24 results on '"Fearn PA"'
Search Results
2. Pretreatment prostate-specific antigen (PSA) velocity and doubling time are associated with outcome but neither improves prediction of outcome beyond pretreatment PSA alone in patients treated with radical prostatectomy.
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O'Brien MF, Cronin AM, Fearn PA, Smith B, Stasi J, Guillonneau B, Scardino PT, Eastham JA, Vickers AJ, Lilja H, O'Brien, Matthew Frank, Cronin, Angel M, Fearn, Paul A, Smith, Brandon, Stasi, Jason, Guillonneau, Bertrand, Scardino, Peter T, Eastham, James A, Vickers, Andrew J, and Lilja, Hans
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- 2009
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3. Multicenter analysis of effect of high biologic effective dose on biochemical failure and survival outcomes in patients with Gleason score 7-10 prostate cancer treated with permanent prostate brachytherapy.
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Stone NN, Potters L, Davis BJ, Ciezki JP, Zelefsky MJ, Roach M, Shinohara K, Fearn PA, Kattan MW, and Stock RG
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- 2009
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4. Conventional (clear cell) renal carcinoma metastases have greater bcl-2 expression than high-risk primary tumors.
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Lee CT, Genega EM, Hutchinson B, Fearn PA, Kattan MW, Russo P, Reuter VE, Lee, Cheryl T, Genega, Elizabeth M, Hutchinson, Brian, Fearn, Paul A, Kattan, Michael W, Russo, Paul, and Reuter, Victor E
- Abstract
Bcl-2 antagonizes p53-induced apoptosis and may contribute to chemoresistance. In renal cell carcinoma (RCC), the role of bcl-2 is not well-defined, though its expression is reportedly low in primary tumors and lacks prognostic value. This study evaluates patterns of bcl-2 expression in high-risk (pT(3)) primary tumors and in matched patient metastases. Immunohistochemical analysis of bcl-2 was performed on 149 cases of conventional (clear cell) RCC (112 pT(3) primaries, 37 metastases). Paraffin-embedded tissues were obtained from nephrectomies and metastatic resections. Median follow up was 48 months in the entire cohort and 69 months in living patients. We evaluated associations between bcl-2 expression and tumor recurrence or patient survival with the Cox regression test, and used the t-test and Pearson correlation methods to evaluate bcl-2 expression in primary and metastatic cases. Bcl-2 expression was observed at a higher frequency in metastases (21/37 cases; 57%) compared to primary tumors (24/112 cases; 21%; P < 0.001). The percentage of cells stained was greater in metastases than primary tumors (P = 0.003). This finding was also noted when expression in metastatic cases was compared with matched primaries (P = 0.05). Bcl-2 expression did not predict disease-free (P = 0.30), disease-specific (P = 0.90), or overall (P = 0.51) survival. Most RCC primary tumors have low-to-absent levels of bcl-2 protein, whereas most RCC metastases display greater protein levels. Bcl-2 expression in primary tumors does not predict clinical outcome. However, expression of bcl-2 protein occurs at a high frequency in RCC metastases when compared to primary tumors. It may be reasonable to target RCC patients displaying altered bcl-2 levels for molecular therapies, such as anti-bcl2, should metastatic disease develop. [ABSTRACT FROM AUTHOR]
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- 2003
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5. Classifying cancer pathology reports with hierarchical self-attention networks.
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Gao S, Qiu JX, Alawad M, Hinkle JD, Schaefferkoetter N, Yoon HJ, Christian B, Fearn PA, Penberthy L, Wu XC, Coyle L, Tourassi G, and Ramanathan A
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- Deep Learning, Humans, Natural Language Processing, Neoplasms classification, Neural Networks, Computer, Neoplasms pathology
- Abstract
We introduce a deep learning architecture, hierarchical self-attention networks (HiSANs), designed for classifying pathology reports and show how its unique architecture leads to a new state-of-the-art in accuracy, faster training, and clear interpretability. We evaluate performance on a corpus of 374,899 pathology reports obtained from the National Cancer Institute's (NCI) Surveillance, Epidemiology, and End Results (SEER) program. Each pathology report is associated with five clinical classification tasks - site, laterality, behavior, histology, and grade. We compare the performance of the HiSAN against other machine learning and deep learning approaches commonly used on medical text data - Naive Bayes, logistic regression, convolutional neural networks, and hierarchical attention networks (the previous state-of-the-art). We show that HiSANs are superior to other machine learning and deep learning text classifiers in both accuracy and macro F-score across all five classification tasks. Compared to the previous state-of-the-art, hierarchical attention networks, HiSANs not only are an order of magnitude faster to train, but also achieve about 1% better relative accuracy and 5% better relative macro F-score., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2019
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6. Scalable deep text comprehension for Cancer surveillance on high-performance computing.
