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MR method for measuring microscopic histologic soft tissue textures. Magnetic resonance in medicine Sonn, G. A., Fan, R. E., Kunder, C. A., Gold, G. E., James, K. M., Parker, I. D., Carlson, J. M., Cannizzaro, S. M., James, T. W. 2021
Abstract

PURPOSE: Provide a direct, non-invasive diagnostic measure of microscopic tissue texture in the size scale between tens of microns and the much larger scale measurable by clinical imaging. This paper presents a method and data demonstrating the ability to measure these microscopic pathologic tissue textures (histology) in the presence of subject motion in an MR scanner. This size range is vital to diagnosing a wide range of diseases.THEORY/METHODS: MR micro-Texture (MRT) resolves these textures by a combination of measuring a targeted set of k-values to characterize texture-as in diffraction analysis of materials, performing a selective internal excitation to isolate a volume of interest (VOI), applying a high k-value phase encode to the excited spins in the VOI, and acquiring each individual k-value data point in a single excitation-providing motion immunity and extended acquisition time for maximizing signal-to-noise ratio. Additional k-value measurements from the same tissue can be made to characterize the tissue texture in the VOI-there is no need for these additional measurements to be spatially coherent as there is no image to be reconstructed. This method was applied to phantoms and tissue specimens including human prostate tissue.RESULTS: Data demonstrating resolution <50 m, motion immunity, and clearly differentiating between normal and cancerous tissue textures are presented.CONCLUSION: The data reveal textural differences not resolvable by standard MR imaging. As MRT is a pulse sequence, it is directly translatable to MRI scanners currently in clinical practice to meet the need for further improvement in cancer imaging.

View details for DOI 10.1002/mrm.28731

View details for PubMedID 33608954
3D Registration of pre-surgical prostate MRI and histopathology images via super-resolution volume reconstruction. Medical image analysis Sood, R. R., Shao, W., Kunder, C., Teslovich, N. C., Wang, J. B., Soerensen, S. J., Madhuripan, N., Jawahar, A., Brooks, J. D., Ghanouni, P., Fan, R. E., Sonn, G. A., Rusu, M. 2021; 69: 101957
Abstract

The use of MRI for prostate cancer diagnosis and treatment is increasing rapidly. However, identifying the presence and extent of cancer on MRI remains challenging, leading to high variability in detection even among expert radiologists. Improvement in cancer detection on MRI is essential to reducing this variability and maximizing the clinical utility of MRI. To date, such improvement has been limited by the lack of accurately labeled MRI datasets. Data from patients who underwent radical prostatectomy enables the spatial alignment of digitized histopathology images of the resected prostate with corresponding pre-surgical MRI. This alignment facilitates the delineation of detailed cancer labels on MRI via the projection of cancer from histopathology images onto MRI. We introduce a framework that performs 3D registration of whole-mount histopathology images to pre-surgical MRI in three steps. First, we developed a novel multi-image super-resolution generative adversarial network (miSRGAN), which learns information useful for 3D registration by producing a reconstructed 3D MRI. Second, we trained the network to learn information between histopathology slices to facilitate the application of 3D registration methods. Third, we registered the reconstructed 3D histopathology volumes to the reconstructed 3D MRI, mapping the extent of cancer from histopathology images onto MRI without the need for slice-to-slice correspondence. When compared to interpolation methods, our super-resolution reconstruction resulted in the highest PSNR relative to clinical 3D MRI (32.15�dB vs 30.16�dB for BSpline interpolation). Moreover, the registration of 3D volumes reconstructed via super-resolution for both MRI and histopathology images showed the best alignment of cancer regions when compared to (1) the state-of-the-art RAPSODI approach, (2) volumes that were not reconstructed, or (3) volumes that were reconstructed using nearest neighbor, linear, or BSpline interpolations. The improved 3D alignment of histopathology images and MRI facilitates the projection of accurate cancer labels on MRI, allowing for the development of improved MRI interpretation schemes and machine learning models to automatically detect cancer on MRI.

View details for DOI 10.1016/j.media.2021.101957

View details for PubMedID 33550008
Clinical -Prostate cancer Multicenter analysis of clinical and MRI characteristics associated with detecting clinically significant prostate cancer in PI-RADS (v2.0) category 3 lesions UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS Al Awamlh, B., Marks, L. S., Sonn, G. A., Natarajan, S., Fan, R. E., Gross, M. D., Mauer, E., Banerjee, S., Hectors, S., Carlsson, S., Margolis, D. J., Hu, J. C. 2020; 38 (7)
View details for Web of Science ID 000542437900009
Registration of pre-surgical MRI and histopathology images from radical prostatectomy via RAPSODI. Medical physics Rusu, M., Shao, W., Kunder, C. A., Wang, J. B., Soerensen, S. J., Teslovich, N. C., Sood, R. R., Chen, L. C., Fan, R. E., Ghanouni, P., Brooks, J. D., Sonn, G. A. 2020
Abstract

PURPOSE: Magnetic resonance imaging (MRI) has great potential to improve prostate cancer diagnosis, however, subtle differences between cancer and confounding conditions render prostate MRI interpretation challenging. The tissue collected from patients who undergo radical prostatectomy provides a unique opportunity to correlate histopathology images of the prostate with pre-operative MRI to accurately map the extent of cancer from histopathology images onto MRI. We seek to develop an open-source, easy-to-use platform to align pre-surgical MRI and histopathology images of resected prostates in patients who underwent radical prostatectomy to create accurate cancer labels on MRI.METHODS: Here, we introduce RAdiology Pathology Spatial Open-Source multi-Dimensional Integration (RAPSODI), the first open-source framework for the registration of radiology and pathology images. RAPSODI relies on three steps. First, it creates a 3D reconstruction of the histopathology specimen as a digital representation of the tissue before gross sectioning. Second, RAPSODI registers corresponding histopathology and MRI slices. Third, the optimized transforms are applied to the cancer regions outlined on the histopathology images to project those labels onto the pre-operative MRI.RESULTS: We tested RAPSODI in a phantom study where we simulated various conditions, e.g., tissue shrinkage during fixation. Our experiments showed that RAPSODI can reliably correct multiple artifacts. We also evaluated RAPSODI in 157 patients from three institutions that underwent radical prostatectomy and have very different pathology processing and scanning. RAPSODI was evaluated in 907 corresponding histpathology-MRI slices and achieved a Dice coefficient of 0.97�0.01 for the prostate, a Hausdorff distance of 1.99�0.70 mm for the prostate boundary, a urethra deviation of 3.09�1.45 mm, and a landmark deviation of 2.80�0.59 mm between registered histopathology images and MRI.CONCLUSION: Our robust framework successfully mapped the extent of cancer from histopathology slices onto MRI providing labels from training machine learning methods to detect cancer on MRI.

View details for DOI 10.1002/mp.14337

View details for PubMedID 32564359
Ga-68-PSMA-11 PET/MR Imaging before prostatectomy: correlation with surgical pathology and two-year follow up Moradi, F., Baratto, L., Duan, H., Hatami, N., Davidzon, G., Sonn, G., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2020
View details for Web of Science ID 000568290500168
ProsRegNet: A deep learning framework for registration of MRI and histopathology images of the prostate. Medical image analysis Shao, W., Banh, L., Kunder, C. A., Fan, R. E., Soerensen, S. J., Wang, J. B., Teslovich, N. C., Madhuripan, N., Jawahar, A., Ghanouni, P., Brooks, J. D., Sonn, G. A., Rusu, M. 2020; 68: 101919
Abstract

Magnetic resonance imaging (MRI) is an increasingly important tool for the diagnosis and treatment of prostate cancer. However, interpretation of MRI suffers from high inter-observer variability across radiologists, thereby contributing to missed clinically significant cancers, overdiagnosed low-risk cancers, and frequent false positives. Interpretation of MRI could be greatly improved by providing radiologists with an answer key that clearly shows cancer locations on MRI. Registration of histopathology images from patients who had radical prostatectomy to pre-operative MRI allows such mapping of ground truth cancer labels onto MRI. However, traditional MRI-histopathology registration approaches are computationally expensive and require careful choices of the cost function and registration hyperparameters. This paper presents ProsRegNet, a deep learning-based pipeline to accelerate and simplify MRI-histopathology image registration in prostate cancer. Our pipeline consists of image preprocessing, estimation of affine and deformable transformations by deep neural networks, and mapping cancer labels from histopathology images onto MRI using estimated transformations. We trained our neural network using MR and histopathology images of 99 patients from our internal cohort (Cohort 1) and evaluated its performance using 53 patients from three different cohorts (an additional 12 from Cohort 1 and 41 from two public cohorts). Results show that our deep learning pipeline has achieved more accurate registration results and is at least 20 times faster than a state-of-the-art registration algorithm. This important advance will provide radiologists with highly accurate prostate MRI answer keys, thereby facilitating improvements in the detection of prostate cancer on MRI. Our code is freely available at https://github.com/pimed//ProsRegNet.

View details for DOI 10.1016/j.media.2020.101919

View details for PubMedID 33385701
Multicenter analysis of clinical and MRI characteristics associated with detecting clinically significant prostate cancer in PI-RADS (v2.0) category 3 lesions. Urologic oncology Al Hussein Al Awamlh, B., Marks, L. S., Sonn, G. A., Natarajan, S., Fan, R. E., Gross, M. D., Mauer, E., Banerjee, S., Hectors, S., Carlsson, S., Margolis, D. J., Hu, J. C. 2020
Abstract

We sought to identify clinical and magnetic resonance imaging (MRI) characteristics in men with the Prostate Imaging - Reporting and Data System (PI-RADS) category 3 index lesions that predict clinically significant prostate cancer (CaP) on MRI targeted biopsy.Multicenter study of prospectively collected data for biopsy-naive men (n?=?247) who underwent MRI-targeted and systematic biopsies for PI-RADS 3 index lesions. The primary endpoint was diagnosis of clinically significant CaP (Grade Group ?2). Multivariable logistic regression models assessed for factors associated with clinically significant CaP. The probability distributions of clinically significant CaP based on different levels of predictors of multivariable models were plotted in a heatmap.Men with clinically significant CaP had smaller prostate volume (39.20 vs. 55.10 ml, P < 0.001) and lower apparent diffusion coefficient (ADC) values (973 vs. 1068 ?m2/s, P = 0.013), but higher prostate-specific antigen (PSA) density (0.21 vs. 0.13 ng/ml2, P?=?0.027). On multivariable analyses, lower prostate volume (odds ratio [OR]: 0.95, 95% confidence interval [CI]: 0.92-0.97), lower ADC value (OR: 0.99, 95% CI: 0.99-1.00), and Prostate-specific antigen density >0.15 ng/ml2 (OR: 3.51, 95% CI 1.61-7.68) were independently associated with significant CaP.Higher PSA density, lower prostate volume and ADC values are associated with clinically significant CaP in biopsy-na�ve men with PI-RADS 3 lesions. We present regression-derived probabilities of detecting clinically significant CaP based on various clinical and imaging values that can be used in decision-making. Our findings demonstrate an opportunity for MRI refinement or biomarker discovery to improve risk stratification for PI-RADS 3 lesions.

View details for DOI 10.1016/j.urolonc.2020.03.019

View details for PubMedID 32307327
Identification of Diagnostic Metabolic Signatures in Clear Cell Renal Cell Carcinoma Using Mass Spectrometry Imaging. International journal of cancer Vijayalakshmi, K., Shankar, V., Bain, R. M., Nolley, R., Sonn, G. A., Kao, C., Zhao, H., Tibshirani, R., Zare, R. N., Brooks, J. D. 2019
Abstract

Clear cell renal cell carcinoma (ccRCC) is the most common and lethal subtype of kidney cancer. Intraoperative frozen section (IFS) analysis is used to confirm the diagnosis during partial nephrectomy (PN). However, surgical margin evaluation using IFS analysis is time consuming and unreliable, leading to relatively low utilization. In this study, we demonstrated the use of desorption electrospray ionization mass spectrometry imaging (DESI-MSI) as a molecular diagnostic and prognostic tool for ccRCC. DESI-MSI was conducted on fresh-frozen 23 normal-tumor paired nephrectomy specimens of ccRCC. An independent validation cohort of 17 normal-tumor pairs were analyzed. DESI-MSI provides two-dimensional molecular images of tissues with mass spectra representing small metabolites, fatty acids, and lipids. These tissues were subjected to histopathologic evaluation. A set of metabolites that distinguish ccRCC from normal kidney were identified by performing least absolute shrinkage and selection operator (Lasso) and log-ratio Lasso analysis. Lasso analysis with leave-one-patient-out cross validation selected 57 peaks from over 27,000 metabolic features across 37,608 pixels obtained using DESI-MSI of ccRCC and normal tissues. Baseline Lasso of metabolites predicted the class of each tissue to be normal or cancerous tissue with an accuracy of 94% and 76%, respectively. Combining the baseline Lasso with the ratio of glucose to arachidonic acid could potentially reduce scan time and improve accuracy to identify normal (82%) and ccRCC (88%) tissue. DESI-MSI allows rapid detection of metabolites associated with normal and ccRCC with high accuracy. As this technology advances, it could be used for rapid intraoperative assessment of surgical margin status. This article is protected by copyright. All rights reserved.

