Cancer survivors often experience long-term consequences affecting their Health-Related Quality of Life (HRQoL). Sociodemographic factors, clinical characteristics, and health-related behaviours influence HRQoL, making some individuals vulnerable to adverse HRQoL. This study develops linear regression and machine learning models to predict HRQoL two-year post-diagnosis and to identify key vulnerability factors. This longitudinal study included data of survivors of seven cancer types. Nineteen predictor variables were derived from questionnaires completed within three months post-diagnosis (baseline) from the Netherlands Cancer Registry. Linear regression, random forest, XGBoost, neural network, and Support Vector Machine (SVM) regressors were employed to predict the EORTC QLQ-C30 summary score 1.5–2.5 years post-diagnosis. Permutation testing assessed vulnerability factors. The analyses included 4,538 individuals. All models achieved similar R2 (0.3) and RMSE (9) scores. Linear regression, random forest, XGBoost, and SVM models identified lower physical, cognitive, and emotional functioning at diagnosis, along with more comorbidities, cancer type (especially endometrial), and higher BMI as the top vulnerability factors. Treatment, age, and education were not associated with vulnerability. All models tended to overestimate low HRQoL which might be due to the limited number of observations with low HRQoL values. The predictors used in this analysis explained only 30

PURPOSE:Depression is a heterogeneous construct comprising distinct symptom domains, including motivational anhedonia, consummatory anhedonia, and negative affect, commonly experienced by colorectal cancer (CRC) survivors. Inflammation has been implicated in depression, its association with specific depressive symptom domains in CRC survivors remains insufficiently characterized. METHODS:CRC patients (n = 497) completed questionnaires assessing depressive symptoms 12- and 24-months post-diagnosis: motivational anhedonia (Multidimensional Fatigue Inventory), consummatory anhedonia (Hospital Anxiety and Depression Scale-depression), and negative affect (EORTC QLQ-C30, emotional functioning). Associations between 11 inflammatory markers (CRP, IL-1α, IL-1β, IL-6, IL-8, IL-10, IL-17A, IL-22, IFN-γ, sTNFRI, and sTNFRII) at 12-months and depressive symptoms at 12- and 24-months were examined using linear mixed models. RESULTS:IL-1β (Est = 0.089, p = 0.003) and IFN-γ (Est = 0.067, p = 0.001) were associated with more consummatory anhedonia symptoms across time, and a small sTNFRI × time interaction was found (Est = 0.000, p = 0.007). Negative affect was associated with IL-1β (Est = -0.496, p < 0.001), IFN-γ (Est = -0.354, p < 0.001), and sTNFRI (Est = -0.003, p < 0.001). A significant IL-1α × time interaction was observed (Est = 0.250, p = 0.038) for motivational anhedonia. CONCLUSIONS:Most consistently IL-1β, IFN-γ, and sTNFRI was associated with greater consummatory anhedonia and more negative affect in CRC survivors. In addition, inflammatory correlates (IL-1α and sTNFRI) of motivational anhedonia and consummatory anhedonia changed over time. These findings suggest that selected inflammatory pathways may contribute to specific depressive symptom domains during colorectal cancer survivorship. Given the exploratory nature of the analyses, replication in independent cohorts is required before clinical implications can be drawn.

Studies on patient-reported outcomes (PROs) among cancer survivors are increasing but are most often limited to PRO and clinical data. To better understand the underlying biological mechanisms that mediate a decline in health after cancer, several PROFILES-registry studies were enriched with biological data. This paper summarizes lessons learned from collecting blood samples to obtain biomarker data among survivors and controls in large-scale ambulatory cohort studies. These lessons address financial challenges, ethical issues, insurance, legal matters, standardization of assessment, recruitment, communication with participants, lab facilities and protocols, transportation, the need for a biobank, and the value of a normative population. We also describe our experiences with collecting remote blood samples in these studies among cancer patient populations and a study in our normative population to illustrate these issues further.