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Qiu JX, Yoon HJ, Srivastava K, Watson TP, Blair Christian J, Ramanathan A, Wu XC, Fearn PA, and Tourassi GD
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- Comprehension, Humans, Neoplasms pathology, Neural Networks, Computer, Computing Methodologies, Deep Learning trends, Neoplasms diagnosis
- Abstract
Background: Deep Learning (DL) has advanced the state-of-the-art capabilities in bioinformatics applications which has resulted in trends of increasingly sophisticated and computationally demanding models trained by larger and larger data sets. This vastly increased computational demand challenges the feasibility of conducting cutting-edge research. One solution is to distribute the vast computational workload across multiple computing cluster nodes with data parallelism algorithms. In this study, we used a High-Performance Computing environment and implemented the Downpour Stochastic Gradient Descent algorithm for data parallelism to train a Convolutional Neural Network (CNN) for the natural language processing task of information extraction from a massive dataset of cancer pathology reports. We evaluated the scalability improvements using data parallelism training and the Titan supercomputer at Oak Ridge Leadership Computing Facility. To evaluate scalability, we used different numbers of worker nodes and performed a set of experiments comparing the effects of different training batch sizes and optimizer functions., Results: We found that Adadelta would consistently converge at a lower validation loss, though requiring over twice as many training epochs as the fastest converging optimizer, RMSProp. The Adam optimizer consistently achieved a close 2nd place minimum validation loss significantly faster; using a batch size of 16 and 32 allowed the network to converge in only 4.5 training epochs., Conclusions: We demonstrated that the networked training process is scalable across multiple compute nodes communicating with message passing interface while achieving higher classification accuracy compared to a traditional machine learning algorithm.
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- 2018
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7. Hierarchical attention networks for information extraction from cancer pathology reports.
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Gao S, Young MT, Qiu JX, Yoon HJ, Christian JB, Fearn PA, Tourassi GD, and Ramanthan A
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Objective: We explored how a deep learning (DL) approach based on hierarchical attention networks (HANs) can improve model performance for multiple information extraction tasks from unstructured cancer pathology reports compared to conventional methods that do not sufficiently capture syntactic and semantic contexts from free-text documents., Materials and Methods: Data for our analyses were obtained from 942 deidentified pathology reports collected by the National Cancer Institute Surveillance, Epidemiology, and End Results program. The HAN was implemented for 2 information extraction tasks: (1) primary site, matched to 12 International Classification of Diseases for Oncology topography codes (7 breast, 5 lung primary sites), and (2) histological grade classification, matched to G1-G4. Model performance metrics were compared to conventional machine learning (ML) approaches including naive Bayes, logistic regression, support vector machine, random forest, and extreme gradient boosting, and other DL models, including a recurrent neural network (RNN), a recurrent neural network with attention (RNN w/A), and a convolutional neural network., Results: Our results demonstrate that for both information tasks, HAN performed significantly better compared to the conventional ML and DL techniques. In particular, across the 2 tasks, the mean micro and macro F-scores for the HAN with pretraining were (0.852,0.708), compared to naive Bayes (0.518, 0.213), logistic regression (0.682, 0.453), support vector machine (0.634, 0.434), random forest (0.698, 0.508), extreme gradient boosting (0.696, 0.522), RNN (0.505, 0.301), RNN w/A (0.637, 0.471), and convolutional neural network (0.714, 0.460)., Conclusions: HAN-based DL models show promise in information abstraction tasks within unstructured clinical pathology reports., (© The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association.)
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- 2018
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8. Deep Learning for Automated Extraction of Primary Sites From Cancer Pathology Reports.
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Qiu JX, Yoon HJ, Fearn PA, and Tourassi GD
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- Humans, Support Vector Machine, Artificial Intelligence, Diagnosis, Computer-Assisted methods, Electronic Health Records, Neoplasms classification, Neoplasms diagnosis, Neoplasms pathology
- Abstract
Pathology reports are a primary source of information for cancer registries which process high volumes of free-text reports annually. Information extraction and coding is a manual, labor-intensive process. In this study, we investigated deep learning and a convolutional neural network (CNN), for extracting ICD-O-3 topographic codes from a corpus of breast and lung cancer pathology reports. We performed two experiments, using a CNN and a more conventional term frequency vector approach, to assess the effects of class prevalence and inter-class transfer learning. The experiments were based on a set of 942 pathology reports with human expert annotations as the gold standard. CNN performance was compared against a more conventional term frequency vector space approach. We observed that the deep learning models consistently outperformed the conventional approaches in the class prevalence experiment, resulting in micro- and macro-F score increases of up to 0.132 and 0.226, respectively, when class labels were well populated. Specifically, the best performing CNN achieved a micro-F score of 0.722 over 12 ICD-O-3 topography codes. Transfer learning provided a consistent but modest performance boost for the deep learning methods but trends were contingent on the CNN method and cancer site. These encouraging results demonstrate the potential of deep learning for automated abstraction of pathology reports.
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- 2018
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9. Designing a public square for research computing.
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Masys DR, Harris PA, Fearn PA, and Kohane IS
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- Animals, Attitude to Computers, Biomedical Research economics, Cooperative Behavior, Humans, International Cooperation, National Institutes of Health (U.S.), Research Support as Topic, United States, Biomedical Research methods, Computational Biology economics, Information Storage and Retrieval economics, Research Personnel economics, Research Personnel psychology, Software Design
- Abstract
A set of principles is proposed for sponsors and developers of research computing applications that can increase the likelihood of successful adoption by researchers.
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- 2012
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10. Evaluation of prediagnostic prostate-specific antigen dynamics as predictors of death from prostate cancer in patients treated conservatively.