View details for DOI 10.1002/ijc.32843

View details for PubMedID 31863456
Reply by Authors. The Journal of urology Gross, M. D., Marks, L. S., Sonn, G. A., Green, D. A., Wang, G. J., Shoag, J. E., Cabezon, E., Margolis, D. J., Robinson, B. D., Hu, J. C. 2019: 101097JU000000000000053402
View details for DOI 10.1097/JU.0000000000000534.02

View details for PubMedID 31789578
Multimodality Hyperpolarized C-13 MRS/PET/Multiparametric MR Imaging for Detection and Image-Guided Biopsy of Prostate Cancer: First Experience in a Canine Prostate Cancer Model MOLECULAR IMAGING AND BIOLOGY Bachawal, S. V., Park, J., Valluru, K. S., Loft, M., Felt, S. A., Vilches-Moure, J. G., Saenz, Y. F., Daniel, B., Iagaru, A., Sonn, G., Cheng, Z., Spielman, D. M., Willmann, J. K. 2019; 21 (5): 861?70
View details for DOI 10.1007/s11307-018-1235-6

View details for Web of Science ID 000483788100009
Variation in MRI-Ultrasound Fusion Targeted Biopsy Outcomes in Asian-American Men: A Multi-Center Study. The Journal of urology Gross, M. D., Marks, L. S., Sonn, G. A., Green, D. A., Wang, G. J., Shoag, J. E., Cabezon, E., Margolis, D. J., Robinson, B. D., Hu, J. C. 2019: 101097JU0000000000000534
Abstract

PURPOSE: Asian-American men have distinctly different prostate cancer epidemiology compared to other men. The role of multiparametric magnetic resonance imaging and targeted biopsy for elevated PSA in this population has not been assessed. We sought to define imaging and targeted biopsy outcomes in Asian-American men compared to other men.MATERIALS AND METHODS: A multicenter, prospective cohort of men who underwent magnetic resonance imaging-targeted with systematic biopsy for elevated prostate specific antigen was accrued. Outcome of interest was diagnosis of clinically significant prostate cancer (Gleason Grade Group?2), stratified by PI-RADS score and history of negative biopsy. Multivariable logistic regression was used to assess the effect of Asian-American race on cancer detection.RESULTS: Of 2,571 men, 275 (11%) were Asian-American. Clinically significant prostate cancer was detected in 37% of Asian-American men compared to 48% in men of other races (p<0.001). Asian-American men were also less likely to be diagnosed with grade group 1 cancer (12% vs 18%, p=0.007). Additionally, there was significantly lower detection of significant cancer for PIRADS 3 in Asian-Americans vs. other races (12% vs. 21%, p=0.032). In adjusted analysis, Asian-Americans were less likely to be diagnosed with both significant cancer (OR 0.57, 95% CI 0.42-0.79, p<0.001) and grade group 1 cancer (OR 0.57, 95% CI 0.38-0.84, p=0.005) compared to non-Asians.CONCLUSIONS: Asian-Americans are less likely to be diagnosed with clinically significant prostate cancer on targeted biopsy, illustrating different performance of PI-RADS in this population. Conventional risk assessment tools should be modified when selecting Asian-American men for biopsy.

View details for DOI 10.1097/JU.0000000000000534

View details for PubMedID 31502942
Simultaneous transrectal ultrasound and photoacoustic human prostate imaging. Science translational medicine Kothapalli, S., Sonn, G. A., Choe, J. W., Nikoozadeh, A., Bhuyan, A., Park, K. K., Cristman, P., Fan, R., Moini, A., Lee, B. C., Wu, J., Carver, T. E., Trivedi, D., Shiiba, L., Steinberg, I., Huland, D. M., Rasmussen, M. F., Liao, J. C., Brooks, J. D., Khuri-Yakub, P. T., Gambhir, S. S. 2019; 11 (507)
Abstract

Imaging technologies that simultaneously provide anatomical, functional, and molecular information are emerging as an attractive choice for disease screening and management. Since the 1980s, transrectal ultrasound (TRUS) has been routinely used to visualize prostatic anatomy and guide needle biopsy, despite limited specificity. Photoacoustic imaging (PAI) provides functional and molecular information at ultrasonic resolution based on optical absorption. Combining the strengths of TRUS and PAI approaches, we report the development and bench-to-bedside translation of an integrated TRUS and photoacoustic (TRUSPA) device. TRUSPA uses a miniaturized capacitive micromachined ultrasonic transducer array for simultaneous imaging of anatomical and molecular optical contrasts [intrinsic: hemoglobin; extrinsic: intravenous indocyanine green (ICG)] of the human prostate. Hemoglobin absorption mapped vascularity of the prostate and surroundings, whereas ICG absorption enhanced the intraprostatic photoacoustic contrast. Future work using the TRUSPA device for biomarker-specific molecular imaging may enable a fundamentally new approach to prostate cancer diagnosis, prognostication, and therapeutic monitoring.

View details for DOI 10.1126/scitranslmed.aav2169

View details for PubMedID 31462508
Prostate Magnetic Resonance Imaging Interpretation Varies Substantially Across Radiologists EUROPEAN UROLOGY FOCUS Sonn, G. A., Fan, R. E., Ghanouni, P., Wang, N. N., Brooks, J. D., Loening, A. M., Daniel, B. L., To'o, K. J., Thong, A. E., Leppert, J. T. 2019; 5 (4): 592?99
View details for DOI 10.1016/j.euf.2017.11.010

View details for Web of Science ID 000486156800014
Point Shear Wave Elastography Using Machine Learning to Differentiate Renal Cell Carcinoma and Angiomyolipoma. Ultrasound in medicine & biology Sagreiya, H., Akhbardeh, A., Li, D., Sigrist, R., Chung, B. I., Sonn, G. A., Tian, L., Rubin, D. L., Willmann, J. K. 2019
Abstract

The question of whether ultrasound point shear wave elastography can differentiate renal cell carcinoma (RCC) from angiomyolipoma (AML) is controversial. This study prospectively enrolled 51 patients with 52 renal tumors (42 RCCs, 10 AMLs). We obtained 10 measurements of shear wave velocity (SWV) in the renal tumor, cortex and medulla. Median SWV was first used to classify RCC versus AML. Next, the prediction accuracy of 4 machine learning algorithms-logistic regression, naive Bayes, quadratic discriminant analysis and support vector machines (SVMs)-was evaluated, using statistical inputs from the tumor, cortex and combined statistical inputs from tumor, cortex and medulla. After leave-one-out cross validation, models were evaluated using the area under the receiver operating characteristic (ROC) curve (AUC). Tumor median SWV performed poorly (AUC?=?0.62; p?=?0.23). Except logistic regression, all machine learning algorithms reached statistical significance using combined statistical inputs (AUC?=?0.78-0.98; p < 7.1?*?10-3). SVMs demonstrated 94% accuracy (AUC?=?0.98; p?=?3.13?*?10-6) and clearly outperformed median SWV in differentiating RCC from AML (p?=?2.8?*?10-4).

View details for DOI 10.1016/j.ultrasmedbio.2019.04.009

View details for PubMedID 31133445
How Often is the Dynamic Contrast Enhanced Score Needed in PI-RADS Version 2? Current problems in diagnostic radiology Roh, A. T., Fan, R. E., Sonn, G. A., Vasanawala, S. S., Ghanouni, P., Loening, A. M. 2019
Abstract

BACKGROUND: Prostate imaging reporting and data system version 2 (PI-RADS v2) relegates dynamic contrast enhanced (DCE) imaging to a minor role. We sought to determine how often DCE is used in PI-RADS v2 scoring.MATERIALS AND METHODS: We retrospectively reviewed data from 388 patients who underwent prostate magnetic resonance imaging and subsequent biopsy from January 2016 through December 2017. In accordance with PI-RADS v2, DCE was deemed necessary if a peripheral-zone lesion had a diffusion-weighted imaging score of 3, or if a transition-zone lesion had a T2 score of 3 and diffusion-weighted imaging experienced technical failure. Receiver operating characteristic curve analysis assessed the accuracy of prostate-specific antigen density (PSAD) at different threshold values for differentiating lesions that would be equivocal with noncontrast technique. Accuracy of PSAD was compared to DCE using McNemar's test.RESULTS: Sixty-nine lesions in 62 patients (16%) required DCE for PI-RADS scoring. Biopsy of 10 (14%) of these lesions showed clinically significant cancer (Gleason score ?7). In the subgroup of patients with equivocal lesions, those with clinically significant cancer had significantly higher PSADs than those with clinically insignificant lesions (means of 0.18 and 0.13 ng/mL/mL, respectively; P= 0.038). In this subgroup, there was no statistical difference in accuracy in determining clinically significant cancer between a PSAD threshold value of 0.13 and DCE (P= 0.25).CONCLUSIONS: Only 16% of our patients needed DCE to generate the PI-RADS version 2 score, raising the possibility of limiting the initial screening prostate MRI to a noncontrast exam. PSAD may also be used to further decrease the need for or to replace DCE altogether.

View details for DOI 10.1067/j.cpradiol.2019.05.008

View details for PubMedID 31126664
AUTOMATED DETECTION OF PROSTATE CANCER ON MULTIPARAMETRIC MRI USING DEEP NEURAL NETWORKS TRAINED ON SPATIAL COORDINATES AND PATHOLOGY OF BIOPSY CORES Chen, L., Bien, N., Fan, R., Cheong, R., Rajpurkar, P., Thong, A., Wang, N., Ahmadi, S., Rusu, M., Brooks, J., Ng, A., Sonn, G. LIPPINCOTT WILLIAMS & WILKINS. 2019: E1098
View details for Web of Science ID 000473345203470
Multimodality Hyperpolarized C-13 MRS/PET/Multiparametric MR Imaging for Detection and Image-Guided Biopsy of Prostate Cancer: First Experience in a Canine Prostate Cancer Model. Molecular imaging and biology : MIB : the official publication of the Academy of Molecular Imaging Bachawal, S. V., Park, J. M., Valluru, K. S., Loft, M. D., Felt, S. A., Vilches-Moure, J. G., Saenz, Y. F., Daniel, B., Iagaru, A., Sonn, G., Cheng, Z., Spielman, D. M., Willmann, J. K. 2019
Abstract

PURPOSE: To assess whether simultaneous hyperpolarized C-13 magnetic resonance spectroscopy (MRS)/positron emission tomography (PET)/multiparametric magnetic resonance (mpMR) imaging is feasible in an orthotopic canine prostate cancer (PCa) model using a clinical PET/MR system and whether the combined imaging datasets can be fused with transrectal ultrasound (TRUS) in real time for multimodal image fusion-guided targeted biopsy of PCa.PROCEDURES: Institutional Animal Care and Use Committee approval was obtained for this study. Canine prostate adenocarcinoma (Ace-1) cells were orthotopically injected into the prostate of four dogs. Once tumor engraftment was confirmed by TRUS, simultaneous hyperpolarized C-13 MRS of [1-13C]pyruvate, PET (2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG), [68Ga]NODAGA-SCH1), and mpMR (T2W, DWI) imaging was performed using a clinical PET/MR system. Multimodality imaging data sets were then fused with TRUS and image-guided targeted biopsy was performed. Imaging results were then correlated with histological findings.RESULTS: Successful tumor engraftment was histologically confirmed in three of the four dogs (dogs 2, 3, and 4) and simultaneous C-13 MRS/PET/mpMR was feasible in all three. In dog 2, C-13 MRS showed increased lactate signal in the tumor (lactate/totalC=0.47) whereas mpMR did not show any signal changes. In dog 3, [18F]FDG-PET (SUVmean=1.90) and C-13 MRS (lactate/totalC=0.59) showed elevated metabolic activity in the tumor. In dog 4, [18F]FDG (SUVmean=2.43), [68Ga]NODAGA-SCH1 (SUVmean=0.75), and C-13 MRS (Lac/totalC=0.53) showed elevated uptake in tumor compared to control tissue and multimodal image fusion-guided biopsy of the tumor was successfully performed.CONCLUSION: Simultaneous C-13 MRS/PET/mpMR imaging and multimodal image fusion-guided biopsy is feasible in a canine PCa model.

View details for PubMedID 30793241
Applying the PRECISION approach in biopsy na�ve and previously negative prostate biopsy patients. Urologic oncology Wang, N. N., Teslovich, N. C., Fan, R. E., Ghanouni, P., Leppert, J. T., Brooks, J. D., Ahmadi, S., Sonn, G. A. 2019
Abstract

The PRECISION trial provides level 1 evidence supporting prebiopsy multiparametric magnetic resonance imaging (mpMRI) followed by targeted biopsy only when mpMRI is abnormal [1]. This approach reduced over-detection of low-grade cancer while increasing detection of clinically significant cancer (CSC). Still, important questions remain regarding the reproducibility of these findings outside of a clinical trial and quantifying missed CSC diagnoses using this approach. To address these issues, we retrospectively applied the PRECISION strategy in men who each underwent prebiopsy mpMRI followed by systematic and targeted biopsy.Clinical, imaging, and pathology data were prospectively collected from 358 biopsy na�ve men and 202 men with previous negative biopsies. To apply the PRECISION approach, a retrospective analysis was done comparing the cancer yield from 2 diagnostic strategies: (1) mpMRI followed by targeted biopsy alone for men with Prostate Imaging Reporting and Data System ? 3 lesions and (2) systematic biopsy alone for all men. Primary outcomes were biopsies avoided and the proportion of CSC cancer (Grade Group 2-5) and non-CSC (Grade Group 1).In biopsy na�ve patients, the mpMRI diagnostic strategy would have avoided 19% of biopsies while detecting 2.5% more CSC (P= 0.480) and 12% less non-CSC (P< 0.001). Thirteen percent (n= 9) of men with normal mpMRI had CSC on systematic biopsy. For previous negative biopsy patients, the mpMRI diagnostic strategy avoided 21% of biopsies, while detecting 1.5% more CSC (P= 0.737) and 13% less non-CSC (P< 0.001). Seven percent (n= 3) of men with normal mpMRI had CSC on systematic biopsy.Our results provide external validation of the PRECISION finding that mpMRI followed by targeted biopsy of suspicious lesions reduces biopsies and over-diagnosis of low-grade cancer. Unlike PRECISION, we did not find increased diagnosis of CSC. This was true in both biopsy na�ve and previously negative biopsy cohorts. We have incorporated this information into shared decision making, which has led some men to choose to avoid biopsy. However, we continue to recommend targeted and systematic biopsy in men with abnormal MRI.

