scholarly journals Predicting Advanced Prostate Cancer from Modeling Early Indications in Biopsy and Prostatectomy Samples via Transductive Semi-Supervised Survival Analysis

2018 ◽  
Vol 2018 ◽  
pp. 1-12
Author(s):  
Faisal M. Khan
Keyword(s):  
Prostate Cancer ◽  
Survival Analysis ◽  
Cancer Progression ◽  
Advanced Prostate Cancer ◽  
Complex Disease ◽  
Treatment Plan ◽  
The United States ◽  
Censored Samples ◽  
Psa Recurrence ◽  
Regression Techniques

Prostate cancer is the most prevalent form of cancer and the second most common cause of cancer deaths among men in the United States. Accurate prognosis is important as it is the principal factor in determining the treatment plan. Prostate cancer is a complex disease which advances in stages. While clinical failure (including metastasis) is a significant endpoint following a radical prostatectomy, it can often take years to manifest, usually too late to be optimistically treated. In practice, the earlier endpoint of PSA Recurrence is frequently used as a surrogate in prognostic modeling. The central issue in these models is managing censored observations which challenge traditional regression techniques. The true target times of a majority of instances are unknown; what is known is a censored target representing some earlier indeterminate time. In this work we apply a novel transduction approach for semi-supervised survival analysis which has previously been shown to be powerful in medical prognosis. The approach considers censored samples as semi-supervised regression targets leveraging the partial nature of unsupervised information. We explore the use of this approach in building prostate cancer progression models from multimodal characteristics extracted from both biopsy and prostatectomy tissues samples. In this work, the approach leads to a significant increase in performance for predicting advanced prostate cancer from earlier endpoints and may also be useful in other diseases for predicting advanced endpoints from earlier stages of the disease.

scholarly journals Making Sense of a Complex Disease: A Practical Approach to Managing Neuroendocrine Tumors

2021 ◽  
Author(s):  
Janie Y. Zhang ◽  
Pamela L. Kunz
Keyword(s):  
Functional Status ◽  
Neuroendocrine Tumors ◽  
Complex Disease ◽  
Treatment Plan ◽  
Performance Status ◽  
Somatostatin Receptor ◽  
The United States ◽  
Making Sense ◽  
Pathologic Classification ◽  
Therapeutic Decision Making

Neuroendocrine tumors (NETs) are a heterogeneous clinical entity with a broad range of grade, pace of disease, functional status, and primary sites. Pathologic classification, diagnostic modalities, and therapeutic options for NETs have evolved considerably in the past decade. In part driven by these advances, incidence and prevalence of NETs are rising in the United States and the practicing oncologist is likely to encounter these in the clinic. However, there are no clear lines of therapy for unresectable or metastatic NETs, and sequencing of systemic therapies depends on consideration of patient and tumor characteristics including extent of disease, grade, pace of growth, functional status, primary site, somatostatin receptor status, performance status, and comorbidities. Familiarity with ongoing clinical trials will guide therapeutic decision making as well. In this review, we seek to provide a framework to formulate and tailor an individualized treatment plan for each patient with a NET.

scholarly journals In vitro engineering of a bone metastases model allows for study of the effects of antiandrogen therapies in advanced prostate cancer

2021 ◽  
Vol 7 (27) ◽  
pp. eabg2564
Author(s):  
Nathalie Bock ◽  
Thomas Kryza ◽  
Ali Shokoohmand ◽  
Joan Röhl ◽  
Akhilandeshwari Ravichandran ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Advanced Prostate Cancer ◽  
Adaptive Responses ◽  
Metastatic Tissue ◽  
Metastatic Lesions ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

While androgen-targeted therapies are routinely used in advanced prostate cancer (PCa), their effect is poorly understood in treating bone metastatic lesions and ultimately results in the development of metastatic castrate resistant prostate cancer (mCRPC). Here, we used an all-human microtissue-engineered model of mineralized metastatic tissue combining human osteoprogenitor cells, 3D printing and prostate cancer cells, to assess the effects of the antiandrogens, bicalutamide, and enzalutamide in this microenvironment. We demonstrate that cancer/bone stroma interactions and antiandrogens drive cancer progression in a mineralized microenvironment. Probing the bone microenvironment with enzalutamide led to stronger cancer cell adaptive responses and osteomimicry than bicalutamide. Enzalutamide presented with better treatment response, in line with enzalutamide delaying time to bone-related events and enzalutamide extending survival in mCRPC. The all-human microtissue-engineered model of mineralized metastatic tissue presented here represents a substantial advance to dissect the role of the bone tumor microenvironment and responses to therapies for mCPRC.

