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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
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
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
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
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.
Physical Activity Is Associated with Improved Overall Survival among Patients with Metastatic Colorectal Cancer21 februari 2022
Physical activity is linked to longer survival among non-metastasized colorectal cancer patients. It is unclear if physical activity is also beneficial for survival among patients with metastatic colorectal cancer. We researched this question in our study of 293 patients with metastatic colorectal cancer. We found that participants who reported higher levels of physical activity at diagnosis lived longer compared to patients who reported low activity levels. Furthermore, adherence to the physical activity guidelines for cancer survivors was related to prolonged survival. Our findings suggest that patients with metastatic colorectal cancer also benefit from being physically active. Future studies are needed to investigate whether improving exercise levels after diagnosis of metastasis is also beneficial and what kind of exercise interventions are most optimal for possibly improving survival time of patients with metastatic colorectal cancer.
Regular physical activity (PA) is associated with improved overall survival (OS) in stage I–III colorectal cancer (CRC) patients. This association is less defined in patients with metastatic CRC (mCRC). We therefore conducted a study in mCRC patients participating in the Prospective Dutch Colorectal Cancer cohort. PA was assessed with the validated SQUASH questionnaire, filled-in within a maximum of 60 days after diagnosis of mCRC. PA was quantified by calculating Metabolic Equivalent Task (MET) hours per week. American College of Sports and Medicine (ACSM) PA guideline adherence, tertiles of moderate to vigorous PA (MVPA), and sport and leisure time MVPA (MVPA-SL) were assessed as well. Vital status was obtained from the municipal population registry. Cox proportional-hazards models were used to study the association between PA determinants and all-cause mortality adjusted for prognostic patient and treatment-related factors. In total, 293 mCRC patients (mean age 62.9 ± 10.6 years, 67% male) were included in the analysis. Compared to low levels, moderate and high levels of MET-hours were significantly associated with longer OS (fully adjusted hazard ratios: 0.491, (95% CI 0.299–0.807, p value = 0.005) and 0.485 (95% CI 0.303–0.778, p value = 0.003), respectively), as were high levels of MVPA (0.476 (95% CI 0.278–0.816, p value = 0.007)) and MVPA-SL (0.389 (95% CI 0.224–0.677, p value < 0.001)), and adherence to ACSM PA guidelines compared to non-adherence (0.629 (95% CI 0.412–0.961, p value = 0.032)). The present study provides evidence that higher PA levels at diagnosis of mCRC are associated with longer OS.Bekijk deze publicatie