View details for DOI 10.1016/j.urolonc.2019.05.002

View details for PubMedID 31151788
Framework for the co-registration of MRI and Histology Images in Prostate Cancer Patients with Radical Prostatectomy Rusu, M., Kunder, C., Fan, R., Ghanouni, P., West, R., Sonn, G., Brooks, J., Angelini, E. D., Landman, B. A. SPIE-INT SOC OPTICAL ENGINEERING. 2019
View details for DOI 10.1117/12.2513099

View details for Web of Science ID 000483012700057
GENERALIZABLE MULTI-SITE TRAINING AND TESTING OF DEEP NEURAL NETWORKS USING IMAGE NORMALIZATION Onofrey, J. A., Casetti-Dinescu, D. I., Lauritzen, A. D., Sarkar, S., Venkataraman, R., Fan, R. E., Sonn, G. A., Sprenkle, P. C., Staib, L. H., Papademetris, X., IEEE IEEE. 2019: 348?51
View details for Web of Science ID 000485040000074
GENERALIZABLE MULTI-SITE TRAINING AND TESTING OF DEEP NEURAL NETWORKS USING IMAGE NORMALIZATION. Proceedings. IEEE International Symposium on Biomedical Imaging Onofrey, J. A., Casetti-Dinescu, D. I., Lauritzen, A. D., Sarkar, S., Venkataraman, R., Fan, R. E., Sonn, G. A., Sprenkle, P. C., Staib, L. H., Papademetris, X. 2019; 2019: 348?51
Abstract

The ability of medical image analysis deep learning algorithms to generalize across multiple sites is critical for clinical adoption of these methods. Medical imging data, especially MRI, can have highly variable intensity characteristics across different individuals, scanners, and sites. However, it is not practical to train algorithms with data from all imaging equipment sources at all possible sites. Intensity normalization methods offer a potential solution for working with multi-site data. We evaluate five different image normalization methods on training a deep neural network to segment the prostate gland in MRI. Using 600 MRI prostate gland segmentations from two different sites, our results show that both intra-site and inter-site evaluation is critical for assessing the robustness of trained models and that training with single-site data produces models that fail to fully generalize across testing data from sites not included in the training.

View details for DOI 10.1109/isbi.2019.8759295

View details for PubMedID 32874427

View details for PubMedCentralID PMC7457546
Validation of an epigenetic field of susceptibility to detect significant prostate cancer from non-tumor biopsies. Clinical epigenetics Yang, B., Etheridge, T., McCormick, J., Schultz, A., Khemees, T. A., Damaschke, N., Leverson, G., Woo, K., Sonn, G. A., Klein, E. A., Fumo, M., Huang, W., Jarrard, D. F. 2019; 11 (1): 168
Abstract

An epigenetic field of cancer susceptibility exists for prostate cancer (PC) that gives rise to multifocal disease in the peripheral prostate. In previous work, genome-wide DNA methylation profiling identified altered regions in the normal prostate tissue of men with PC. In the current multicenter study, we examined the predictive strength of a panel of loci to detect cancer presence and grade in patients with negative biopsy tissue.Four centers contributed benign prostate biopsy tissues blocks from 129 subjects that were either tumor associated (TA, Grade Group [GG] ? 2, n = 77) or non-tumor associated (NTA, n = 52). Biopsies were analyzed using pyrosequencing for DNA methylation encompassing CpG loci near CAV1, EVX1, FGF1, NCR2, PLA2G16, and SPAG4 and methylation differences were detected within all gene regions (p < 0.05). A multiplex regression model for biomarker performance incorporating a gene combination discriminated TA from NTA tissues (area under the curve [AUC] 0.747, p = 0.004). A multiplex model incorporating all the above genes and clinical information (PSA, age) identified patients with GG ? 2 PC (AUC 0.815, p < 0.0001). In patients with cancer, increased variation in gene methylation levels occurs between biopsies across the prostate.A widespread epigenetic field defect is utilized to detect GG ? 2 PC in patients with histologically negative biopsies. These alterations in non-tumor cells display increased heterogeneity of methylation extent and are spatially distant from tumor foci. These findings have the potential to decrease the need for repeated prostate biopsy.

View details for DOI 10.1186/s13148-019-0771-5

View details for PubMedID 31779677
Teaching Urologists "How to Read Multi-Parametric Prostate MRIs Using PIRADSv2": Results of an iBook Pilot Study. Urology Wang, N. N., Fan, R. E., Ghanouni, P., Sonn, G. A. 2019
Abstract

To create an online resource that teaches urologists how to interpret prostate multi-parametric MRIs (mpMRI). As prostate mpMRI becomes widely adopted for cancer diagnosis and targeted biopsy, it is increasingly important that urologists are comfortable and experienced in assessing the images. The purpose of this study was to create an online mpMRI ibook and measure its effect on instilling proficiency amongst urology residents.We created a case-based ibook aimed at teaching clinicians how to identify and score prostate lesions on mpMRI using the Prostate Imaging and Reporting Data System (PIRADS) v2. Residents completed a 43-question pre-test before gaining access to the ibook for one month. The test asks participants to identify and score visible lesions using interactive mpMRI images. After a formal review of the material, they completed a post-test. Participants also rated their diagnostic confidence on a scale of 1 to 10 before and after reviewing the ibook. The change in performance and confidence scores for each resident was compared using Wilcoxon Signed-Rank test.Eleven urology residents completed the pre-test, review session and post-test. The mean test score rose from 37% (median 40%) to 57% (median 58%) after reviewing the ibook. Improvement was significant (p=0.0039). Confidence scores also improved (p=0.001).We created an interactive ibook that teaches urologists how to evaluate prostate mpMRIs and demonstrated improved performance in interpretation amongst urology residents. This effective module can be incorporated into resident education on a national level and offered as a self-teaching resource for practicing urologists.

View details for DOI 10.1016/j.urology.2019.04.040

View details for PubMedID 31150691
Diagnostic Accuracy of Multiparametric Magnetic Resonance Imaging and Fusion Guided Targeted Biopsy Evaluated by Transperineal Template Saturation Prostate Biopsy for the Detection and Characterization of Prostate Cancer EDITORIAL COMMENT JOURNAL OF UROLOGY Wang, N. N., Sonn, G. A. 2018; 200 (2): 318
View details for Web of Science ID 000438718000081
Gallium 68 PSMA-11 PET/MR Imaging in Patients with Intermediate- or High-Risk Prostate Cancer. Radiology Park, S. Y., Zacharias, C., Harrison, C., Fan, R. E., Kunder, C., Hatami, N., Giesel, F., Ghanouni, P., Daniel, B., Loening, A. M., Sonn, G. A., Iagaru, A. 2018: 172232
Abstract

Purpose To report the results of dual-time-point gallium 68 (68Ga) prostate-specific membrane antigen (PSMA)-11 positron emission tomography (PET)/magnetic resonance (MR) imaging prior to prostatectomy in patients with intermediate- or high-risk cancer. Materials and Methods Thirty-three men who underwent conventional imaging as clinically indicated and who were scheduled for radical prostatectomy with pelvic lymph node dissection were recruited for this study. A mean dose of 4.1 mCi � 0.7 (151.7 MBq � 25.9) of 68Ga-PSMA-11 was administered. Whole-body images were acquired starting 41-61 minutes after injection by using a GE SIGNA PET/MR imaging unit, followed by an additional pelvic PET/MR imaging acquisition at 87-125 minutes after injection. PET/MR imaging findings were compared with findings at multiparametric MR imaging (including diffusion-weighted imaging, T2-weighted imaging, and dynamic contrast material-enhanced imaging) and were correlated with results of final whole-mount pathologic examination and pelvic nodal dissection to yield sensitivity and specificity. Dual-time-point metabolic parameters (eg, maximum standardized uptake value [SUVmax]) were compared by using a paired t test and were correlated with clinical and histopathologic variables including prostate-specific antigen level, Gleason score, and tumor volume. Results Prostate cancer was seen at 68Ga-PSMA-11 PET in all 33 patients, whereas multiparametric MR imaging depicted Prostate Imaging Reporting and Data System (PI-RADS) 4 or 5 lesions in 26 patients and PI-RADS 3 lesions in four patients. Focal uptake was seen in the pelvic lymph nodes in five patients. Pathologic examination confirmed prostate cancer in all patients, as well as nodal metastasis in three. All patients with normal pelvic nodes in PET/MR imaging had no metastases at pathologic examination. The accumulation of 68Ga-PSMA-11 increased at later acquisition times, with higher mean SUVmax (15.3 vs 12.3, P < .001). One additional prostate cancer was identified only at delayed imaging. Conclusion This study found that 68Ga-PSMA-11 PET can be used to identify prostate cancer, while MR imaging provides detailed anatomic guidance. Hence, 68Ga-PSMA-11 PET/MR imaging provides valuable diagnostic information and may inform the need for and extent of pelvic node dissection.

View details for PubMedID 29786490
Editorial Comment. The Journal of urology Wang, N. N., Sonn, G. A. 2018
View details for PubMedID 29684305
The Research Implications of PSA Registry Errors: Data from the Veterans Health Administration. The Journal of urology Guo, D. P., Thomas, I., Mittakanti, H. R., Shelton, J. B., Makarov, D. V., Skolarus, T. A., Cooperberg, M. R., Sonn, G. A., Chung, B. I., Brooks, J. D., Leppert, J. T. 2018
Abstract

INTRODUCTION: We sought to characterize the effects of PSA registry errors on clinical research by comparing cohorts based on cancer registry PSA values with those based directly on results in the electronic health record.METHODS: We defined example cohorts of men with prostate cancer using data from the Veterans Health Administration: those with a PSA values less than 4.0 ng/mL, 4.0 to 10.0 ng/mL, 10.0 to 20.0 ng/mL, and 20.0 to 98.0 ng/mL. We compared the composition of each cohort and overall patient survival when using PSA values from either the VA Central Cancer Registry versus the gold standard electronic health record laboratory file results.RESULTS: There was limited agreement between cohorts defined using either the cancer registry PSA values versus the laboratory file of the electronic health record. The least agreement was seen in patients with PSA values < 4.0 ng/mL (58%) and greatest among patients with PSA values between 4.0 and 10.0 ng/mL (89%). In each cohort, patients assigned to a cohort based only on the cancer registry PSA value had significantly different overall survival when compared with patients assigned based on both the registry and laboratory file PSA values.CONCLUSIONS: Cohorts based exclusively on cancer registry PSA values may have high rates of misclassification that can introduce concerning differences in key characteristics and result in measurable differences in clinical outcomes.

View details for PubMedID 29630980
The impact of computed high b-value images on the diagnostic accuracy of DWI for prostate cancer: A receiver operating characteristics analysis. Scientific reports Ning, P., Shi, D., Sonn, G. A., Vasanawala, S. S., Loening, A. M., Ghanouni, P., Obara, P., Shin, L. K., Fan, R. E., Hargreaves, B. A., Daniel, B. L. 2018; 8 (1): 3409
Abstract

To evaluate the performance of computed high b value diffusion-weighted images (DWI) in prostate cancer detection. 97 consecutive patients who had undergone multiparametric MRI of the prostate followed by biopsy were reviewed. Five radiologists independently scored 138 lesions on native high b-value images (b?=?1200?s/mm2), apparent diffusion coefficient (ADC) maps, and computed high b-value images (contrast equivalent to b?=?2000 s/mm2) to compare their diagnostic accuracy. Receiver operating characteristic (ROC) analysis and McNemar's test were performed to assess the relative performance of computed high b value DWI, native high b-value DWI and ADC maps. No significant difference existed in the area under the curve (AUC) for ROCs comparing B1200 (b?=?1200?s/mm2) to computed B2000 (c-B2000) in 5 readers. In 4 of 5 readers c-B2000 had significantly increased sensitivity and/or decreased specificity compared to B1200 (McNemar's p?
View details for PubMedID 29467370
Reduction of Muscle Contractions during Irreversible Electroporation Therapy Using High-Frequency Bursts of Alternating Polarity Pulses: A Laboratory Investigation in an ExVivo Swine Model. Journal of vascular and interventional radiology : JVIR Sano, M. B., Fan, R. E., Cheng, K., Saenz, Y., Sonn, G. A., Hwang, G. L., Xing, L. 2018; 29 (6): 893
Abstract

PURPOSE: To compare the intensity of muscle contractions in irreversible electroporation (IRE) treatments when traditional IRE and high-frequency IRE (H-FIRE) waveforms are used in combination with a single applicator and distal grounding pad (A+GP) configuration.MATERIALS AND METHODS: An exvivo in situ porcine model was used to compare muscle contractions induced by traditional monopolar IRE waveforms vs high-frequency bipolar IRE waveforms. Pulses with voltages between 200 and 5,000 V were investigated, and muscle contractions were recorded by using accelerometers placed on or near the applicators.RESULTS: H-FIRE waveforms reduced the intensity of muscle contractions in comparison with traditional monopolar IRE pulses. A high-energy burst of 2-mus alternating-polarity pulses energized for 200 mus at 4,500 V produced less intense muscle contractions than traditional IRE pulses, which were 25-100 mus in duration at 3,000 V.CONCLUSIONS: H-FIRE appears to be an effective technique to mitigate the muscle contractions associated with traditional IRE pulses. This may enable the use of voltages greater than 3,000 V necessary for the creation of large ablations invivo.

