Long-term Colorectal Cancer Survivors Research Articles

Health-Related Quality of Life in Long-Term Colorectal Cancer Survivors

The aim of our study is to evaluate the relationship between sociodemographic and clinical characteristics of individuals with Colorectal Cancer (CRC), tumour-intrinsic characteristics and treatment received with health-related quality of life (HRQoL). Methods: Cross-sectional analysis of data from 805 survivors from the MCC study was conducted. HRQoL was assessed through a general and specific questionnaire, SF-12 and FCSI (Colorectal Symptom Index). Statistical analyses were performed with linear regression with adjustment for sociodemographic variables, stage at diagnosis and histological grade. Results: Participants had survived a median of 7.9 years from diagnosis (IQR 7.1–8.5 years). Age at diagnosis, sex and area showed a clear association with HRQoL in both physical and mental dimensions of the SF-12 questionnaire. A direct association between CRC recurrence was also found in the PCS-12 and MCS-12 dimensions and radical surgery in the PCS-12. Regarding the scores in FCSI questionnaire, statistically significant differences were observed by sex, age and area, with older women being the most impaired (p < 0.001). Conclusions: Age, sex and area was associated with lower scores of HRQoL among CRC survivors. Knowing the determinants related to HRQoL would allow us to lay the groundwork to develop strategies that help reduce morbidity and mortality, relapses and increase HRQoL.

A novel conditional survival nomogram for monitoring real-time prognosis of non-metastatic colorectal cancer

AimsThe aim of this study is to enhance the accuracy of monitoring and treatment information for patients diagnosed with colorectal cancer (CRC).MethodsUtilizing the Surveillance, Epidemiology, and End Results (SEER) database, a cohort of 335,948 eligible CRC patients was included in this investigation. Conditional survival probability and actuarial overall survival were employed as methodologies to investigate the association between clinicopathological characteristics and cancer prognosis.ResultsAmong CRC patients, the 5-year survival rate was 59%, while the 10-year survival rate was 42%. Over time, conditional survival showed a consistent increase, with rates reaching 45% and 48% for individuals surviving 1 and 2 years, respectively. Notably, patients with unfavorable tumor stages exhibited substantial improvements in conditional survival, thereby narrowing the disparity with actuarial overall survival over time.ConclusionThis study underscores the significance of time-dependent conditional survival probability, particularly for patients with a poorer prognosis. The findings suggest that long-term CRC survivors may experience improved cancer prognosis over time.

The Effectiveness of 23-valent Pneumococcal Polysaccharide Vaccine on Elderly Colorectal Cancer Long-Term Survivors: A population-based exact-matched cohort study

ABSTRACT Colorectal cancer (CRC) long-term survivor is a rapid enlarging group. However, the effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPSV23) on this group is unknown. This nationwide population-based study in Taiwan was designed to examine the effect of PPSV23 on incidence rate ratio (IRR) of pneumonia hospitalization, cumulative incidence, and overall survival rate for these long-term CRC survivors. This cohort study was based on the Taiwan Cancer Registry and Taiwan National Health Insurance Research Database from 2000–2017. After individual exact matching to covariates with 1:1 ratio, there were a total of 1,355 vaccinated and 1,355 unvaccinated survivors. After adjusted by multivariate Poisson regression model, vaccinated group had a non-significantly lower pneumonia hospitalization risk than unvaccinated, with an adjusted IRR of 0.879 (p = .391). Besides, vaccinated group had both lower cumulative incidence rate and higher overall survival time than unvaccinated.

Missingness mechanisms and generalizability of patient reported outcome measures in colorectal cancer survivors – assessing the reasonableness of the “missing completely at random” assumption

