First-line PD-1 +/- CTLA-4 blockade in patients with deficient mismatch repair and/or microsatellite instability-high metastatic colorectal cancer.

Background: Patients with deficient mismatch repair (dMMR) and/or microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) show marked sensitivity to immune checkpoint inhibitors (ICIs). Dual PD-1/CTLA-4 blockade with nivolumab and ipilimumab showed superior progression-free survival (PFS) over chemotherapy and anti-PD-1 monotherapy, but data on treatment-naïve patients is not available yet.

Methods: This international multicenter study included patients with dMMR/MSI-H mCRC receiving either chemotherapy with or without biologics, or anti-PD-1 monotherapy, or dual PD-1/CTLA-4 blockade as a first-line treatment.

Associations between early tumor shrinkage/depth of response and survival from the ARCAD database.

Background: Early tumor shrinkage and depth of response have emerged as potential prognostic indicators in metastatic colorectal cancer (CRC). However, their associations with overall survival, progression-free survival (PFS), and postprogression survival in patients receiving anti-epidermal growth factor receptor (EGFR) antibodies or bevacizumab remain unclear.

Methods: We analyzed 3219 treatment-naive patients with RAS wild-type metastatic CRC from 8 randomized studies (CRYSTAL, OPUS, PRIME, CAIRO2, CALGB80405, WJOG4407G, ATOM, PARADIGM) in the Aid and Research in Digestive Cancerology database.

Treatment Adherence to Adjuvant Chemotherapy According to the New Standard 3-month CAPOX Regimen in High-risk Stage II and Stage III Colon Cancer: A Population-based Evaluation in The Netherlands.

Background: A 3-month adjuvant treatment regimen with capecitabine and oxaliplatin (CAPOX) for high-risk stage II (T4N0) and stage III (node-positive) colon cancer was implemented in the Netherlands in 2017. The IDEA trial showed a clinically irrelevant difference in long-term outcomes in combination with a substantial decrease in toxicity in comparison with a 6-month regimen. A significantly increased dose intensity was observed in the 3-month arm, which might be essential to achieve optimal long-term outcomes.

Real-world treatment patterns and outcomes based on RAS/BRAF status in metastatic colorectal cancer-Analysis of the Prospective Dutch Colorectal Cancer cohort.

The treatment landscape for metastatic colorectal cancer (mCRC) has evolved into a continuum of care with an essential role for biomarkers and molecular subgroups. Treatment guidelines are primarily based on trial results; however, populations and outcomes differ from clinical practice. To support the interpretation of trial results and to assist in tailored patient counseling, we evaluated real-world treatment patterns and outcomes according to RAS/BRAF status.

Sex and outcomes of patients with microsatellite instability-high and V600E mutated metastatic colorectal cancer receiving immune checkpoint inhibitors.

Background: Immune checkpoint inhibitors (ICIs) are the gold standard therapy in patients with deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC). A significant proportion of patients show resistance, making the identification of determinants of response crucial. Growing evidence supports the role of sex in determining susceptibility to anticancer therapies, but data is lacking for patients with MSI-H CRC.

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.

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.