Time Of Colorectal Cancer Diagnosis Research Articles

Abstract 6294: Subclinical atherosclerosis in newly diagnosed colorectal cancer patients

Abstract Introduction: Recent advances in early detection and treatment have improved survival rates for patients with colorectal cancer (CRC), and emerging data suggests patients may be at elevated risk of cardiovascular disease (CVD). However, there are no standard recommendations for assessing CVD risk in patients with CRC. Coronary artery calcium (CAC) is a measure of the quantity of coronary artery calcification using noninvasive scanning and has been shown to be predictive of CVD risk. This prospective cohort study utilizes CAC to evaluate the occurrence of subclinical atherosclerosis at the time of CRC diagnosis and the risk of major adverse cardiovascular events (MACE). Methods: The ColoCare Study is a prospective cohort study across six U.S. and European sites. Data from one of the ColoCare consortium sites in Los Angeles, California was analyzed. Adults with newly diagnosed stage I- IV colorectal cancer and available non-contrast CT scans were included. Electronic medical records were reviewed for assessment of baseline cardiovascular risk factors and adverse events. Subclinical atherosclerosis was defined as the presence of CAC (CAC>0). CAC was manually measured from routine oncologic diagnostic CT and PET-CT scans at the time of cancer diagnosis using the Agatston method. MACE was defined as hospitalization due to heart failure, cardiomyopathy, ischemic heart disease, or ischemic stroke after the diagnosis of CRC cancer. Multivariable-adjusted Cox regression was used to evaluate the association between CAC at diagnosis and the risk of MACE. Results: Among 109 individuals with CAC measured at the time of CRC diagnosis, 41 (37.6%) had subclinical atherosclerosis (CAC=1-399 [n=29], CAC>400 [n=12]). Individuals with CAC>0 were older (67.0 vs. 51.9 years, p<0.01), more likely to be former or current smokers (48.0 vs. 29.0 years, p=0.04), and to have hypertension (61% vs. 23%, p<0.01) compared to those without CAC (CAC=0). Among individuals with CAC (n=41), 51.2% had scores >100, and 29.2% had scores >400, indicating moderate and severe atherosclerosis respectively. Among patients with moderate or greater CAC burden (>100; statin therapy indicated), 28.6% were not on statin therapy. CAC>0 was associated with an increased incidence of MACE (13% vs. 53%, p<0.01). Discussion: Subclinical atherosclerosis was observed in nearly 40% of patients with CRC at diagnosis and MACE occurred in 38.2% of patients. Most patients were under-optimized for CVD risk, with nearly 30% of statin-eligible patients with at least moderate CAC burden not prescribed statin therapy. These findings highlight an opportunity for improved CVD risk mitigation in patients with CRC, including guidelines-based CVD risk factor modification. Citation Format: Julia A. Levy, Maimoona Nadri, Elham Kazemian, Katelyn M. Atkins, Jordan O. Gasho, Katrina D. Silos, Cody Ramin, Andriana P. Nikolova, Erin M. Siegel, Biljana Gigic, Adetunji T. Toriola, Jennifer Ose, Christopher I. Li, David Shibata, Cornelia M. Ulrich, Jane C. Figueiredo. Subclinical atherosclerosis in newly diagnosed colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6294.

Influence of the duration of type 2 diabetes mellitus on colorectal cancer outcomes

Type 2 diabetes mellitus (T2DM) is a progressive disease, which affects colorectal cancer (CRC) survival. However, data on the relationship between CRC survival and T2DM duration is scarce and controversial. A retrospective observational study was conducted. Sub-cohorts were created based on the duration of T2DM as follows, ≤ or > 5/10/15/20 years. 204 of the 817 (24.95%) included study participants had T2DM at any point of CRC. 160 of the 204 CRC + T2DM patients had detailed T2DM duration data. At the time of CRC diagnosis, 85, 50, 31, and 11 patients had T2DM for > 5/10/15/20 years, respectively, which increased to 110, 71, 45, and 17 during the course of the study. Despite constant glycated hemoglobin values throughout the study, shorter overall and disease-specific survival times were observed for the > 5/10/15 years cohorts and longitudinal survival modeling techniques confirmed the significant effect of T2DM duration in all cohorts. While in the first 3 years after CRC diagnosis, the best survival was found for the ≤ 5 years cohort, all diabetes cohorts had the same survival thereafter. T2DM duration affected CRC survival significantly, therefore, a closer follow-up of this sub-populations is suggested.