Background:A brain tumor can lead to functional impairment, which is particularly concerning for adolescents and young adults (AYA). Patient-reported outcomes (PROs) have typically been examined as isolated domains, rather than as covarying symptoms. This study modeled PRO networks, symptom clustering, and topology among AYA oncology survivors. Methods:Patient-reported outcome networks from 4005 survivors were compared in topology between survivors of primary CNS tumors (n = 164) and non-CNS tumors (n = 3841). Survivors were diagnosed between 1999 and 2015 at ages 18 to 39 years, who completed the EORTC QLQ-SURV100 (Mdn follow-up = 12.31 years). Group-specific networks were estimated based on 33 health-related quality of life (HRQoL) scale scores using graphical LASSO. Wilcoxon rank-sum tests and the Network Comparison Test assessed group differences in the original PRO scales and their network centrality, respectively. Within the CNS subgroup (n = 164), associations with tumor-related and treatment-related characteristics were explored. Results:Survivors of central nervous system (CNS) tumors reported higher symptom burden on most PRO scales, along with a more diffuse network showing weaker within-domain cohesion (lower nodal strength and expected influence) and limited cross-domain integration (lower bridge strength). A small subset of nodes showed higher bridge expected influence (ie, fatigue, physical functioning, sexual problems when sexually active, work), which may represent key targets for intervention. Across both groups, negative health outlook, health distress, and physical functioning emerged as consistent core targets. Conclusion:Core symptoms may warrant prioritization in clinical follow-up and treatment of cancer survivors. These findings contribute to further development and optimization of tailored neurorehabilitation programs in neuro-oncological care.

Purpose Supportive care resources are limited, requiring a strategic, tailored approach, especially with the growing population of breast cancer patients. We examined whether routinely collected Patient-Reported Outcome Measures (PROMs) can identify meaningful health-related quality of life (HRQoL) trajectories and help guide resource allocation of supportive care. Methods As part of routine care at the Netherlands Cancer Institute, 2181 early-stage breast cancer patients completed the EORTC QLQ-C30 and BR23 before treatment and six months later. Through Latent Class and Latent Transition Analyses, we identified HRQoL subgroups and transitions between subgroups over time. Multinomial regression examined sociodemographic and clinical correlates. Network analysis detected key domains and inter-domain connections within subgroups. Results Three HRQoL subgroups were identified at baseline: Excellent HRQoL (53%), Good HRQoL with Psychosocial concerns (33%), and Poor HRQoL with severe functional limitations (13%). Multiple comorbidities and history of depression were independently and strongly associated with membership to less favorable subgroups. Subgroup transitions were rare (1–5%). Network analysis showed subgroup-specific key domains: emotional functioning in the Psychosocial concerns -subgroup, and menopausal symptoms, social, and role functioning in the Poor HRQoL -subgroup; the latter subgroup showing the highest interconnectivity between HRQoL-domains. Conclusion Baseline HRQoL and sociodemographic factors, independent of treatment, is associated with HRQoL trajectories and can guide efficient re-allocation of resources to those patients with complex needs. Most patients maintain excellent HRQoL and may benefit from low-intensity or self-management support, whereas targeted, multidisciplinary interventions should be prioritized for those with complex needs. Different key domains and connectivity suggest different types of supportive care are needed for different subgroups.

OBJECTIVE:Following treatment, cancer survivors often struggle to resume their life in several life domains. Although supportive care is increasingly available and can assist survivors in improving their quality of life, it often falls short in meeting the needs of the diverse and growing group of cancer survivors. Understanding the perceptions of key stakeholders is crucial for improving supportive care. This study aims to explore the perceptions of cancer survivors and healthcare professionals (HCPs) regarding the provision of adequate supportive care after treatment. METHODS:We conducted 22 interviews with cancer survivors, varying in (time since) diagnosis, sex and age. Additionally, four focus groups were conducted with 25 HCPs, including medical specialists, general practitioners, psychologists, occupational physicians and informal caregivers. Interviews and focus groups were conducted using pre-defined topic guides, were audio-taped, and transcribed verbatim. A thematic content analysis was performed, consisting of several coding phases. RESULTS:Cancer survivors emphasized the importance of a person-centered approach, with supportive care tailored to individual values and needs. They valued accessible supportive care extending beyond medical needs, including work-related support and peer support. HCPs similarly stressed the importance of person-centered supportive care, and promoting cancer survivors' empowerment. They also highlighted limited awareness of supportive care options among HCPs, the need for clear role division, multidisciplinary collaboration, integration into clinical care, and an overview of supportive care referral options. CONCLUSION:While both cancer survivors and HCPs emphasized the importance of comprehensive, person-centered supportive care, its implementation in clinical practice remains challenging. Key requirements, such as greater awareness of the importance of supportive care among HCPs, knowledge of reliable referral options, and interdisciplinary collaboration, are often unmet. Efforts should focus on improving HCPs' awareness and integrating supportive care into clinical practice. The findings of this study informed the development of the online tool 'Back on Track with Cancer'. This tool supports the identification of supportive care needs, provides personalized supportive care options, and facilitates shared decision making with HCPs.