BackgroundPatient-Reported Outcome Measures (PROM) provide important information, however, missing PROM data threaten the interpretability and generalizability of findings by introducing potential bias. This study aims to provide insight into missingness mechanisms and inform future researchers on generalizability and possible methodological solutions to overcome missing PROM data problems during data collection and statistical analyses.MethodsWe identified 10,236 colorectal cancer survivors (CRCs) above 18y, diagnosed between 2014 and 2018 through the Danish Clinical Registries. We invited a random 20% (2,097) to participate in a national survey in May 2023. We distributed reminder e-mails at day 10 and day 20, and compared Initial Responders (response day 0–9), Subsequent Responders (response day 10–28) and Non-responders (no response after 28 days) in demographic and cancer-related characteristics and PROM-scores using linear regression.ResultsOf the 2,097 CRCs, 1,188 responded (57%). Of these, 142 (7%) were excluded leaving 1,955 eligible CRCs. 628 (32%) were categorized as initial responders, 418 (21%) as subsequent responders, and 909 (47%) as non-responders. Differences in demographic and cancer-related characteristics between the three groups were minor and PROM-scores only marginally differed between initial and subsequent responders.ConclusionIn this study of long-term colorectal cancer survivors, we showed that initial responders, subsequent responders, and non-responders exhibit comparable demographic and cancer-related characteristics. Among respondents, Patient-Reported Outcome Measures were also similar, indicating generalizability. Assuming Patient-Reported Outcome Measures of subsequent responders represent answers by the non-responders (would they be available), it may be reasonable to judge the missingness mechanism as Missing Completely At Random.

Validity and screening capacity of the FCR-1r for fear of cancer recurrence in long-term colorectal cancer survivors

PurposeExisting fear of cancer recurrence (FCR) screening measures is being shortened to facilitate clinical use. This study aimed to evaluate the validity and screening capacity of a single-item FCR screening measure (FCR-1r) in long-term colorectal cancer (CRC) survivors with no recurrence and assess whether it performs as well in older as in younger survivors.MethodsAll Danish CRC survivors above 18, diagnosed and treated with curative intent between 2014 and 2018, were located through a national patient registry. A questionnaire including the FCR-1r, which measures FCR on a 0–10 visual analog scale, alongside the validated Fear of Cancer Recurrence Inventory Short Form (FCRI-SF) as a reference standard was distributed between November 2021 and May 2023. Screening capacity and cut-offs were evaluated with a receiver-operating characteristic analysis (ROC) in older (≥ 65 years) compared to younger (< 65 years) CRC survivors. Hypotheses regarding associations with other psychological variables were tested as indicators of convergent and divergent validity.ResultsOf the CRC survivors, 2,128/4,483 (47.5%) responded; 1,654 (36.9%) questionnaires were eligible for analyses (median age 76 (range 38–98), 47% female). Of the responders, 85.2% were aged ≥ 65. Ninety-two participants (5.6%) reported FCRI-SF scores ≥ 22 indicating clinically significant FCR. A FCR-1r cut-off ≥ 5/10 had 93.5% sensitivity and 80.4% specificity for detecting clinically significant FCR (AUC = 0.93, 95% CI 0.91–0.94) in the overall sample. The discrimination ability was significantly better in older (AUC = 0.93, 95% CI 0.91–0.95) compared to younger (0.87, 95% (0.82–0.92), p = 0.04) CRC survivors. The FCR-1r demonstrated concurrent validity against the FCRI-SF (r = 0.71, p < 0.0001) and convergent validity against the short-versions of the Symptom Checklist-90-R subscales for anxiety (r = 0.38, p < 0.0001), depression (r = 0.27, p < 0.0001), and emotional distress (r = 0.37, p < 0.0001). The FCR-1r correlated weakly with employment status (r = − 0.09, p < 0.0001) and not with marital status (r = 0.01, p = 0.66) indicating divergent validity.ConclusionsThe FCR-1r is a valid tool for FCR screening in CRC survivors with excellent ability to discriminate between clinical and non-clinical FCR, particularly in older CRC survivors.

Patient-reported unmet supportive care needs in long-term colorectal cancer survivors after curative treatment in an Asian population