View details for PubMedID 29628296
EDITORIAL COMMENTS JOURNAL OF UROLOGY Sonn, G. 2018; 199 (1): 104?5
View details for DOI 10.1016/j.juro.2017.07.108

View details for Web of Science ID 000419429700071
Performance of multiparametric MRI appears better when measured in patients who undergo radical prostatectomy. Research and reports in urology Wang, N. N., Fan, R. E., Leppert, J. T., Ghanouni, P., Kunder, C. A., Brooks, J. D., Chung, B. I., Sonn, G. A. 2018; 10: 233?35
Abstract

Utilization of pre-biopsy multiparametric MRI (mpMRI) is increasing. To optimize the usefulness of mpMRI, physicians should accurately quote patients a numerical risk of cancer based on their MRI. The Prostate Imaging Reporting and Data System (PIRADS) standardizes interpretation of mpMRI; however, reported rates of clinically significant prostate cancer (CSC) stratified by PIRADS score vary widely. While some publications use radical prostatectomy (RP) specimens as gold standard, others use biopsy. We hypothesized that much of the variation in CSC stems from differences in cancer prevalence in RP cohorts (100% prevalence) vs biopsy cohorts. To quantify the impact of this selection bias on cancer yield according to PIRADS score, we analyzed data from 614 men with 854 lesions who underwent targeted biopsy from 2014 to 2018. Of these, 125 men underwent RP. We compared the PIRADS detection rates of CSC (Gleason ?7) on targeted biopsy between the biopsy-only and RP cohorts. For all PIRADS scores, CSC yield was much greater in patients who underwent RP. For example, CSC was found in 30% of PIRADS 3 lesions in men who underwent RP vs 7.6% in men who underwent biopsy. Our results show that mpMRI performance appears to be better in men who undergo RP compared with those who only receive biopsy. Physicians should understand the effect of this selection bias and its magnitude when discussing mpMRI results with patients considering biopsy, and take great caution in quoting CSC yields from publications using RP as gold standard.

View details for PubMedID 30538970
Performance of multiparametric MRI appears better when measured in patients who undergo radical prostatectomy RESEARCH AND REPORTS IN UROLOGY Wang, N. N., Fan, R. E., Leppert, J. T., Ghanouni, P., Kunder, C. A., Brooks, J. D., Chung, B., Sonn, G. A. 2018; 10: 233?35
View details for DOI 10.2147/RRU.S178064

View details for Web of Science ID 000451113100001
Ga-68 PSMA 11 PET/MRI in Patients with Newly Diagnosed Intermediate and High-Risk Prostate Cancers Zacharias, C., Harrison, C., Ghanouni, P., Sonn, G., Iagaru, A. SOC NUCLEAR MEDICINE INC. 2017
View details for Web of Science ID 000404949902137
Mass spectrometric imaging of prostate biopsy samples: Cancer margin assessment from the distribution of small metabolites and lipids Banerjee, S., Zare, R. N., Tibshirani, R., Kunder, C., Nolley, R., Fan, R., Brooks, J. D., Sonn, G. AMER CHEMICAL SOC. 2017
View details for Web of Science ID 000430568500539
Diagnosis of prostate cancer by desorption electrospray ionization mass spectrometric imaging of small metabolites and lipids PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Banerjee, S., Zare, R. N., Tibshirani, R. J., Kunder, C. A., Nolley, R., Fan, R., Brooks, J. D., Sonn, G. A. 2017; 114 (13): 3334-3339
Abstract

Accurate identification of prostate cancer in frozen sections at the time of surgery can be challenging, limiting the surgeon's ability to best determine resection margins during prostatectomy. We performed desorption electrospray ionization mass spectrometry imaging (DESI-MSI) on 54 banked human cancerous and normal prostate tissue specimens to investigate the spatial distribution of a wide variety of small metabolites, carbohydrates, and lipids. In contrast to several previous studies, our method included Krebs cycle intermediates (m/z <200), which we found to be highly informative in distinguishing cancer from benign tissue. Malignant prostate cells showed marked metabolic derangements compared with their benign counterparts. Using the "Least absolute shrinkage and selection operator" (Lasso), we analyzed all metabolites from the DESI-MS data and identified parsimonious sets of metabolic profiles for distinguishing between cancer and normal tissue. In an independent set of samples, we could use these models to classify prostate cancer from benign specimens with nearly 90% accuracy per patient. Based on previous work in prostate cancer showing that glucose levels are high while citrate is low, we found that measurement of the glucose/citrate ion signal ratio accurately predicted cancer when this ratio exceeds 1.0 and normal prostate when the ratio is less than 0.5. After brief tissue preparation, the glucose/citrate ratio can be recorded on a tissue sample in 1 min or less, which is in sharp contrast to the 20 min or more required by histopathological examination of frozen tissue specimens.

View details for DOI 10.1073/pnas.1700677114

View details for Web of Science ID 000397607300049

View details for PubMedID 28292895

View details for PubMedCentralID PMC5380053
Contemporary Use of Partial Nephrectomy: Are Older Patients With Impaired Kidney Function Being Left Behind? UROLOGY Leppert, J. T., Mittakanti, H. R., Thomas, I., Lamberts, R. W., Sonn, G. A., Chung, B. I., Skinner, E. C., Wagner, T. H., Chertow, G. M., Brooks, J. D. 2017; 100: 65-71
View details for DOI 10.1016/j.urology.2016.08.044

View details for Web of Science ID 000397168900017
Commentary regarding a recent collaborative consensus statement addressing prostate MRI and MRI-targeted biopsy in patients with a prior negative prostate biopsy ABDOMINAL RADIOLOGY Verma, S., Rosenkrantz, A. B., Choyke, P., Eberhardt, S. C., Eggener, S. E., Gaitonde, K., Haider, M. A., Margolis, D. J., Marks, L. S., Pinto, P., Sonn, G. A., Taneja, S. S. 2017; 42 (2): 346?49
View details for PubMedID 27670878
Incident CKD after Radical or Partial Nephrectomy. Journal of the American Society of Nephrology : JASN Leppert, J. T., Lamberts, R. W., Thomas, I. C., Chung, B. I., Sonn, G. A., Skinner, E. C., Wagner, T. H., Chertow, G. M., Brooks, J. D. 2017
Abstract

The comparative effectiveness of partial nephrectomy versus radical nephrectomy to preserve kidney function has not been well established. We determined the risk of clinically significant (stage 4 and higher) CKD after radical or partial nephrectomy among veterans treated for kidney cancer in the Veterans Health Administration (2001-2013). Among patients with preoperative eGFR?30 ml/min per 1.73 m(2), the incidence of CKD stage 4 or higher after radical (n=9759) or partial nephrectomy (n=4370) was 7.9% overall. The median time to stage 4 or higher CKD after surgery was 5 months, after which few patients progressed. In propensity score-matched cohorts, partial nephrectomy associated with a significantly lower relative risk of incident CKD stage 4 or higher (hazard ratio, 0.34; 95% confidence interval [95% CI], 0.26 to 0.43, versus radical nephrectomy). In a parallel analysis of patients with normal or near-normal preoperative kidney function (eGFR?60 ml/min per 1.73 m(2)), partial nephrectomy was also associated with a significantly lower relative risk of incident CKD stage 3b or higher (hazard ratio, 0.15; 95% CI, 0.11 to 0.19, versus radical nephrectomy) in propensity score-matched cohorts. Competing risk regression models produced consistent results. Finally, patients treated with a partial nephrectomy had reduced risk of mortality (hazard ratio, 0.55; 95% CI, 0.49 to 0.62). In conclusion, compared with radical nephrectomy, partial nephrectomy was associated with a marked reduction in the incidence of clinically significant CKD and with enhanced survival. Postoperative decline in kidney function occurred mainly in the first year after surgery and appeared stable over time.

View details for PubMedID 29018140
Prostate Magnetic Resonance Imaging Interpretation Varies Substantially Across Radiologists. European urology focus Sonn, G. A., Fan, R. E., Ghanouni, P., Wang, N. N., Brooks, J. D., Loening, A. M., Daniel, B. L., To'o, K. J., Thong, A. E., Leppert, J. T. 2017
Abstract

Multiparametric magnetic resonance imaging (mpMRI) interpreted by experts is a powerful tool for diagnosing prostate cancer. However, the generalizability of published results across radiologists of varying expertise has not been verified.To assess variability in mpMRI reporting and diagnostic accuracy across radiologists of varying experience in routine clinical care.Men who underwent mpMRI and MR-fusion biopsy between 2014-2016. Each MRI scan was read by one of nine radiologists using the Prostate Imaging Reporting and Data System (PIRADS) and was not re-read before biopsy. Biopsy histopathology was the reference standard.Outcomes were the PIRADS score distribution and diagnostic accuracy across nine radiologists. We evaluated the association between age, prostate-specific antigen, PIRADS score, and radiologist in predicting clinically significant cancer (Gleason ?7) using multivariable logistic regression. We conducted sensitivity analyses for case volume and changes in accuracy over time.We analyzed data for 409 subjects with 503 MRI lesions. While the number of lesions (mean 1.2 lesions/patient) did not differ across radiologists, substantial variation existed in PIRADS distribution and cancer yield. The significant cancer detection rate was 3-27% for PIRADS 3 lesions, 23-65% for PIRADS 4, and 40-80% for PIRADS 5 across radiologists. Some 13-60% of men with a PIRADS score of <3 on MRI harbored clinically significant cancer. The area under the receiver operating characteristic curve varied from 0.69 to 0.81 for detection of clinically significant cancer. PIRADS score (p<0.0001) and radiologist (p=0.042) were independently associated with cancer in multivariable analysis. Neither individual radiologist volume nor study period impacted the results. MRI scans were not retrospectively re-read by all radiologists, precluding measurement of inter-observer agreement.We observed considerable variability in PIRADS score assignment and significant cancer yield across radiologists. We advise internal evaluation of mpMRI accuracy before widespread adoption.We evaluated the interpretation of multiparametric magnetic resonance imaging of the prostate in routine clinical care. Diagnostic accuracy depends on the Prostate Imaging Reporting and Data System score and the radiologist.

View details for PubMedID 29226826
Contemporary Use of Partial Nephrectomy: Are Older Patients With Impaired Kidney Function Being Left Behind? Urology Leppert, J. T., Mittakanti, H. R., Thomas, I., Lamberts, R. W., Sonn, G. A., Chung, B. I., Skinner, E. C., Wagner, T. H., Chertow, G. M., Brooks, J. D. 2016
Abstract

To assess whether patient factors, such as age and preoperative kidney function, were associated with receipt of partial nephrectomy in a national integrated healthcare system.We identified patients treated with a radical or partial nephrectomy from 2002 to 2014 in the Veterans Health Administration. We examined associations among patient age, sex, race or ethnicity, multimorbidity, baseline kidney function, tumor characteristics, and receipt of partial nephrectomy. We estimated the odds of receiving a partial nephrectomy and assessed interactions between covariates and the year of surgery to explore whether patient factors associated with partial nephrectomy changed over time.In our cohort of 14,186 patients, 4508 (31.2%) received a partial nephrectomy. Use of partial nephrectomy increased from 17% in 2002 to 32% in 2008 and to 38% in 2014. Patient race or ethnicity, age, tumor stage, and year of surgery were independently associated with receipt of partial nephrectomy. Black veterans had significantly increased odds of receipt of partial nephrectomy, whereas older patients had significantly reduced odds. Partial nephrectomy utilization increased for all groups over time, but older patients and patients with worse baseline kidney function showed the least increase in odds of partial nephrectomy.Although the utilization of partial nephrectomy increased for all groups, the greatest increase occurred in the youngest patients and those with the highest baseline kidney function. These trends warrant further investigation to ensure that patients at the highest risk of impaired kidney function are considered for partial nephrectomy whenever possible.