Cancer-related fatigue (CRF) is a prevalent symptom among colorectal cancer (CRC) survivors. While inflammation is a proposed underlying mechanism, longitudinal evidence including pre-treatment assessments remains scarce. Within the population-based PROCORE study, newly diagnosed CRC patients provided blood samples and completed questionnaires at diagnosis (n = 411; 60.6% male; age = 67.0 years), 12- (n = 304), and 24-month follow-up (n = 252). Eleven inflammatory biomarkers (CRP, IFN-γ, IL-1α, IL-1β, IL-6, IL-8, IL-10, IL-17A, IL-22, sTNFRI, and sTNFRII) were assayed; CRF was measured with the Multidimensional Fatigue Inventory. Hybrid linear mixed models disentangled between- and within-subject associations, controlling for sociodemographic (e.g., age), clinical (e.g., cancer treatment), and lifestyle covariates (e.g., BMI), sleep quality, and pain. A normative age- and sex matched sample (n = 204; 52.5% male; age = 64.3 years) was included for comparison. Soluble TNF receptors (sTNFRI/II) were most robustly and positively associated with nearly all fatigue dimensions. CRP was positively associated with mental and physical fatigue; IL-8 positively associated with multiple domains including reduced motivation; and IFN-γ positively associated with general fatigue and reduced activity. Lower IL-1α was associated with more mental fatigue. Between-subject effects mirrored overall results; within-subject effects were more selective. Associations were most consistently observed for mental fatigue. In controls, less associations were significant; CRP was the most robust marker and positively associated with general fatigue, reduced activity, and reduced motivation. CRC survivors exhibited a broader, mostly TNF-α driven inflammatory signature of fatigue than controls. Findings highlight inflammation as a potential target underlying CRF, informing survivorship care strategies.

INTRODUCTION:Lifestyle factors are involved in carcinogenesis and disease progression in colorectal cancer (CRC) and contribute to systemic inflammation. We examined individual and group-level trajectories of associations between lifestyle factors (smoking, alcohol use, body mass index (BMI), and physical activity) and systemic inflammation from diagnosis until 24 months thereafter. METHODS:We used data from the PROCORE-study, a prospective cohort of stage I-IV CRC patients (n = 411). Patients completed lifestyle questionnaires and provided blood samples at diagnosis (pre-treatment), and 12 and 24 months thereafter. Linear mixed models examined associations between lifestyle and inflammation (C-Reactive Protein (CRP), interleukin-(IL)1α, IL-1β, IL-6, IL-8, IL-10, IL-17A, IL-22, Interferon-gamma (IFN-γ), soluble Tumor Necrosis Factor Receptors (sTNFR)I/II), while adjusting for demographics, cancer stage, comorbidities, and time since diagnosis. RESULTS:Biomarkers remained largely stable, though IL-22 declined, whereas TNFRII increased over time. IL-8, IL-1β, and IL-10, levels decreased at 12 and increased at 24 months follow-up. Smoking was associated with higher CRP (p = .003). Obese patients showed elevated IFN-γ (p = .001) and sTNFRI (p < .001), while overweight patients had increased sTNFRI (p = .014) and IL-1α (p = .040), and reduced IL-1β (p = .039). Underweight patients displayed higher IL-22 (p = .038). Physical activity was associated with lower IFN-γ (p = .020) and sTNFRII (p = .044). Alcohol consumption was linked to lower IL-1β and IL-10, while occasional and moderate use were related to lower IL-17A and IFN-γ. CONCLUSION:Smoking, obesity, and alcohol use were linked to higher inflammation, whereas physical activity showed protective effects in CRC patients. Findings highlight the importance of integrating lifestyle support into survivorship care.