Despite an increase in colorectal cancer (CRC) survival, less is known about CRC-specific long-term unmet supportive needs in Asian patients. This study aimed to examine the prevalence of long-term unmet needs and identify clinical and socio-demographic factors associated with increased unmet needs in Asian CRC survivors. We conducted a cross-sectional study that assessed unmet needs using the Cancer Survivors' Unmet Needs scale. CRC survivors of at least two years after undergoing curative surgery were recruited from an outpatient clinic of a large public hospital in Singapore. In total, 400 CRC survivors with a mean age of 64 and a median survival time post-surgery of 78 months participated in the study. Approximately half of patients (52%) reported at least one unmet need. Male gender (RR 1.19, p=0.01), age greater than 65 years (RR 0.63, p<0.0001), longer follow up of more than 5 years (RR 0.80, p=0.009), presence of a permanent stoma (RR 1.78, p<0.0001), prior radiotherapy in treatment course (RR 1.99, p<0.0001), higher educational status (RR 1.30, p=0.0002), currently employed (RR 0.84, p=0.014), currently married (RR 0.84, p=0.01) were significant predictors for increased unmet needs. There is a high prevalence of unmet needs in long-term Asian CRC survivors, which underscores the importance of screening patients to allow for early detection of unmet needs. Our findings on sociodemographic and clinical predictors can inform the development of targeted interventions tailored to the need domains and improvement of survivorship programmes.

"It's Probably Just Hemorrhoids": A Qualitative Exploration of the Lived Experiences and Perceptions of Long-term Survivors of Early-Onset Colorectal Cancer.

Colorectal cancer among adults aged <50 years [early-onset colorectal cancer (EOCRC)] is projected to be the leading cause of cancer-related death by 2030. Although evidence-based guidelines for colorectal cancer screening now recommend beginning screening at age 45, the needs of many at-risk young adults are potentially being overlooked. Unanswered questions also remain regarding the effects of EOCRC on quality-of-life and psychosocial outcomes. This qualitative study explored the lived experiences and perceptions of a sample of adult EOCRC survivors in the United States through one-on-one interviews. An EOCRC advocate survivor team member led 27 structured virtual interviews using a 10-question interview guide. Data were analyzed using a 9-step inductive approach. Participants were geographically diverse. Most were women (66.6%) who self-identified as non-Hispanic White (85.2%). The mean age at interview was 40.19 ± 5.99; at diagnosis, 33.93 ± 5.90. Six overarching themes emerged: signs and symptoms, risk factors, system-level factors, quality of life, social support, and reflection. The specific needs of individuals in this younger population of patients with colorectal cancer should be considered during treatment and future interventions and throughout survivorship. While the reasons for the increasing incidence of EOCRC are currently unknown, the lived experiences and perceptions of EOCRC survivors noted in this study highlight specific needs of this population that can inform educational materials, comprehensive care, future research, and policy change.

Relative Burden of Cancer and Noncancer Mortality Among Long-Term Survivors of Breast, Prostate, and Colorectal Cancer in the US

Improvements in cancer outcomes have led to a need to better understand long-term oncologic and nononcologic outcomes and quantify cancer-specific vs noncancer-specific mortality risks among long-term survivors. To assess absolute and relative cancer-specific vs noncancer-specific mortality rates among long-term survivors of cancer, as well as associated risk factors. This cohort study included 627 702 patients in the Surveillance, Epidemiology, and End Results cancer registry with breast, prostate, or colorectal cancer who received a diagnosis between January 1, 2003, and December 31, 2014, who received definitive treatment for localized disease and who were alive 5 years after their initial diagnosis (ie, long-term survivors of cancer). Statistical analysis was conducted from November 2022 to January 2023. Survival time ratios (TRs) were calculated using accelerated failure time models, and the primary outcome of interest examined was death from index cancer vs alternative (nonindex cancer) mortality across breast, prostate, colon, and rectal cancer cohorts. Secondary outcomes included subgroup mortality in cancer-specific risk groups, categorized based on prognostic factors, and proportion of deaths due to cancer-specific vs noncancer-specific causes. Independent variables included age, sex, race and ethnicity, income, residence, stage, grade, estrogen receptor status, progesterone receptor status, prostate-specific antigen level, and Gleason score. Follow-up ended in 2019. The study included 627 702 patients (mean [SD] age, 61.1 [12.3] years; 434 848 women [69.3%]): 364 230 with breast cancer, 118 839 with prostate cancer, and 144 633 with colorectal cancer who survived 5 years or more from an initial diagnosis of early-stage cancer. Factors associated with shorter median cancer-specific survival included stage III disease for breast cancer (TR, 0.54; 95% CI, 0.53-0.55) and colorectal cancer (colon: TR, 0.60; 95% CI, 0.58-0.62; rectal: TR, 0.71; 95% CI, 0.69-0.74), as well as a Gleason score of 8 or higher for prostate cancer (TR, 0.61; 95% CI, 0.58-0.63). For all cancer cohorts, patients at low risk had at least a 3-fold higher noncancer-specific mortality compared with cancer-specific mortality at 10 years of diagnosis. Patients at high risk had a higher cumulative incidence of cancer-specific mortality than noncancer-specific mortality in all cancer cohorts except prostate. This study is the first to date to examine competing oncologic and nononcologic risks focusing on long-term adult survivors of cancer. Knowledge of the relative risks facing long-term survivors may help provide pragmatic guidance to patients and clinicians regarding the importance of ongoing primary and oncologic-focused care.

