Outcomes Following a False-Positive Multi-Cancer Early Detection Test: Results from DETECT-A, the First Large, Prospective, Interventional MCED Study.

Guideline recommended standard of care screening is available for four cancer types; most cancer-related deaths are caused by cancers without standard of care screening. DETECT-A is the first prospective interventional trial evaluating a multi-cancer early detection (MCED) blood test (CancerSEEK) in women without a history of cancer, providing the first opportunity to assess the long-term outcomes of individuals with false-positive (FP) MCED results. This prospective analysis of DETECT-A participants with FP results evaluates the performance of an imaging-based diagnostic workflow and examines cancer risk following a FP result.

Multiyear Clinical Outcomes of Cancers Diagnosed Following Detection by a Blood-Based Multicancer Early Detection Test.

In the US, <20% of cancers are diagnosed by standard-of-care (SoC) screening. Multicancer early detection (MCED) tests offer the opportunity to expand cancer screening. Understanding the characteristics and clinical outcomes of MCED-detected cancers is critical to clarifying MCED tests' potential impact.

External validation of a multi-biomarker-based score for predicting risk of cardiovascular disease in patients with rheumatoid arthritis.

Background: A multi-biomarker disease activity (MBDA)-based cardiovascular disease (CVD) risk score was developed and internally validated in a Medicare cohort to predict 3-year risk for myocardial infarction (MI), stroke or CVD death in patients with rheumatoid arthritis (RA). It combines the MBDA score, leptin, MMP-3, TNF-R1, age and four clinical variables. We are now externally validating it in a younger RA cohort.

Outcomes following a false positive multi-cancer early detection (MCED) test: Results from DETECT-A, the first large, prospective, interventional MCED study.

Guideline recommended standard of care (SoC) screening is available for four cancer types; most cancer-related deaths are caused by cancers without SoC screening. DETECT-A is the first prospective interventional trial evaluating an MCED blood test (CancerSEEK) in women without a history of cancer, providing the first opportunity to assess the long-term outcomes of individuals with false positive (FP) MCED results. This prospective analysis of DETECT-A participants with FP results evaluates the performance of an imaging-based diagnostic workflow and examines cancer risk following a FP result.

Development and validation of a cell cycle progression signature for decentralized testing of men with prostate cancer.

The 46-gene Prolaris cell cycle progression test provides information on the risk of prostate cancer progression. Here we developed and validated a 16-gene kit-based version. RNA was extracted from prostate cancer biopsy tissue.

Hereditary cancer risk assessment and genetic testing in the community urology practice setting.

Objectives: To evaluate the feasibility of integrating a hereditary cancer risk assessment (HCRA) process in the community urology practice setting for patients with prostate cancer (PCa).

Methods: In this prospective intervention, an HCRA process was implemented across six different community urology clinics between May 2019 and April 2020. The intervention included a process integration during which the workflow at each site was refined, a post-integration period during which HCRA was conducted in all patients with PCa, and a follow-up period during which healthcare providers and patients reported their satisfaction with the HCRA and genetic testing process.

The Clinical Cell-Cycle Risk (CCR) Score Is Associated With Metastasis After Radiation Therapy and Provides Guidance on When to Forgo Combined Androgen Deprivation Therapy With Dose-Escalated Radiation.

Purpose: The clinical cell-cycle risk (CCR) score, which combines the University of California, San Francisco's Cancer of the Prostate Risk Assessment (CAPRA) and the cell cycle progression (CCP) molecular score, has been validated to be prognostic of disease progression for men with prostate cancer. This study evaluated the ability of the CCR score to prognosticate the risk of metastasis in men receiving dose-escalated radiation therapy (RT) with or without androgen deprivation therapy (ADT).

Methods And Materials: This retrospective, multi-institutional cohort study included men with localized National Comprehensive Cancer Network (NCCN) intermediate-, high-, and very high-risk prostate cancer (N = 741).

Validation of the cell cycle progression score to differentiate indolent from aggressive prostate cancer in men diagnosed through transurethral resection of the prostate biopsy.

Background: Validation of biomarker-based prognostic models to improve risk stratification in men with localized prostate cancer (PrCa) remains a clinical need. It has previously been shown that the cell cycle progression (CCP) test provides significant, independent prognostic information for men who were incidentally diagnosed with PrCa after transurethral resection of the prostate (TURP) and were conservatively managed.

Aim: The results have been extended in a newly analyzed retrospective cohort of UK men diagnosed through TURP biopsy (TURP1B; N = 305).

