Objective: Germline pathogenic variants (PVs) are known to cause ~4% of prostate cancer, but other homologous repair genes, and Lynch syndrome genes are also involved. Our objective was to assess the contribution of germline and somatic gene variants to prostate cancer.
Methods And Analysis: We reviewed germline/tumour DNA testing from 450 localised or metastatic prostate cancer cases in NW England mainly from 2022 to 2024.
Prostate cancer is characterized by profound heterogeneity in its clinical trajectory. While genomic heterogeneity has been well-characterized, epigenomic heterogeneity remains less understood. To fill this gap, we compiled 2,149 multi-ancestric prostate methylomes spanning normal tissue through localized disease of varying grades to poly-metastatic disease, most with multi-omic DNA and/or RNA characterization.
View Article and Find Full Text PDFNewly diagnosed prostate cancers differ dramatically in mutational composition and lethality. The most accurate clinical predictor of lethality is tumor tissue architecture, quantified as tumor grade. To interrogate the evolutionary origins of prostate cancer heterogeneity, we analyzed 666 prostate tumor whole genomes.
View Article and Find Full Text PDFObjective: To assess pathological characteristics, clinical features and outcomes of patients diagnosed with peripheral zone (PZ) and transition zone (TZ) prostate cancer after prostatectomy.
Methods And Analysis: We systematically reviewed PubMed, EMBASE and MEDLINE. Primary endpoints were biochemical relapse-free survival (bRFS) and distant metastases rate; secondary endpoints included clinical and pathological features.
Objective: The aim of this study was to examine disparities in 20-year incidence trends and mutations in advanced-stage uterine cancer in the United States, given poor survival rates.
Methods: Data were obtained from the United States Cancer Statistics for patients from 2001 to 2019 with International Federation of Gynecology and Obstetrics 2009 stage IVA and IVB uterine cancer. SEER∗Stat 8.
Intratumour hypoxia is a feature of all heterogenous solid tumours. Increased levels or subregions of tumour hypoxia are associated with an adverse clinical prognosis, particularly when this co-occurs with genomic instability. Experimental evidence points to the acquisition of DNA and chromosomal alterations in proliferating hypoxic cells secondary to inhibition of DNA repair pathways such as homologous recombination, base excision repair and mismatch repair.
View Article and Find Full Text PDFObjective: To evaluate the correlation in temporal trends in obesity and endometrioid endometrial cancer incidence in the United States using two comprehensive national databases.
Methods: This is a cohort study in which data on endometrioid endometrial cancer were obtained from the U.S.
This article addresses the role of surgery in the management of gynecologic cancers with liver metastases. The authors review the short-term and long-term outcomes of aggressive resection through retrospective and randomized studies. Although the data supporting aggressive resection of liver metastasis are largely retrospective and case based, the randomized control data to address neoadjuvant versus chemotherapy have been widely criticized.
View Article and Find Full Text PDFBackground: Current treatment strategies for primary epithelial ovarian cancer (EOC) have significantly evolved, and the value of complete cytoreduction has not yet been reassessed. The study aimed to investigate the impact of residual disease after cytoreductive surgery for EOC on survival outcomes within the recent paradigm of frontline ovarian cancer treatment.
Methods: We searched relevant literature from the MEDLINE, Embase, and Cochrane Library databases to identify randomized controlled trials and prospective clinical trials of primary EOC published between 1 January 2000 and 22 September 2022.
Purpose: Men with high-risk prostate cancer (PCa) are treated with androgen deprivation therapy (ADT) and radiation therapy, but the disease reoccurs in 30% of patients. Biochemical recurrence of PCa after treatment is influenced by tumor hypoxia. Tumors with high levels of hypoxia are aggressive, resistant to treatment, and have increased metastatic capacity.
View Article and Find Full Text PDFTo ensure timely duplication of the entire eukaryotic genome, thousands of replication machineries (replisomes) act on genomic DNA at any time during S phase. In the final stages of this process, replisomes are unloaded from chromatin. Unloading is driven by polyubiquitylation of MCM7, a subunit of the terminated replicative helicase, and processed by p97/VCP segregase.