Factors associated with long-term gastrointestinal toxicity in colorectal cancer survivors in the women’s health initiatives (WHI) study.

e24057 Background: Colorectal cancer (CRC) survivors often experience long-term symptom toxicity after cancer treatments. We described persistent gastrointestinal (GI) toxicity related to cancer and treatments in long-term CRC survivors and assessed the risk and life impact factors of GI toxicity. Methods: A cross-sectional study utilized data from the Women’s Health Initiative (WHI) Life and Longevity After Cancer (LILAC) study that recruited postmenopausal women. CRC survivors after cancer treatments were included (N = 413). Pearson correlations/A Chi-square test and multivariable linear regression models were used to identify risk and impact factors of GI toxicity. Results: 81% of CRC survivors experienced persistent GI toxicity. Bloating/gas was the most prevalent (54.2%) and severe, followed by constipation (34.1%), diarrhea (33.4%), and abdominal/pelvic pain (28.6%). Time since cancer diagnosis (&lt; 5 years), advanced cancer stage, low income, high psychological distress, poor dietary habits and physical activity, and impaired life impact measures (health-related quality of life, daily life interferences, and body image) were significantly associated with several GI toxicities. Fatigue and sleep disturbance were the most significantly associated with long-term GI toxicity (Table 1). Abdominal/pelvic pain significantly influenced life impact measures. Conclusions: GI toxicities are highly prevalent among CRC survivors, specifically in patients with high psychological distress. A better understanding of the long-term GI toxicity in CRC survivors and identifying those more vulnerable may inform future directions for managing CRC survivorship. An individualized, multifaceted intervention is warranted to consider psychosocial support, lifestyle intervention, and physical rehabilitation. [Table: see text]

Persisting Deficits in Health-Related Quality of Life of Colorectal Cancer Survivors 14-24 Years Post-Diagnosis: A Population-Based Study.

(1) Background: The health-related quality of life (HRQOL) of colorectal cancer (CRC) survivors >10 years post-diagnosis is understudied. We aimed to compare the HRQOL of CRC survivors 14-24 years post-diagnosis to that of age- and sex-matched non-cancer controls, stratified by demographic and clinical factors. (2) Methods: We used data from 506 long-term CRC survivors and 1489 controls recruited from German population-based multi-regional studies. HRQOL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Core-30 (EORTC QLQ-C30) questionnaire. We estimated differences in the HRQOL of CRC survivors and controls with multiple regression, adjusted for age at survey, sex, and education, where appropriate. (3) Results: CRC survivors reported poorer social functioning but better health status/QOL than controls. CRC survivors, in general, had higher levels of symptom burden, and in particular diarrhea and constipation, regardless of demographic or clinical factors. In stratified analyses, HRQOL differed by age, sex, cancer type, and having a permanent stoma. (4) Conclusions: Although CRC survivors may have a comparable health status/QOL to controls 14-24 years after diagnosis, they still live with persistent bowel dysfunction that can negatively impact aspects of functioning. Healthcare providers should provide timely and adapted follow-up care to ameliorate potential long-term suffering.