Bioinformatic analysis of the obesity paradox and possible associated factors in colorectal cancer using TCGA cohorts.

Colorectal cancer (CRC) is a common malignancy worldwide and the second leading cause of cancer-related deaths. Obesity is an important determinant of CRC incidence; however, obese patients have also shown better long-term survival than non-obese patients, suggesting that the development and progression of CRC are associated with different mechanisms. This study compares the expression of genes, tumor-infiltrating immune cells, and intestinal microbiota between high- and low-body mass index (BMI) patients at the time of CRC diagnosis. The results revealed that high-BMI patients with CRC have better prognosis, higher levels of resting CD4+ T cells, lower levels of T follicular helper cells, and different levels of intratumoral microbiota than low-BMI patients. Our study highlights that tumor-infiltrating immune cells and intratumoral microbe diversity are major features of the obesity paradox in CRC.

No evidence of delay in colorectal cancer diagnosis during the COVID-19 pandemic in Gwangju and Jeonnam, Korea

We evaluated whether the coronavirus disease 2019 (COVID-19) pandemic caused delays in the diagnosis and treatment of colorectal cancer (CRC) in Korea, where there have been no regional or hospital lockdowns during the pandemic period. Data on CRC patients (n=1,445) diagnosed in Gwangju Metropolitan City and Jeonnam Province between January 2019 and December 2021 were assessed. The stage at the time of CRC diagnosis, route to diagnosis, time to initial cancer treatment, and length of hospital admission were compared before and during the COVID-19 pandemic. Logistic regression was also performed to identify factors associated with the risk for diagnosis in an advanced stage. No negative effects indicating a higher CRC stage at diagnosis or delayed treatment during the pandemic were observed. Instead, the risk for an advanced stage at diagnosis (TNM stage III/IV) decreased in CRC patients diagnosed during the pandemic (odds ratio, 0.768; 95% confidence interval, 0.647 to 0.911). No significant differences in the interval from diagnosis to operation or chemotherapy were observed. No negative effects on CRC diagnosis and treatment were found until the end of 2021, which may be related to the small magnitude of the COVID-19 epidemic, the absence of a lockdown policy in Korea, and the rebound in the number of diagnostic colonoscopy procedures in 2021.

1564P Cancer-related fatigue in colorectal cancer patients at the time of diagnosis

Cancer-related fatigue (CRF) is one of most prevalent and distressing symptoms among cancer survivors. It is a subjective experience that should be systematically evaluated in patients with colorectal cancer (CRC). The PERFORM questionnaire (PQ) was developed among Spanish speaking patients for the assessment of fatigue. It ranges from 12-60, with higher scores indicating less fatigue. PQ scores lower than 46 are associated with poor quality of life. Controversy exists regarding the influence of gender, primary tumour and also the effect of oncological treatments in CRF. Information about CRF at the time of diagnosis is lacking and could be essential to anticipate recommendations and to manage CRF during oncological treatment and after it. Cross-sectional study. Patients with recent diagnosis of CRC, ECOG 0-2, able to walk a mile and willing to wear an accelerometer could be included. Cardiorespiratory fitness was estimated through the one-mile walk test. Muscular strength was evaluated through dynamometry (handgrip) and through the sit to stand test. Patients who completed PQ are analyzed. 188 (125 male/63 female) patients were included. 111 stage II-III/ 77 stage IV. Average score for the total population was 51. There were significant differences (p < 0.00) between men (PQ 52.9) and women (PQ 46.5). However, there were no differences between patients with metastatic (50.5) and localized (51.4) CRC. Some variables related with physical condition, namely BMI, waist perimeter, handgrip and sit to stand test were associated with PQ scores of fatigue. However weekly physical activity, basal heart rate and cardiorespiratory condition were not associated with fatigue. Fatigue is a prevalent symptom among women with a recent diagnosis of CRC before initiating chemotherapy. In the total population, gender (male), BMI (higher) and muscular strength were associated with less fatigue. However cardiorespiratory fitness and weekly PA were not associated with fatigue at the time of CRC diagnosis. Surprisingly, metastatic patients do not report more fatigue than patients with localized disease. Screening of fatigue is specially recommended in women at the time of diagnosis of CRC.

