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intermediate risk prostate cancer genomic

Michael S Leapman, Peter R Carroll
INTRODUCTION: Selective treatment approaches for prostate cancer (PCa) are warranted given the highly varied nature of the disease and the consequences associated with definitive therapy. MATERIALS AND METHODS: We present a stepwise overview of strategies to not treat PCa, ranging from improved early detection practices that seek to improve the yield at initial diagnosis, as well as refinements to risk prediction and the performance of active surveillance. RESULTS: Adherence to screening guidelines is non-uniform...
October 13, 2016: Urologic Oncology
Jeffrey J Tosoian, Michael A Gorin, Ashley E Ross, Kenneth J Pienta, Phuoc T Tran, Edward M Schaeffer
The oligometastatic state has been proposed as an intermediate stage of cancer spread between localized disease and widespread metastases. With improvements in diagnostic modalities such as functional imaging, oligometastatic prostate cancer is being diagnosed with greater frequency than ever before. Furthermore, the paradigm for treatment of advanced prostate cancers is shifting toward a more aggressive approach. Many questions surround the understanding of the process and consequences of oligometastasis, meaning that the contemporary literature offers a wide variety of definitions of oligometastatic prostate cancer...
October 11, 2016: Nature Reviews. Urology
Emily Eva Holmes, Diane Goltz, Verena Sailer, Maria Jung, Sebastian Meller, Barbara Uhl, Jörn Dietrich, Magda Röhler, Jörg Ellinger, Glen Kristiansen, Dimo Dietrich
BACKGROUND: Molecular biomarkers that might help to distinguish between more aggressive and clinically insignificant prostate cancers (PCa) are still urgently needed. Aberrant DNA methylation as a common molecular alteration in PCa seems to be a promising source for such biomarkers. In this study, PITX3 DNA methylation (mPITX3) and its potential role as a prognostic biomarker were investigated. Furthermore, mPITX3 was analyzed in combination with the established PCa methylation biomarker PITX2 (mPITX2)...
2016: Clinical Epigenetics
P L Nguyen, N E Martin, B J Palmer-Aronsten, V Choeurng, T Kolisnik, C J Beard, M D Nezolosky, Y W Chen, H Shin, E Davicioni, F Feng
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
Milan S Geybels, Jonathan L Wright, Marina Bibikova, Brandy Klotzle, Jian-Bing Fan, Shanshan Zhao, Ziding Feng, Elaine A Ostrander, Daniel W Lin, Peter S Nelson, Janet L Stanford
BACKGROUND: Identifying the subset of patients with clinically localized prostate cancer (PCa) at the highest risk of recurrence remains challenging, and better prognostic markers are needed. Gleason score is the best predictor of PCa aggressiveness and prognosis. In the present study, we generated an epigenetic signature based on high versus low Gleason score tumors and evaluated its ability to predict recurrence after radical prostatectomy. METHODS: Genome-wide DNA methylation data from The Cancer Genome Atlas (TCGA; no...
2016: Clinical Epigenetics
R B Den, M Santiago-Jimenez, J Alter, M Schliekelman, J R Wagner, J F Renzulli Ii, D I Lee, C G Brito, K Monahan, B Gburek, N Kella, G Vallabhan, F Abdollah, E J Trabulsi, C D Lallas, L G Gomella, T L Woodlief, Z Haddad, L L C Lam, S Deheshi, Q Wang, V Choeurng, M du Plessis, J Jordan, B Parks, H Shin, C Buerki, K Yousefi, E Davicioni, V R Patel, N L Shah
BACKGROUND: Currently, there are multiple commercially available RNA-based biomarkers that are Medicare approved and suggested for use by the National Comprehensive Cancer Network guidelines. There is uncertainty as to which patients benefit from genomic testing and for whom these tests should be ordered. Here, we examined the correlation patterns of Decipher assay to understand the relationship between the Decipher and patient tumor characteristics. METHODS: De-identified Decipher test results (including Decipher risk scores and clinicopathologic data) from 2 342 consecutive radical prostatectomy (RP) patients tested between January and September 2015 were analyzed...