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O'Brien MF, Cronin AM, Fearn PA, Savage CJ, Smith B, Stasi J, Scardino PT, Fisher G, Cuzick J, Møller H, Oliver RT, Berney DM, Foster CS, Eastham JA, Vickers AJ, and Lilja H
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- Aged, Cohort Studies, Humans, Male, Proportional Hazards Models, Prostatic Neoplasms mortality, Prostatic Neoplasms therapy, Prostate-Specific Antigen blood, Prostatic Neoplasms blood, Survival Analysis
- Abstract
Prostate-specific antigen (PSA) dynamics have been proposed to predict outcome in men with prostate cancer. We assessed the value of PSA velocity (PSAV) and PSA doubling time (PSADT) for predicting prostate cancer-specific mortality (PCSM) in men with clinically localized prostate cancer undergoing conservative management or early hormonal therapy. From 1990 to 1996, 2,333 patients were identified, of whom 594 had two or more PSA values before diagnosis. We examined 12 definitions for PSADT and 10 for PSAV. Because each definition required PSA measurements at particular intervals, the number of patients eligible for each definition varied from 40 to 594 and number of events from 10 to 119. Four PSAV definitions, but no PSADT, were significantly associated with PCSM after adjustment for PSA in multivariable Cox proportional hazards regression. All four could be calculated only for a proportion of events, and the enhancements in predictive accuracy associated with PSAV had very wide confidence intervals. There was no clear benefit of PSAV in men with low PSA and Gleason grade 6 or less. Although evidence that certain PSAV definitions help to predict PCSM in the cohort exist, the value of incorporating PSAV in predictive models to assist in determining eligibility for conservative management is, at best, uncertain., (Copyright © 2010 UICC.)
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- 2011
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11. Postoperative nomogram predicting the 9-year probability of prostate cancer recurrence after permanent prostate brachytherapy using radiation dose as a prognostic variable.
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Potters L, Roach M 3rd, Davis BJ, Stock RG, Ciezki JP, Zelefsky MJ, Stone NN, Fearn PA, Yu C, Shinohara K, and Kattan MW
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- Adult, Aged, Aged, 80 and over, Disease Progression, Dose-Response Relationship, Radiation, Humans, Male, Middle Aged, Neoplasm Recurrence, Local blood, Probability, Prognosis, Prostate-Specific Antigen blood, Prostatic Neoplasms blood, Radiotherapy Dosage, Regression Analysis, Brachytherapy methods, Neoplasm Recurrence, Local diagnosis, Nomograms, Prostatic Neoplasms diagnosis, Prostatic Neoplasms radiotherapy
- Abstract
Purpose: To report a multi-institutional outcomes study on permanent prostate brachytherapy (PPB) to 9 years that includes postimplant dosimetry, to develop a postimplant nomogram predicting biochemical freedom from recurrence., Methods and Materials: Cox regression analysis was used to model the clinical information for 5,931 patients who underwent PPB for clinically localized prostate cancer from six centers. The model was validated against the dataset using bootstrapping. Disease progression was determined using the Phoenix definition. The biological equivalent dose was calculated from the minimum dose to 90% of the prostate volume (D90) and external-beam radiotherapy dose using an alpha/beta of 2., Results: The 9-year biochemical freedom from recurrence probability for the modeling set was 77% (95% confidence interval, 73-81%). In the model, prostate-specific antigen, Gleason sum, isotope, external beam radiation, year of treatment, and D90 were associated with recurrence (each p < 0.05), whereas clinical stage was not. The concordance index of the model was 0.710., Conclusion: A predictive model for a postimplant nomogram for prostate cancer recurrence at 9-years after PPB has been developed and validated from a large multi-institutional database. This study also demonstrates the significance of implant dosimetry for predicting outcome. Unique to predictive models, these nomograms may be used a priori to calculate a D90 that likely achieves a desired outcome with further validation. Thus, a personalized dose prescription can potentially be calculated for each patient., (Copyright 2010 Elsevier Inc. All rights reserved.)
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- 2010
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12. Customized dose prescription for permanent prostate brachytherapy: insights from a multicenter analysis of dosimetry outcomes.
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Stone NN, Potters L, Davis BJ, Ciezki JP, Zelefsky MJ, Roach M, Fearn PA, Kattan MW, and Stock RG
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- Humans, Male, Palladium therapeutic use, Prostatic Neoplasms blood, Radioisotopes therapeutic use, Radiotherapy Dosage, Reference Values, Relative Biological Effectiveness, Risk, Brachytherapy, Iodine Radioisotopes therapeutic use, Prostate-Specific Antigen blood, Prostatic Neoplasms radiotherapy
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Purpose: To investigate the biochemical control rate in patients undergoing permanent prostate brachytherapy as a function of the biologically effective dose (BED) and risk group., Methods and Materials: Six centers provided data on 3,928 permanent brachytherapy patients with postimplant dosimetry results. The mean prostate-specific antigen level was 8.9 ng/mL. (125)I was used in 2,293 (58%), (103)Pd in 1,635, and supplemental external beam radiotherapy in 882 (22.5%) patients. The patients were stratified into low- (n = 2,188), intermediate- (n = 1,188), and high- (n = 552) risk groups and into three BED groups of < 140 Gy (n = 524), 140-200 Gy (n = 2284), and >200 Gy (n = 1,115). Freedom from biochemical disease progression (biochemical freedom from failure [bFFF]) was determined using the American Society for Therapeutic Radiology Oncology and Phoenix definitions and calculated using the Kaplan-Meier method, with factors compared using the log-rank test., Results: The 10-year prostate-specific antigen bFFF rate for the American Society for Therapeutic Radiology Oncology and Phoenix definitions was 79.2% and 70%, respectively. The corresponding bFFF rates for the low-, intermediate-, and high-risk groups was 84.1% and 78.1%, 76.8% and 63.6%, and 64.4% and 58.2%, respectively (p < 0.0001). The corresponding bFFF rate for the three BED groups was 56.1% and 41.4%, 80% and 77.9%, and 91.1% and 82.9% (p < 0.0001). The corresponding bFFF rate for the low-risk patients by dose group was 69.8% and 49.8%, 86% and 85.2%, and 88.1% and 88.3% for the low-, intermediate, and high-dose group, respectively (p <0.0001). The corresponding bFFF rate for the intermediate-risk patients by dose group was 52.9% and 23.1%, 74.1% and 77.7%, and 94.3% and 88.8% for the low-, intermediate-, and high-dose group, respectively (p < 0.0001). The corresponding bFFF rate for high-risk patients by dose group was 19.2% and 41.7%, 61.8% and 53.2%, and 90% and 69.6% for the low-, intermediate-, and high-dose group, respectively (p < 0.0001)., Conclusions: These data suggest that permanent brachytherapy dose prescriptions can be customized to risk status. In low-risk patients, achieving a BED of >or=140 Gy might be adequate for prostate-specific antigen control. However, high-risk disease might require a BED dose of >or=200 Gy.