Longitudinal changes in personalized platelet count metrics are good indicators of initial 3-year outcome in colorectal cancer.

BACKGROUNDPlatelet count or complete blood count (CBC)-based ratios including lymphocyte-to-monocyte (LMR), neutrophil-to-lymphocyte (NLR), hemoglobin-to-platelet (HPR), red blood cell count distribution width-to-platelet (RPR), and platelet-to-lymphocyte (PLR) ratio are good predictors of colorectal cancer (CRC) survival. Their change in time is not well documented, however.AIMTo investigate the effect of longitudinal CBC ratio changes on CRC survival and their possible associations with clinicopathological properties, comorbidities, and anamnestic data.METHODSA retrospective longitudinal observational study was conducted with the inclusion of 835 CRC patients, who attended at Semmelweis University, Budapest. CBC ratios and two additional newly defined personalized platelet count metrics (pPLTD and pPLTS, the platelet counts relative to the measurement at the time of CRC diagnosis and to the one 4-6 wk after tumor removal surgery, respectively) were recorded.RESULTSThe 835 CRC patients had a total of 4608 measurements (5.52 visits/patient, in average). Longitudinal survival models revealed that the increases/decreases in LMR [hazard ratio (HR): 0.4989, P < 0.0001], NLR (HR: 1.0819, P < 0.0001), HPR (HR: 0.0533, P = 0.0038), pPLTD (HR: 4.9229, P < 0.0001), and pPLTS (HR: 4.7568, P < 0.0001) values were poor prognostic signs of disease-specific survival. The same was obtained for all-cause mortality. Most abnormal changes occurred within the first 3 years after the diagnosis of CRC. RPR and PLR had an only marginal effect on disease-specific (P = 0.0675) and all-cause mortality (Bayesian 95% credible interval: 0.90–186.05), respectively.CONCLUSIONLMR, NLR, and HPR are good metrics to follow the prognosis of the disease. pPLTD and pPLTS perform just as well as the former, while the use of RPR and PLR with the course of the disease is not recommended. Early detection of the abnormal changes in pPLTD, pPLTS, LMR, NLR, or HPR may alert the practicing oncologist for further therapy decisions in a timely manner.

The Impact of Primary Care Physicians on the Surgical Presentation and Outcomes of Colorectal Cancer in Vulnerable Populations.

Multiple socioeconomic and clinical factors have been implicated in the health disparities that exist amongst vulnerable populations with colorectal cancer. Efforts have been directed toward addressing these factors to improve outcomes. We evaluate the impact of primary care physicians (PCP) on the surgical presentation and outcomes of colorectal cancer at a safety-net hospital. A retrospective chart review of 331 patients diagnosed with colorectal adenocarcinoma between 2014 and 2020 at a single-institution urban county medical center. The cohort was predominantly male (59%) and Hispanic (52.1%). Thirty-two percent of patients had a PCP at time of diagnosis. Patients with PCPs compared to those without PCPs had significantly lower rates of acute presentation (perforation or obstruction) (17.0 vs 38.1%, P < .001), higher rates of surgical resection (83.0 vs 70.7%, P = .016), and were less likely to have metastatic disease at presentation (20.4 vs 33.5%, P = .02). Overall, having a PCP also improved probability of survival (HR 1.36, P < .04). Having a PCP at the time of colorectal cancer diagnosis is associated with improved outcomes in a safety-net population, with significant differences in surgical presentation and resection.

Clinical Nutrition Markers as Indicators of Colorectal Cancer (CRC) Disease Stage in a Public Hospital in New York City

