Estimating the Opportunity for Early Detection of Ovarian Cancer Using Individual-Patient Data from a Large Randomized Controlled Trial.

Background: The UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) did not detect a reduction in ovarian cancer (OC) mortality with either multimodal screening (MMS) or transvaginal ultrasound screening (USS) compared to no screening. The trial data provide an invaluable resource to quantify the opportunity for interception in OC.

Methods: We used Bayesian inference to estimate OC natural history based on individual screening and cancer diagnosis records from UKCTOCS, a randomized controlled OC screening trial conducted in England, Wales, and Northern Ireland.

Cancer outcomes in women without upfront surgery for ductal carcinoma in situ: observational cohort study.

Objective: To determine the risk of subsequent ipsilateral invasive breast cancer in women who do not receive upfront surgery on diagnosis of ductal carcinoma in situ (DCIS).

Design: Observational cohort study using data abstracted directly from patients' medical records and from a national cancer registry in patients with primary DCIS diagnosed between 2008 and 2015.

Setting: Commission on Cancer accredited facilities (n=1330) in the US.

Current Challenges in Imaging-Based Cancer Screening, From the Special Series on Screening.

The early detection of cancer confers many significant benefits for patients, primarily by enabling less invasive and more effective treatments and thus lowering disease mortality. Radiology is integral to early cancer detection, playing either a primary or complementary role in screening programs. Imaging-based screening is often performed in conjunction with other screening tests and may involve multiple modalities depending on patient demographics and cancer type.

Evolutionary measures show that recurrence of DCIS is distinct from progression to breast cancer.

Background: Progression from pre-cancers like ductal carcinoma in situ (DCIS) to invasive disease (cancer) is driven by somatic evolution and is altered by clinical interventions. We hypothesized that genetic and/or phenotypic intra-tumor heterogeneity would predict clinical outcomes for DCIS since it serves as the substrate for natural selection among cells.

Methods: We profiled two samples from two geographically distinct foci from each DCIS in both cross-sectional (n = 119) and longitudinal cohorts (n = 224), with whole exome sequencing, low-pass whole genome sequencing, and a panel of immunohistochemical markers.

Trends in young-onset cancer incidence: a modeling perspective.

Background: Recent increases in the diagnosis of certain cancers among younger individuals are generating intense concern. Many studies attribute the increase in the so-called "young-onset" cancer to an etiologic cause but questions have also arisen about the role of earlier diagnosis.

Methods: We simulated incidence trends from a natural history model that includes healthy, preclinical, and clinical disease states, where the transition from the healthy to the preclinical state represents disease onset and the transition from the preclinical to the clinical state represents diagnosis.

An updated understanding of the natural history of cervical human papillomavirus infection-clinical implications.

Recently, the International Papillomavirus Society convened a working group on cervical human papillomavirus latency, which resulted in an updated understanding of the human papillomavirus natural history. While the previous human papillomavirus natural history model considered human papillomavirus detection to be a result of human papillomavirus acquisition or possibly reinfection, and loss of human papillomavirus detection to be a result of viral clearance, the updated understanding of the human papillomavirus natural history is more nuanced. Thus, human papillomavirus detection may occur as a result of autoinoculation, deposition from a recent sex act, or as a redetection of a previously acquired infection.

Active Monitoring With or Without Endocrine Therapy for Low-Risk Ductal Carcinoma In Situ: The COMET Randomized Clinical Trial.

Importance: Active monitoring for low-risk ductal carcinoma in situ (DCIS) of the breast has been proposed as an alternative to guideline-concordant care, but the safety of this approach is unknown.

Objective: To compare rates of invasive cancer in patients with low-risk DCIS receiving active monitoring vs guideline-concordant care.

Design, Setting, And Participants: Prospective, randomized noninferiority trial enrolling 995 women aged 40 years or older with a new diagnosis of hormone receptor-positive grade 1 or grade 2 DCIS without invasive cancer at 100 US Alliance Cancer Cooperative Group clinical trial sites from 2017 to 2023.

Impact of an online decision support tool for ductal carcinoma in situ (DCIS) using a pre-post design (AFT-25).

Background: The heterogeneous biology of ductal carcinoma in situ (DCIS), as well as the variable outcomes, in the setting of numerous treatment options have led to prognostic uncertainty. Consequently, making treatment decisions is challenging and necessitates involved communication between patient and provider about the risks and benefits. We developed and investigated an interactive decision support tool (DST) designed to improve communication of treatment options and related long-term risks for individuals diagnosed with DCIS.

Evolutionary Measures Show that Recurrence of DCIS is Distinct from Progression to Breast Cancer.

Progression from pre-cancers like ductal carcinoma (DCIS) to invasive disease (cancer) is driven by somatic evolution and is altered by clinical interventions. We hypothesized that genetic and/or phenotypic intra-tumor heterogeneity would predict clinical outcomes for DCIS since it serves as the substrate for natural selection among cells. We profiled two samples from two geographically distinct foci from each DCIS in both cross-sectional (N = 119) and longitudinal cohorts (N = 224), with whole exome sequencing, low-pass whole genome sequencing, and a panel of immunohistochemical markers.

