Proteomics of colorectal tumors identifies the role of CAVIN1 in tumor relapse.

Colorectal cancer molecular signatures derived from omics data can be employed to stratify CRC patients and aid decisions about therapies or evaluate prognostic outcome. However, molecular biomarkers for identification of patients at increased risk of disease relapse are currently lacking. Here, we present a comprehensive multi-omics analysis of a Danish colorectal cancer tumor cohort composed of 412 biopsies from tumors of 371 patients diagnosed at TNM stage II or III.

Timing of ctDNA Analysis Aimed at Guiding Adjuvant Treatment in Colorectal Cancer.

Purpose: Multiple clinical trials are investigating ctDNA to guide adjuvant chemotherapy (ACT) in colorectal cancer. Timely ACT initiation necessitates early ctDNA testing, but the impact of postoperative cell-free DNA (cfDNA) and ctDNA dynamics remains unclear, particularly with cost-reducing input caps employed in some assays. This study investigates ctDNA detection at day 14 versus day 30, comparing whole-sample analysis with capping the cfDNA input, and evaluates single and dual timepoint assessments for ACT allocation.

Whole-genome sequencing of cell-free DNA reveals DNA of tumor origin in plasma from patients with colorectal adenomas.

The presence of circulating tumor DNA (ctDNA) in patients with colorectal adenomas remains uncertain. Studies using tumor-agnostic approaches report ctDNA in 10-15% of patients, though with uncertainty as to whether the signal originates from the adenoma. To obtain an accurate estimate of the proportion of patients with ctDNA, a sensitive tumor-informed strategy is preferred, as it ensures the detected signal originates from the adenoma.

Risk of recurrence in early-onset versus late-onset non-metastatic colorectal cancer, 2004-2019: a nationwide cohort study.

Background: The incidence of colorectal cancer (CRC) in individuals younger than 50 years of age (early-onset CRC) is increasing. Early-onset CRC often present at advanced stage, suggesting a more aggressive cancer course compared to late-onset CRC (age 50-79). This nationwide cohort study estimates the incidence of recurrence following early-onset CRC and late-onset CRC.

Circulating tumour DNA and risk of recurrence in patients with asymptomatic versus symptomatic colorectal cancer.

Background: Multiple initiatives aim to develop circulating tumour DNA (ctDNA) tests for early cancer detection in asymptomatic individuals. The few studies describing ctDNA-testing in both asymptomatic and symptomatic patients report lower ctDNA detection in the asymptomatic patients. Here, we explore if asymptomatic patients differ from symptomatic patients e.

Ultrasensitive plasma-based monitoring of tumor burden using machine-learning-guided signal enrichment.

In solid tumor oncology, circulating tumor DNA (ctDNA) is poised to transform care through accurate assessment of minimal residual disease (MRD) and therapeutic response monitoring. To overcome the sparsity of ctDNA fragments in low tumor fraction (TF) settings and increase MRD sensitivity, we previously leveraged genome-wide mutational integration through plasma whole-genome sequencing (WGS). Here we now introduce MRD-EDGE, a machine-learning-guided WGS ctDNA single-nucleotide variant (SNV) and copy-number variant (CNV) detection platform designed to increase signal enrichment.

Incidence of late recurrence and second primary cancers 5-10 years after non-metastatic colorectal cancer.

The fraction of patients who are cancer-free survivors 5 years after curative-intended surgery for colorectal cancer (CRC) is increasing, suggesting that extending surveillance beyond 5 years may be indicated. Here we estimate the incidence of late recurrence, metachronous CRC, and second primary cancers 5-10 years postoperative. All patients resected for UICC stage I-III CRC in Denmark through 2004-2013 were identified.

Incidence of Recurrence and Time to Recurrence in Stage I to III Colorectal Cancer: A Nationwide Danish Cohort Study.

Importance: Management of colorectal cancer (CRC) has been updated continuously over the past 2 decades. While the combination of these initiatives has had implications for improved survival, the implications for rates of recurrence remain unexplored.

Objective: To ascertain the rates of recurrence and describe time to recurrence within 5 years of surgery with curative intent for stages I to III CRC.

DREAMS: deep read-level error model for sequencing data applied to low-frequency variant calling and circulating tumor DNA detection.

Circulating tumor DNA detection using next-generation sequencing (NGS) data of plasma DNA is promising for cancer identification and characterization. However, the tumor signal in the blood is often low and difficult to distinguish from errors. We present DREAMS (Deep Read-level Modelling of Sequencing-errors) for estimating error rates of individual read positions.

Identifying Recurrences Among Non-Metastatic Colorectal Cancer Patients Using National Health Data Registries: Validation and Optimization of a Registry-Based Algorithm in a Modern Danish Cohort.

Purpose: Colorectal cancer (CRC) recurrence is not routinely recorded in Danish health data registries. Here, we aimed to revalidate a registry-based algorithm to identify recurrences in a contemporary cohort and to investigate the accuracy of estimating the time to recurrence (TTR).

Patients And Methods: We ascertained data on 1129 patients operated for UICC TNM stage I-III CRC during 2012-2017 registered in the CRC biobank at the Department of Molecular Medicine, Aarhus University Hospital, Denmark.

Impact of Whole Genome Doubling on Detection of Circulating Tumor DNA in Colorectal Cancer.

Objective: Circulating tumor DNA (ctDNA) is a candidate biomarker of cancer with practice-changing potential in the detection of both early and residual disease. Disease stage and tumor size affect the probability of ctDNA detection, whereas little is known about the influence of other tumor characteristics on ctDNA detection. This study investigates the impact of tumor cell whole-genome doubling (WGD) on the detection of ctDNA in plasma collected preoperatively from newly diagnosed colorectal cancer (CRC) patients.

Peritoneal metastases found in routinely resected specimens after cytoreductive surgery and heated intraperitoneal chemotherapy.

Introduction: Peritoneal metastases (PM) originating from colorectal cancer (CRC) and pseudomyxoma peritonei (PMP) can be treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Certain sites in the peritoneal cavity are prone to contain PM and are, therefore, routinely resected. The aim of this study is to investigate the frequency of disease in CRS specimens routinely resected.

Postoperative paralytic ileus after cytoreductive surgery combined with heated intraperitoneal chemotherapy.

Background: Patients with peritoneal malignancy treated by cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) are prone to develop postoperative paralytic ileus (POI). POI is associated with significant increase in both morbidity and mortality. CRS and HIPEC commonly result in prolonged POI (PPOI).

Leakage Rate After Laparoscopic Ileocolic Intracorporeal Anastomosis.

Background And Aims: The prevailing technique in laparoscopic resection of the right colon has been laparoscopic-assisted procedure with externalization of the bowel for extracorporeal creation of the ileocolic anastomosis. The total laparoscopic technique performing all steps intracorporeally, however, has gained increasing interest. The purpose of this study was to describe our experience with creation of an ileocolic intracorporeal anastomosis (IIA) and to determine anastomotic leakage (AL) rate and short-term outcome of performing IIA.

Perioperative lipid-enriched enteral nutrition versus standard care in patients undergoing elective colorectal surgery (SANICS II): a multicentre, double-blind, randomised controlled trial.

Background: Postoperative ileus and anastomotic leakage severely impair recovery after colorectal resection. We investigated the effect of perioperative lipid-enriched enteral nutrition versus standard care on the risk of postoperative ileus, anastomotic leakage, and other clinical outcomes.

Methods: We did an international, multicentre, double-blind, randomised, controlled trial of patients (≥18 years) undergoing elective colorectal surgery with primary anastomosis at six clinical centres in the Netherlands and Denmark.