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Determinants of Physical Activity among Patients with Colorectal Cancer: From Diagnosis to Five Years after Diagnosis11 december 2023
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.
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.
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.
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.Bekijk deze publicatie
The impact on health-related quality of a stoma or poor functional outcomes after rectal cancer surgery in Dutch patients: A prospective cohort study23 april 2023
As the survival of patients with rectal cancer has improved in recent decades, more and more patients have to live with the consequences of rectal cancer surgery. An influential factor in long-term Health-related Quality of Life (HRQoL) is the presence of a stoma. This study aimed to better understand the long-term consequences of a stoma and poor functional outcomes.
Patients who underwent curative surgery for a primary tumor located in the rectosigmoid and rectum between 2013 and 2020 were identified from the nationwide Prospective Dutch Colorectal Cancer (PLCRC) cohort study. Patients received the following questionnaires: EORTC-QLQ-CR29, EORTC-QLQ-C30, and the LARS-score at 12 months, 24 months and 36 months after surgery.
A total of 1,170 patients were included of whom 751 (64.2%) had no stoma, 122 (10.4%) had a stoma at primary surgery, 45 (3.8%) had a stoma at secondary surgery and 252 (21.5%) patients that underwent abdominoperineal resection (APR). Of all patients without a stoma, 41.4% reported major low-anterior resection syndrome (LARS). Patients without a stoma reported significantly better HRQoL. Moreover, patients without a stoma significantly reported an overall better HRQoL.
The presence of a stoma and poor functional outcomes were both associated with reduced HRQoL. Patients with poor functional outcomes, defined as major LARS, reported a similar level of HRQoL compared to patients with a stoma. In addition, the HRQoL after rectal cancer surgery does not change significantly after the first year after surgery.
Health-related quality-of-life trajectories during/after surgery and adjuvant chemotherapy in patients with colon cancer25 maart 2023
This study aims to evaluate quality of life trajectory during the first year after surgical treatment in patients with resectable primary colon cancer.
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.
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.
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.Bekijk deze publicatie
Quality of life of patients with rare cancer: a comparison with patients with colorectal cancer and the association with disease trajectory-related factors31 december 2022
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.Bekijk deze publicatie
The impact of surgery and adjuvant chemotherapy on health-related quality of life in patients with colon cancer: Changes at group level versus individual level30 november 2022
Objective: This study aims to evaluate changes in health-related quality of life (HR-QoL) 1 year after surgical treatment in patients with primary resectable colon cancer and to assess whether changes at group level differ from changes at individual level. In addition, we assess which characteristics are associated with a decline of HR-QoL.
Methods: Patients with primary resectable colon cancer who received surgical treatment and adjuvant chemotherapy if indicated were selected from the Prospective Dutch ColoRectal Cancer cohort (PLCRC). HR-QoL was assessed using EORTC-QLQ-C30 questionnaire before surgery and 12 months post-surgery. Outcomes were assessed at group and individual levels. Logistic regression analysis was conducted to assess which socio-demographic and clinical characteristics were associated with a clinically relevant decline of HR-QoL at 12 months.
Results: Of all 324 patients, the baseline level of HR-QoL summary score was relatively high with a mean of 88.1 (SD 11.4). On group level, the change of HR-QoL at 12 months varied between -2% for cognitive functioning and +9% for emotional functioning. On individual level, 15% of all patients experienced a clinically relevant decline in HR-QoL summary score at 12 months. Older age, comorbidity burden or the reception of adjuvant chemotherapy was independently associated with a decline of HR-QoL in one of the functional subscales of EORTC-QLQ-C30 at 12 months.
Conclusion: Only trivial changes of HR-QoL were observed after colon cancer treatment on group level, whereas on individual level, at least 1 out of 10 patients experienced a decline of HR-QoL 12 months post-surgery. It is important to consider individual differences while making a treatment decision.Bekijk deze publicatie
External Validation of the Colon Life Nomogram for Predicting 12-Week Mortality in Dutch Metastatic Colorectal Cancer Patients Treated with Trifluridine/Tipiracil in Daily Practice18 oktober 2022
Predicting prognosis in refractory metastatic colorectal cancer (mCRC) patients is needed to guide decision making. The Colon Life nomogram was developed to predict 12-week mortality in refractory mCRC patients. The aim of this study is to validate the Colon Life nomogram in last line/refractory patients receiving trifluridine/tipiracil (FTD/TPI) in daily practice.
The validation cohort consists of 150 QUALITAS study patients, an observational substudy of the Prospective Dutch CRC cohort, who were treated with FTD/TPI between 2016 and 2019. Model performance was assessed on discrimination, calibration, and clinical usefulness. The additional prognostic value of baseline quality of life (QoL) and thymidine kinase (TK1) expression in tissue was explored.
Of the 150 patients, 25 (16.7%) died within 12 weeks of starting FTD/TPI treatment. The C-statistic was 0.63 (95% C.I. 0.56-0.70). The observed/expected ratio was 0.52 (0.37-0.73). The calibration intercept and slope were -1.06 (-1.53 to -0.58) and 0.41 (0.01-0.81), respectively, which indicated overestimation of 12-week mortality by the nomogram. Decision curve analysis showed the nomogram did not yield a positive net benefit at clinically meaningful thresholds for predicted 12-week mortality. Addition of QoL to the nomogram improved the C-statistic to 0.85 (0.81-0.89). TK1 expression was associated with progression-free survival but not with overall survival.