View details for DOI 10.1016/j.urology.2016.08.044

View details for PubMedID 27634733
Production of Spherical Ablations Using Nonthermal Irreversible Electroporation: A Laboratory Investigation Using a Single Electrode and Grounding Pad. Journal of vascular and interventional radiology Sano, M. B., Fan, R. E., Hwang, G. L., Sonn, G. A., Xing, L. 2016; 27 (9): 1432-1440 e3
Abstract

To mathematically model and test ex vivo a modified technique of irreversible electroporation (IRE) to produce large spherical ablations by using a single probe.Computed simulations were performed by using varying voltages, electrode exposure lengths, and tissue types. A vegetable (potato) tissue model was then used to compare ablations created by conventional and high-frequency IRE protocols by using 2 probe configurations: a single probe with two collinear electrodes (2EP) or a single electrode configured with a grounding pad (P+GP). The new P+GP electrode configuration was evaluated in ex vivo liver tissue.The P+GP configuration produced more spherical ablation volumes than the 2EP configuration in computed simulations and tissue models. In prostate tissue, computed simulations predicted ablation volumes at 3,000 V of 1.6 cm(3) for the P+GP configurations, compared with 0.94 cm(3) for the 2EP configuration; in liver tissue, the predicted ablation volumes were 4.7 times larger than those in the prostate. Vegetable model studies verify that the P+GP configuration produces larger and more spherical ablations than those produced by the 2EP. High-frequency IRE treatment of ex vivo liver with the P+GP configuration created a 2.84 � 2.21-cm ablation zone.Computer modeling showed that P+GP configuration for IRE procedures yields ablations that are larger than the 2EP configuration, creating substantial ablation zones with a single electrode placement. When tested in tissue models and an ex vivo liver model, the P+GP configuration created ablation zones that appear to be of clinically relevant size and shape.

View details for DOI 10.1016/j.jvir.2016.05.032

View details for PubMedID 27478129
Prostate Magnetic Resonance Imaging and Magnetic Resonance Imaging Targeted Biopsy in Patients with a Prior Negative Biopsy: A Consensus Statement by AUA and SAR. journal of urology Rosenkrantz, A. B., Verma, S., Choyke, P., Eberhardt, S. C., Eggener, S. E., Gaitonde, K., Haider, M. A., Margolis, D. J., Marks, L. S., Pinto, P., Sonn, G. A., Taneja, S. S. 2016
Abstract

After an initial negative biopsy there is an ongoing need for strategies to improve patient selection for repeat biopsy as well as the diagnostic yield from repeat biopsies.As a collaborative initiative of the AUA (American Urological Association) and SAR (Society of Abdominal Radiology) Prostate Cancer Disease Focused Panel, an expert panel of urologists and radiologists conducted a literature review and formed consensus statements regarding the role of prostate magnetic resonance imaging and magnetic resonance imaging targeted biopsy in patients with a negative biopsy, which are summarized in this review.The panel recognizes that many options exist for men with a previously negative biopsy. If a biopsy is recommended, prostate magnetic resonance imaging and subsequent magnetic resonance imaging targeted cores appear to facilitate the detection of clinically significant disease over standardized repeat biopsy. Thus, when high quality prostate magnetic resonance imaging is available, it should be strongly considered for any patient with a prior negative biopsy who has persistent clinical suspicion for prostate cancer and who is under evaluation for a possible repeat biopsy. The decision of whether to perform magnetic resonance imaging in this setting must also take into account the results of any other biomarkers and the cost of the examination, as well as the availability of high quality prostate magnetic resonance imaging interpretation. If magnetic resonance imaging is done, it should be performed, interpreted and reported in accordance with PI-RADS version 2 (v2) guidelines. Experience of the reporting radiologist and biopsy operator are required to achieve optimal results and practices integrating prostate magnetic resonance imaging into patient care are advised to implement quality assurance programs to monitor targeted biopsy results.Patients receiving a PI-RADS assessment category of 3 to 5 warrant repeat biopsy with image guided targeting. While transrectal ultrasound guided magnetic resonance imaging fusion or in-bore magnetic resonance imaging targeting may be valuable for more reliable targeting, especially for lesions that are small or in difficult locations, in the absence of such targeting technologies cognitive (visual) targeting remains a reasonable approach in skilled hands. At least 2 targeted cores should be obtained from each magnetic resonance imaging defined target. Given the number of studies showing a proportion of missed clinically significant cancers by magnetic resonance imaging targeted cores, a case specific decision must be made whether to also perform concurrent systematic sampling. However, performing solely targeted biopsy should only be considered once quality assurance efforts have validated the performance of prostate magnetic resonance imaging interpretations with results consistent with the published literature. In patients with negative or low suspicion magnetic resonance imaging (PI-RADS assessment category of 1 or 2, respectively), other ancillary markers (ie PSA, PSAD, PSAV, PCA3, PHI, 4K) may be of value in identifying patients warranting repeat systematic biopsy, although further data are needed on this topic. If a repeat biopsy is deferred on the basis of magnetic resonance imaging findings, then continued clinical and laboratory followup is advised and consideration should be given to incorporating repeat magnetic resonance imaging in this diagnostic surveillance regimen.

View details for DOI 10.1016/j.juro.2016.06.079

View details for PubMedID 27320841
Prostate Cancer Early Detection, Version 2.2016 JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Carroll, P. R., Parsons, J. K., Andriole, G., Bahnson, R. R., Castle, E. P., Catalona, W. J., Dahl, D. M., Davis, J. W., Epstein, J. I., Etzioni, R. B., Farrington, T., Hemstreet, G. P., Kawachi, M. H., Kim, S., Lange, P. H., Loughlin, K. R., Lowrance, W., Maroni, P., Mohler, J., Morgan, T. M., Moses, K. A., Nadler, R. B., Poch, M., Scales, C., Shaneyfelt, T. M., Smaldone, M. C., Sonn, G., Sprenkle, P., Vickers, A. J., Wake, R., Shead, D. A., Freedman-Cass, D. A. 2016; 14 (5): 509-519
Abstract

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate Cancer Early Detection provide recommendations for prostate cancer screening in healthy men who have elected to participate in an early detection program. The NCCN Guidelines focus on minimizing unnecessary procedures and limiting the detection of indolent disease. These NCCN Guidelines Insights summarize the NCCN Prostate Cancer Early Detection Panel's most significant discussions for the 2016 guideline update, which included issues surrounding screening in high-risk populations (ie, African Americans, BRCA1/2 mutation carriers), approaches to refine patient selection for initial and repeat biopsies, and approaches to improve biopsy specificity.

View details for Web of Science ID 000375888500007
NCCN Guidelines Insights: Prostate Cancer Early Detection, Version 2.2016. Journal of the National Comprehensive Cancer Network Carroll, P. R., Parsons, J. K., Andriole, G., Bahnson, R. R., Castle, E. P., Catalona, W. J., Dahl, D. M., Davis, J. W., Epstein, J. I., Etzioni, R. B., Farrington, T., Hemstreet, G. P., Kawachi, M. H., Kim, S., Lange, P. H., Loughlin, K. R., Lowrance, W., Maroni, P., Mohler, J., Morgan, T. M., Moses, K. A., Nadler, R. B., Poch, M., Scales, C., Shaneyfelt, T. M., Smaldone, M. C., Sonn, G., Sprenkle, P., Vickers, A. J., Wake, R., Shead, D. A., Freedman-Cass, D. A. 2016; 14 (5): 509-519
Abstract

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate Cancer Early Detection provide recommendations for prostate cancer screening in healthy men who have elected to participate in an early detection program. The NCCN Guidelines focus on minimizing unnecessary procedures and limiting the detection of indolent disease. These NCCN Guidelines Insights summarize the NCCN Prostate Cancer Early Detection Panel's most significant discussions for the 2016 guideline update, which included issues surrounding screening in high-risk populations (ie, African Americans, BRCA1/2 mutation carriers), approaches to refine patient selection for initial and repeat biopsies, and approaches to improve biopsy specificity.

View details for PubMedID 27160230
PROSTATE CANCER YIELD IN MRI LESIONS VARIES ACROSS RADIOLOGISTS Sonn, G., Fan, R., Li, S., Ghanouni, P., Loening, A., Daniel, B., To'o, K., Gill, H., Chung, B., Brooks, J. ELSEVIER SCIENCE INC. 2016: E42
View details for DOI 10.1016/j.juro.2016.02.1992

View details for Web of Science ID 000375278600096
Accuracy of Prostate-Specific Antigen Values in Prostate Cancer Registries. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Mittakanti, H. R., Thomas, I. C., Shelton, J. B., Makarov, D. V., Skolarus, T. A., Cooperberg, M. R., Chung, B. I., Sonn, G. A., Brooks, J. D., Leppert, J. T. 2016
View details for PubMedID 27458297
Prostate Cancer Early Detection, Version 2.2015 Clinical Practice Guidelines in Oncology JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Carroll, P. R., Parsons, J. K., Andriole, G., Bahnson, R. R., Barocas, D. A., Castle, E. P., Catalona, W. J., Dahl, D. M., Davis, J. W., Epstein, J. I., Etzioni, R. B., Farrington, T., Hemstreet, G. P., Kawachi, M. H., Lange, P. H., Loughlin, K. R., Lowrance, W., Maroni, P., Mohler, J., Morgan, T. M., Nadler, R. B., Poch, M., Scales, C., Shaneyfelt, T. M., Smaldone, M. C., Sonn, G., Sprenke, P., Vickers, A. J., Wake, R., Shead, D. A., Freedman-Cass, D. 2015; 13 (12): 1534-1561
Abstract

Prostate cancer represents a spectrum of disease that ranges from nonaggressive, slow-growing disease that may not require treatment to aggressive, fast-growing disease that does. The NCCN Guidelines for Prostate Cancer Early Detection provide a set of sequential recommendations detailing a screening and evaluation strategy for maximizing the detection of prostate cancer that is potentially curable and that, if left undetected, represents a risk to the patient. The guidelines were developed for healthy men who have elected to participate in the early detection of prostate cancer, and they focus on minimizing unnecessary procedures and limiting the detection of indolent disease.

View details for Web of Science ID 000367021100010
Gleason 6 Prostate Cancer: Translating Biology into Population Health JOURNAL OF UROLOGY Eggener, S. E., Badani, K., Barocas, D. A., Barrisford, G. W., Cheng, J., Chin, A. I., Corcoran, A., Epstein, J. I., George, A. K., Gupta, G. N., Hayn, M. H., Kauffman, E. C., Lane, B., Liss, M. A., Mirza, M., Morgan, T. M., Moses, K., Nepple, K. G., Preston, M. A., Rais-Bahrami, S., Resnick, M. J., Siddiqui, M. M., Silberstein, J., Singer, E. A., Sonn, G. A., Sprenkle, P., Stratton, K. L., Taylor, J., Tomaszewski, J., Tollefson, M., Vickers, A., White, W. M., Lowrance, W. T. 2015; 194 (3): 626-634
Abstract

Gleason 6 (3+3) is the most commonly diagnosed prostate cancer among men with prostate specific antigen screening, the most histologically well differentiated and is associated with the most favorable prognosis. Despite its prevalence, considerable debate exists regarding the genetic features, clinical significance, natural history, metastatic potential and optimal management.Members of the Young Urologic Oncologists in the Society of Urologic Oncology cooperated in a comprehensive search of the peer reviewed English medical literature on Gleason 6 prostate cancer, specifically focusing on the history of the Gleason scoring system, histological features, clinical characteristics, practice patterns and outcomes.The Gleason scoring system was devised in the early 1960s, widely adopted by 1987 and revised in 2005 with a more restrictive definition of Gleason 6 disease. There is near consensus that Gleason 6 meets pathological definitions of cancer, but controversy about whether it meets commonly accepted molecular and genetic criteria of cancer. Multiple clinical series suggest that the metastatic potential of contemporary Gleason 6 disease is negligible but not zero. Population based studies in the U.S. suggest that more than 90% of men newly diagnosed with prostate cancer undergo treatment and are exposed to the risk of morbidity for a cancer unlikely to cause symptoms or decrease life expectancy. Efforts have been proposed to minimize the number of men diagnosed with or treated for Gleason 6 prostate cancer. These include modifications to prostate specific antigen based screening strategies such as targeting high risk populations, decreasing the frequency of screening, recommending screening cessation, incorporating remaining life expectancy estimates, using shared decision making and novel biomarkers, and eliminating prostate specific antigen screening entirely. Large nonrandomized and randomized studies have shown that active surveillance is an effective management strategy for men with Gleason 6 disease. Active surveillance dramatically reduces the number of men undergoing treatment without apparent compromise of cancer related outcomes.The definition and clinical relevance of Gleason 6 prostate cancer have changed substantially since its introduction nearly 50 years ago. A high proportion of screen detected cancers are Gleason 6 and the metastatic potential is negligible. Dramatically reducing the diagnosis and treatment of Gleason 6 disease is likely to have a favorable impact on the net benefit of prostate cancer screening.