August 30, 2016: Prostate Cancer and Prostatic Diseases
Lei Wei, Jianmin Wang, Erika Lampert, Simon Schlanger, Adam D DePriest, Qiang Hu, Eduardo Cortes Gomez, Mitsuko Murakam, Sean T Glenn, Jeffrey Conroy, Carl Morrison, Gissou Azabdaftari, James L Mohler, Song Liu, Hannelore V Heemers
BACKGROUND: Next-generation sequencing is revealing genomic heterogeneity in localized prostate cancer (CaP). Incomplete sampling of CaP multiclonality has limited the implications for molecular subtyping, stratification, and systemic treatment. OBJECTIVE: To determine the impact of genomic and transcriptomic diversity within and among intraprostatic CaP foci on CaP molecular taxonomy, predictors of progression, and actionable therapeutic targets. DESIGN, SETTING, AND PARTICIPANTS: Four consecutive patients with clinically localized National Comprehensive Cancer Network intermediate- or high-risk CaP who did not receive neoadjuvant therapy underwent radical prostatectomy at Roswell Park Cancer Institute in June-July 2014...
July 20, 2016: European Urology
A E Ross, R B Den, K Yousefi, B J Trock, J Tosoian, E Davicioni, D J S Thompson, V Choeurng, Z Haddad, P T Tran, E J Trabulsi, L G Gomella, C D Lallas, F Abdollah, F Y Feng, E A Klein, A P Dicker, S J Freedland, R J Karnes, E M Schaeffer
BACKGROUND: To date, there have been no published trials examining the impact of salvage radiation therapy (SRT) in the post-operative setting for prostate cancer (PCa). We conducted a retrospective, comparative study of post-operative radiation following radical prostatectomy (RP) for men with pT3 disease or positive margins (adverse pathological features, APF). METHODS: 422 PCa men treated at four institutions with RP and having APF were analyzed with a primary end point of metastasis...
September 2016: Prostate Cancer and Prostatic Diseases
Marco Moschini, Martin Spahn, Agostino Mattei, John Cheville, R Jeffrey Karnes
Localized prostate cancer (PCa) is a clinically heterogeneous disease, which presents with variability in patient outcomes within the same risk stratification (low, intermediate or high) and even within the same Gleason scores. Genomic tools have been developed with the purpose of stratifying patients affected by this disease to help physicians personalize therapies and follow-up schemes. This review focuses on these tissue-based tools. At present, four genomic tools are commercially available: Decipher™, Oncotype DX®, Prolaris® and ProMark®...
2016: BMC Medicine
Stephen J Freedland, Voleak Choeurng, Lauren Howard, Amanda De Hoedt, Marguerite du Plessis, Kasra Yousefi, Lucia L Lam, Christine Buerki, Seong Ra, Bruce Robbins, Edouard J Trabulsi, Nikhil L Shah, Firas Abdollah, Felix Y Feng, Elai Davicioni, Adam P Dicker, Robert J Karnes, Robert B Den
BACKGROUND: Despite salvage radiation therapy (SRT) for recurrent prostate cancer (PCa) after radical prostatectomy (RP), some patients still progress to metastases. Identifying these men would allow them to undergo systemic therapy including testing novel therapies to reduce metastases risk. OBJECTIVE: To test whether the genomic classifier (GC) predicts development of metastatic disease. DESIGN, SETTING, AND PARTICIPANTS: Retrospective multi-center and multi-ethnic cohort study from two academic centers and one Veterans Affairs Medical Center in the United States involving 170 men receiving SRT for recurrent PCa post-RP...
January 21, 2016: European Urology
Anna Wilkins, David Dearnaley, Navita Somaiah
Localised prostate cancer, in particular, intermediate risk disease, has varied survival outcomes that cannot be predicted accurately using current clinical risk factors. External beam radiotherapy (EBRT) is one of the standard curative treatment options for localised disease and its efficacy is related to wide ranging aspects of tumour biology. Histopathological techniques including immunohistochemistry and a variety of genomic assays have been used to identify biomarkers of tumour proliferation, cell cycle checkpoints, hypoxia, DNA repair, apoptosis, and androgen synthesis, which predict response to radiotherapy...