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- 2007
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13. Evaluation of postradiotherapy PSA patterns and correlation with 10-year disease free survival outcomes for prostate cancer.
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Zelefsky MJ, Ben-Porat L, Chan HM, Fearn PA, and Venkatraman ES
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- Aged, Aged, 80 and over, Androgen Antagonists therapeutic use, Disease-Free Survival, Humans, Male, Middle Aged, Neoadjuvant Therapy, Radiotherapy, Conformal, Time Factors, Prostate-Specific Antigen blood, Prostatic Neoplasms blood, Prostatic Neoplasms radiotherapy
- Abstract
Purpose: To describe the prostate-specific antigen (PSA) pattern profiles observed after external beam radiotherapy with and without short-term neoadjuvant androgen deprivation therapy (ST-ADT) and to report the association of established posttreatment PSA patterns with long-term disease-free survival outcomes., Methods and Materials: A total of 1,665 patients were treated with conformal external beam radiotherapy for clinically localized prostate cancer. Of 570 patients who had the requisite>10 consecutive PSA measurements for statistical analysis, 194 patients received a median of 3 months of ADT before radiotherapy and 376 were treated with radiotherapy alone. The median follow up was 103 months., Results: In the group treated with ST-ADT, three distinct postradiotherapy PSA patterns were identified: a stable trend (44%), an increasing trend followed by stabilization of the PSA (25%), and an increasing trend (31%). Among the subgroup that demonstrated a rising and subsequent stabilizing patterns, PSA levels had gradually risen to a median value of 0.9 ng/mL after therapy, stabilized, and remained durably suppressed. The only identified trends among patients treated with external beam radiotherapy without ST-ADT were declining PSA levels followed by stable PSA trends or declining patterns followed by rising levels. Patients whose PSA levels stabilized after an initial rise or those with slowly rising PSA profiles had a lower incidence of distant metastasis compared to those with accelerated rises after therapy., Conclusions: For those treated with external beam radiotherapy in conjunction with ST-ADT, a significant percentage who develop a rising PSA after treatment are expected to manifest subsequent stabilization at plateaued levels of approximately 1.0 ng/mL, which can remain durably suppressed. The likelihood of distant metastasis in these patients is low despite the PSA stabilization at levels 1.0 ng/mL or higher and comparable to outcomes observed for those with lower nonrising PSA values.
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- 2006
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14. Cancer-specific survival and predictors of prostate-specific antigen recurrence and survival in patients with seminal vesicle invasion after radical prostatectomy.
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Secin FP, Bianco FJ Jr, Vickers AJ, Reuter V, Wheeler T, Fearn PA, Eastham JA, and Scardino PT
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- Aged, Disease-Free Survival, Humans, Male, Middle Aged, Neoplasm Invasiveness pathology, Neoplasm Staging, Prognosis, Prostatic Neoplasms diagnosis, Prostatic Neoplasms surgery, Survival Rate, Neoplasm Recurrence, Local diagnosis, Neoplasm Recurrence, Local mortality, Neoplasm Recurrence, Local surgery, Prostate-Specific Antigen blood, Prostatectomy, Prostatic Neoplasms mortality, Seminal Vesicles pathology
- Abstract
Background: The objectives of the current study were to determine the long-term biochemical recurrence (BCR) and cancer-specific survival (CSS) rates for men with seminal vesicle invasion (SVI) and to identify risk factors for freedom from BCR and CSS in patients who received treatment in the prostate-specific antigen era and who had SVI identified at the time of radical prostatectomy (RP)., Methods: Prospective clinical, pathologic, and outcome data were collected for 5377 men who underwent RP between June 1983 and August 2004. There were 936 patients who were excluded because they received treatment before RP. Multivariable analysis was used to identify the factors that predicted BCR and CSS., Results: Among 4441 eligible patients, 387 patients (8.7%) had SVI, and 91 of those 387 patients (24%) had lymph node involvement (LNI). In total, 210 patients experienced BCR. For patients without LNI, the 10-year and 15-year freedom from BCR rates were 36% and 32%, respectively, and the corresponding CSS rates were 89% and 81%, respectively. For the 91 men who had SVI and LNI, the 10-year BCR-free probability was 10%, but the 10-year CSS probability was 74%. By 10 years, patients with LNI were 3 times more likely to die from cancer than from other causes; nonetheless, 66% of patients were alive despite their advanced stage. The preoperative prostate-specific antigen level, extracapsular extension, LNI, and Gleason grade were associated independently with BCR. Gleason scores of 8 to 10 and LNI were significant predictors of CSS., Conclusions: SVI does not invariably signal BCR or death from cancer in patients who undergo RP and pelvic lymph node dissection. Fifteen years later, approximately 33% of men with SVI and negative lymph nodes are expected remain free of BCR, and CSS was surprisingly good., (Copyright (c) 2006 American Cancer Society.)