ObjectivesThe interrelationships between clinical nutrition markers and colorectal cancer (CRC), including the stage at disease onset, are not well defined. We evaluate nutritional indicators as a function of CRC disease stage. We seek to estimate the nutrition markers’ relative importance in the identification of advanced disease and poor prognosis.MethodsWe utilized a retrospective cross-sectional database of CRC patients treated at two inner-city public hospitals from January 1, 2016, to June 1, 2021. The database includes demographic and routine clinical variables collected at the time of CRC diagnosis. Nutrition markers of interest included hemoglobin, albumin, and body mass index (BMI). Demographic and clinical variables of interest encompassed age, sex, race, smoking status, indication for colonoscopy (screening versus diagnostic), and continuity of care. Continuity of care was defined as having a primary care evaluation at least once within 5 years of a CRC diagnosis. Data were evaluated using one-way multivariate analysis of variance (MANOVA).ResultsAnalysis was conducted on 259 patients (Gender: M = 119, F = 138; Race: White = 15.1%, African American/Black = 43.2%, Hispanic = 30.9%, Asian = 6.9%, Other = 4%). Data were divided into five cancer stages based upon CRC disease progression, with stages 0–2 representing cancer limited to the colonic wall, and stages 3–4 where the tumor extends beyond the colonic wall. MANOVA rejected hypothesis of equality of means between different stages (P = 0.0097). Individual one-way ANOVA for testing equality of means for different clinical stages with each outcome variable (adjusted for multiplicity of testing) produced significant results for albumin (P = 0.0099) and hemoglobin (P = 0.01), but not BMI (P = 0.06). When the mean of patients in stages 0–2 was compared to those in stages 3–4 (advanced versus non-advanced disease), significant differences were observed for albumin (P = 0.024) and hemoglobin (P = 0.017).ConclusionsOur results suggest that nutritional alterations are not observed in CRC patients until the tumor has advanced beyond the colonic wall (stages 3–4); our data were derived from a largely minority population. Future investigations should seek to replicate this work with more precise definitions of malnutrition, including more specific inflammatory markers besides albumin.Funding SourcesNone.

High plasma CD40 ligand level is associated with more advanced stages and worse prognosis in colorectal cancer.

BACKGROUNDColorectal cancer (CRC) is often associated with elevated platelet count (> 400 × 109/L), known as thrombocytosis. The role of CD40 ligand (CD40L), a member of the tumor necrosis factor family, is controversial in CRC. Circulating CD40L is higher in CRC, but its relationship with disease staging and local and distant metastasis is not clear. Although most of the circulating CD40L is produced by platelets, no previous study investigated its relationship with CRC-related thrombocytosis.AIMTo investigate the role of CD40L to predict the outcome of CRC and its relation to thrombocytosis.METHODSA total of 106 CRC patients and 50 age and sex-matched control subjects were enrolled for the study. Anamnestic data including comorbidities and histopathological data were collected. Laboratory measurements were performed at the time of CRC diagnosis and 1.5 mo and at least 6 mo after the surgical removal of the tumor. Plasma CD40L and thrombopoietin were measured via enzyme-linked immunosorbent assay, while plasma interleukin-6 was measured via electrochemiluminescence immunoassay. Patient follow-ups were terminated on January 31, 2021.RESULTSPlasma CD40L of CRC patients was tendentiously higher, while platelet count (P = 0.0479), interleukin-6 (P = 0.0002), and thrombopoietin (P = 0.0024) levels were significantly higher as opposed to the control subjects. Twelve of the 106 CRC patients (11.3%) had thrombocytosis. Significantly higher CD40L was found in the presence of distant metastases (P = 0.0055) and/or thrombocytosis (P = 0.0294). A connection was found between CD40L and platelet count (P = 0.0045), interleukin-6 (P = 0.0130), and thrombocytosis (P = 0.0155). CD40L was constant with the course of CRC, and all baseline differences persisted throughout the whole study. Both pre- and postoperative elevated platelet count, CD40L, and interleukin-6 level were associated with poor overall and disease-specific survival of patients. The negative effect of CD40L and interleukin-6 on patient survival remained even after the stratification by thrombocytosis.CONCLUSIONCD40L levels of CRC patients do not change with the course of the disease. The CD40L level is strongly correlated with platelet count, interleukin-6, thrombocytosis, and the presence of distant metastases.

Frailty and health related quality of life three months after non-metastatic colorectal cancer diagnosis in older patients: A multi-centre prospective observational study