With the rising prevalence of cancer, longitudinal research on survivorship increasingly emphasizes patient-reported outcomes (PROs). Traditionally, these outcomes have relied on self-report questionnaires and clinical data, which provide valuable insights but may not fully capture underlying biological and physiological processes. To bridge this gap, the PROFILES registry was recently expanded to incorporate objective, home-based measures that participants can perform independently, such as food diaries, body composition scales, and activity trackers. This paper summarizes lessons learned from implementing home-use bioelectrical impedance analysis (BIA) scales, online food diaries, and tape measures to assess body composition and nutritional intake in large-scale ambulatory studies. Such studies, conducted in participants’ everyday living environments rather than clinical settings, provide ecologically valid insights but also raise methodological and practical challenges. When selecting self-monitoring tools for research, reliability and validity remain essential, yet other considerations are equally important. Widely used tools facilitate comparability and generalizability across studies, while feasibility, practicality, sensitivity to change, and standardization determine their practical value. Clear instructions, efficient logistics, and user-friendliness support sustained participant engagement. Furthermore, legal and ethical requirements must be carefully addressed to ensure data privacy and compliance with regulatory standards. Integrating objective measures with PROs enhances accuracy, allows triangulation of self-reported and observed outcomes, and improves prediction of long-term survivorship trajectories. Since 2009, PROFILES data have been shared globally for non-commercial research, and upcoming expansions to include objective measures will further strengthen its impact. These experiences offer valuable guidance for future survivorship research and beyond.

OBJECTIVE:To examine how dyadic patient- and partner-related risk and protective factors are interconnected with caregiver burden among partners of patients with advanced cancer using a network approach. METHODS:We conducted network and shortest-path analyses using cross-sectional baseline data from the eQuiPe study, including 564 patient-partner caregiver couples. The network included patient- and partner-reported physical, emotional, and sleep problems, social and partner support, continuity of care, and caregiver burden. RESULTS:Shortest-path analysis identified patient-perceived continuity of care as the only patient-related protective factor directly connected to lower caregiver burden. Patients' physical problems were indirectly linked to caregiver burden via emotional problems of both patients and partners. CONCLUSIONS:Continuity of care and the interdependence between patient and partner emotional problems appeared to be important dyadic protective and risk factors of partners' caregiver burden. Improving continuity of palliative care and offering dyadic interventions targeting emotional functioning of both partners may help reduce caregiver burden. To further improve our understanding of caregiver burden and its dyadic factors, future studies should apply intensive longitudinal designs to explore how these components interact over time.

PURPOSE:This study aimed to examine health care use in a cross-sectional sample of Dutch cancer survivors > 2 years post-diagnosis. METHODS:The Dutch Federation of Cancer Patient Organizations (NFK), together with patient representatives and researchers, developed a cross-sectional online survey on life after cancer, which was distributed via email, websites, and social media. RESULTS:The study included 5710 respondents (> 2 years post-diagnosis). Among those who reported long-term cancer/treatment-related consequences (approximately 89% of participants), one-third (33%) had received professional care or support for these issues in the past 3 months. Those reporting more cancer- or treatment related consequences, those diagnosed 2-5 years ago, those (probably) not (getting) better, and those currently under treatment were more likely to receive professional care or support. Care was primarily provided by medical specialists (47%), physical therapists (37%), and/or general practitioners (32%). 15% expressed a desire for care or support that they did not receive, indicating reasons such as a long time since diagnosis or affordability. Overall, 68% knew where to turn for help; among those with consequences, 19% received peer/volunteer support and 10% wanted it but did not receive it. CONCLUSION:A significant proportion of long-term cancer survivors in our sample reported unmet support needs (15% for professional care, 10% for peer support). Efforts should focus on improving access to affordable professional care, expanding peer support networks, providing personalized long-term follow-up care, and reducing stigma around seeking help, particularly within the context of the Dutch healthcare system.