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- 2006
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15. Preoperative nomogram predicting the 10-year probability of prostate cancer recurrence after radical prostatectomy.
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Stephenson AJ, Scardino PT, Eastham JA, Bianco FJ Jr, Dotan ZA, Fearn PA, and Kattan MW
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- Aged, Biopsy, Disease Progression, Disease-Free Survival, Humans, Male, Middle Aged, Multivariate Analysis, Neoplasm Recurrence, Local epidemiology, Predictive Value of Tests, Proportional Hazards Models, Prostate-Specific Antigen blood, Prostatic Neoplasms immunology, Prostatic Neoplasms pathology, Prostatic Neoplasms surgery, Risk Factors, Nomograms, Prostatectomy, Prostatic Neoplasms diagnosis
- Abstract
An existing preoperative nomogram predicts the probability of prostate cancer recurrence, defined by prostate-specific antigen (PSA), at 5 years after radical prostatectomy based on clinical stage, serum PSA, and biopsy Gleason grade. In an updated and enhanced nomogram, we have extended the predictions to 10 years, added the prognostic information of systematic biopsy results, and enabled the predictions to be adjusted for the year of surgery. Cox regression analysis was used to model the clinical information for 1978 patients treated by two high-volume surgeons from our institution. The nomogram was externally validated on an independent cohort of 1545 patients with a concordance index of 0.79 and was well calibrated with respect to observed outcome. The inclusion of the number of positive and negative biopsy cores enhanced the predictive accuracy of the model. Thus, a new preoperative nomogram provides robust predictions of prostate cancer recurrence up to 10 years after radical prostatectomy.
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- 2006
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16. The association between total and positive lymph node counts, and disease progression in clinically localized prostate cancer.
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Masterson TA, Bianco FJ Jr, Vickers AJ, DiBlasio CJ, Fearn PA, Rabbani F, Eastham JA, and Scardino PT
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- Aged, Disease Progression, Humans, Lymph Node Excision, Lymphatic Metastasis, Male, Middle Aged, Prostatic Neoplasms surgery, Prostatic Neoplasms pathology
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Purpose: We examined the association between the number of LNs removed, the number of positive LNs and disease progression in patients undergoing pelvic lymph node dissection and radical retropubic prostatectomy for clinically localized prostate cancer., Materials and Methods: We analyzed 5,038 consecutive patients who underwent radical retropubic prostatectomy between 1983 and 2003. Clinicopathological parameters, including the administration of neoadjuvant hormonal therapy, preoperative prostate specific antigen, specimen Gleason score, surgeon and pathological stage, were collected prospectively in our prostate cancer database. We excluded men treated with radiation or chemotherapy before surgery. BCR was defined as 2 postoperative prostate specific antigen increases greater than 0.2 ng/ml. Cox models were used to determine whether the number of nodes removed or the number of positive nodes predicted freedom from BCR after adjustment for prognostic covariates., Results: The 4,611 eligible patients had a median of 9 LNs (IQR 5 to 13) removed. Positive nodes were found in 175 patients (3.8%). Overall the number of LNs removed did not predict freedom from BCR (HR per additional 10 nodes removed 1.02, 95% CI 0.92 to 1.13, p = 0.7). Results were similar in patients receiving and not receiving neoadjuvant hormonal therapy. Finding any LN involvement was associated with a BCR HR of 5.2 (95% CI 4.2 to 6.4, p <0.0005). However, in men without nodal involvement an increased number of nodes removed correlated significantly with freedom from BCR (p = 0.01)., Conclusions: Nodal disease increased the risk of progression. Extensive lymphadenectomy enhances the accuracy of surgical staging. However, we were unable to determine that removing more nodes improves freedom from BCR uniformly. Since the proportion of patients with prostate cancer with positive nodes is low, the value of extensive lymphadenectomy requires a multi-institutional, randomized clinical trial.
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- 2006
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17. Long-term oncologic results of salvage radical prostatectomy for locally recurrent prostate cancer after radiotherapy.
