Genomic profiling of prostate cancer at a diverse academic center.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 64-64
Author(s):  
Robert Lopez ◽  
Anna C. Ferrari ◽  
Sanjay Goel ◽  
Stephen Peeke ◽  
Janaki Neela Sharma ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Demographic Data ◽  
Gene Mutations ◽  
Genomic Analysis ◽  
Clinical Trial Data ◽  
Cancer Center ◽  
Minority Population ◽  
Tissue Sampling ◽  
Therapeutic Decisions ◽  
Race Ethnicity

64 Background: According to recent reports, ~1 in 4 patients with metastatic prostate cancer may harbor alterations in DNA damage repair (DDR) genes. Clinical trial data demonstrates that prostate cancer patients with DDR mutations may respond to poly-ADP ribose polymerase (PARP) inhibitors. Less is known about the mutational profile in minority patients with prostate cancer. We sought to determine the genomic profile of prostate cancer in an ethnically diverse patient population at a single center. Methods: We performed a retrospective review of men with prostate cancer at the Montefiore-Einstein Cancer Center who had next generation sequencing (NGS) with FoundationOne solid tumor testing between 2/2016 - 8/2019. Individual chart review was used to obtain clinical and demographic data including self-reported race/ethnicity. Results: NGS was attempted on archival tissue from 95 patients and results were obtained for 85. Among patients with results, the self-reported race/ethnicity was: Hispanic (H) 37.6%, Non-Hispanic Black (NHB) 52.9%, Non-Hispanic White (NHW) 4.7%, and Other (O) 4.7%. At the time of tissue sampling, 61 patients had metastatic disease and 10 were castration-resistant. 63 samples were from the prostate, 7 from bone, 7 from lymph node, 3 from liver and 5 from other soft tissue sites. The most commonly altered genes included: TP53 (26%), TMPRSS2-ERG fusion (23%), and PTEN (17%). Alterations in the androgen receptor were identified in 5 samples (all with CRPC). 32.8% had alterations in DDR genes including BRCA2 9 (10.6%), ATM 7 (8.2%), ATR 4 (4.7%), BRIP1 2 (2.3%), CDK12 3 (3.5%), FANCA 2 (2.3%), and PALB2 1 (1.2%). Alterations in mismatch repair genes (MSH2, MLH1, MSH6, PMS2) were present in 4 (4.7%) patients (3 of these were MSI-H). In samples where tumor mutational burden (TMB) was reported, 4 (4.7%) were TMB-high (3 MSI-H and 1 with POLE mutation). Conclusions: DDR gene mutations are common in this primarily minority population. As DDR mutations become more common in the CRPC setting, our data may underestimate the frequency of DDR mutations as only 10 patients had CRPC at the time of tissue sampling. Minority men, like all men, with prostate cancer should be considered for genomic analysis as results are likely to guide therapeutic decisions.

scholarly journals New Developments in the Treatment of Castration-Resistant Prostate Cancer

2014 ◽  
Vol 12 (5S) ◽  
pp. 773-776
Author(s):  
Celestia S. Higano
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial Data ◽  
Annual Conference ◽  
Castration Resistant Prostate Cancer ◽  
New Developments ◽  
Castration Resistant ◽  
Therapeutic Decisions ◽  
Clinical Scenarios ◽  
Hormonal Therapies ◽  
The Right

During the past 4 years, a host of new agents have been approved for the treatment of patients with advanced prostate cancer. As a result, selecting the right agent for the right patient at the right time is a clinical challenge. At the NCCN 19th Annual Conference, Dr. Celestia Higano explored the rationale behind such therapeutic decisions and the supporting clinical trial data. She reviewed the different classes of therapeutic agents, from immunotherapy and hormonal therapies to chemotherapy and radioisotopes, and offered suggestions for the clinical scenarios in which they may be used most successfully.

966: Radical Prostatectomy for Lymph Node Positive Prostate Cancer: The M.D. Anderson Cancer Center Experience

2006 ◽  
Vol 175 (4S) ◽  
pp. 311-312
Author(s):  
Philippe E. Spiess ◽  
Joseph E. Busby ◽  
Jennifer Jordan ◽  
Mike Hernandez ◽  
Patricia Troncoso ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lymph Node ◽  
Radical Prostatectomy ◽  
Cancer Center ◽  
Node Positive ◽  
Lymph Node Positive

1068: TP53 Gene Mutations as a Prognostic Marker for PSA Progression in Early Stage Prostate Cancer

2004 ◽  
Vol 171 (4S) ◽  
pp. 282-282
Author(s):  
Markus D. Sachs ◽  
Horst Schlechte ◽  
Katrin Schiemenz ◽  
Severin V. Lenk ◽  
Dietmar Schnorr ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prognostic Marker ◽  
Early Stage ◽  
Gene Mutations ◽  
Tp53 Gene ◽  
Psa Progression ◽  
Tp53 Gene Mutations

scholarly journals Differential Expression of a Panel of Ten CNTN1-Associated Genes during Prostate Cancer Progression and the Predictive Properties of the Panel towards Prostate Cancer Relapse

