NanoCMSer: a consensus molecular subtype stratification tool for fresh-frozen and paraffin-embedded colorectal cancer samples.

Colorectal cancer (CRC) is a significant contributor to cancer-related mortality, emphasizing the need for advanced biomarkers to guide treatment. As part of an international consortium, we previously categorized CRCs into four consensus molecular subtypes (CMS1-CMS4), showing promise for outcome prediction. To facilitate clinical integration of CMS classification in settings where formalin-fixed paraffin-embedded (FFPE) samples are routinely used, we developed NanoCMSer, a NanoString-based CMS classifier using 55 genes.

The nationwide Dietary Intake after Diagnosis and Colorectal Cancer Outcomes (PLCRC-PROTECT) cohort: Study design, clinical characteristics and baseline health behaviors.

Purpose: The nationwide Dietary Intake After Diagnosis and Colorectal Cancer Outcomes (PROTECT) study is a prospective cohort study investigating how lifestyle-related factors including dietary intake and physical activity are associated with health-related quality of life (HRQoL), recurrence, and survival after a colorectal cancer (CRC) diagnosis.

Methods: Patients participating in the Prospective Dutch Colorectal Cancer (PLCRC) cohort with newly diagnosed stage I to IV colorectal cancer were recruited for PROTECT shortly after diagnosis, between 2015 and 2022. While patient-reported quality of life, physical activity, and sedentary behavior, as well as body composition data are available from PLCRC, patient-reported measurements in PROTECT included anthropometrics, dietary intake, dietary supplement use, and taste and smell alterations.

Efficacy and safety in early-phase clinical trials for refractory colorectal cancer: A meta-analysis.

Background: Despite recent metastatic colorectal cancer (mCRC) therapeutic innovations a comprehensive synthesis of patient outcome and risk-benefit assessment of phase 1/2 trials is missing. The aim of this meta-analysis is to assess efficacy, safety, and trends over time for phase 1 and 2 mCRC trials by examining clinical benefit rate (CBR), overall response rate (ORR), grade 3 or higher adverse events (AE), and discontinuation due to AE.

Methods: The PRISMA guidelines were followed.

Early evaluation of the effectiveness and cost-effectiveness of ctDNA-guided selection for adjuvant chemotherapy in stage II colon cancer.

Background: Current patient selection for adjuvant chemotherapy (ACT) after curative surgery for stage II colon cancer (CC) is suboptimal, causing overtreatment of high-risk patients and undertreatment of low-risk patients. Postoperative circulating tumor DNA (ctDNA) could improve patient selection for ACT.

Objectives: We conducted an early model-based evaluation of the (cost-)effectiveness of ctDNA-guided selection for ACT in stage II CC in the Netherlands to assess the conditions for cost-effective implementation.

Discovering novel germline genetic variants linked to severe fluoropyrimidine-related toxicity in- and outside DPYD.

Background: The Alpe-DPD study (NCT02324452) demonstrated that prospective genotyping and dose-individualization using four alleles in DPYD (DPYD*2A/rs3918290, c.1236G > A/rs75017182, c.2846A > T/rs67376798 and c.

Benefit of adjuvant chemotherapy on recurrence free survival per consensus molecular subtype in stage III colon cancer.

The consensus molecular subtype (CMS) classification divides colon tumors into four subtypes holding promise as a predictive biomarker. However, the effect of adjuvant chemotherapy on recurrence free survival (RFS) per CMS in stage III patients remains inadequately explored. With this intention, we selected stage III colon cancer (CC) patients from the MATCH cohort (n = 575) and RadboudUMC (n = 276) diagnosed between 2005 and 2018.

Dietary and lifestyle inflammation scores in relation to colorectal cancer recurrence and all-cause mortality: A longitudinal analysis.

Aim: The aim of this study was to longitudinally investigate dietary and lifestyle inflammation scores and their interaction in relation to risk of colorectal cancer (CRC) recurrence and all-cause mortality.

Methods: Data of two prospective cohort studies among CRC survivors was used. Information about diet and/or lifestyle was available for 2739 individuals for at least one of the following time points: at diagnosis, six months after diagnosis and two years after diagnosis.

Survival and patient-reported outcomes of real-world high-risk stage II and stage III colon cancer patients after reduction of adjuvant CAPOX duration from 6 to 3 months.

Aim: Adjuvant chemotherapy has been advised for high-risk stage II and III colon cancer since 2004. After the IDEA study showed no clinically relevant difference in outcome, reduction of adjuvant CAPOX duration from 6 to 3 months was rapidly adopted in the Dutch treatment guideline in 2017. This study investigates the real-world impact of the guideline change on overall survival (OS) and patient-reported outcomes (PROs).