View details for DOI 10.1016/j.juro.2015.01.126

View details for Web of Science ID 000359157200007

View details for PubMedCentralID PMC4551510
Magnetic Resonance Imaging-Ultrasound Fusion Biopsy for Prediction of Final Prostate Pathology JOURNAL OF UROLOGY Le, J. D., Stephenson, S., Brugger, M., Lu, D. Y., Lieu, P., Sonn, G. A., Natarajan, S., Dorey, F. J., Huang, J., Margolis, D. J., Reiter, R. E., Marks, L. S. 2014; 192 (5): 1367-1373
Abstract

We explored the impact of magnetic resonance imaging-ultrasound fusion prostate biopsy on the prediction of final surgical pathology.A total of 54 consecutive men undergoing radical prostatectomy at UCLA after fusion biopsy were included in this prospective, institutional review board approved pilot study. Using magnetic resonance imaging-ultrasound fusion, tissue was obtained from a 12-point systematic grid (mapping biopsy) and from regions of interest detected by multiparametric magnetic resonance imaging (targeted biopsy). A single radiologist read all magnetic resonance imaging, and a single pathologist independently rereviewed all biopsy and whole mount pathology, blinded to prior interpretation and matched specimen. Gleason score concordance between biopsy and prostatectomy was the primary end point.Mean patient age was 62 years and median prostate specific antigen was 6.2 ng/ml. Final Gleason score at prostatectomy was 6 (13%), 7 (70%) and 8-9 (17%). A tertiary pattern was detected in 17 (31%) men. Of 45 high suspicion (image grade 4-5) magnetic resonance imaging targets 32 (71%) contained prostate cancer. The per core cancer detection rate was 20% by systematic mapping biopsy and 42% by targeted biopsy. The highest Gleason pattern at prostatectomy was detected by systematic mapping biopsy in 54%, targeted biopsy in 54% and a combination in 81% of cases. Overall 17% of cases were upgraded from fusion biopsy to final pathology and 1 (2%) was downgraded. The�combination of targeted biopsy and systematic mapping biopsy was needed to obtain the best predictive accuracy.In this pilot study magnetic resonance imaging-ultrasound fusion biopsy allowed for the prediction of final prostate pathology with greater accuracy than that reported previously using conventional methods (81% vs 40% to�65%). If confirmed, these results will have important clinical implications.

View details for DOI 10.1016/j.juro.2014.04.094

View details for Web of Science ID 000343856900015

View details for PubMedCentralID PMC4201866
Magnetic resonance imaging-ultrasound fusion biopsy for prediction of final prostate pathology. journal of urology Le, J. D., Stephenson, S., Brugger, M., Lu, D. Y., Lieu, P., Sonn, G. A., Natarajan, S., Dorey, F. J., Huang, J., Margolis, D. J., Reiter, R. E., Marks, L. S. 2014; 192 (5): 1367-1373
Abstract

We explored the impact of magnetic resonance imaging-ultrasound fusion prostate biopsy on the prediction of final surgical pathology.A total of 54 consecutive men undergoing radical prostatectomy at UCLA after fusion biopsy were included in this prospective, institutional review board approved pilot study. Using magnetic resonance imaging-ultrasound fusion, tissue was obtained from a 12-point systematic grid (mapping biopsy) and from regions of interest detected by multiparametric magnetic resonance imaging (targeted biopsy). A single radiologist read all magnetic resonance imaging, and a single pathologist independently rereviewed all biopsy and whole mount pathology, blinded to prior interpretation and matched specimen. Gleason score concordance between biopsy and prostatectomy was the primary end point.Mean patient age was 62 years and median prostate specific antigen was 6.2 ng/ml. Final Gleason score at prostatectomy was 6 (13%), 7 (70%) and 8-9 (17%). A tertiary pattern was detected in 17 (31%) men. Of 45 high suspicion (image grade 4-5) magnetic resonance imaging targets 32 (71%) contained prostate cancer. The per core cancer detection rate was 20% by systematic mapping biopsy and 42% by targeted biopsy. The highest Gleason pattern at prostatectomy was detected by systematic mapping biopsy in 54%, targeted biopsy in 54% and a combination in 81% of cases. Overall 17% of cases were upgraded from fusion biopsy to final pathology and 1 (2%) was downgraded. The�combination of targeted biopsy and systematic mapping biopsy was needed to obtain the best predictive accuracy.In this pilot study magnetic resonance imaging-ultrasound fusion biopsy allowed for the prediction of final prostate pathology with greater accuracy than that reported previously using conventional methods (81% vs 40% to�65%). If confirmed, these results will have important clinical implications.

View details for DOI 10.1016/j.juro.2014.04.094

View details for PubMedID 24793118
Initial experience with electronic tracking of specific tumor sites in men undergoing active surveillance of prostate cancer. Urologic oncology Sonn, G. A., Filson, C. P., Chang, E., Natarajan, S., Margolis, D. J., Macairan, M., Lieu, P., Huang, J., Dorey, F. J., Reiter, R. E., Marks, L. S. 2014; 32 (7): 952-957
Abstract

Targeted biopsy, using magnetic resonance (MR)-ultrasound (US) fusion, may allow tracking of specific cancer sites in the prostate. We aimed to evaluate the initial use of the technique to follow tumor sites in men on active surveillance of prostate cancer.A total of 53 men with prostate cancer (all T1c category) underwent rebiopsy of 74 positive biopsy sites, which were tracked and targeted using the Artemis MR-US fusion device (Eigen, Grass Valley, CA) from March 2010 through January 2013. The initial biopsy included 12 cores from a standard template (mapped by software) and directed biopsies from regions of interest seen on MR imaging (MRI). In the repeat biopsy, samples were taken from sites containing cancer at the initial biopsy. Outcomes of interest at second MR-US biopsy included (a) presence of any cancer and (b) presence of clinically significant cancer.All cancers on initial biopsy had either Gleason score 3+3 = 6 (n = 63) or 3+4 = 7 (n = 11). At initial biopsy, 23 cancers were within an MRI target, and 51 were found on systematic biopsy. Cancer detection rate on repeat biopsy (29/74, 39%) was independent of Gleason score on initial biopsy (P = not significant) but directly related to initial cancer core length (P<0.02). Repeat sampling of cancerous sites within MRI targets was more likely to show cancer than resampling of tumorous systematic sites (61% vs. 29%, P = 0.005). When initial cancer core length was?4 mm within an MRI target, more than 80% (5/6) of follow-up tracking biopsies were positive. An increase of Gleason score was uncommon (9/74, 12%).Monitoring of specific prostate cancer-containing sites may be achieved in some men using an electronic tracking system. The chances of finding tumor on repeat specific-site sampling was directly related to the length of tumor in the initial biopsy core and presence of tumor within an MRI target; upgrading of Gleason score was uncommon. Further research is required to evaluate the potential utility of site-specific biopsy tracking for patients with prostate cancer on active surveillance.

View details for DOI 10.1016/j.urolonc.2014.04.003

View details for PubMedID 25027689
Initial experience with electronic tracking of specific tumor sites in men undergoing active surveillance of prostate cancer UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS Sonn, G. A., Filson, C. P., Chang, E., Natarajan, S., Margolis, D. J., Macairan, M., Lieu, P., Huang, J., Dorey, F. J., Reiter, R. E., Marks, L. S. 2014; 32 (7): 952-957
Abstract

Targeted biopsy, using magnetic resonance (MR)-ultrasound (US) fusion, may allow tracking of specific cancer sites in the prostate. We aimed to evaluate the initial use of the technique to follow tumor sites in men on active surveillance of prostate cancer.A total of 53 men with prostate cancer (all T1c category) underwent rebiopsy of 74 positive biopsy sites, which were tracked and targeted using the Artemis MR-US fusion device (Eigen, Grass Valley, CA) from March 2010 through January 2013. The initial biopsy included 12 cores from a standard template (mapped by software) and directed biopsies from regions of interest seen on MR imaging (MRI). In the repeat biopsy, samples were taken from sites containing cancer at the initial biopsy. Outcomes of interest at second MR-US biopsy included (a) presence of any cancer and (b) presence of clinically significant cancer.All cancers on initial biopsy had either Gleason score 3+3 = 6 (n = 63) or 3+4 = 7 (n = 11). At initial biopsy, 23 cancers were within an MRI target, and 51 were found on systematic biopsy. Cancer detection rate on repeat biopsy (29/74, 39%) was independent of Gleason score on initial biopsy (P = not significant) but directly related to initial cancer core length (P<0.02). Repeat sampling of cancerous sites within MRI targets was more likely to show cancer than resampling of tumorous systematic sites (61% vs. 29%, P = 0.005). When initial cancer core length was?4 mm within an MRI target, more than 80% (5/6) of follow-up tracking biopsies were positive. An increase of Gleason score was uncommon (9/74, 12%).Monitoring of specific prostate cancer-containing sites may be achieved in some men using an electronic tracking system. The chances of finding tumor on repeat specific-site sampling was directly related to the length of tumor in the initial biopsy core and presence of tumor within an MRI target; upgrading of Gleason score was uncommon. Further research is required to evaluate the potential utility of site-specific biopsy tracking for patients with prostate cancer on active surveillance.

View details for DOI 10.1016/j.urolonc.2014.04.003

View details for Web of Science ID 000343968900003

View details for PubMedCentralID PMC4254112
Target detection: Magnetic resonance imaging-ultrasound fusion-guided prostate biopsy UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS Sonn, G. A., Margolis, D. J., Marks, L. S. 2014; 32 (6): 903-911
Abstract

Recent advances in multiparametric magnetic resonance imaging (MRI) have enabled image-guided detection of prostate cancer. Fusion of MRI with real-time ultrasound (US) allows the information from MRI to be used to direct biopsy needles under US guidance in an office-based procedure. Fusion can be performed either cognitively or electronically, using a fusion device. Fusion devices allow superimposition (coregistration) of stored MRI images on real-time US images; areas of suspicion found on MRI can then serve as targets during US-guided biopsy. Currently available fusion devices use a variety of technologies to perform coregistration: robotic tracking via a mechanical arm with built-in encoders (Artemis/Eigen, BioJet/Geoscan); electromagnetic tracking (UroNav/Philips-Invivo, Hi-RVS/Hitachi); or tracking with a 3D US probe (Urostation/Koelis). Targeted fusion biopsy has been shown to identify more clinically significant cancers and fewer insignificant cancers than conventional biopsy. Fusion biopsy appears to be a major advancement over conventional biopsy because it allows (1) direct targeting of suspicious areas not seen on US and (2) follow-up biopsy of specific cancerous sites in men undergoing active surveillance.

View details for DOI 10.1016/j.urolonc.2013.08.006

View details for Web of Science ID 000340343400024
Target detection: magnetic resonance imaging-ultrasound fusion-guided prostate biopsy. Urologic oncology Sonn, G. A., Margolis, D. J., Marks, L. S. 2014; 32 (6): 903-911
Abstract

Recent advances in multiparametric magnetic resonance imaging (MRI) have enabled image-guided detection of prostate cancer. Fusion of MRI with real-time ultrasound (US) allows the information from MRI to be used to direct biopsy needles under US guidance in an office-based procedure. Fusion can be performed either cognitively or electronically, using a fusion device. Fusion devices allow superimposition (coregistration) of stored MRI images on real-time US images; areas of suspicion found on MRI can then serve as targets during US-guided biopsy. Currently available fusion devices use a variety of technologies to perform coregistration: robotic tracking via a mechanical arm with built-in encoders (Artemis/Eigen, BioJet/Geoscan); electromagnetic tracking (UroNav/Philips-Invivo, Hi-RVS/Hitachi); or tracking with a 3D US probe (Urostation/Koelis). Targeted fusion biopsy has been shown to identify more clinically significant cancers and fewer insignificant cancers than conventional biopsy. Fusion biopsy appears to be a major advancement over conventional biopsy because it allows (1) direct targeting of suspicious areas not seen on US and (2) follow-up biopsy of specific cancerous sites in men undergoing active surveillance.

View details for DOI 10.1016/j.urolonc.2013.08.006

View details for PubMedID 24239473
Targeted Prostate Biopsy to Select Men for Active Surveillance: Do the Epstein Criteria Still Apply? The Journal of urology Hu, J. C., Chang, E., Natarajan, S., Margolis, D. J., Macairan, M., Lieu, P., Huang, J., Sonn, G., Dorey, F. J., Marks, L. S. 2014
Abstract

The Epstein histologic criteria (Gleason score <6, <2 cores positive, <50% of any core), established in 1994, have been widely used to select men for active surveillance. However, with the advent of targeted biopsy, which may be more accurate than conventional biopsy, we re-evaluated the likelihood of re-classification upon confirmatory re-biopsy using multi-parametric MRI-ultrasound fusion (mpMRI-US).We identified 113 subjects enrolled in the UCLA active surveillance meeting Epstein Criteria who subsequently underwent confirmatory, targeted biopsy via mpMRI-US. Median age was 64 years, PSA 4.2 ng/ml and prostate volume 46.8 cc. Targets, or regions of interest on mpMRI, were graded by level of suspicion and were biopsied at 3 mm intervals along their longest axis (median 10.5 mm). Additionally, 12 systematic cores were obtained during confirmatory re-biopsy. Our reporting is consistent with START criteria.Overall, confirmatory fusion biopsy resulted in re-classification for 41 men (36%), 26 (23%) due to Gleason grade >6, and 15 (13%) due to high volume Gleason 6 disease. When stratified by suspicion on mpMRI, the likelihood of reclassification was 24% to 29% for men with target grade 0 to 3, 45% for grade 4, and 100% for grade 5 (p=0.001). Men with grade 4 and 5 versus lower grade targets were >3 times (Odds Ratio 3.2, 95% Confidence Interval 1.4, 7.1, p=0.006) more likely to be reclassified.Upon confirmatory re-biopsy using mpMRI-US, men with high-suspicion mpMRI targets were frequently reclassified (45%-100%). Criteria for active surveillance should be re-evaluated when mpMRI-guided prostate biopsy is employed.

