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

Development of a prediction model for clinically-relevant fatigue: a multi-cancer approach

Purpose

Fatigue is the most prevalent symptom across cancer types. To support clinicians in providing fatigue-related supportive care, this study aims to develop and compare models predicting clinically relevant fatigue (CRF) occurring between two and three years after diagnosis, and to assess the validity of the best-performing model across diverse cancer populations.

Methods

Patients with non-metastatic bladder, colorectal, endometrial, ovarian, or prostate cancer who completed a questionnaire within three months after diagnosis and a subsequent questionnaire between two and three years thereafter, were included. Predictor variables included clinical, socio-demographic, and patient-reported variables. The outcome was CRF (EORTC QLQC30 fatigue ≥ 39). Logistic regression using LASSO selection was compared to more advanced Machine Learning (ML) based models, including Extreme gradient boosting (XGBoost), support vector machines (SVM), and artificial neural networks (ANN). Internal-external cross-validation was conducted on the best-performing model.

Results 

3160 patients were included. The logistic regression model had the highest C-statistic (0.77) and balanced accuracy (0.65), both indicating good discrimination between patients with and without CRF. However, sensitivity was low across all models (0.22-0.37). Following internal-external validation, performance across cancer types was consistent (C-statistics 0.73-0.82).

Conclusion

Although the models' discrimination was good, the low balanced accuracy and poor calibration in the presence of CRF indicates a relatively high likelihood of underdiagnosis of future CRF. Yet, the clinical applicability of the model remains uncertain. The logistic regression performed better than the ML-based models and was robust across cohorts, suggesting an advantage of simpler models to predict CRF.

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

Physical activity at diagnosis is associated with tumor downstaging after neoadjuvant chemoradiotherapy in patients with rectal cancer

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).

Methods: 

Patients with high-risk stage II (pT4 +) and III (pN+) colon cancer were selected from the Netherlands Cancer Registry, based on surgical resection and adjuvant CAPOX before (2015-2016) versus after (2018-2019) the guideline change. Both groups were compared on OS, using multivariable Cox regression, and on PROs.

Results: 

Patients treated before (n = 2330) and after (n = 2108) the guideline change showed similar OS (HR 1.02; 95 %CI [0.89-1.16]), also in high-risk stage III (pT4/N2, HR 1.06 [0.89-1.26]). After the guideline change, 90 % of patients were treated for 3 months with no inferior OS to those still receiving 6 months (HR 0.89 [0.66-1.20]). PROs 2 years after CAPOX completion, available for a subset of patients, suggest a lower neuropathy (n = 366; 26.2 [21.3-31.1] to 16.5 [14.4-18.6]) and better quality of life (n = 396; 80.9 [78.6-83.2] to 83.9 [82.8-84.9]), but no significant difference in workability (n = 120; 31.5 [27.9-35.1]) to 35.3 [33.8-36.7]), with reduction from 6 to 3 months of CAPOX.

Conclusion: 

This real-world study confirmed that shorter adjuvant CAPOX did not compromise OS and may improve PROs, complementing the IDEA study and supporting 3 months of adjuvant CAPOX in daily clinical practice.

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

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

Abstract

Results from the UNITED study: a multicenter study validating the prognostic effect of the tumor-stroma ratio in colon cancer

Background

The TNM (tumorenodeemetastasis) Evaluation Committee of Union for International Cancer Control (UICC) and College of American Pathologists (CAP) recommended to prospectively validate the cost-effective and robust tumorestroma ratio (TSR) as an independent prognostic parameter, since high intratumor stromal percentages have previously predicted poor patient-related outcomes.

Patients and methods

The ‘Uniform Noting for International application of Tumor-stroma ratio as Easy Diagnostic tool’ (UNITED) study enrolled patients in 27 participating centers in 12 countries worldwide. The TSR, categorized as stromahigh (>50%) or stroma-low (50%), was scored through standardized microscopic assessment by certified pathologists, and effect on disease-free survival (DFS) was evaluated with 3-year median follow-up. Secondary endpoints were benefit assessment of adjuvant chemotherapy (ACT) and overall survival (OS).

Results

A total of 1537 patients were included, with 1388 eligible stage II/III patients curatively operated between 2015 and 2021. DFS was significantly shorter in stroma-high (n ¼ 428) than in stroma-low patients (n ¼ 960) (3-year rates 70% versus 83%; P < 0.001). In multivariate analysis, TSR remained an independent prognosticator for DFS (P < 0.001, hazard ratio 1.49, 95% confidence interval 1.17-1.90). As secondary outcome, DFS was also worse in stage II and III stroma-high patients despite adjuvant treatment (3-year rates stage II 73% versus 92% and stage III 66% versus 80%; P ¼ 0.008 and P ¼ 0.011, respectively). In stage II patients not receiving ACT (n ¼ 322), the TSR outperformed the American Society of Clinical Oncology (ASCO) criteria in identifying patients at risk of events (event rate 21% versus 9%), with a higher discriminatory 3-year DFS rate (stroma-high 80% versus ASCO high risk 91%). A trend toward worse 5-year OS in stroma-high was noticeable (74% versus 83% stroma-low; P ¼ 0.102).

Conclusion

The multicenter UNITED study unequivocally validates the TSR as an independent prognosticator, confirming worse outcomes in stroma-high patients. The TSR improved current selection criteria for patients at risk of events, and stroma-high patients potentially experienced chemotherapy resistance. TSR implementation in pathology diagnostics and international guidelines is highly recommended as aid in personalized treatment.

Key words: colon cancer, tumor microenvironment, tumorestroma ratio, disease-free survival, pathology

Determinants of Physical Activity among Patients with Colorectal Cancer: From Diagnosis to Five 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 five years post-diagnosis.

Methods: 

Sociodemographic and disease-related factors of participants of two large CRC cohort studies were combined. Moderate-to-vigorous PA during sport and leisure time (MVPA-SL) was measured at diagnosis (T0) and six, twelve, twenty-four, and sixty (T6 to T60) months post-diagnosis, using the SQUASH questionnaire. Mixed-effects models were performed to identify sociodemographic and disease-related determinants of MVPA-SL, separately for stage I-III colon (CC), stage I-III rectal cancer (RC), and stage IV CRC (T0 and T6 only). Associations were defined as consistently present when significant at ≥4 timepoints for the stage I-III subsets. MVPA-SL levels were compared with an age- and sex-matched sample of the general Dutch population.

Results: 

In total, 2905 CC, 1459 RC and 436 stage IV CRC patients were included. Patients with higher fatigue scores, and women compared to men had consistently lower MVPA-SL levels over time, regardless of tumor type and stage. At T6, having a stoma was significantly associated with lower MVPA-SL among stage I-III RC patients. Systemic therapy and radiotherapy were not significantly associated with MVPA-SL changes at T6. Compared to the general population, MVPA-SL levels of CRC patients were lower at all timepoints, most notably at T6.

Conclusions: 

Female sex and higher fatigue scores were consistent determinants of lower MVPA-SL levels among all CRC patients, and MVPA-SL levels were lowest at six months post-diagnosis. Our results can inform the design of intervention studies aimed at improving PA, and guide healthcare professionals in optimizing individualized support.

The impact on health-related quality of a stoma or poor functional outcomes after rectal cancer surgery in Dutch patients: A prospective cohort study