MP78-17 FACTORS ASSOCIATED WITH INITIAL THERAPY FOR REGIONALLY ADVANCED PROSTATE CANCER IN THE UNITED STATES

2014 ◽  
Vol 191 (4S) ◽  
Author(s):  
Thomas Jang ◽  
Neal Patel ◽  
Shunhua Shen ◽  
Michael Karellas ◽  
Robert DiPaola ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
United States ◽  
Advanced Prostate Cancer ◽  
The United States ◽  
Initial Therapy ◽  
Factors Associated

Variation in UDP glucouronyltransferase (UGT) genes associated with prostate cancer mortality.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 44-44
Author(s):  
M. Kohli ◽  
D. W. Mahoney ◽  
H. S. Chai ◽  
D. W. Hillman ◽  
D. R. Rider ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Advanced Prostate Cancer ◽  
Cox Regression ◽  
Prostate Cancer Progression ◽  
Androgen Ablation ◽  
Principle Components Analysis ◽  
Specific Mortality ◽  
Cancer Specific Mortality

44 Background: We investigated the association of germline genetic variation in hormone biosynthesis and metabolism genes with prostate cancer specific mortality in a cohort of advanced prostate cancer patients. Methods: We successfully genotyped 852 single nucleotide polymorphisms (SNPs) from 97 genes in a cohort of 267 advanced prostate cancer patients at the time of progression to castration recurrence (CRPC) during on-going androgen ablation. Tagging SNPs with minor allele frequency (MAF) of >5% and r2 ≥0.8 were selected from HapMap, NIEHS and Seattle SNP databases. Medical records were queried for cause of death. The primary endpoint of time to prostate cancer specific mortality (PCSM), was pre-defined as time from development of CRPC to death from prostate cancer progression. Principle components analysis was used for gene-levels tests, and to account for multiple testing, we calculated the false discovery rate (FDR). For SNP level results, hazard ratios (HR) and 95% confidence intervals (CI) were estimated using cox regression. Results: The median age of the cohort was 72 years at CRPC. 43% had a Gleason score (GS)=8-10, 33% a GS=7, and 24% a GS<7. After a median follow-up of 1.8 years (IQ range: 0.8–3.3 years), 139 patients died, of which 107 were due to prostate cancer progression. In unadjusted gene level analyses, UGT1A7 (p=0.0059; FDR=0.19), UGT1A10 (p=0.0017; FDR=0.17) and UGT1A3 (p=0.0037; FDR=0.18) were associated with PCSM. After adjusting for age and GS, SNPs strongly associated with PCSM are listed in the Table . Conclusions: Variation in UGT genes involved in hormone metabolism yield prognostic information in CRPC. Further validation is needed to develop these as prognostic biomarkers. [Table: see text] No significant financial relationships to disclose.

Prevalence of pathogenic germline variants in DNA repair by race, age, and ethnicity in men with prostate cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5062-5062
Author(s):  
Alexandria Mara ◽  
Jason Zhu ◽  
Yuan Wu ◽  
Tom Callis ◽  
Shan Yang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Family History ◽  
Advanced Prostate Cancer ◽  
Final Analysis ◽  
The United States ◽  
National Study ◽  
Germline Variants ◽  
Variant Of Uncertain Significance ◽  
Race Ethnicity ◽  
Germline Testing

5062 Background: Patients with advanced prostate cancer (PC) frequently harbor pathogenic or likely pathogenic (P/LP) germline variants (GVs) in mismatch repair (MMR) and homologous repair (HR) enzymes which have clinical and treatment implications. However, whether the prevalence of such GVs differ by race, ethnicity, family history, or age is unknown in men with PC. Methods: This is a retrospective analysis of germline DNA from men with PC in the United States, tested by Invitae. Baseline characteristics including self-identified race, ethnicity, family history (FH), and age were recorded. Race and ethnicity were analyzed by 3 cohorts: non-Ashkenazi Caucasian Americans (CA), non-Ashkenazi African Americans (AA), and Ashkenazi Jewish Americans (AJ). Chi-square testing was performed to identify significant differences across these categories between the three cohorts, with respect to combined and individual pathogenic MMR (MSH2/6, MLH1, PMS2, and MUTYH) and HR genes (BRCA1/2, ATM, CHEK2, RAD51D, and PALB2). Results: 3057 men were included in the final analysis: 2248 (74%) men were CA, 229 (7%) were AA, and 210 (7%) were AJ. Of these, 2665 (87%) men had a FH of PC and 463 (15%) had a P/LP GV. In addition, 1068 (35%) were found to have a variant of uncertain significance, and 35 (1.6%) had the HOXB13 G84E variant. There were no significant differences in the overall prevalence of MMR (CA 1.5% vs AA 0.9% vs AJ 1.4%, p = 0.89) or HR genes (CA 7.8% vs AA 7.9% vs AJ 10.5%, p = 0.37) by race/ethnicity. With respect to individual genes, AJ had a higher prevalence of pathogenic BRCA1 alterations (AJ 3.3% vs CA 0.8% vs AA 1.7%, p = 0.0034) and CHEK2 alterations (AJ 4.3% vs CA 2.8% vs AA 0.4%, p = 0.02). There were no significant differences in the prevalence of individual or specific classes of GVs between those with or without a self-reported FH of prostate or breast/ovarian cancers. There was also no association between prevalence of HR genes and age at germline testing (p = 0.40). Conclusions: This national study found that the overall prevalence of pathogenic GVs in MMR and HR genes do not differ by race, ethnicity, or age at the time of testing, and suggests that all men with advanced prostate cancer should be offered germline testing.