Adolescent and young adult cancer survivors (AYAs; 18–39 years old at initial cancer diagnosis) face unique challenges throughout their disease trajectory and are, therefore, a distinct population within the oncology community. A common side effect of some cancer treatments is neuropathy, which can affect patients’ quality of life ongoing. AYA-specific studies on long-term effects, such as neuropathy, are lacking. This study investigated the prevalence of, and factors associated with self-reported peripheral neuropathic symptoms in long-term AYA cancer survivors. This questionnaire study (SURVAYA study) examined patient-reported outcomes among long-term AYA cancer survivors (5–20 years post-diagnosis). Data were collected through a questionnaire and by the Netherlands Cancer Registry. Analyses included descriptive statistics and multivariable logistic regression. Three thousand seven hundred forty-one AYAs were included in this secondary analysis. Overall, the prevalence of self-reported peripheral neuropathic symptoms was 19.8

ABSTRACT Background Inflammation‐related biomarkers have been implicated in a wide range of cancer‐related symptoms and patient‐reported outcomes (PROs), including fatigue, pain, and depression. To interpret biomarker data among cancer patients, normative reference values from healthy populations are essential. Objective This cross‐sectional study aimed to provide sex‐ and age‐stratified reference data distributions for 12 inflammation‐related serum biomarkers in a representative sample of Dutch adults without a history of cancer. Methods Adults from the LISS panel were selected to match cancer cohorts from the PROFILES registry in age and sex. Participants completed questionnaires and optionally provided blood samples using harmonized protocols aligned with the PROFILES registry. Serum levels of IL‐1α, IL‐1β, IL‐6, IL‐8, IL‐10, IL‐17A, IL‐22, CRP, TGF‐α, IFN‐γ, IL‐1RA, and soluble TNF receptors I and II (sTNFRI/II) were quantified using the Meso Scale Discovery (MSD) platform. Cytokine levels were stratified by demographics, lifestyle factors, and self‐reported health conditions. ANOVAs were used to compare groups. Results In total 720 panel members filled out the questionnaires, of which 265 (mean age = 59.0, 47.9% male) provided additional serum blood samples. Biomarker levels varied by sex, age, BMI, smoking status, and number of health conditions. Notably, higher levels of IL‐1RA and sTNFRI/II were observed in individuals with obesity or diabetes. Individuals with osteoarthritis exhibited elevated IL‐6 and IL‐1β levels. Conclusion This study offers a robust reference dataset for key inflammatory biomarkers, stratified by relevant demographics, lifestyle factors, and self‐reported health conditions. These data facilitate interpretation of biomarker–PRO relationships in cancer survivors and support comparative research across chronic disease populations.

BACKGROUND:This study aimed to determine whether: 1) sleep quality was associated with overall survival (OS) among a heterogeneous sample of cancer survivors; 2) this association differed per cancer diagnosis; 3) aspects of sleep quality (e.g., sleep latency, daytime dysfunction) were associated with OS among a subsample of colorectal cancer (CRC) survivors; and 4) adjustment for depressive symptoms changed these associations. METHODS:Several cohorts from the population-based PROFILES registry, including adult cancer survivors diagnosed between 1990 and 2014 with 11 cancer diagnoses, were used. Data on sleep quality (3 categories: no, non-clinically, and clinically important sleep quality impairment) was collected through the insomnia scale of the EORTC QLQ-C30 and the PSQI for CRC survivors only (n = 1245). Clinical data were obtained through the Netherlands Cancer Registry. Cox regression analysis was used to assess adjusted hazard ratios (HRs). RESULTS:7195 participants were included, of which 36 % died (median follow-up since inclusion, 9 years). Clinically impaired sleep quality was associated with lower OS (HR, 1.17[1.05; 1.30]) compared to no sleep problems. Stratification by cancer diagnosis suggested a consistent pattern. After adjusting for depressive symptoms, sleep quality was no longer significantly associated with OS (HR, 1.10[0.97; 1.24]). Daytime dysfunction and long sleep duration were significantly associated with lower OS in CRC survivors, also after adjustment for depressive symptoms. CONCLUSION:Cancer patients reporting clinically low sleep quality had a lower OS. However, this might be partly explained by patients' depressive symptoms. In CRC survivors, daytime dysfunction and long sleep duration were, independent of depressive symptoms, related to lower OS.