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 257
Author(s):  
Yan Gu ◽  
Mathilda Jing Chow ◽  
Anil Kapoor ◽  
Xiaozeng Lin ◽  
Wenjuan Mei ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Differential Expression ◽  
Cancer Progression ◽  
Lncap Cell ◽  
Endocrine Resistance ◽  
Gene Panel ◽  
The Cancer Genome Atlas ◽  
Cancer Center ◽  
Poor Overall Survival ◽  
Cell Renal Cell Carcinoma

Contactin 1 (CNTN1) is a new oncogenic protein of prostate cancer (PC); its impact on PC remains incompletely understood. We observed CNTN1 upregulation in LNCaP cell-derived castration-resistant PCs (CRPC) and CNTN1-mediated enhancement of LNCaP cell proliferation. CNTN1 overexpression in LNCaP cells resulted in enrichment of the CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_3 gene set that facilitates endocrine resistance in breast cancer. The leading-edge (LE) genes (n = 10) of this enrichment consist of four genes with limited knowledge on PC and six genes novel to PC. These LE genes display differential expression during PC initiation, metastatic progression, and CRPC development, and they predict PC relapse following curative therapies at hazard ratio (HR) 2.72, 95% confidence interval (CI) 1.96–3.77, and p = 1.77 × 10−9 in The Cancer Genome Atlas (TCGA) PanCancer cohort (n = 492) and HR 2.72, 95% CI 1.84–4.01, and p = 4.99 × 10−7 in Memorial Sloan Kettering Cancer Center (MSKCC) cohort (n = 140). The LE gene panel classifies high-, moderate-, and low-risk of PC relapse in both cohorts. Additionally, the gene panel robustly predicts poor overall survival in clear cell renal cell carcinoma (ccRCC, p = 1.13 × 10−11), consistent with ccRCC and PC both being urogenital cancers. Collectively, we report multiple CNTN1-related genes relevant to PC and their biomarker values in predicting PC relapse.

scholarly journals POS0548 OPTIMAL ASSESSMENT OF THE RHEUMATOID ARTHRITIS ANKLE AND HINDFOOT: A COMPARATIVE STUDY BETWEEN CLINICAL EXAMINATION AND ULTRASONOGRAPHY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 508.2-509
Author(s):  
K. Maatallah ◽  
H. Boussaa ◽  
H. Riahi ◽  
H. Ferjani ◽  
M. Habechi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Examination ◽  
Demographic Data ◽  
Power Doppler ◽  
Cross Sectional Study ◽  
P Value ◽  
Cross Sectional ◽  
Therapeutic Decisions ◽  
The Mean ◽  
Foot Disease

Background:Foot disease is a common problem in rheumatoid arthritis (RA). Therapeutic decisions are often based on clinical examination (CE) alone, which can be adversely affected by factors such as deformity, obesity, and peripheral edema. Ultrasonography (US) has previously been shown to be more sensitive than CE for detecting synovitis and tenosynovitis in RA forefeet, but few data exist for the hindfoot and ankle.Objectives:The aim of this study was to compare CE and US for the detection of hindfoot and ankle synovitis and tenosynovitis in patients with established RA.Methods:We conducted a cross-sectional study including patients with RA (ACR/EULAR 2010). Demographic data and disease parameters were collected. CE was performed by a rheumatologist for the presence or absence of tenderness, swelling, and mobility restriction of both ankles. The following tendons were examined for tenosynovitis: tibialis anterior (TA) and posterior (TP), fibularis longus (FL), and brevis (FB) (assessed together). In a second time, US examination of the tibiotalar, talonavicular, and subtalar joints and the same tendons as CE was performed by a blinded radiologist experienced in musculoskeletal imaging using a Philips HD11 device with a high-frequency linear transducer. The presence or absence of synovitis and tenosynovitis was recorded, and the composite synovitis score (power doppler / grayscale ultrasound (PDUS)) was measured for each joint. The US score of each patient was defined by the sum of the composite scores of the joints studied (0-30). A p-value <0.05 was considered significant.Results:Sixty-two feet were examined in 31 RA patients (25 women and six men) with a mean age of 54.8±10.8 years old [32-70]. The mean disease duration was 8.5±7.2 years [1-37]. Rheumatoid Factor (RF) and Anti-Citrullinated Peptides Antibodies (ACPA) were positive in 61.3% and 83.8% of cases. The mean DAS28 ESR was 3.8±1.5 [0.6-7].Clinical examination of ankles revealed tenderness in 57.4% of cases, swelling in 38.8% of cases, and restriction in the range of motion in 11.1% of cases. TA tenosynovitis was noted in 14.8% of cases, TP tenosynovitis in 22.2% of cases, and FL and FB tenosynovitis in 31.5% of cases.US showed tibiotalar synovitis in 59.3% of cases, talonavicular synovitis in 64.8% of cases, and subtalar synovitis in 46.3% of cases. TA tenosynovitis was noted in 5.6% of cases, TP tenosynovitis in 22.2% of cases, and FB and FL tenosynovitis in 25% and 11.1% of cases respectively.An association was found between clinical tenderness and US synovitis of the tibiotalar joint (p=0.013) and the talonavicular joint (p=0.027). No association was noted between clinical swelling and US synovitis in these joints.No association was noted between clinical and US tenosynovitis of TA (p=0.279), TP (p=0.436), FB (p=0.495) and FL (p=0.315).Conclusion:Clinical examination of RA ankles may be challenging and needs to be coupled with US, which is more sensitive and accurate in the detection of synovitis and tenosynovitis.Disclosure of Interests:None declared