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Bianco FJ Jr, Scardino PT, Stephenson AJ, Diblasio CJ, Fearn PA, and Eastham JA
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- Adult, Aged, Analysis of Variance, Disease Progression, Follow-Up Studies, Humans, Male, Middle Aged, Neoplasm Recurrence, Local blood, Neoplasm Recurrence, Local mortality, Prostate-Specific Antigen blood, Prostatic Neoplasms blood, Prostatic Neoplasms mortality, Prostatic Neoplasms radiotherapy, Treatment Outcome, Neoplasm Recurrence, Local surgery, Prostatectomy methods, Prostatic Neoplasms surgery, Salvage Therapy methods
- Abstract
Purpose: Salvage radical prostatectomy (RP) may potentially cure patients who have isolated local prostate cancer recurrence after radiotherapy (RT). We report the long-term cancer control associated with salvage RP in a consecutive cohort of patients and identify the variables associated with disease progression and cancer survival., Methods and Materials: A total of 100 consecutive patients underwent salvage RP with curative intent for biopsy-confirmed, locally recurrent, prostate cancer after RT. Disease progression after salvage RP was defined as a prostate-specific antigen (PSA) level of > or =0.2 ng/mL or by initiation of androgen deprivation therapy. Cancer-specific mortality was defined as active clinical disease progression despite castration. Cox regression analysis was used to evaluate these endpoints. The median follow-up from RT was 10 years (range, 3-27 years) and from salvage RP was 5 years (range, 1-20 years)., Results: Overall, the 5-year progression-free probability was 55% (95% confidence interval, 46-64%), and the median progression-free interval was 6.4 years. The preoperative PSA level was the only significant pretreatment predictor of disease progression in the multivariate analysis (p = 0.01). The 5-year progression-free probability for patients with a preoperative PSA level of <4, 4-10, and >10 ng/mL was 86%, 55%, and 37%, respectively. The 10-year and 15-year cancer-specific mortality after salvage RP was 27% and 40%, respectively. The median time from disease progression to cancer-specific death was 10.3 years (95% confidence interval, 7.6-12.9). After multivariate analysis, the preoperative serum PSA level and seminal vesicle or lymph node status correlated independently with disease progression., Conclusions: Greater preoperative PSA levels are associated with disease progression and cancer-specific death. Long-term control of locally recurrent prostate cancer after definitive RT is possible when salvage RP is performed early in the course of recurrent disease.
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- 2005
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18. Outcome predictors for the increasing PSA state after definitive external-beam radiotherapy for prostate cancer.
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Zelefsky MJ, Ben-Porat L, Scher HI, Chan HM, Fearn PA, Fuks ZY, Leibel SA, and Venkatraman ES
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- Adult, Aged, Aged, 80 and over, Humans, Male, Middle Aged, Neoplasm Metastasis, Neoplasm Staging, Prostatic Neoplasms blood, Prostatic Neoplasms pathology, Retrospective Studies, Prostate-Specific Antigen blood, Prostatic Neoplasms radiotherapy, Radiotherapy, Conformal
- Abstract
Purpose: To identify predictors of distant metastases (DM) among patients who develop an isolated prostate-specific antigen (PSA) relapse after definitive external-beam radiotherapy for clinically localized prostate cancer., Materials and Methods: A total of 1,650 patients with clinical stage T1 to T3 prostate cancer were treated with high-dose three-dimensional conformal radiotherapy. Of these, 381 patients subsequently developed three consecutive increasing PSA values and were characterized as having a biochemical relapse. The median follow-up time was 92 months from the completion of radiotherapy., Results: The 5-year incidence of DM after an established PSA relapse was 29%. In a multivariate analysis, PSA doubling time (PSA-DT; P < .001), the clinical T stage (P < .001), and Gleason score (P = .007) were independent variables predicting for DM after established biochemical failure. The PSA-DT for favorable-, intermediate-, and unfavorable-risk patients who developed a biochemical failure was 20.0, 13.2, and 8.2 months, respectively (P < .001). The 3-year incidence of DM for patients with PSA-DT of 0 to 3, 3 to 6, 6 to 12, and more than 12 months was 49%, 41%, 20%, and 7%, respectively (P < .001). Patients with PSA-DT of 0 to 3 and 3 to 6 months demonstrated a 7.0 and 6.6 increased hazard of developing DM or death, respectively, compared with patients with a DT more than 12 months., Conclusion: In addition to clinical stage and Gleason score, PSA-DT was a powerful predictor of DM among patients who develop an isolated PSA relapse after external-beam radiotherapy for prostate cancer. Patients who develop biochemical relapse with PSA-DT < or = 6 months should be considered for systemic therapy or experimental protocols because of the high propensity for rapid DM development.
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- 2005
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19. Morbidity and functional outcomes of salvage radical prostatectomy for locally recurrent prostate cancer after radiation therapy.
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Stephenson AJ, Scardino PT, Bianco FJ Jr, DiBlasio CJ, Fearn PA, and Eastham JA
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- Aged, Humans, Male, Middle Aged, Postoperative Complications epidemiology, Postoperative Complications etiology, Prostatic Neoplasms radiotherapy, Recovery of Function, Salvage Therapy, Neoplasm Recurrence, Local surgery, Prostatectomy adverse effects, Prostatic Neoplasms surgery
- Abstract
Purpose: Few patients with locally recurrent prostate cancer after external beam (EB) or interstitial (I) radiotherapy (RT) are considered candidates for salvage radical prostatectomy (RP) due to high reported rates of major complications and urinary incontinence. We report the morbidity associated with salvage RP in 100 consecutive patients., Materials and Methods: From 1984 to 2003 salvage RP was performed for recurrent prostate cancer following EBRT in 58 cases, and IRT in 42 (28 retropubic) and (14 transperineal). Clinical information was obtained from a prospective database., Results: Since 1993, the major complication rate has decreased significantly (13% vs 33%, p = 0.02), including the rectal injury rate (2% vs 15%, p = 0.01). Compared with retropubic IRT and/or pre-radiotherapy pelvic lymph node dissection the risk of major complications following EBRT or transperineal IRT was significantly less (OR 0.2, p = 0.006). At 5 years an estimated 39% of patients were dry and 68% required 1 pad daily or less. A total of 23 patients with moderate-severe incontinence underwent artificial sphincter placement. The anastomotic stricture rate was 30%. The 5-year potency rate was 28% following unilateral or bilateral nerve sparing RP and 45% in previously potent patients., Conclusions: Due to patient selection the major complication rate after salvage RP has improved significantly with time and it is similar to that of standard RP. Rates of anastomotic stricture and moderate to severe incontinence are higher than those observed after standard RP. However, most patients recover reasonable urinary continence and a substantial number of select patients recover potency. The acceptable morbidity profile of salvage RP following EBRT and transperineal IRT should persuade more physicians to consider patients for this potentially curative procedure.