2015: BioMed Research International
Ashley E Ross, Michael H Johnson, Kasra Yousefi, Elai Davicioni, George J Netto, Luigi Marchionni, Helen L Fedor, Stephanie Glavaris, Voleak Choeurng, Christine Buerki, Nicholas Erho, Lucia L Lam, Elizabeth B Humphreys, Sheila Faraj, Stephania M Bezerra, Misop Han, Alan W Partin, Bruce J Trock, Edward M Schaeffer
BACKGROUND: Radical prostatectomy (RP) is a primary treatment option for men with intermediate- and high-risk prostate cancer. Although many are effectively cured with local therapy alone, these men are by definition at higher risk of adverse pathologic features and clinical disease recurrence. It has been shown that the Decipher test predicts metastatic progression in cohorts that received adjuvant and salvage therapy following RP. OBJECTIVE: To evaluate the Decipher genomic classifier in a natural history cohort of men at risk who received no additional treatment until the time of metastatic progression...
January 2016: European Urology
Mariam Imnadze, Daniel D Sjoberg, Andrew J Vickers
BACKGROUND: Up to 30% of patients with low-risk prostate cancer (PCa) are found to have features of aggressive disease at radical prostatectomy (RP). Several predictive nomograms and novel genomic markers have been developed to estimate the risk of adverse pathology in men eligible for active surveillance (AS). However, oncologic risk associated with these findings remains unknown. OBJECTIVE: To determine if the presence of adverse pathologic features at RP in patients eligible for AS is prognostic of poor oncologic outcome independent of pretreatment risk status...
January 2016: European Urology
Li Hsu, Jihyoun Jeon, Hermann Brenner, Stephen B Gruber, Robert E Schoen, Sonja I Berndt, Andrew T Chan, Jenny Chang-Claude, Mengmeng Du, Jian Gong, Tabitha A Harrison, Richard B Hayes, Michael Hoffmeister, Carolyn M Hutter, Yi Lin, Reiko Nishihara, Shuji Ogino, Ross L Prentice, Fredrick R Schumacher, Daniela Seminara, Martha L Slattery, Duncan C Thomas, Mark Thornquist, Polly A Newcomb, John D Potter, Yingye Zheng, Emily White, Ulrike Peters
BACKGROUND & AIMS: Risk for colorectal cancer (CRC) can be greatly reduced through screening. To aid in the development of screening strategies, we refined models designed to determine risk of CRC by incorporating information from common genetic susceptibility loci. METHODS: By using data collected from more than 12,000 participants in 6 studies performed from 1990 through 2011 in the United States and Germany, we developed risk determination models based on sex, age, family history, genetic risk score (number of risk alleles carried at 27 validated common CRC susceptibility loci), and history of endoscopic examinations...
June 2015: Gastroenterology
Eric A Klein, Kasra Yousefi, Zaid Haddad, Voleak Choeurng, Christine Buerki, Andrew J Stephenson, Jianbo Li, Michael W Kattan, Cristina Magi-Galluzzi, Elai Davicioni
BACKGROUND: Surgery is a standard first-line therapy for men with intermediate- or high-risk prostate cancer. Clinical factors such as tumor grade, stage, and prostate-specific antigen (PSA) are currently used to identify those who are at risk of recurrence and who may benefit from adjuvant therapy, but novel biomarkers that improve risk stratification and that distinguish local from systemic recurrence are needed. OBJECTIVE: To determine whether adding the Decipher genomic classifier, a validated metastasis risk-prediction model, to standard risk-stratification tools (CAPRA-S and Stephenson nomogram) improves accuracy in predicting metastatic disease within 5 yr after surgery (rapid metastasis [RM]) in an independent cohort of men with adverse pathologic features after radical prostatectomy (RP)...