scholarly journals Head-to-Head Comparison of Two Nomograms Predicting Probability of Lymph Node Invasion in Prostate Cancer and the Therapeutic Impact of Higher Nomogram Threshold

2021 ◽  
Vol 10 (5) ◽  
pp. 999
Author(s):  
Zilvinas Venclovas ◽  
Tim Muilwijk ◽  
Aivaras J. Matjosaitis ◽  
Mindaugas Jievaltas ◽  
Steven Joniau ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lymph Node ◽  
Area Under The Curve ◽  
Pelvic Lymph Node ◽  
Cancer Center ◽  
Study Cohort ◽  
Net Benefit ◽  
Characteristic Analysis ◽  
Therapeutic Impact ◽  
Mskcc Nomogram

Introduction: The aim of the study was to compare the performance of the 2012 Briganti and Memorial Sloan Kettering Cancer Center (MSKCC) nomograms as a predictor for pelvic lymph node invasion (LNI) in men who underwent radical prostatectomy (RP) with pelvic lymph node dissection (PLND), to examine their performance and to analyse the therapeutic impact of using 7% nomogram cut-off. Materials and Methods: The study cohort consisted of 807 men with clinically localised prostate cancer (PCa) who underwent open RP with PLND between 2001 and 2019. The area under the curve (AUC) of the receiver operator characteristic analysis was used to quantify the accuracy of the 2012 Briganti and MSKCC nomograms to predict LNI. Calibration plots were used to visualise over or underestimation by the models and a decision curve analysis (DCA) was performed to evaluate the net benefit associated with the used nomograms. Results: A total of 97 of 807 patients had LNI (12%). The AUC of 2012 Briganti and MSKCC nomogram was 80.6 and 79.2, respectively. For the Briganti nomogram using the cut-off value of 7% would lead to reduce PLND in 47% (379/807), while missing 3.96% (15/379) cases with LNI. For the MSKCC nomogram using the cut-off value of 7% a PLND would be omitted in 44.5% (359/807), while missing 3.62% (13/359) of cases with LNI. Conclusions: Both analysed nomograms demonstrated high accuracy for prediction of LNI. Using a 7% nomogram cut-off would allow the avoidance up to 47% of PLNDs, while missing less than 4% of patients with LNI.

scholarly journals Treatment of nonmetastatic castration-resistant prostate cancer: focus on second-generation androgen receptor inhibitors

2021 ◽  
Author(s):  
Fred Saad ◽  
Martin Bögemann ◽  
Kazuhiro Suzuki ◽  
Neal Shore
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Second Generation ◽  
Imaging Techniques ◽  
Specific Antigen ◽  
Conventional Imaging ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Therapeutic Decisions ◽  
Consensus Statements

Abstract Background Nonmetastatic castration-resistant prostate cancer (nmCRPC) is defined as a rising prostate-specific antigen concentration, despite castrate levels of testosterone with ongoing androgen-deprivation therapy or orchiectomy, and no detectable metastases by conventional imaging. Patients with nmCRPC progress to metastatic disease and are at risk of developing cancer-related symptoms and morbidity, eventually dying of their disease. While patients with nmCRPC are generally asymptomatic from their disease, they are often older and have chronic comorbidities that require long-term concomitant medication. Therefore, careful consideration of the benefit–risk profile of potential treatments is required. Methods In this review, we will discuss the rationale for early treatment of patients with nmCRPC to delay metastatic progression and prolong survival, as well as the factors influencing this treatment decision. We will focus on oral pharmacotherapy with the second-generation androgen receptor inhibitors, apalutamide, enzalutamide, and darolutamide, and the importance of balancing the clinical benefit they offer with potential adverse events and the consequential impact on quality of life, physical capacity, and cognitive function. Results and conclusions While the definition of nmCRPC is well established, the advent of next-generation imaging techniques capable of detecting hitherto undetectable oligometastatic disease in patients with nmCRPC has fostered debate on the criteria that inform the management of these patients. However, despite these developments, published consensus statements have maintained that the absence of metastases on conventional imaging suffices to guide such therapeutic decisions. In addition, the prolonged metastasis-free survival and recently reported positive overall survival outcomes of the three second-generation androgen receptor inhibitors have provided further evidence for the early use of these agents in patients with nmCRPC in order to delay metastases and prolong survival. Here, we discuss the benefit–risk profiles of apalutamide, enzalutamide, and darolutamide based on the data available from their pivotal clinical trials in patients with nmCRPC.

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