Colorectal cancer survivors’ long-term recollections of their illness and therapy up to seven years after enrolment into a randomised controlled clinical trial

BackgroundAs a consequence of effective treatment procedures, the number of long-term survivors of colorectal cancer is ever increasing. Adopting the method of a previous study on breast cancer patients, the goal of the present research was to investigate colorectal cancer patients’ recollections of their illness and treatment experiences up to seven years after they have been enrolled in a randomised controlled clinical trial on the direct improvement of quality of life (RCT DIQOL).MethodsColorectal cancer survivors in Bavaria, Germany were mailed a questionnaire on average 78·3 months after the start of their therapy and enrolment into RCT DIQOL. The questionnaire enquired about their worst experience during the colorectal cancer episode, positive aspects of the illness, and any advice they would give to newly diagnosed patients. Patient responses were categorised by two independent raters and cross-checked by a third independent rater. Frequencies of these categories were then quantitatively analysed using descriptive statistics.ResultsOf 146 remaining survivors initially enrolled in RCT DIQOL, 96 (66%) returned the questionnaire. The majority (33%) of statements regarding the worst experience was referring to “psychological distress”, followed by “indigestion and discomfort during defecation” (17%), and “cancer diagnosis” (16%). Among survivors with history of a stoma, the majority (36%) regarded “stoma” as their worst experience. With 45%, “change in life priorities” has been the most frequent positive category before “support by physicians/ nurses” (25%). 43% of the survivors deemed “fighting spirit” as most important advice to overcome the disease.ConclusionEven after many years, colorectal cancer survivors clearly remember experiences from the time of their illness. Echoing the results of the previous breast cancer survivors’ study, “psychological distress”, “change in life priorities” and “fighting spirit” emerged as prominent concepts. In addition, some aspects like the impact of a stoma are of specific importance for colorectal cancer survivors. These findings can be used to inform programmes to improve patient- and quality of life centred aftercare of tumour patients.Clinical trial informationNCT04930016, date of registration 18.06.2021.

Correlates of Health-Related Quality of Life in a National Sample of Older Adult, Long-Term Survivors of Colorectal Cancer.

Most survivors of colorectal cancer (CRC) are older adults who are at high risk of experiencing adverse effects and decreased health-related quality of life (HRQOL) related to cancer and its treatments. This study aimed to describe HRQOL and the demographic and clinical factors associated with HRQOL among older adult, long-term survivors of CRC. A sample of older adult, long-term survivors of CRC (N = 14 458) from the Surveillance Epidemiology and End Results-Medicare Health Outcomes Survey dataset was selected. Hierarchical multiple regression was used to analyze the contribution of demographic and clinical variables to HRQOL as measured by the Veterans Rand 12-item scale. The mean respondent age was 79 years with an average time from diagnosis to survey being about 13 years. In the final model, gender, race, education, income, previous radiation treatment, cardiovascular disease, inflammatory bowel disease, depression, pain, fatigue, functional status, and general health perception were all significantly correlated with mental HRQOL (R2 = 0.53). For physical HRQOL, age at diagnosis, race, marital status, education, time since diagnosis, comorbid conditions, depression, pain, fatigue, functional status, and general health perception were all significant correlates (R2 = 0.85). Symptoms were the largest contributors to mental and physical HRQOL, accounting for 43% and 50% of the variance, respectively. Pain, depression, and fatigue significantly affect the HRQOL of older adult survivors of CRC, underscoring the need for long-term survivorship care. Aggressive symptom assessment and management may be key to improving the HRQOL in this population.

Change Toward Healthier Lifestyles Is Associated With Better Health-Related Quality of Life in Long-Term Colorectal Cancer Survivors.

Little is known about how changes in a constellation of lifestyle factors affect health-related quality of life (HRQoL) in colorectal cancer (CRC) survivors. Our study aimed to investigate the association between changes in healthy lifestyle and HRQoL over time in survivors of stage I-IV CRC. We included 2,283 long-term (≥5 years postdiagnosis) survivors. A healthy lifestyle score (HLS) comprising smoking, alcohol consumption, diet, physical activity, and body fatness was derived at diagnosis and 5-year follow-up (5YFU) and categorized as low, moderate, or high. We assessed HRQoL with the EORTC Quality of Life Questionnaire-Core 30 at 5YFU and 10-year follow-up. We used multivariable linear regression and linear mixed models to explore associations between changes in HLS and HRQoL over follow-up. A low baseline HLS was associated with poorer functioning and global health/QoL and a higher symptom burden at 5YFU compared with a high baseline HLS. An improved HLS from baseline to 5YFU was associated with better functioning, higher global health/QoL, and fewer symptoms at 5YFU than a maintained-high HLS. In longitudinal analyses, improved HLS was associated with better functioning at follow-up. Survivors with a maintained-high or an improved HLS reported generally less fatigue, pain, and dyspnea at follow-ups compared with survivors with a maintained-low or decreased HLS. Change toward a healthier lifestyle since diagnosis was associated with better HRQoL in long-term CRC survivors. Our results support the importance of maintaining and/or promoting a healthier lifestyle among CRC survivors postdiagnosis.