BACKGROUND:Colorectal cancer (CRC) treatment commonly involves surgery combined with chemotherapy (CT) and/or radiotherapy (RT), which can trigger acute and chronic immune alterations. Understanding treatment-related inflammation is critical, as persistent immune dysregulation may influence therapeutic response, toxicity, and long-term outcomes. This study investigates longitudinal changes in inflammatory markers among CRC patients from pre-treatment to 2 years post-diagnosis and compares them to a matched cancer-free control group to isolate treatment-related effects. MATERIALS AND METHODS:Data were drawn from the PROCORE study (n = 411), and a sex- and age-matched normative sample (n = 204). Inflammatory markers (IL-1α, IL-1β, IL-6, IL-8, IL-10, IL-17A, IL-22, CRP, IFN-γ, sTNFRI, sTNFRII) were measured at diagnosis (pre-treatment), and 12- and 24-month follow-ups. Linear mixed models assessed longitudinal biomarker trajectories across treatment groups (CT, RT, both, neither), controlling for demographic and clinical covariates. Group differences in inflammatory markers were compared to normative reference values. RESULTS:Across timepoints, CRC patients exhibited persistently altered biomarker levels compared with controls (higher IFN-γ, IL-1β, IL-10; lower IL-6, IL-8, sTNFRI), partly independent of treatment modality. Significant time x treatment interactions were visible for IL-6, IL-8, IL-17A, IL-22, sTNFRI and sTNFRII, with most post-hoc differences between RT only and CT only groups. CONCLUSION:Chronic immune alterations in CRC patients appear only partly attributable to treatment type, suggesting broader cancer-related immune dysregulation. These findings highlight the importance of incorporating immune monitoring into clinical care and raise the potential for therapeutic strategies targeting inflammation to mitigate late effects.

Background:Online self-management interventions for cancer survivors are increasingly being used, but engagement is often difficult for patients. Given the importance of engagement for intervention effectiveness, identifying patient-reported barriers and facilitators is essential. Objective:The aim of this study was to qualitatively examine barriers and facilitators influencing engagement with an online self-management intervention, offered with or without guidance, for cancer survivors experiencing chronic painful chemotherapy-induced peripheral neuropathy (CIPN). Methods:Patients who took part in the Embrace Pain randomized controlled trial, conducted between December 2021 and July 2024, were invited to participate in this study. Eligible participants were adults with chronic painful CIPN, based on criteria including pain, completion of chemotherapy, and European Organisation for Research and Treatment of Cancer QLQ-CIPN20 Questionnaire (ie, cancer-specific measure of sensory, motor, and autonomic neuropathy). The Embrace Pain randomized controlled trial involved evaluating an online self-management acceptance and commitment therapy intervention for pain interference in daily life, with some participants receiving email guidance and others not. Thereafter, 12 patients experiencing chronic painful CIPN participated in semistructured interviews. Data were analyzed using thematic analysis. An inductive coding approach was applied, and Atlas.ti (Lumivero) was used for coding. Results:In total, 2 themes and 17 codes emerged from the data, namely 7 codes for barriers and 10 codes for facilitators. Barriers included program schedule, burden, lack of guidance, irrelevance, mindfulness exercises, usability, and missing content. Facilitators included usability, recognition, positive self-management, program schedule, symptom management, relevance, guidance, experiential exercises, mindfulness exercises, and value-based living. Program schedule, guidance, mindfulness exercises, and usability proved to be barriers for some, while others indicated that they were facilitators for their use. Conclusions:Participants' perceptions of the intervention varied, with engagement influenced by individual circumstances. These variations highlight the importance of personal context in shaping both uptake and effectiveness, indicating a need for tailored approaches to address diverse needs and challenges faced by participants.