Personalizing Localized Prostate Cancer: Validation of a Combined Clinical Cell-cycle Risk (CCR) Score Threshold for Prognosticating Benefit From Multimodality Therapy.

Introduction: The combined clinical cell-cycle risk (CCR) score is a validated model that combines the cell-cycle progression (CCP) score with the University of California San Francisco Cancer of the Prostate Risk Assessment (CAPRA) score. This score determines the risk of progressive disease for men with prostate cancer. Here, we further validate the prognostic ability of the CCR score and evaluate its ability to help determine which patients may safely forgo multimodality therapy.

Validation of the adjusted multi-biomarker disease activity score as a prognostic test for radiographic progression in rheumatoid arthritis: a combined analysis of multiple studies.

Background: The multi-biomarker disease activity (MBDA) test measures 12 serum protein biomarkers to quantify disease activity in RA patients. A newer version of the MBDA score, adjusted for age, sex, and adiposity, has been validated in two cohorts (OPERA and BRASS) for predicting risk for radiographic progression. We now extend these findings with additional cohorts to further validate the adjusted MBDA score as a predictor of radiographic progression risk and compare its performance with that of other risk factors.

Derivation and internal validation of a multi-biomarker-based cardiovascular disease risk prediction score for rheumatoid arthritis patients.

Background: Rheumatoid arthritis (RA) patients have increased risk for cardiovascular disease (CVD). Accurate CVD risk prediction could improve care for RA patients. Our goal is to develop and validate a biomarker-based model for predicting CVD risk in RA patients.

Prognostic capabilities and clinical utility of cell cycle progression testing, prostate imaging reporting and data system, version 2, and clinicopathologic data in management of localized prostate cancer.

Objectives: To compare the prognostic capabilities and clinical utility of the cell cycle progression (CCP) gene expression classifier test, multiparametric magnetic resonance imaging (mpMRI) with Prostate Imaging Reporting and Data System (PI-RADS) scoring, and clinicopathologic data in select prostate cancer (PCa) medical management scenarios.

Patients And Methods: Retrospective, observational analysis of patients (N = 222) ascertained sequentially from a single urology practice from January 2015 to June 2018. Men were included if they had localized PCa, a CCP score, and an mpMRI PI-RADS v2 score.

Evaluation of the impact of age and adiposity on a multi-biomarker disease activity score before and after adjustment.

Purpose: We assessed the impact of adjustment of the multi-biomarker disease activity score (MBDA) for age, sex, and leptin, over the range of age and adiposity, and assessed relationships with clinical disease activity.

Methods: Patients with RA, ages 18-75 years, were recruited from clinical practices and completed whole-body DXA to quantify fat mass indices (FMI, kg/m). FMI Z-scores were calculated based on distributions in a reference population.

Predicting Expected Absolute Chemotherapy Treatment Benefit in Women With Early-Stage Breast Cancer Using EndoPredict, an Integrated 12-Gene Clinicomolecular Assay.

Purpose: Previous studies have shown EndoPredict (EPclin), a test that integrates 12-gene expression data with nodal status and tumor size, to be predictive for risk of distant recurrence in women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative early-stage breast cancer. Here, we modeled expected absolute chemotherapy benefit on the basis of EPclin test results.

Methods: The effect of chemotherapy was modeled using previously validated 10-year risk of distant recurrence as a function of EPclin score for patients treated without chemotherapy.

Evaluation of the 12-Gene Molecular Score and the 21-Gene Recurrence Score as Predictors of Response to Neo-adjuvant Chemotherapy in Estrogen Receptor-Positive, HER2-Negative Breast Cancer.

Background: Neo-adjuvant chemotherapy (NaCT) facilitates complete surgical resection in locally advanced breast cancer. Due to its association with improved outcome, complete pathologic response (pCR) to neo-adjuvant treatment has been accepted as a surrogate for long-term outcome in clinical trials of human epidermal growth factor receptor 2 (HER2)-positive, triple-negative, or luminal B breast cancer patients. In contrast, NaCT is effective in only ~ 7-10% of estrogen receptor (ER)-positive, HER2-negative disease.

Adjustment of the multi-biomarker disease activity score to account for age, sex and adiposity in patients with rheumatoid arthritis.

Objective: To develop and evaluate an adjusted score for the multi-biomarker disease activity (MBDA) test to account for the effects of age, sex and adiposity in patients with RA.