- Published
- 2004
- Full Text
- View/download PDF
20. Mode of presentation of renal cell carcinoma provides prognostic information.
- Author
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Lee CT, Katz J, Fearn PA, and Russo P
- Subjects
- Carcinoma, Renal Cell classification, Carcinoma, Renal Cell mortality, Carcinoma, Renal Cell pathology, Disease-Free Survival, Female, Follow-Up Studies, Humans, Kidney Neoplasms classification, Kidney Neoplasms mortality, Kidney Neoplasms pathology, Male, Middle Aged, Nephrectomy, Prognosis, Retrospective Studies, Survival Analysis, Time Factors, Treatment Failure, Treatment Outcome, Carcinoma, Renal Cell diagnosis, Kidney Neoplasms diagnosis
- Abstract
Purpose: Broadened applications of imaging modalities have increased the incidental detection of renal cell carcinoma (RCC) over the past decade. Previous small series have suggested a prognostic benefit for incidental presentation. This study utilizes a large contemporary patient cohort to examine patterns of RCC presentation and their clinical implications., Materials and Methods: Retrospective analysis was performed on 721 patients (260 women, 461 men) who underwent 750 nephrectomies for treatment of RCC between 7/1/89 and 12/31/97; 29 patients required two operations for bilateral RCC. Median age and follow-up were 63 years and 41 months, respectively. Indicators of symptomatic presentation included flank pain, flank mass, hematuria, varicocele, constitutional symptoms, paraneoplastic syndromes, and bone pain related to metastatic disease. Mode of presentation was compared with clinicopathologic parameters using Chi-square and t-test analyses. Survival analysis was performed using Kaplan-Meier estimates (log-rank test) and Cox regression modeling., Results: Incidental and symptomatic presentation occurred in 57% and 42% of cases, respectively. When compared to incidental cases, symptomatic presentation was predominantly detected in younger patients (mean age, 59 years; P < .001), in males (P < .04), and in tumors with conventional (clear cell) histology (P < .001), larger size (mean, 8 cm; P < .001), and non-organ confined pathology (P < .001). In univariate analysis, symptomatic cases had a more adverse disease-free (P < .0001) and disease-specific (P < .0001) survival. In multivariate analysis, mode of presentation was an independent predictor of disease-free (P < 0.0001) and disease-specific survival (P < 0.005)., Conclusions: Symptomatic presentation correlates with an aggressive histology and advanced disease. Incidental tumors may be frequently detected in female and elderly patients, as these groups traditionally seek general medical care more regularly. Mode of presentation can independently predict an adverse patient outcome and should be included in RCC-specific modeling systems.
- Published
- 2002
- Full Text
- View/download PDF
21. Potency after permanent prostate brachytherapy for localized prostate cancer.
- Author
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Potters L, Torre T, Fearn PA, Leibel SA, and Kattan MW
- Subjects
- Adenocarcinoma complications, Adenocarcinoma drug therapy, Adenocarcinoma pathology, Adenocarcinoma psychology, Aged, Aged, 80 and over, Antineoplastic Agents, Hormonal therapeutic use, Brachytherapy methods, Brachytherapy psychology, Cohort Studies, Combined Modality Therapy, Confounding Factors, Epidemiologic, Erectile Dysfunction drug therapy, Erectile Dysfunction epidemiology, Erectile Dysfunction psychology, Follow-Up Studies, Humans, Life Tables, Male, Middle Aged, Neoadjuvant Therapy, Neoplasm Staging, New York epidemiology, Piperazines therapeutic use, Proportional Hazards Models, Prospective Studies, Prostatic Neoplasms complications, Prostatic Neoplasms drug therapy, Prostatic Neoplasms pathology, Prostatic Neoplasms psychology, Purines, Quality of Life, Radiation Injuries epidemiology, Radiation Injuries psychology, Radiotherapy, High-Energy adverse effects, Sildenafil Citrate, Sulfones, Vasculitis complications, Vasculitis epidemiology, Adenocarcinoma radiotherapy, Brachytherapy adverse effects, Erectile Dysfunction etiology, Prostatic Neoplasms radiotherapy, Radiation Injuries etiology
- Abstract
Purpose: The evaluation of potency preservation after treatment of localized prostate cancer with transperineal permanent prostate brachytherapy (PPB) and the efficacy of sildenafil were studied., Methods and Materials: This study comprised 482 patients who were able to maintain an erection suitable for intercourse before treatment from a cohort of 1166 patients with clinically localized prostate cancer treated with PPB. All patients have been followed prospectively, and actuarial analysis was performed to assess potency preservation over time. Patients treated with sildenafil were evaluated as to its efficacy., Results: The median follow-up of this cohort was 34 months (6--92), with a median age of 68 years (47--80). Potency was preserved in 311 of the 482 patients, with a 5-year actuarial potency rate of 52.7%. The 5-year actuarial potency rate for patients treated with PPB as monotherapy was 76%, and, for those treated with combination external beam radiotherapy (EBT) + PPB, 56% (p = 0.08). Patients treated with neoadjuvant androgen deprivation (NAAD) + PPB had a 5-year potency rate of 52%, whereas those with combination EBT + PPB + NAAD had a potency rate of 29% (p = 0.13). Cox regression analysis identified that pretreatment use of NAAD and patient age predicted for impotence (p = 0.0001 and 0.04, respectively). Of 84 patients treated with sildenafil, 52 had a successful outcome (62%). The response to sildenafil was significantly better in those patients not treated with NAAD (p = 0.04)., Conclusions: The actuarial potency rates at 5 years for patients treated with PPB are lower than generally acknowledged, except for those patients treated with PPB as monotherapy. Patients who received sildenafil exhibited improved potency in a majority of cases.