April 2015: European Urology
Jennifer Cullen, Inger L Rosner, Timothy C Brand, Nan Zhang, Athanasios C Tsiatis, Joel Moncur, Amina Ali, Yongmei Chen, Dejan Knezevic, Tara Maddala, H Jeffrey Lawrence, Phillip G Febbo, Shiv Srivastava, Isabell A Sesterhenn, David G McLeod
BACKGROUND: Biomarkers that are validated in independent cohorts are needed to improve risk assessment for prostate cancer (PCa). OBJECTIVE: A racially diverse cohort of men (20% African American [AA]) was used to evaluate the association of the clinically validated 17-gene Genomic Prostate Score (GPS) with recurrence after radical prostatectomy and adverse pathology (AP) at surgery. DESIGN, SETTING, AND PARTICIPANTS: Biopsies from 431 men treated for National Comprehensive Cancer Network (NCCN) very low-, low-, or intermediate-risk PCa between 1990 and 2011 at two US military medical centers were tested to validate the association between GPS and biochemical recurrence (BCR) and to confirm the association with AP...
July 2015: European Urology
Emilie Lalonde, Adrian S Ishkanian, Jenna Sykes, Michael Fraser, Helen Ross-Adams, Nicholas Erho, Mark J Dunning, Silvia Halim, Alastair D Lamb, Nathalie C Moon, Gaetano Zafarana, Anne Y Warren, Xianyue Meng, John Thoms, Michal R Grzadkowski, Alejandro Berlin, Cherry L Have, Varune R Ramnarine, Cindy Q Yao, Chad A Malloff, Lucia L Lam, Honglei Xie, Nicholas J Harding, Denise Y F Mak, Kenneth C Chu, Lauren C Chong, Dorota H Sendorek, Christine P'ng, Colin C Collins, Jeremy A Squire, Igor Jurisica, Colin Cooper, Rosalind Eeles, Melania Pintilie, Alan Dal Pra, Elai Davicioni, Wan L Lam, Michael Milosevic, David E Neal, Theodorus van der Kwast, Paul C Boutros, Robert G Bristow
BACKGROUND: Clinical prognostic groupings for localised prostate cancers are imprecise, with 30-50% of patients recurring after image-guided radiotherapy or radical prostatectomy. We aimed to test combined genomic and microenvironmental indices in prostate cancer to improve risk stratification and complement clinical prognostic factors. METHODS: We used DNA-based indices alone or in combination with intra-prostatic hypoxia measurements to develop four prognostic indices in 126 low-risk to intermediate-risk patients (Toronto cohort) who will receive image-guided radiotherapy...
December 2014: Lancet Oncology
Yonggang He, Jian Gu, Sara Strom, Christopher J Logothetis, Jeri Kim, Xifeng Wu
PURPOSE: Gleason score (GS) 7 prostate cancer is a heterogeneous disease with different clinical behavior. We sought to identify genetic biomarkers that may predict the aggressiveness of GS 7 diseases. EXPERIMENTAL DESIGN: We genotyped 72 prostate cancer susceptibility SNPs identified in genome-wide association studies in 1,827 white men with histologically confirmed prostate adenocarcinoma. SNPs associated with disease aggressiveness were identified by comparing high-aggressive (GS ≥8) and low-aggressive (GS ≤6) cases...
October 1, 2014: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Robert B Den, Felix Y Feng, Timothy N Showalter, Mark V Mishra, Edouard J Trabulsi, Costas D Lallas, Leonard G Gomella, W Kevin Kelly, Ruth C Birbe, Peter A McCue, Mercedeh Ghadessi, Kasra Yousefi, Elai Davicioni, Karen E Knudsen, Adam P Dicker
PURPOSE: To test the hypothesis that a genomic classifier (GC) would predict biochemical failure (BF) and distant metastasis (DM) in men receiving radiation therapy (RT) after radical prostatectomy (RP). METHODS AND MATERIALS: Among patients who underwent post-RP RT, 139 were identified for pT3 or positive margin, who did not receive neoadjuvant hormones and had paraffin-embedded specimens. Ribonucleic acid was extracted from the highest Gleason grade focus and applied to a high-density-oligonucleotide microarray...
August 1, 2014: International Journal of Radiation Oncology, Biology, Physics
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