External validation and updating of prediction models for estimating the 1-year risk of low health-related quality of life in colorectal cancer survivors

ObjectivesTimely identification of colorectal cancer (CRC) survivors at risk of experiencing low health-related quality of life (HRQoL) in the near future is important for enabling appropriately tailored preventive actions. We previously developed and internally validated risk prediction models to estimate the 1-year risk of low HRQoL in long-term CRC survivors. In this article, we aim to externally validate and update these models in a population of short-term CRC survivors. Study Design and SettingIn a pooled cohort of 1,596 CRC survivors, seven HRQoL domains (global QoL, cognitive/emotional/physical/role/social functioning, and fatigue) were measured prospectively at approximately 5 months postdiagnosis (baseline for prediction) and approximately 1 year later by a validated patient-reported outcome measure (European Organization for Research and Treatment of Cancer Quality of life Questionnaire–Core 30). For each HRQoL domain, 1-year scores were dichotomized into low vs. normal/high HRQoL. Performance of the previously developed multivariable logistic prediction models was evaluated (calibration and discrimination). Models were updated to create a more parsimonious predictor set for all HRQoL domains. ResultsUpdated models showed good calibration and discrimination (AUC ≥0.75), containing a single set of 15 predictors, including nonmodifiable (age, sex, education, time since diagnosis, chemotherapy, radiotherapy, stoma, and comorbidities) and modifiable predictors (body mass index, physical activity, smoking, anxiety/depression, and baseline fatigue and HRQoL domain scores). ConclusionExternally validated and updated prediction models performed well for estimating the 1-year risk of low HRQoL in CRC survivors within 6 months postdiagnosis. The impact of implementing the models in oncology practice to improve HRQoL outcomes in CRC survivors needs to be evaluated.

Long-term survivors of metastatic colorectal cancer treated with trifluridine/tipiracil.

Long-term survivors of metastatic colorectal cancer treated with trifluridine/tipiracil.

Abstract A045: Multiple roles for plasticity in metastasis and therapy resistance in long-term survivors of metastatic colorectal cancer

Abstract Long-term survivors (LS) of metastatic colorectal cancer (mCRC) who experience multiple recurrences with resectable oligometastatic disease provide an opportunity to explore co-evolution of the tumor and immune microenvironment. We profiled 16 LS of mCRC with a median follow-up of 9.3 years and median of 3 biopsies/resections per patient (range 2-7). We performed multi-omic profiling of 56 primary and 176 metastatic samples from formalin-fixed paraffin-embedded tissue using low pass whole genome sequencing, 3’ RNA sequencing and DNA methylation arrays. A machine learning cell classifier was used to quantify immune cell and fibroblast infiltration from hematoxylin and eosin staining. Copy number profiling showed that the fraction of genome altered remained relatively stable across time and tissue type but that already-altered segments underwent progressive fragmentation. Inter-timepoint divergence of copy number alterations was significantly higher than intra-timepoint divergence, and intra-timepoint divergence was lower for liver and lung metastases than for primary tumors. Chemotherapy treatment did not significantly affect either divergence type. Differential expression and gene set enrichment analysis (GSEA) revealed common pathways dysregulated in metastases compared to primaries, including reductions in E2F (important in G1/S checkpoint) and G2M checkpoint, suggestive of the onset of senescence in metastases. Tumors underwent progressive hypomethylation over time and analysis of genes with concordant changes in promoter methylation and expression revealed dysregulation in pathways related to endocytosis, cell adhesion and migration. This suggests an important role for phenotypic plasticity in driving the metastatic phenotype. There were transient increases in the proportion of macrophages, lymphocytes and neutrophils in tumors that had undergone neoadjuvant chemotherapy in the 6 months prior to resection and slight increases in M1 macrophage activity (by GSEA) in tumors that were previously therapy naïve. There were concordant transient increases in pathways associated with immune response (MYC V1 and MTORC1), as well as xenobiotic metabolism. The latter is a known mechanism of drug resistance to both the platinum- and fluoropyridine-based therapies used in CRC. There were also more sustained increases post-chemotherapy in inflammatory and immune pathways associated with the adaptive immune response and tissue injury and repair. These findings were corroborated by concordant changes in promoter methylation. These data suggest that there is a threshold level of aneuploidy required to facilitate CRC metastasis but the migratory phenotype and adaptation to the metastatic niche are driven by plasticity. Chemotherapy induces differing short-term and long-term anti-tumor immune responses in the local microenvironment. We see evidence that mCRCs are able to mount plastic pro-survival mechanisms in response to chemotherapy. Citation Format: Alison May Berner, Calum Gabbutt, Salpie Nowinski, Jacob Househam, Nick Trahearn, George D. Cresswell, Vinaya Srirangam Nadhamuni, Christopher Kimberley, Matteo Fassan, Ann-Marie Baker, Andrea Sottoriva, Christina Thirlwell, John Bridgewater, Trevor Graham. Multiple roles for plasticity in metastasis and therapy resistance in long-term survivors of metastatic colorectal cancer [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr A045.