View details for DOI 10.1016/j.juro.2014.02.005

View details for PubMedID 24512956
The role of magnetic resonance imaging in delineating clinically significant prostate cancer. Urology Chamie, K., Sonn, G. A., Finley, D. S., Tan, N., Margolis, D. J., Raman, S. S., Natarajan, S., Huang, J., Reiter, R. E. 2014; 83 (2): 369?75
Abstract

To determine whether multiparametric magnetic resonance imaging might improve the identification of patients with higher risk disease at diagnosis and thereby reduce the incidence of undergrading or understaging.We retrospectively reviewed the clinical records of 115 patients who underwent multiparametric magnetic resonance imaging before radical prostatectomy. We used Epstein's criteria of insignificant disease with and without a magnetic resonance imaging (MRI) parameter (apparent diffusion coefficient) to calculate sensitivity, specificity, as well as negative and positive predictive values [NPV and PPV] across varying definitions of clinically significant cancer based on Gleason grade and tumor volume (0.2 mL, 0.5 mL, and 1.3 mL) on whole-mount prostate specimens. Logistic regression analysis was performed to determine the incremental benefit of MRI in delineating significant cancer.The majority had a prostate-specific antigen from 4.1-10.0 (67%), normal rectal examinations (90%), biopsy Gleason score�?6 (68%), and�?2 cores positive (55%). Of the 58 patients pathologically staged with Gleason 7 or pT3 disease at prostatectomy, Epstein's criteria alone missed 12 patients (sensitivity of 79% and NPV of 68%). Addition of apparent diffusion coefficient improved the sensitivity and NPV for predicting significant disease at prostatectomy to 93% and 84%, respectively. MRI improved detection of large Gleason 6 (?1.3 mL, P�= .006) or Gleason�?7 lesions of any size (P�<.001).Integration of MRI with existing clinical staging criteria helps identify patients with significant cancer. Clinicians should consider utilizing MRI in the decision-making process.

View details for DOI 10.1016/j.urology.2013.09.045

View details for PubMedID 24468511
Deletions of chromosomes 3p and 14q molecularly subclassify clear cell renal cell carcinoma CANCER Kroeger, N., Klatte, T., Chamie, K., Rao, P. N., Birkhaeuser, F. D., Sonn, G. A., Riss, J., Kabbinavar, F. F., Belldegrun, A. S., Pantuck, A. J. 2013; 119 (8): 1547-1554
View details for DOI 10.1002/cncr.27947

View details for Web of Science ID 000317618700014
Targeted Biopsy in the Detection of Prostate Cancer Using an Office Based Magnetic Resonance Ultrasound Fusion Device JOURNAL OF UROLOGY Sonn, G. A., Natarajan, S., Margolis, D. J., Macairan, M., Lieu, P., Huang, J., Dorey, F. J., Marks, L. S. 2013; 189 (1): 86-91
Abstract

Targeted biopsy of lesions identified on magnetic resonance imaging may enhance the detection of clinically relevant prostate cancers. We evaluated prostate cancer detection rates in 171 consecutive men using magnetic resonance ultrasound fusion prostate biopsy.Subjects underwent targeted biopsy for active surveillance (106) or persistently increased prostate specific antigen but negative prior conventional biopsy (65). Before biopsy, each man underwent multiparametric magnetic resonance imaging at 3.0 Tesla. Lesions on magnetic resonance imaging were outlined in 3 dimensions and assigned increasing cancer suspicion levels (image grade 1 to 5) by a uroradiologist. A biopsy tracking system was used to fuse the stored magnetic resonance imaging with real-time ultrasound, generating a 3-dimensional prostate model on the fly. Working from the 3-dimensional model, transrectal biopsy of target lesions and 12 systematic biopsies were performed with the patient under local anesthesia in the clinic.A total of 171 subjects (median age 65 years) underwent targeted biopsy. At biopsy, median prostate specific antigen was 4.9 ng/ml and prostate volume was 48 cc. A targeted biopsy was 3 times more likely to identify cancer than a systematic biopsy (21% vs 7%). Prostate cancer was found in 53% of men, 38% of whom had Gleason grade 7 or greater cancer. Of the men with Gleason 7 or greater cancer 38% had disease detected only on targeted biopsies. Targeted biopsy findings correlated with level of suspicion on magnetic resonance imaging. Of 16 men 15 (94%) with an image grade 5 target (highest suspicion) had prostate cancer, including 7 with Gleason 7 or greater cancer.Prostate lesions identified on magnetic resonance imaging can be accurately targeted using magnetic resonance ultrasound fusion biopsy by a urologist in clinic. Biopsy findings correlate with level of suspicion on magnetic resonance imaging.

View details for DOI 10.1016/j.juro.2012.08.095

View details for Web of Science ID 000312604800029

View details for PubMedID 23158413
Differing Perceptions of Quality of Life in Patients With Prostate Cancer and Their Doctors JOURNAL OF UROLOGY Sonn, G. A., Sadetsky, N., Presti, J. C., Litwin, M. S. 2013; 189 (1): S59-S65
Abstract

As the number of prostate cancer survivors increases, urologists must recognize their quality of life impairment. In the past physician ratings of patient symptoms did not correlate with patient self-assessments. We determined if urologists have improved their reporting of patient health related quality of life. We also investigated if urologists assessed health related quality of life more accurately in the short or long term.We identified 1,366 men from CaPSURE?, a national, prospective cohort, who had undergone prostatectomy, brachytherapy or external beam radiation therapy. At each visit urologists assessed fatigue, pain, and sexual, urinary and bowel dysfunction. Participants independently completed the SF-36? and the UCLA-PCI. We contrasted the frequency of impairment reported by physicians and participants in select health related quality of life domains in the short (less than 1 year) and long (greater than 2 years) term. We also compared physician-patient concordance between the periods 1995 to 2000 and 2001 to 2007.In short-term and long-term followup, and for the 1995 to 2000 and 2001 to 2007 cohorts, physician and participant assessments differed in all analyzed domains. Urologists noted impairment in urinary and sexual function more often than fatigue or pain. Disagreement between physician and participant ratings did not vary dramatically from short-term to long-term followup, or from the earlier to the later cohort.In men treated for localized prostate cancer physician ratings of symptoms do not correlate well with patient self-assessments of health related quality of life. Physician reporting did not improve over time. It is increasingly important to recognize and address impairments in quality of life from prostate cancer and its treatment.

View details for DOI 10.1016/j.juro.2012.11.032

View details for Web of Science ID 000312100000016

View details for PubMedID 23234635
Gain of chromosome 8q is associated with metastases and poor survival of patients with clear cell renal cell carcinoma. Cancer Klatte, T., Kroeger, N., Rampersaud, E. N., Birkh�user, F. D., Logan, J. E., Sonn, G., Riss, J., Rao, P. N., Kabbinavar, F. F., Belldegrun, A. S., Pantuck, A. J. 2012; 118 (23): 5777-5782
Abstract

The aim of this study was to evaluate the prevalence of chromosome 8q gain in clear cell renal cell carcinoma (CCRCC) and to correlate the findings with tumor phenotype and disease-specific survival (DSS).The tumor karyotypes of 336 consecutive patients with CCRCC were prospectively evaluated with classical cytogenetic analysis. Chromosome 8q status was correlated with clinicopathological variables, and its impact on DSS was evaluated.Gain of 8q occurred in 28 tumors (8.3%). Gain of 8q was associated with a higher risk of regional lymph node (21.4% vs 6.2%, P = .011) and distant metastases (50.0% vs 24.4%, P = .006), and greater tumor sizes (P = .030). Patients with gain of 8q had a 3.22-fold increased risk of death from CCRCC (P < .001). In multivariable analysis, gain of 8q was identified as an independent prognostic factor (hazard ratio, 2.37; P = .006). The concordance index of a multivariable base model increased significantly following inclusion of 8q gain (P = .0015).Gain of chromosome 8q occurs in a subset of CCRCCs and is associated with an increased risk of metastases and death from CCRCC. Because the proto-oncogene c-MYC is among the list of candidate genes located on 8q, our data suggest that these tumors may have unique pathways activated, which are associated with an aggressive tumor phenotype. If confirmed, defining tumors with gain of 8q may assist in identifying patients who would benefit for specific c-MYC inhibitors or agents that target the MAPK/ERK (mitogen-activated protein kinase) pathway.

View details for DOI 10.1002/cncr.27607

View details for PubMedID 22605478
VALUE OF TARGETED BIOPSY IN DETECTING PROSTATE CANCER USING AN OFFICE-BASED MR-US FUSION DEVICE Annual Meeting of the American-Urological-Association (AUA) Sonn, G. A., Natarajan, S., Margolis, D., Macairan, M., Lieu, P., Huang, J., Dorey, F. J., Marks, L. S. ELSEVIER SCIENCE INC. 2012: E829?E829
View details for Web of Science ID 000302912503350
Systemic therapy for metastatic renal cell carcinoma: a review and update. Reviews in urology Logan, J. E., Rampersaud, E. N., Sonn, G. A., Chamie, K., Belldegrun, A. S., Pantuck, A. J., Slamon, D. J., Kabbinavar, F. F. 2012; 14 (3-4): 65-78
Abstract

An in-depth understanding of metastatic renal cell carcinoma (mRCC) is important so that practitioners can make informed evidenced-based decisions with patients to optimize not only quantity of life but quality of life as well. Therefore, this review focuses on the biology of mRCC as it relates to targets for therapy, as well as on the small molecules rationally designed with these targets in mind. In addition, anticipated emerging therapies are highlighted, including the new tyrosine kinase inhibitors axitinib and tivozanib, as well as new immune-based therapies such as dendritic cell-based vaccines and antibodies. We also briefly review recent reports from the emerging field of predicting drug response based on molecular markers. And finally, management of metastatic non-clear cell RCC histologies are discussed focusing on available evidence to direct decision making when assessing therapeutic options.

View details for PubMedID 23526579
Dynamic Real-time Microscopy of the Urinary Tract Using Confocal Laser Endomicroscopy UROLOGY Wu, K., Liu, J., Adams, W., Sonn, G. A., Mach, K. E., Pan, Y., Beck, A. H., Jensen, K. C., Liao, J. C. 2011; 78 (1): 225-231
Abstract

To develop the diagnostic criteria for benign and neoplastic conditions of the urinary tract using probe-based confocal laser endomicroscopy (pCLE), a new technology for dynamic, in vivo imaging with micron-scale resolution. The suggested diagnostic criteria will formulate a guide for pCLE image interpretation in urology.Patients scheduled for transurethral resection of bladder tumor (TURBT) or nephrectomy were recruited. After white-light cystoscopy (WLC), fluorescein was administered as contrast. Different areas of the urinary tract were imaged with pCLE via direct contact between the confocal probe and the area of interest. Confocal images were subsequently compared with standard hematoxylin and eosin analysis.pCLE images were collected from 66 participants, including 2 patients who underwent nephrectomy. We identified key features associated with different anatomic landmarks of the urinary tract, including the kidney, ureter, bladder, prostate, and urethra. In vivo pCLE of the bladder demonstrated distinct differences between normal mucosa and neoplastic tissue. Using mosaicing, a post hoc image-processing algorithm, individual image frames were juxtaposed to form wide-angle views to better evaluate tissue microarchitecture.In contrast to standard pathologic analysis of fixed tissue with hematoxylin and eosin, pCLE provides real time microscopy of the urinary tract to enable dynamic interrogation of benign and neoplastic tissues in vivo. The diagnostic criteria developed in this study will facilitate adaptation of pCLE for use in conjunction with WLC to expedite diagnosis of urinary tract pathology, particularly bladder cancer.

View details for DOI 10.1016/j.urology.2011.02.057

View details for Web of Science ID 000292080300062

View details for PubMedID 21601243

View details for PubMedCentralID PMC4038103
Electrochemical immunosensor detection of urinary lactoferrin in clinical samples for urinary tract infection diagnosis BIOSENSORS & BIOELECTRONICS Pan, Y., Sonn, G. A., Sin, M. L., Mach, K. E., Shih, M., Gau, V., Wong, P. K., Liao, J. C. 2010; 26 (2): 649-654
Abstract

Urine is the most abundant and easily accessible of all body fluids and provides an ideal route for non-invasive diagnosis of human diseases, particularly of the urinary tract. Electrochemical biosensors are well suited for urinary diagnostics due to their excellent sensitivity, low-cost, and ability to detect a wide variety of target molecules including nucleic acids and protein biomarkers. We report the development of an electrochemical immunosensor for direct detection of the urinary tract infection (UTI) biomarker lactoferrin from infected clinical samples. An electrochemical biosensor array with alkanethiolate self-assembled monolayer (SAM) was used. Electrochemical impedance spectroscopy was used to characterize the mixed SAM, consisted of 11-mercaptoundecanoic acid and 6-mercapto-1-hexanol. A sandwich amperometric immunoassay was developed for detection of lactoferrin from urine, with a detection limit of 145 pg/ml. We validated lactoferrin as a biomarker of pyuria (presence of white blood cells in urine), an important hallmark of UTI, in 111 patient-derived urine samples. Finally, we demonstrated multiplex detection of urinary pathogens and lactoferrin through simultaneous detection of bacterial nucleic acid (16S rRNA) and host immune response protein (lactoferrin) on a single sensor array. Our results represent first integrated sensor platform capable of quantitative pathogen identification and measurement of host immune response, potentially providing clinical diagnosis that is not only more expeditious but also more informative than the current standard.