To gain more insight into promising strategies to achieve sustained optimal lifestyle and body composition changes among breast cancer survivors, which may improve health-related outcomes, this systematic review aimed to synthesise scientific evidence on maintenance of intervention effects on lifestyle and body composition in breast cancer survivors and to identify, describe and synthesise methods and strategies associated with effectiveness. Four databases (PubMed, PsychINFO, CINAHL, MEDLINE) were systematically searched for papers from 2010 onwards. Randomised controlled trials assessing the effectiveness of lifestyle interventions among breast cancer survivors reporting outcomes (physical (in)activity, diet, body composition, sleep, alcohol consumption and/or smoking) at baseline, end of intervention and follow-up were included. Behaviour change techniques were coded using the Behaviour Change Technique Taxonomy. Risk of bias and reporting completeness were evaluated using the RoB2 and the CONSORT checklist. Thirty papers were included. Few studies found intervention effects at end of intervention and at follow-up: 3 out of 17 assessing physical (in)activity, 3/6 assessing dietary outcomes, 1/8 assessing body composition and 1/8 assessing sleep. The low number of effective interventions hampered the synthesis of methods and strategies associated with effectiveness. This detailed overview of current scientific evidence provides guidance for future research.

Purpose Peripheral neuropathy (PN) is a disabling side-effect of cancer itself and of neurotoxic chemotherapy, which is part of recommended treatment for colorectal cancer (CRC). The incidence of CRC is rising among younger, working-age adults. This study aimed to quantify the association of PN with work outcomes among participants with CRC.Methods participants with CRC from the PROCORE study were analyzed. Baseline characteristics were collected from the Netherlands Cancer Registry (NCR). Work-related details were self-reported. PN was assessed using the EORTC QLQ-CIPN20 questionnaire at baseline(T1), one(T2) and two years(T3) post-diagnosis. The minimally clinical important difference (MCID) classified participants into present and absent sensory or motor PN groups.Results Similar proportions of participants with present or absent PN reported work absenteeism. The median duration of absenteeism was significantly longer for participants with present sensory PN (22 weeks longer at T2; 13,5 weeks at T3) and present motor PN (16 weeks longer at T2; 13 weeks at T3) compared to those with absent PN. Participants who reported job changes or limitations in job performance were more likely to have sensory and/or motor PN. Self-employment was associated with poorer outcomes.Conclusion This study revealed that sensory and/or motor PN was negatively associated with various aspects of CRC survivors’work life, particularly among self-employed individuals, for up to two years after diagnosis. These findings highlight the need for an effective treatment for PN to enhance survivors’ work ability. Patients undergoing neurotoxic chemotherapy should be informed that PN may adversely affect their work life.

Peripheral neuropathy (PN) and accelerated biological ageing are common in colorectal cancer (CRC) patients. In vitro and in vivo studies suggest links between biological ageing, oxidative stress, and PN. This longitudinal study examined associations between markers of accelerated ageing (leukocyte telomere length (LTL) and plasma NAD+ levels) and oxidative stress (protein carbonyl content (PCC)) with PN in CRC patients. Newly diagnosed CRC patients (n = 457) were recruited in a Dutch prospective cohort. LTL, plasma NAD+ levels, PCC, and PN (self-reported using the EORTC QLQ-CIPN20) were measured at baseline (prior to treatment), 1-year, and 2-years follow-up. Associations between biomarkers and PN were analyzed using a confounder-adjusted linear mixed model. Longer LTL was associated with higher PN scores, including Sensory PN (SPN) and Motor PN (MPN), while lower plasma NAD+ levels were linked to higher SPN complaints (β:-2.29;95%CI:-4.31,-.27). These associations were primarily driven by inter-individual changes over time. Among chemotherapy-treated patients, lower plasma NAD+ levels were associated with higher total PN scores, SPN, and autonomic PN symptoms. Lower NAD+ levels were longitudinally associated with higher SPN complaints, especially among those treated with chemotherapy. These findings emphasize the potential for targeting NAD+ metabolism to mitigate PN in CRC.