Lack of cognitive impairment in long-term survivors of colorectal cancer

BackgroundOur longitudinal study reported cognitive impairment in 43% of people following diagnosis of localised colorectal cancer (CRC) versus 15% in healthy controls (p < 0.001) and 50% versus 13% 1–2 years later (p < 0.001). Here we evaluate cognitive function and neuroimaging in a subgroup at long-term follow-up.Patients and methodsCancer-free Australian participants in the study, and controls, completed cognitive and functional assessments. Neuroimaging was optional. Blood tests included inflammatory markers, clotting factors, sex hormones and apolipoprotein E genotype. The primary endpoint was demographically and practice effect-corrected cognitive scores comparing CRC survivors with controls over time examined using a linear mixed model, adjusted for baseline performance. Secondary endpoints included cognitive impairment rate using the Global Deficit Score [GDS > 0.5], Functional Deficit Score, blood results and neuroimaging.ResultsThe study included 25 CRC survivors (60% men, median age 72) at mean 9 years after baseline (9 received adjuvant chemotherapy) and 25 controls (44% men, median age 68) at mean 6 years after baseline. There were no significant differences in cognitive scores or proportion with cognitive impairment (16 vs. 8%) between survivors and controls and no evidence of accelerated ageing in CRC survivors. Baseline cognitive performance predicted for subsequent cognitive function. There were no differences in functional tests or blood tests between groups. In 18 participants undergoing neuroimaging, 10 CRC survivors had higher myoinositol levels than 8 controls, and lower volume in the right amygdala and caudate and left hippocampal regions.ConclusionsThere was no difference in cognitive capacity and function between CRC survivors and controls 6–12 years after diagnosis. Differences in neuroimaging require confirmation in a larger sample.Highlights• No evidence of long term cognitive impairment in colorectal cancer survivors compared to controls 6–12 years after diagnosis• No evidence of accelerated cognitive ageing in colorectal cancer survivors• No evidence of long-term functional impairment in colorectal cancer survivors

Estimating Risk of Cardiovascular Disease Among Long-Term Colorectal Cancer Survivors: A Nationwide Cohort Study.