MP14-15 INCREASE IN THE INCIDENCE OF ADVANCED PROSTATE CANCER IN THE UNITED STATES

2017 ◽  
Vol 197 (4S) ◽  
Author(s):  
Jonathan Shoag ◽  
Art Sedrakyan ◽  
Joshua Halpern ◽  
Wei-Chun Hsu ◽  
Jim Hu
Keyword(s):  
Prostate Cancer ◽  
United States ◽  
Advanced Prostate Cancer ◽  
The United States

scholarly journals Redefining Hormone Sensitive Disease in Advanced Prostate Cancer

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Xiaoyu Hou ◽  
Thomas W. Flaig
Keyword(s):  
Prostate Cancer ◽  
Hormonal Therapy ◽  
Advanced Prostate Cancer ◽  
The United States ◽  
Castration Resistant ◽  
Hormonal Resistance ◽  
Hormone Sensitive ◽  
Hormone Resistant Prostate Cancer ◽  
Term Management

Prostate cancer is the most common cancer among men in the United States. For decades, the cornerstone of medical treatment for advanced prostate cancer has been hormonal therapy, intended to lower testosterone levels, known as Androgen Deprivation Therapy (ADT). The development of hormone-resistant prostate cancer (now termed castration-resistant prostate cancer:CRPC) remains the key roadblock in successful long-term management of prostate cancer. New advancements in medical therapy for prostate cancer have added to the hormonal therapy armamentarium. These new therapeutic agents not only provide a survival benefit but also show potential for reversing hormonal resistance in metastatic CRPC, and thus redefining hormonally sensitive disease.

scholarly journals Early national dissemination of abiraterone and enzalutamide for advanced prostate cancer in Medicare Part D.

2017 ◽  
Vol 35 (8_suppl) ◽  
pp. 35-35
Author(s):  
Megan Veresh Caram ◽  
Tudor Borza ◽  
Hye-Sung Min ◽  
Jennifer J. Griggs ◽  
David Christopher Miller ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
United States ◽  
Regional Variation ◽  
Advanced Prostate Cancer ◽  
Medicare Part D ◽  
The United States ◽  
Medicare Part ◽  
Part D ◽  
Hospital Referral ◽  
Early National

35 Background: Abiraterone and enzalutamide are oral medications approved by the Food & Drug Administration in 2011 and 2012 to treat men with advanced castration-resistant prostate cancer. Most men with advanced prostate cancer are over age 65 and thus eligible for Medicare Part D. We conducted a study to better understand the early dissemination of these drugs across the United States using national Medicare Part D data. Methods: We evaluated the number of prescriptions for abiraterone and enzalutamide by provider specialty and hospital referral region (HRR) using Medicare Part D and Dartmouth Atlas data. We categorized HRRs by abiraterone and enzalutamide prescriptions, adjusted for prostate cancer incidence, and examined factors associated with regional variation using multilevel regression models. Results: Among all providers who wrote prescriptions for abiraterone or enzalutamide in 2013 (n=2121), 87.5% were medical oncologists, 3.3% urologists, and 9.2% were listed as other provider specialties. Among those who prescribed either drug, 5% of providers were responsible for 75% of the claims for abiraterone, and 7% were responsible for 75% of the claims for enzalutamide. Some HRRs demonstrated low-prescribing rates despite average medical oncology and urology physician workforce density. Conclusions: The majority of prescriptions written for abiraterone and enzalutamide through Medicare Part D in 2013 were written by a minority of providers with marked regional variation across the United States. Better understanding the early national dissemination of these effective but expensive drugs can help inform strategies to optimize introduction of new, evidence-based advanced prostate cancer treatments.

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