- Published
- 2001
- Full Text
- View/download PDF
22. Time trade-off utility modified to accommodate degenerative and life-threatening conditions.
- Author
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Kattan MW, Fearn PA, and Miles BJ
- Subjects
- Decision Support Techniques, Health Status, Humans, Male, Pilot Projects, Prostatic Neoplasms, Terminally Ill, Value of Life, Attitude to Health, Life Expectancy, Quality-Adjusted Life Years
- Abstract
The time trade-off is often argued to be the preferred utility assessment method. When measuring current health in its classic form, it involves a comparison of two certainties: perfect health and current health, each for a fixed period of time and followed by death. This makes the time trade-off insensitive to patient fears regarding premature death or worsening health. We suggest the classic time trade-off be modified to include subjective rather than actuarial life expectancy, and relaxation of the current health option to include uncertainty in quantity and quality of life. We illustrate the mechanics of this modified time trade-off and report a preliminary application to 122 men presenting to a prostate cancer screening program. Further analysis of this modified time trade-off appears warranted.
- Published
- 2001
23. The definition of biochemical failure in patients treated with definitive radiotherapy.
- Author
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Kattan MW, Fearn PA, Leibel S, and Potters L
- Subjects
- Brachytherapy, Disease-Free Survival, Follow-Up Studies, Humans, Male, Neoplasm Recurrence, Local diagnosis, Prostatic Neoplasms diagnosis, Radiation Oncology standards, Societies, Medical, Time Factors, Treatment Failure, Neoplasm Recurrence, Local blood, Practice Guidelines as Topic, Prostate-Specific Antigen blood, Prostatic Neoplasms blood, Prostatic Neoplasms radiotherapy
- Abstract
Purpose: The American Society for Therapeutic Radiology and Oncology (ASTRO) published a definition for biochemical failure following treatment of prostate cancer. Others have noted difficulties with interpreting this definition and recommended modifications to accommodate special recurrence patterns. We have compared various modifications to the original ASTRO definition on our series of 1213 patients treated with transperineal permanent prostate brachytherapy., Methods and Materials: The ASTRO modifications we considered adjusted for (1) early censoring of nonrecurrent patients with rising prostate-specific antigen levels (PSA), (2) cumulative rather than consecutive rises (without a decrease) as evidence of recurrence, (3) both of the above, and (4) waiting 2 years before data analysis. The Kaplan-Meier method was used to compute the effects on recurrence rate for patients treated with and without neoadjuvant hormones., Results: With the original ASTRO definition, freedom from recurrence in our series of men who did not receive neoadjuvant hormones was 83% at 4 years. All of the modifications considered had statistically insignificant effects on freedom from recurrence rates, varying from 80% to 83% at 4 years. Patients treated with neoadjuvant hormones also showed very little sensitivity to the recurrence definition employed., Conclusion: Early censoring of equivocal patients and counting cumulative rather than consecutive rises in PSA (without a decrease) had little empiric effect on the ASTRO recurrence rates. However, we favor the addition of both these modifications to the ASTRO definition on conceptual grounds for evaluating patients following any modality (radiation or surgery), whereby a trend over multiple PSA values is used to judge failure.
- Published
- 2000
- Full Text
- View/download PDF
24. Telephone interviews vs. workstation sessions for acquiring quality of life data.
- Author
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Kattan MW, Fearn PA, Cantor SB, Hu J, Cowen ME, Giesler RB, and Miles BJ
- Subjects
- Analysis of Variance, Humans, Linear Models, Telephone, Computers, Interviews as Topic, Quality of Life, Surveys and Questionnaires
- Abstract
Patient quality of life data can be acquired in a variety of ways, including over the telephone and through computerized questionnaires. However, if the method of collection produces different results, medical decisions regarding appropriate and cost-effective care may be influenced by collection method. We conducted an experiment where subjects had two quality of life measures, the time trade-off and rating scale utilities, assessed both in telephone interivews and via computer touchscreens. The order of telephone and touchscreen was randomized. We found that rating scale utilities were similar whether obtained via the telephone or via touchscreen regardless of which was done first. However, patients who had their time trade-off utilities assessed over the telephone first did not provide as consistent responses as those elicited first via touchscreen (p = 0.01). Caution is suggested when considering eliciting time trade-off over the telephone with subjects who have not had time trade-off elicited previously.
- Published
- 1999
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