Pre-malignant conditions diagnosed following a positive cancer signal from a multi-cancer early detection test.

Blood-based tests for multi-cancer early detection (MCED) are being developed to facilitate the detection of various cancer types. The Detecting cancers Earlier Through Elective mutation-based blood Collection and Testing study (DETECT-A) study evaluated an MCED test in 9,911 women, age 65-75, without personal history of cancer. In a analysis, we report on the detection of precancerous neoplasms consequent to MCED testing and follow-up.

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.

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.

Real-time evaluation and adaptation to facilitate rapid recruitment in a large, prospective cohort study.

Background: Recruiting large cohorts efficiently can speed the translation of findings into care across a range of scientific disciplines and medical specialties. Recruitment can be hampered by factors such as financial barriers, logistical concerns, and lack of resources for patients and clinicians. These and other challenges can lead to underrepresentation in groups such as rural residents and racial and ethnic minorities.

Machine learning to detect the SINEs of cancer.

We previously described an approach called RealSeqS to evaluate aneuploidy in plasma cell-free DNA through the amplification of ~350,000 repeated elements with a single primer. We hypothesized that an unbiased evaluation of the large amount of sequencing data obtained with RealSeqS might reveal other differences between plasma samples from patients with and without cancer. This hypothesis was tested through the development of a machine learning approach called Alu Profile Learning Using Sequencing (A-PLUS) and its application to 7615 samples from 5178 individuals, 2073 with solid cancer and the remainder without cancer.

Impact of preoperative endoscopic procedures on adverse event rates after surgical resection for main-duct and mixed-type intraductal papillary mucinous neoplasms (IPMNs).

Background: Main-duct (MD-) and mixed-type (MT-) IPMNs harbor an increased risk of pancreatic cancer and warrant surgical resection. Preoperative endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) are important in the diagnosis of IPMNs. The aim of this study was to investigate whether endoscopic procedures manipulating the MD impact postoperative adverse events in patients with MD- and MT-IPMNs.

Diagnostic Performance of a Tumor Marker Gene Test to Personalize Serum CA19-9 Reference Ranges.

Purpose: CA19-9 synthesis is influenced by common variants in the fucosyltransferase (FUT) enzymes FUT3 and FUT2. We developed a clinical test to detect FUT variants, and evaluated its diagnostic performance for pancreatic ductal adenocarcinoma (PDAC).

Experimental Design: A representative set of controls from the Cancer of the Pancreas Screening study was identified for each FUT functional group.

Surveillance for Presumed BD-IPMN of the Pancreas: Stability, Size, and Age Identify Targets for Discontinuation.

Background & Aims: Currently, most patients with branch duct intraductal papillary mucinous neoplasms (BD-IPMN) are offered indefinite surveillance, resulting in health care costs with questionable benefits regarding cancer prevention. This study sought to identify patients in whom the risk of cancer is equivalent to an age-matched population, thereby justifying discontinuation of surveillance.

Methods: International multicenter study involving presumed BD-IPMN without worrisome features (WFs) or high-risk stigmata (HRS) at diagnosis who underwent surveillance.

Predictive ability of pancreatic cyst fluid biomarkers: A systematic review and meta-analysis.

Background: Mucinous pancreatic cysts harbor the potential to progress to highly lethal pancreatic ductal adenocarcinoma (PDAC). Since these precursor cysts require cancer surveillance or surgical resection, they need to be reliably distinguished from harmless pancreatic cysts. Current clinical and radiographic assessment is imperfect and the value of cyst fluid analysis for differential diagnosis is unclear.

Screening for pancreatic cancer has the potential to save lives, but is it practical?

Introduction: Most patients with pancreatic cancer present with advanced stage, incurable disease. However, patients with high-grade precancerous lesions and many patients with low-stage disease can be cured with surgery, suggesting that early detection has the potential to improve survival. While serum CA19.

Classification of pancreatic cystic neoplasms using radiomic feature analysis is equivalent to an experienced academic radiologist: a step toward computer-augmented diagnostics for radiologists.

Purpose: A wide array of benign and malignant lesions of the pancreas can be cystic and these cystic lesions can have overlapping imaging appearances. The purpose of this study is to compare the diagnostic accuracy of a radiomics-based pancreatic cyst classifier to an experienced academic radiologist.

Methods: In this IRB-approved retrospective single-institution study, patients with surgically resected pancreatic cysts who underwent preoperative abdominal CT from 2003 to 2016 were identified.

Risk of Pancreatic Cancer in the Long-Term Prospective Follow-Up of Familial Pancreatic Cancer Kindreds.

Background: A family history of pancreatic cancer is associated with increased pancreatic cancer risk. However, risk estimates for individuals in kindreds with an aggregation of pancreatic cancer (>1 relative) are imprecise because of small samples sizes or potentially impacted by biases inherent in retrospective data.

Objective: The objective of this study is to determine the age-specific pancreatic cancer risk as a function of family history using prospective data.

RAD51B Harbors Germline Mutations Associated With Pancreatic Ductal Adenocarcinoma.

Purpose: Genetic alterations in many components of the homologous recombination, DNA damage response, and repair (HR-DDR) pathway are involved in the hereditary cancer syndromes, including familial pancreatic cancer. HR-DDR genes beyond , , , and may also mutate and confer the HR-DDR deficiency in pancreatic ductal adenocarcinoma (PDAC).

Methods: We conducted a study to examine the genetic alterations using a companion diagnostic 15-gene HR-DDR panel in PDACs.

The Multicenter Cancer of Pancreas Screening Study: Impact on Stage and Survival.

Purpose: To report pancreas surveillance outcomes of high-risk individuals within the multicenter Cancer of Pancreas Screening-5 (CAPS5) study and to update outcomes of patients enrolled in prior CAPS studies.

Methods: Individuals recommended for pancreas surveillance were prospectively enrolled into one of eight CAPS5 study centers between 2014 and 2021. The primary end point was the stage distribution of pancreatic ductal adenocarcinoma (PDAC) detected (stage I higher-stage).

Circulating Tumor DNA Analysis Guiding Adjuvant Therapy in Stage II Colon Cancer.

Background: The role of adjuvant chemotherapy in stage II colon cancer continues to be debated. The presence of circulating tumor DNA (ctDNA) after surgery predicts very poor recurrence-free survival, whereas its absence predicts a low risk of recurrence. The benefit of adjuvant chemotherapy for ctDNA-positive patients is not well understood.