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

Health-related quality-of-life trajectories during/after surgery and adjuvant chemotherapy in patients with colon cancer

Purpose

This study aims to evaluate quality of life trajectory during the first year after surgical treatment in patients with resectable primary colon cancer.

Methods

Patients with resectable primary colon cancer diagnosed between 2013 and 2019 who received surgical treatment and adjuvant chemotherapy if indicated were selected from the Prospective Dutch ColoRectal Cancer cohort study (PLCRC). Health-related quality of life (HR-QoL) was assessed using EORTC-QLQ-C30 questionnaire before surgery, and three and twelve months after surgery. HR-QoL scores varied between 0 and 100 and outcomes were compared according to age (< 70 years, ≥ 70 years), comorbidity (yes, no) and treatment type (adjuvant chemotherapy, surgical treatment only). The extent of resilience, defined as a recovery of HR-QoL to baseline level after a clinically relevant decline in HR-QoL at months, was calculated twelve months post-surgery.

Results

For all 458 patients, the mean age was 66.4 years (SD 9.5), 40% were aged 70 years and older and 68% were men. Baseline level of HR-QoL summary score was relatively high with a mean of 87.9 (SD 11.5), and did not significantly differ between older and younger patients. The strongest decline of HR-QoL compared to baseline was observed at three months with a gradual recovery over time. Fourteen percent of all patients were non-resilient or showed a late decline at twelve months post-surgery. Compared to younger patients, older patients who received adjuvant chemotherapy were less resilient (respectively, 53 and 32%, p = 0.07) and at risk of a late decline in HR-QoL 1 year post-surgery (respectively, 3% versus 16%, p = 0.02). Comorbidity status had no significant impact on the HR-QoL trajectory.

Conclusion

Colon cancer treatment was associated with a decline in HR-QoL three months post-surgery, but most patients return to baseline level within twelve months. Still, particularly older patients who received adjuvant chemotherapy were less resilient and at risk of a late decline in HR-QoL. These data could help in patients counselling regarding colon cancer treatment.

Quality of life of patients with rare cancer: a comparison with patients with colorectal cancer and the association with disease trajectory-related factors

Purpose: Differences in quality of life (QoL) between patients with rare and common cancer might be explained by the specific challenges patients with rare cancer face during their disease trajectory, but research is scarce. This study aimed to (1) assess the difference in QoL between patients with rare and common cancer (i.e. colorectal cancer (CRC)) and (2) examine the association between disease trajectory-related factors and QoL in patients with rare cancer.

Methods: Cross-sectional data were collected among adults with rare cancer by a nationwide online survey in the Netherlands. For comparison with patients with CRC, data from the Prospective Dutch Colorectal Cancer (PLCRC) cohort were used. Associations were assessed by linear regression analyses.

Results: Data from 1525 patients with rare cancer and 1047 patients with CRC were analysed. Having a rare cancer was significantly associated with a lower QoL compared to having CRC (p < 0.001). Disease trajectory-related factors significantly associated with QoL in patients with rare cancer were time until diagnosis, misdiagnoses, information on best treatment options, information on late and/or long-term effects, and both satisfaction with physician and specialized nurse care (all: p < 0.05).

Conclusion: Patients with rare cancers have a lower self-reported QoL than patients with CRC, and several disease trajectory-related factors are associated with QoL in patients with rare cancer.

Implications for cancer survivors: To improve QoL of patients with rare cancer, appropriate guidance and support by healthcare professionals throughout the disease trajectory are needed, as well as early diagnosis and proper referral to centres of expertise.