We demonstrated evident miscalibration of the Colon Life nomogram upon external validation, which hampers its use in clinical practice. We recommend conducting a study with a sufficiently large sample size to update the Colon Life nomogram or to develop a new model including QoL.Bekijk deze publicatie
GITR Ligation Improves Anti-PD1-Mediated Restoration of Human MMR-Proficient Colorectal Carcinoma Tumor-Derived T Cells23 september 2022
Background & aims
In contrast to mismatch repair deficient colorectal carcinoma (CRC), MMR proficient (pMMR) CRC does not respond to immune checkpoint blockade. We studied immune checkpoint stimulation via glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) on ex vivo functionality of human tumor-infiltrating lymphocytes (TIL) isolated from pMMR primary CRC and liver metastases (CRLM).
Using lymphocytes from resected tumor, adjacent tissues, and peripheral blood mononuclear cells (PBMC) of 132 pMMR primary CRC or CRLM patients, we determined GITR expression and the in vitro T-cell agonistic activity of recombinant GITR ligation.
Here, we show that GITR was overexpressed on TIL when compared with other stimulatory immune checkpoints (4-1BB, OX40). Its expression was enhanced in TIL compared with PBMC and adjacent tissues. Among CD4+ TIL, GITR expression was primarily expressed by CD45RA- FoxP3hi activated regulatory T cells. Within CD8+ TIL, GITR was predominantly expressed on functionally exhausted and putative tumor-reactive CD103+ CD39+ TIL. Strikingly, recombinant GITRL reinvigorated ex vivo TIL responses by significantly enhancing CD4+ and CD8+ TIL numbers. Dual treatment with GITRL and nivolumab (anti-PD1) enhanced CD8+ TIL expansion compared with GITRL monotherapy. Moreover, GITRL/anti-PD1 dual therapy further improved anti-PD1-mediated reinvigoration of interferon gamma secretion by exhausted CD8 TIL from primary CRC.
GITR is overexpressed on CD4+ and CD8+ TIL from pMMR CRC and CRLM. Agonistic targeting of GITR enhances ex vivo human TIL functionality and may therefore be a promising approach for novel monotherapy or combined immunotherapies in primary pMRR CRC and CRLM.Bekijk deze publicatie
Evaluation of an individual feedback report on patient‑reported outcomes in the Prospective Dutch ColoRectal Cancer cohort31 mei 2022
Returning patient-reported outcomes to patients might aid patients in detecting symptoms and might facilitate early intervention. This descriptive study evaluates the use of an individual feedback report on patient-reported outcomes for colorectal cancer patients and aims to assess differences in patient, tumor, and treatment characteristics and cohort retention between patients who opt and do not opt for the feedback report.
Patients with colorectal cancer participating in the nationwide Prospective Dutch ColoRectal Cancer Cohort, who filled in questionnaires digitally between June 2018 and January 2019, were included. Participants were given the option to receive a feedback report at baseline, 3, 6, and 12 months. The usefulness, content, and layout of the feedback report were evaluated. Differences in patient, tumor, and treatment characteristics, patientreported outcomes, and cohort retention at subsequent questionnaires between participants who did and did not opt for feedback were assessed.
A total of 484 participants were included of whom 293 (61%) opted for feedback. The feedback report was considered useful by 92%. No differences in patient, tumor, and treatment characteristics, and patient-reported outcomes were found between participants who did and did not opt for feedback. The response rate was higher among patients who opted for feedback compared to patients who did not opt for feedback at T3 (84 vs 74%), but not at T6 and T12.
The feedback report was used by 6 out of 10 patients. The feedback report was considered valuable and associated with a higher subsequent response rate.Bekijk deze publicatie
Quality of life and survival of metastatic colorectal cancer patients treated with trifluridine-tipiracil (QUALITAS)24 maart 2022
Long-Term Safety Data on S-1 Administered After Previous Intolerance to Capecitabine-Containing Systemic Treatment for Metastatic Colorectal Cancer2 maart 2022
The oral fluoropyrimidine S-1 has shown comparable efficacy to capecitabine in Asian and some Western studies on metastatic colorectal cancer. S-1 is associated with a lower incidence of hand-foot syndrome (HFS) and cardiac toxicity. We assessed the long-term tolerability of S-1 in patients who discontinued capecitabine for reasons of HFS or cardiac toxicity.
Patients and Methods
Patients with metastatic colorectal cancer who switched from capecitabine to S-1, given as monotherapy or in combination with other agents, were identified in a Dutch prospective cohort study (2016-2021). The incidence and severity of HFS, cardiotoxicity and other toxicities were assessed.
Forty-seven patients were identified. The median duration of capecitabine treatment was 81 days (range 4-454). In 19 patients (40%) a dose reduction was applied prior to switch to S-1. Reasons for discontinuation of capecitabine were HFS in 36 (77%) patients, coronary artery vasospasms in 10 (21%) patients, and gastrointestinal toxicities in 1 patient (2%). The median number of S-1 cycles was 6 (range 1-36). The median time between last dose of capecitabine and first dose of S-1 was 11 days (range 1-49). After switch to S-1, all patients with prior HFS developed a lower grade or complete resolution of symptoms, and in all other patients symptoms did not recur. Other S-1-related adverse events were limited to grade 1-2. Six patients (13%) discontinued S-1 due to either known fluoropyrimidine-related or bevacizumab-related toxicities. Switch to S-1 did not appear to compromise treatment efficacy.
S-1 is a valid alternative to capecitabine in case HFS or cardiotoxicity occurs.