BackgroundConcerns about a growing number of colorectal cancer survivors have emerged regarding cardiovascular disease (CVD) risks. However, there is not yet a predictive tool that can estimate CVD risk and support the management of healthcare as well as disease prevention in terms of CVD risk among long-term colorectal cancer survivors.AimTo develop predictive tools to estimate individualized overall and each subtype of CVD risk using a nationwide cohort in South Korea.Methods and ResultsA total of 4,709 newly diagnosed patients with colorectal cancer who survived at least 5 years in the National Health Insurance System were analyzed. Cox proportional hazard regression was used for the identification of independent risk factors for the derivation of predictive nomograms, which were validated in an independent cohort (n = 3,957). Age, fasting serum glucose, γ-glutamyl transpeptidase, Charlson comorbidity index, household income, body mass index, history of chemotherapy, cigarette smoking, and alcohol consumption were identified as independent risk factors for either overall CVD or each subtype of CVD subtype. Based on the identified independent risk factors, six independent nomograms for each CVD category were developed. Validation by an independent cohort demonstrated a good calibration with a median C-index of 0.687. According to the nomogram-derived median score, relative risks of 2.643, 1.821, 4.656, 2.629, 4.248, and 5.994 were found for overall CVD, ischemic heart disease, myocardial infarction, total stroke, ischemic stroke, and hemorrhage stroke in the validation cohort.ConclusionsThe predictive tools were developed with satisfactory accuracy. The derived nomograms may support the estimation of overall and individual CVD risk for long-term colorectal cancer survivors.

Post-diagnostic reliance on plant-compared with animal-based foods and all-cause mortality in omnivorous long-term colorectal cancer survivors

Plant-rich diets are associated with lower cardiometabolic risks and longer survival in the general population, but their association with mortality in cancer survivors is still unclear. We aimed to examine the associations of 3 postdiagnostic plant-based diet indices with all-cause mortality in omnivorous long-term colorectal cancer (CRC) survivors. Diet was assessed with FFQs at a median of 6 years after diagnosis in 1404 CRC survivors (56% male; median age, 69 years) in a Northern German prospective cohort study. An overall, a healthful plant-based, and an unhealthful plant-based diet index were derived by scoring intakes of animal foods reversely and intakes of healthy (whole grains, vegetables, fruits, legumes, nuts, oils, tea/coffee) and less healthy plant foods (refined grains, fruit juices, sugar-sweetened beverages, potatoes, sweets/desserts) positively or reversely, depending on the index. Vital status follow-up was conducted via population registries. Cox proportional hazards regression was applied to estimate HRs for all-cause mortality according to plant-based diet adherence. Within 7 years (median) after diet assessment, 204 deaths occurred. The overall plant-based diet index displayed a significant, inverse association with all-cause mortality (HR per 10-point increase in diet index, 0.72; 95% CI, 0.57-0.91). Although not statistically significant, higher healthful plant-based diet scores showed a strong tendency towards lower mortality (HR, 0.82; 95% CI, 0.67-1.01). The unhealthful plant-based diet index was associated with higher mortality, but lost statistical significance after multivariable adjustment (HR, 1.19; 95% CI, 0.96-1.48). A subgroup analysis revealed that the tendency towards a positive association of the unhealthful plant-based diet with mortality was restricted to less physically active individuals (<95 metabolic equivalent of task hours/week). An overall plant-based diet was inversely associated with all-cause mortality in long-term CRC survivors. However, more research is needed to further disentangle the impacts of different qualities of plant-based diets on cancer survivors' health.

Is sleep associated with BMI, waist circumference, and diet among long-term colorectal cancer survivors? Results from the population-based PROFILES registry.

In the general population, poor sleep quality and short sleep duration are associated with a higher body mass index (BMI) and waist circumference (WC), and an unhealthy diet. The aim of this study was to assess if the association between sleep quality and duration and BMI, WC, and diet quality also exists among colorectal cancer (CRC) survivors, as many CRC survivors have an unhealthy weight and diet. Cross-sectional data from a longitudinal CRC cohort were used. In this study, survivors were 4-13years post diagnosis. The Pittsburgh Sleep Quality Index (PSQI) was used to assess both sleep quality and sleep duration. Diet quality was assessed by scoring adherence (low, moderate, high) to the 2007 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) recommendations of five food groups and nutrients: fruit and vegetables, dietary fiber, red and processed meat, alcoholic beverages, and sugary drinks, using a brief diet screener. BMI and WC were self-measured. Associations were analyzed by multivariable linear and multinomial logistic regression analyses. Among 1002 CRC survivors, 23% reported poor sleep quality (PSQI score ≥ 8) and 24% reported short sleep duration (≤ 6h). No associations between sleep and BMI, WC, and diet quality were found. Sleep problems are common in long-term CRC survivors; however, sleep quality and duration was not associated with BMI, WC, and diet quality in this population. It is unknown why the results differ from findings in the general population.