged as potential therapy for both localized and systemic prostate cancer. Gene therapy has been shown to work supra-additively with radiation in controlling prostate cancer in vivo. With further technological advances in radiation therapy, gene therapy, and the understanding of prostate cancer biology, gene therapy will potentially have an important role in prostate cancer therapy.

View details for DOI 10.1053/ctrv.2002.0250

View details for Web of Science ID 000176335900005

View details for PubMedID 12027414

Mark Buyyounouski

Professor of Radiation Oncology (Radiation Therapy) at the Stanford University Medical Center

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