Methods: Two models were developed to adjust MBDA score for age, sex and adiposity, using either serum leptin concentration or BMI as proxies for adiposity. Two cohorts were studied.

Correlation of melanoma gene expression score with clinical outcomes on a series of melanocytic lesions.

A 23-gene expression signature was recently developed as an adjunct to histopathology to differentiate melanocytic nevi from melanoma. The current study correlated the gene expression signature scores to actual clinical outcomes in cases from the first validation study. RNA was extracted from 127 archival formalin-fixed paraffin-embedded tissue sections of melanocytic lesions.

Determination of the minimally important difference (MID) in multi-biomarker disease activity (MBDA) test scores: impact of diurnal and daily biomarker variation patterns on MBDA scores.

The Multi-Biomarker Disease Activity (MBDA) score is a validated rheumatoid arthritis (RA) disease activity measure based on 12 serum biomarkers. Here, we evaluate short-term biological variability of MBDA scores to determine the magnitude of change that might be considered clinically meaningful. Twenty-eight adult seropositive RA patients with clinically stable disease and no changes in RA medications for 4 weeks prior to study were enrolled.

Diagnostic Distinction of Malignant Melanoma and Benign Nevi by a Gene Expression Signature and Correlation to Clinical Outcomes.

Histopathologic examination alone can be inadequate for diagnosis of certain melanocytic neoplasms. Recently, a 23-gene expression signature was clinically validated as an ancillary diagnostic test to differentiate benign nevi from melanoma. The current study assessed the performance of this test in an independent cohort of melanocytic lesions against clinically proven outcomes.

An independent validation of a gene expression signature to differentiate malignant melanoma from benign melanocytic nevi.

Background: Recently, a 23-gene signature was developed to produce a melanoma diagnostic score capable of differentiating malignant and benign melanocytic lesions. The primary objective of this study was to independently assess the ability of the gene signature to differentiate melanoma from benign nevi in clinically relevant lesions.

Methods: A set of 1400 melanocytic lesions was selected from samples prospectively submitted for gene expression testing at a clinical laboratory.

Analytical validation of a melanoma diagnostic gene signature using formalin-fixed paraffin-embedded melanocytic lesions.

Aim: These studies were to validate the analytical performance of a gene expression signature that differentiates melanoma and nevi, using RNA expression from 14 signature genes and nine normalization genes that generates a melanoma diagnostic score (MDS).

Materials & Methods: Formalin-fixed paraffin-embedded melanocytic lesions were evaluated in these studies.

Results: The overall SD of the assay was determined to be 0.

Clinical validation of a gene expression signature that differentiates benign nevi from malignant melanoma.

Background: Histopathologic examination is sometimes inadequate for accurate and reproducible diagnosis of certain melanocytic neoplasms. As a result, more sophisticated and objective methods have been sought. The goal of this study was to identify a gene expression signature that reliably differentiated benign and malignant melanocytic lesions and evaluate its potential clinical applicability.

BRCA1/2 mutations and expression: response to platinum chemotherapy in patients with advanced stage epithelial ovarian cancer.

Objective: Our objective was to determine the rate of BRCA1/2 deficiency in platinum-sensitive and platinum-resistant tumors from a cohort of unselect patients with advanced epithelial ovarian cancer (EOH).

Methods: BRCA1/2 mutation analysis was performed in 29 patients with platinum-sensitive EOC and 24 patients with platinum-resistant disease. Germline DNA was analyzed in mutation carriers when normal tissue was available.

Prognostic value of an RNA expression signature derived from cell cycle proliferation genes in patients with prostate cancer: a retrospective study.

Background: Optimum management of clinically localised prostate cancer presents unique challenges because of the highly variable and often indolent natural history of the disease. To predict disease aggressiveness, clinicians combine clinical variables to create prognostic models, but the models have limited accuracy. We assessed the prognostic value of a predefined cell cycle progression (CCP) score in two cohorts of patients with prostate cancer.

Somatic mutations in BRCA1 and BRCA2 could expand the number of patients that benefit from poly (ADP ribose) polymerase inhibitors in ovarian cancer.

Purpose: The prevalence of BRCA(1/2) mutations in germline DNA from unselected ovarian cancer patients is 11% to 15.3%. It is important to determine the frequency of somatic BRCA(1/2) changes, given the sensitivity of BRCA-mutated cancers to poly (ADP ribose) polymerase-1 (PARP1) inhibitors and platinum analogs.