View details for DOI 10.1016/j.bios.2010.07.002

View details for Web of Science ID 000283804400056

View details for PubMedID 20667707

View details for PubMedCentralID PMC2946447
DYNAMIC REAL TIME MICROSCOPY OF THE URINARY TRACT: AN IMAGING ATLAS BASED ON CONFOCAL LASER ENDOMICROSCOPY Adams, W., Wu, K., Sonn, G., Jensen, K., Liao, J. C. MARY ANN LIEBERT INC. 2010: A278?A278
View details for Web of Science ID 000283864901225
IS SURVEILLANCE FOR STAGE I SEMINOMA TRULY A LOW RISK OPTION?: ESTIMATING IMAGING RELATED RADIATION EXPOSURE AND THE RISK OF SECONDARY MALIGNANCY Tarin, T., Sonn, G., Shinghal, R. ELSEVIER SCIENCE INC. 2010: E325?E326
View details for DOI 10.1016/j.juro.2010.02.2335

View details for Web of Science ID 000209829401682
Differing Perceptions of Quality of Life in Patients With Prostate Cancer and Their Doctors JOURNAL OF UROLOGY Sonn, G. A., Sadetsky, N., Presti, J. C., Litwin, M. S. 2009; 182 (5): 2296-2302
Abstract

As the number of prostate cancer survivors increases, urologists must recognize their quality of life impairment. In the past physician ratings of patient symptoms did not correlate with patient self-assessments. We determined if urologists have improved their reporting of patient health related quality of life. We also investigated if urologists assessed health related quality of life more accurately in the short or long term.We identified 1,366 men from CaPSURE, a national, prospective cohort, who had undergone prostatectomy, brachytherapy or external beam radiation therapy. At each visit urologists assessed fatigue, pain, and sexual, urinary and bowel dysfunction. Participants independently completed the SF-36 and the UCLA-PCI. We contrasted the frequency of impairment reported by physicians and participants in select health related quality of life domains in the short (less than 1 year) and long (greater than 2 years) term. We also compared physician-patient concordance between the periods 1995 to 2000 and 2001 to 2007.In short-term and long-term followup, and for the 1995 to 2000 and 2001 to 2007 cohorts, physician and participant assessments differed in all analyzed domains. Urologists noted impairment in urinary and sexual function more often than fatigue or pain. Disagreement between physician and participant ratings did not vary dramatically from short-term to long-term followup, or from the earlier to the later cohort.In men treated for localized prostate cancer physician ratings of symptoms do not correlate well with patient self-assessments of health related quality of life. Physician reporting did not improve over time. It is increasingly important to recognize and address impairments in quality of life from prostate cancer and its treatment.

View details for DOI 10.1016/j.juro.2009.07.027

View details for Web of Science ID 000270756900063

View details for PubMedID 19758610
Optical Biopsy of Human Bladder Neoplasia With In Vivo Confocal Laser Endomicroscopy JOURNAL OF UROLOGY Sonn, G. A., Jones, S. E., Tarin, T. V., Du, C. B., Mach, K. E., Jensen, K. C., Liao, J. C. 2009; 182 (4): 1299-1305
Abstract

Confocal laser endomicroscopy is a new endoscopic imaging technology that could complement white light cystoscopy by providing in vivo bladder histopathology. We evaluated confocal laser endomicroscopy by imaging normal, malignant appearing and indeterminate bladder mucosa in a pilot study.Patients scheduled to undergo transurethral resection of bladder tumors were recruited during a 3-month period. After standard cystoscopy fluorescein was administered intravesically and/or intravenously as a contrast dye. A 2.6 mm probe based confocal laser endomicroscope was passed through a 26 Fr resectoscope to image normal and abnormal appearing areas. The images were collected with 488 nm excitation at 8 to 12 frames per second. The endomicroscopic images were compared with standard hematoxylin and eosin analysis of transurethral resection of bladder tumor specimens.Of the 27 recruited patients 8 had no cancer, 9 had low grade tumors, 9 had high grade tumors and 1 had a low grade tumor with a high grade focus. Endomicroscopic images demonstrated clear differences between normal mucosa, and low and high grade tumors. In normal urothelium larger umbrella cells are seen most superficially followed by smaller intermediate cells and the less cellular lamina propria. In contrast, low grade papillary tumors demonstrate densely arranged but normal-shaped small cells extending outward from fibrovascular cores. High grade tumors show markedly irregular architecture and cellular pleomorphism.We report the first study to our knowledge of in vivo confocal laser endomicroscopy in the urinary tract. Marked differences among normal urothelium, low grade tumors and high grade tumors were visualized. Pending further clinical investigation and technological improvement, confocal laser endomicroscopy may become a useful adjunct to conventional cystoscopy.

View details for DOI 10.1016/j.juro.2009.06.039

View details for Web of Science ID 000269764100016

View details for PubMedID 19683270
OPTICAL BIOPSY OF HUMAN BLADDER NEOPLASIA WITH IN VIVO CONFOCAL LASER ENDOMICROSCOPY 104th Annual Meeting of the American-Urological-Association Sonn, G. A., Jones, S., Mach, K. E., Du, C. B., Jensen, K., Liao, J. C. ELSEVIER SCIENCE INC. 2009: 414?15
View details for Web of Science ID 000264448501254
Fibered Confocal Microscopy of Bladder Tumors: An ex Vivo Study JOURNAL OF ENDOUROLOGY Sonn, G. A., Mach, K. E., Jensen, K., Hsiung, P., Jones, S., Contag, C. H., Wang, T. D., Liao, J. C. 2009; 23 (2): 197-201
Abstract

The inadequacy of white-light cystoscopy to detect flat bladder tumors is well recognized. Great interest exists in developing other imaging technologies to augment or supplant conventional cystoscopy. Fibered confocal microscopy offers the promise of providing in vivo histopathologic information to help distinguish malignant from benign bladder lesions. We report the initial use of this technology to visualize tumors in the human bladder.We performed ex vivo fibered confocal imaging of fresh radical cystectomy specimens using the Mauna Kea Technologies Cellvizio system. The findings were compared with results from standard histopathology.The bladders of four patients were imaged using the fibered confocal microscope. Normal and neoplastic urothelium manifested differences in cellular and vascular density.This study demonstrates the feasibility of using fibered confocal microscopy to detect histologic differences between normal and neoplastic urothelium, and establishes a foundation for the use of fiber-based confocal microscopy in clinical studies.

View details for DOI 10.1089/end.2008.0524

View details for Web of Science ID 000263355500005

View details for PubMedID 19196063
Estimating the Risk of Cancer Associated With Imaging Related Radiation During Surveillance for Stage I Testicular Cancer Using Computerized Tomography JOURNAL OF UROLOGY Tarin, T. V., Sonn, G., Shinghal, R. 2009; 181 (2): 627-632
Abstract

Computerized tomography has a critical role in the surveillance of stage I nonseminomatous germ cell tumors of the testis. Some protocols call for up to 16 computerized tomography scans over 5 years, thereby exposing young patients to a significant amount of radiation. We estimated the lifetime risk of cancer incidence and cancer death from imaging related radiation received during surveillance of stage I nonseminomatous germ cell tumor.Using a model with a 64-slice computerized tomography scanner obtaining images of the abdomen and pelvis with or without chest in a standardized, phantom male patient, organ specific radiation doses were estimated using Monte Carlo simulation techniques. Lifetime attributable risks of cancer were estimated using the approach outlined in the Biological Effects of Ionizing Radiation VII Phase 2 report.With a 5-year surveillance protocol as suggested by the National Comprehensive Cancer Network, lifetime cancer risk ranged from 1 in 52 (1.9%) for an 18-year-old to 1 in 63 for a 40-year-old patient (1.2%). If chest computerized tomography is also performed the risk increases to 1 in 39 (2.6%) and 1 in 85 (1.6%), respectively. Lung and colon cancer accounted for most of the risk. The relative risk of a secondary malignancy with surveillance compared to a single scan after retroperitoneal lymph node dissection is approximately 15.2.Computerized tomography used in testicular cancer surveillance protocols imparts large radiation doses and is associated with a significant risk of cancer. This risk should be factored into counseling patients with stage I nonseminomatous germ cell tumor.

View details for DOI 10.1016/j.juro.2008.10.005

View details for Web of Science ID 000262419900070

View details for PubMedID 19091344
Management of Wilms tumor: current standard of care NATURE CLINICAL PRACTICE UROLOGY Sonn, G., Shortliffe, L. M. 2008; 5 (10): 551-560
Abstract

Wilms tumor is the most common renal malignancy in children. In the 1930s, overall survival for children with Wilms tumor was approximately 30%. Use of multidisciplinary therapy, guided by results from multi-institutional, randomized trials, has substantially improved overall survival to about 90%. Management of Wilms tumor differs substantially between Europe and the US. In Europe, the International Society of Pediatric Oncology protocols call for management of patients with presumptive Wilms tumor with neoadjuvant chemotherapy followed by nephrectomy and further chemotherapy. In the US, protocols developed by the National Wilms Tumor Study Group advise primary nephrectomy followed by a chemotherapy regimen tailored to the pathologic tumor stage. Despite these disparate strategies, overall survival is similar in patients managed according to European and US protocols. Patients with Wilms tumor now have excellent survival. Therefore, current goals aim to reduce the morbidity associated with therapy. Important complications of treatment for Wilms tumor include cardiomyopathy, renal failure, and increased risk of a secondary malignancy. Currently, the role of laparoscopic surgery in management of Wilms tumor remains extremely limited.

View details for DOI 10.1038/ncpuro1218

View details for Web of Science ID 000259638000010

View details for PubMedID 18836464
Spirituality influences health related quality of life in men with prostate cancer PSYCHO-ONCOLOGY Krupski, T. L., Kwan, L., Fink, A., Sonn, G. A., Maliski, S., Litwin, M. S. 2006; 15 (2): 121-131
Abstract

Spirituality is interdependent with the biological, psychological, and interpersonal aspects of life. Although spirituality has been studied in breast cancer survivors, little work has been done in men with prostate cancer. We sought to determine whether lower spirituality in men with early stage prostate cancer is associated with worse general health-related quality of life (HRQOL), disease-specific HRQOL, or psychosocial health. Two hundred and twenty-two subjects were drawn from a state-funded program providing free prostate cancer treatment to indigent men. Validated instruments captured spirituality, general and disease-specific HRQOL, anxiety, symptom distress, and emotional well-being. We found a consistent relationship between spirituality and the outcomes assessed. Low spirituality was associated with significantly worse physical and mental health, sexual function and more urinary bother after controlling for covariates. All of the psychosocial variables studied reflected worse adjustment in the men with low spirituality. Because the likelihood of prostate cancer survivorship is high, interventions targeting spirituality could impact the physical and psychosocial health of many men.

View details for DOI 10.1002/pon.929

View details for Web of Science ID 000235490000004

View details for PubMedID 15880458
Impact of diet on prostate cancer: a review PROSTATE CANCER AND PROSTATIC DISEASES Sonn, G. A., Aronson, W., Litwin, M. S. 2005; 8 (4): 304-310
Abstract

Epidemiological studies suggest that environmental factors may mediate the transformation of latent prostate cancer into clinically apparent tumors and that diet appears to influence this progression. Close correlations between average per capita fat intake and prostate cancer mortality internationally generated interest in underlying mechanisms for this link, such as through serum levels of androgens, free radicals, proinflammatory fatty acid metabolites, or insulin-like growth factor. Much interest currently lies in the potential of HMG-CoA reductase inhibitors (statins) to play a chemopreventative role in prostate cancer. Lycopene, a potent antioxidant found in tomatoes, may exert a protective effect in the prostate. Selenium and vitamin E have also been shown to decrease the risk of prostate cancer in some men. Calcium may support vitamin D-related antiproliferative effects in prostate cancer. Certain soy proteins, common in the Asian diet, have been shown to inhibit prostate cancer cell growth. Finally, green tea may also have a chemopreventive effect by inducing apoptosis. Despite confounding factors present in clinical studies assessing the effect of diet on cancer risk, the data remain compelling that a variety of nutrients may prevent the development and progression of prostate cancer.

View details for DOI 10.1038/sj.pcan.4500825

View details for Web of Science ID 000234418000002

View details for PubMedID 16130015
Ethnic variation in health-related quality of life among low-income men with prostate cancer ETHNICITY & DISEASE Krupski, T. L., Sonn, G., Kwan, L., Maliski, S., Fink, A., Litwin, M. S. 2005; 15 (3): 461-468
Abstract

To describe and compare health-related quality of life (HRQOL) among Hispanic, African-American, and Caucasian men with localized prostate cancer.Observational study of low-income, ethnically diverse men with non-metastatic prostate cancer.Statewide public assistance program in California.208 men (51 Caucasian, 115 Hispanic, and 42 African-American men) with non-metastatic disease.Radical retropubic prostatectomy, radiation therapy, and hormonal therapy.Validated instruments measured general and disease-specific HRQOL, anxiety and fear of recurrence, spirituality, symptom distress, and self-efficacy.Hispanic men with prostate cancer were less educated, more often in significant relationships, and had more variable incomes compared with men of other ethnic/racial backgrounds. In univariate analyses, Caucasian men reported better physical function but less spirituality, while Hispanic men reported worse sexual function. Multivariate analysis revealed that Hispanic men had significantly worse physical function, bowel function, and bowel bother. African-American men experienced greater anxiety over recurrence. African-American and Hispanic men were more spiritual than Caucasian men.Greater attention to demographic variations in HRQOL may allow physicians to improve outcomes across ethnicities in low-income men with prostate cancer by offering more specialized counseling and providing referral to social support systems.

View details for Web of Science ID 000231199700015

View details for PubMedID 16108307

Geoffrey Sonn

Assistant Professor of Urology and, by courtesy, of Radiology at the Stanford University Medical Center

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