View Article and Find Full Text PDFEndometrial cancer is one of few cancers that has continued to rise in incidence over the past decade, with disproportionate increases in adults younger than 50 years old. We used data from the Surveillance, Epidemiology, and End Results Registry (2000-2019) to examine endometrial cancer incidence trends by race/ethnicity and age of onset among women in the United States. Case counts and proportions, age-adjusted incidence rates (per 100 000), and average annual percent changes were calculated by race/ethnicity, overall and stratified by age of onset (early vs late).
View Article and Find Full Text PDFThis is a protocol for a Cochrane Review (intervention). The objectives are as follows: To evaluate the benefits and harms of secondary CRS and chemotherapy in comparison to chemotherapy alone for women with platinum-sensitive recurrent epithelial ovarian cancer.
View Article and Find Full Text PDFMotivation: Few methods exist for timing individual amplification events in regions of focal amplification. Current methods are also limited in the copy number states that they are able to time. Here we introduce AmplificationTimeR, a method for timing higher level copy number gains and inferring the most parsimonious order of events for regions that have undergone both single gains and whole genome duplication.
View Article and Find Full Text PDFSurgical decision making is complex and involves a combination of analytic, intuitive, and cognitive processes. Medicolegal, infrastructural, and financial factors may influence these processes depending on the context and setting, but to what extent can they influence surgical decision making in gynecologic oncology? This scoping review evaluates existing literature related to medicolegal, infrastructural, and financial aspects of gynecologic cancer surgery and their implications in surgical decision making. Our objective was to summarize the findings and limitations of published research, identify gaps in the literature, and make recommendations for future research to inform policy.
View Article and Find Full Text PDFThe development of cancer is an evolutionary process involving the sequential acquisition of genetic alterations that disrupt normal biological processes, enabling tumor cells to rapidly proliferate and eventually invade and metastasize to other tissues. We investigated the genomic evolution of prostate cancer through the application of three separate classification methods, each designed to investigate a different aspect of tumor evolution. Integrating the results revealed the existence of two distinct types of prostate cancer that arise from divergent evolutionary trajectories, designated as the Canonical and Alternative evolutionary disease types.
View Article and Find Full Text PDFObjective: To quantify the impact on short-term ovarian cancer survival associated with treatment at high-performing hospitals using the observed-to-expected ratio (O/E) for adherence to ovarian cancer treatment guidelines as a risk-adjusted measure of hospital quality care.
Methods: This was a retrospective population-based study of stage I-IV invasive epithelial ovarian cancer reported to California Cancer Registry 1996-2017. A fit logistic regression model, risk-adjusted for patient and disease characteristics, was used to calculate O/E for each hospital stratified by hospital annual case volume.
Purpose: To evaluate the relative effect of percent maximal cytoreductive surgery and other prognostic variables on survival among cohorts of patients with advanced-stage ovarian carcinoma treated with platinum-based chemotherapy.
Materials And Methods: Eighty-one cohorts of patients with stage III or IV ovarian carcinoma (6,885 patients) were identified from articles in MEDLINE (1989 through 1998). Linear regression models, with weighted correlation calculations, were used to assess the effects on log median survival time of the proportion of each cohort undergoing maximal cytoreduction, dose-intensity of the platinum compound administered, proportion of patients with stage IV disease, median age, and year of publication.
Background: Primary vaginal cancer is rare and comprises 1-2% of female genital tract cancers. Among the types of vaginal cancer, adenocarcinoma accounts for only 10% with the peak incidence in women less than 20 years old. Clear cell type vaginal adenocarcinoma is most associated with exposure to diethylstilbestrol (DES) in-utero.
View Article and Find Full Text PDFPurpose: We analyzed adherence to the National Comprehensive Cancer Network treatment guidelines for anal squamous cell carcinoma in California and the associated impacts on survival.
Methods: This was a retrospective study of patients in the California Cancer Registry aged 18 to 79 years with recent diagnoses of anal squamous cell carcinoma. Predefined criteria were used to determine adherence.