Use of automated assessment for determining associations of low muscle mass and muscle loss with overall survival in patients with colorectal cancer - A validation study.

Background: Low muscle mass and skeletal muscle mass (SMM) loss are associated with adverse patient outcomes, but the time-consuming nature of manual SMM quantification prohibits implementation of this metric in clinical practice. Therefore, we assessed the feasibility of automated SMM quantification compared to manual quantification. We evaluated both diagnostic accuracy for low muscle mass and associations of SMM (change) with survival in colorectal cancer (CRC) patients.

Improving sustainability of a patient decision aid for systemic treatment of metastatic colorectal cancer: A qualitative study.

Objective: To improve sustainability of a patient decision aid for systemic treatment of metastatic colorectal cancer, we evaluated real-world experiences and identified ways to optimize decision aid content and future implementation.

Methods: Semi-structured interviews with patients and medical oncologists addressed two main subjects: user experience and decision aid content. Content analysis was applied.

Efficacy-effectiveness analysis on survival in a population-based real-world study of BRAF-mutated metastatic colorectal cancer patients treated with encorafenib-cetuximab.

Background: Encorafenib-cetuximab has been approved for pretreated BRAF-mutated metastatic colorectal cancer (mCRC) patients based on efficacy demonstrated in the randomized phase III BEACON trial. The aim of this real-world effectiveness study is to improve knowledge on the generalizability of trial results.

Methods: This population-based real-world study includes all mCRC patients in the Netherlands treated with encorafenib-cetuximab since approval.

Associations between low- and high-fat dairy intake and recurrence risk in people with stage I-III colorectal cancer differ by sex and primary tumour location.

We previously demonstrated that intake of low-fat dairy, but not high-fat dairy, was associated with a decreased colorectal cancer (CRC) recurrence risk. These risks, however, may differ by sex, primary tumour location, and disease stage. Combining data from two similar prospective cohort studies of people with stage I-III CRC enabled these subgroup analyses.

Organoids as a biomarker for personalized treatment in metastatic colorectal cancer: drug screen optimization and correlation with patient response.

Background: The inability to predict treatment response of colorectal cancer patients results in unnecessary toxicity, decreased efficacy and survival. Response testing on patient-derived organoids (PDOs) is a promising biomarker for treatment efficacy. The aim of this study is to optimize PDO drug screening methods for correlation with patient response and explore the potential to predict responses to standard chemotherapies.

Harnessing the Potential of Real-World Evidence in the Treatment of Colorectal Cancer: Where Do We Stand?

Treatment guidelines for colorectal cancer (CRC) are primarily based on the results of randomized clinical trials (RCTs), the gold standard methodology to evaluate safety and efficacy of oncological treatments. However, generalizability of trial results is often limited due to stringent eligibility criteria, underrepresentation of specific populations, and more heterogeneity in clinical practice. This may result in an efficacy-effectiveness gap and uncertainty regarding meaningful benefit versus treatment harm.

Oncologic outcomes of screen-detected and non-screen-detected T1 colorectal cancers.

Background: The incidence of T1 colorectal cancer (CRC) has increased with the implementation of CRC screening programs. It is unknown whether the outcomes and risk models for T1 CRC based on non-screen-detected patients can be extrapolated to screen-detected T1 CRC. This study aimed to compare the stage distribution and oncologic outcomes of T1 CRC patients within and outside the screening program.

Determinants of Physical Activity among Patients with Colorectal Cancer: From Diagnosis to 5 Years after Diagnosis.

Introduction: Physical activity (PA) is associated with higher quality of life and probably better prognosis among colorectal cancer (CRC) patients. This study focuses on determinants of PA among CRC patients from diagnosis until 5 yr postdiagnosis.

Methods: Sociodemographic and disease-related factors of participants of two large CRC cohort studies were combined.

Adjuvant chemotherapy in patients with clinically node-negative but pathologically node-positive rectal cancer in the Netherlands: A retrospective analysis.

Introduction: Accurate clinical staging of rectal cancer is hampered by suboptimal sensitivity of MRI in the detection of regional lymph node metastases. Consequently, some patients may be understaged and have been withheld neoadjuvant (chemo)radiotherapy in retrospect. Although Dutch guidelines do not advocate adjuvant chemotherapy (ACT) in rectal cancer, some of these clinically understaged patients receive ACT according to local policy.