Association of DCIS size and margin status with risk of developing breast cancer post-treatment: multinational, pooled cohort study.

Objective: To examine the association between size and margin status of ductal carcinoma in situ (DCIS) and risk of developing ipsilateral invasive breast cancer and ipsilateral DCIS after treatment, and stage and subtype of ipsilateral invasive breast cancer.

Design: Multinational, pooled cohort study.

Setting: Four large international cohorts.

Growth Dynamics of Ductal Carcinoma in Situ Recapitulate Normal Breast Development.

Ductal carcinoma in situ (DCIS) and invasive breast cancer share many morphologic, proteomic, and genomic alterations. Yet in contrast to invasive cancer, many DCIS tumors do not progress and may remain indolent over decades. To better understand the heterogenous nature of this disease, we reconstructed the growth dynamics of 18 DCIS tumors based on the geo-spatial distribution of their somatic mutations.

Test sensitivity in a prospective cancer screening program: A critique of a common proxy measure.

The true sensitivity of a cancer screening test, defined as the frequency with which the test returns a positive result if the cancer is present, is a key indicator of diagnostic performance. Given the challenges of directly assessing test sensitivity in a prospective screening program, proxy measures for true sensitivity are frequently reported. We call one such proxy empirical sensitivity, as it is given by the observed ratio of screen-detected cancers to the sum of screen-detected and interval cancers.

Estimation of Breast Cancer Overdiagnosis in a U.S. Breast Screening Cohort.

Background: Mammography screening can lead to overdiagnosis-that is, screen-detected breast cancer that would not have caused symptoms or signs in the remaining lifetime. There is no consensus about the frequency of breast cancer overdiagnosis.

Objective: To estimate the rate of breast cancer overdiagnosis in contemporary mammography practice accounting for the detection of nonprogressive cancer.

A web-based personalized decision support tool for patients diagnosed with ductal carcinoma in situ: development, content evaluation, and usability testing.

Purpose: Patients diagnosed with ductal carcinoma in situ (DCIS) face trade-offs when deciding among different treatments, including surgery, radiation, and endocrine therapy. A less chosen option is active monitoring. While evidence from clinical trials is not yet available, observational studies show comparable results for active monitoring and immediate treatment on cancer outcomes in select subgroups of patients.

Ductal Carcinoma in Situ: State-of-the-Art Review.

Ductal carcinoma in situ (DCIS) is a nonobligate precursor of invasive cancer, and its detection, diagnosis, and management are controversial. DCIS incidence grew with the expansion of screening mammography programs in the 1980s and 1990s, and DCIS is viewed as a major driver of overdiagnosis and overtreatment. For pathologists, the diagnosis and classification of DCIS is challenging due to undersampling and interobserver variability.

A Bayesian hierarchical model to estimate DNA methylation conservation in colorectal tumors.

Motivation: Conservation is broadly used to identify biologically important (epi)genomic regions. In the case of tumor growth, preferential conservation of DNA methylation can be used to identify areas of particular functional importance to the tumor. However, reliable assessment of methylation conservation based on multiple tissue samples per patient requires the decomposition of methylation variation at multiple levels.

Long-term risk of subsequent ipsilateral lesions after surgery with or without radiotherapy for ductal carcinoma in situ of the breast.

Background: Radiotherapy (RT) following breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) reduces ipsilateral breast event rates in clinical trials. This study assessed the impact of DCIS treatment on a 20-year risk of ipsilateral DCIS (iDCIS) and ipsilateral invasive breast cancer (iIBC) in a population-based cohort.

Methods: The cohort comprised all women diagnosed with DCIS in the Netherlands during 1989-2004 with follow-up until 2017.

Relationship Between HCAHPS Scores and Survey Response Rate Is Linked to Hospital Size.

Patient experience is an important dimension of health care quality and is assessed using the standard Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey for inpatients. The HCAHPS scores may vary based on survey response rate and hospital size. The objective of this study was to describe the association between survey response rate and HCAHPS scores and examine whether the relationship varies based on hospital size.

Association of Combined Sero-Positivity to and with Risk of Colorectal Cancer.

Previously, we found that risk of colorectal cancer (CRC) is increased in individuals with serum antibody response to both (HP) Vacuolating Cytotoxin (VacA) toxin or (SGG) pilus protein Gallo2178. In the present analysis, we tested the hypothesis that combined seropositivity to both antigens is a better indicator of CRC risk than seropositivity to single antigens. We used multiplex serologic assays to analyze pre-diagnostic serum for antibody responses from 4063 incident CRC cases and 4063 matched controls from 10 US cohorts.

Auto-antibodies to p53 and the Subsequent Development of Colorectal Cancer in a U.S. Prospective Cohort Consortium.

Background: Auto-antibodies to tumor suppressor p53 are found in a subset of patients with colorectal cancer. A recent prospective study in the United States has reported a significant 1.8-fold increased odds for colorectal cancer development with prediagnostic seropositivity to p53.