BackgroundHealth related quality of life (HRQL) is an important outcome measure in geriatric oncology. Surgery is the main treatment for colorectal cancer (CRC) but has been associated with a loss of HRQL in older patients. This study aimed to identify determinants for a decreased HRQL at three months after CRC diagnosis. MethodThis multi-centre observational cohort study (NCT04443816) included 273 patients aged ≥70 years diagnosed with non-metastatic CRC. A multi-domain frailty screening was performed in each patient. A decreased HRQL was defined as a mean difference ≥ 10 on the EORTC QLQ-C30 questionnaire between baseline and three months after CRC diagnosis. Determinants of a decreased HRQL were analysed using multivariable logistic regression. ResultsA decrease in HRQL occurred in 63 patients (23.1%). Non-surgical patients had the highest risk of decreased HRQL three months after diagnosis (adjusted odds ratio (OR) 6.4 (95% confidence interval (CI) 2.0–19.8)). The Charlson Comorbidity Index (CCI) (aOR 2.3 (95% (CI) 1.2–4.2)), the American Association of Anesthesiologists class (aOR 2.6 (95%CI 1.4–4.9)), impaired daily functioning (aOR 2.7 (95%CI 1.3–5.6)) and dependent living (aOR 1.9 (95%CI 1.1–4.5)) were associated with a decreased HRQL, mainly caused by non-surgical patients. In surgical patients, a major postoperative complication was a strong determinant of decreased HRQL and was associated with preoperative comorbidity and cognitive impairment (aOR 4.0 (95%CI 1.9–8.8)). ConclusionFrailty characteristics are highly prevalent in older patients at time of CRC diagnosis but not strongly associated with a decreased HRQL after three months. Non-surgical patients and patients with major postoperative complications had the highest risk of decreased HRQL.Registered at clinicaltrials.gov trial number: NCT04443816

Nutritional status and outcomes of veterans undergoing curative surgery for colorectal cancer.

e18585 Background: Malnutrition is highly prevalent within the cancer population. Malnourishment has various negative surgical and oncologic impacts. The Veterans Health Administration (VHA) provides comprehensive care to patients in a single-payer system allowing for capture of peri-operative data and the opportunity for focused pre-operative (pre-op) interventions to improve outcomes. We sought to study the effect of pre-op weight and albumin on post-operative (post-op) complications in a contemporaneous group of veterans with colorectal cancer (CRC) at a tertiary care Veterans Affairs (VA) hospital. Methods: This is a retrospective review of 105 patients with colorectal malignancies treated with curative intent surgery at the VA Ann Arbor Healthcare System between January 2015 and January 2020. Patients with distant metastatic disease, neoadjuvant therapy, non-adenocarcinoma histology, or those receiving majority of care outside of the VHA were excluded. We examined BMI trends from one year prior to one year post surgery, rates of nutrition consults, and post-op complications defined as abnormal clinical developments such as, but not limited to, infection and delayed wound healing. Fisher’s exact test was used for analysis. Results: At time of CRC diagnosis, the mean age was 70.3 ± 9.1 and the median stage was T2N0. Surgical resections were 65% (n = 68) laparoscopic. Pre-op weight loss from 6 months prior to diagnosis to time of surgery was observed in the majority of patients (n = 47, 64%). Significant weight loss, defined as ≥3% weight reduction, was seen in 45% (n = 33) of patients. A quarter of patients were identified to have a low pre-op albumin of less than 3.5 (n = 25, 25%). Significant weight loss and low pre-op albumin were each independently associated with increased post-op complications (p &lt; 0.01). Post-op weight loss was seen in 81% (n = 73) and 69% (n = 48) of patients at 30- and 60-days post-op, respectively, and was not associated with post-op complications. Inpatient post-op nutrition consultation was performed in 96% (n = 101) of patients; nutritional supplements were recommended in only 23% (n = 23) of cases. In patients with significant weight loss, pre-op nutrition evaluation was performed in 15% (n = 5) of cases and post-op outpatient nutrition follow up occurred in 18% (n = 6) of cases. Conclusions: 45% of patients had ≥3% weight loss 6 months prior to diagnosis of CRC and 25% of patients had low albumin levels. These led to greater post-operative complications. An intensive nutrition pre-habilitation program to address weight loss and low albumin prior to surgery for CRC is needed and may reduce associated complications.

It's contrary - comorbidity does not affect survival of South Africans with colorectal cancer: An analysis from the Colorectal Cancer in South Africa cohort.

The Colorectal Cancer South Africa (CRCSA) study is an observational cohort of patients with colorectal cancer (CRC) in Johannesburg, South Africa (SA). We found that the mean age at the time of CRC diagnosis was 56.6 years, consistent with studies from SA and sub-Saharan Africa. In high-income settings, comorbidity adversely affects CRC survival, and patients are substantially older at the time of CRC diagnosis. Given the younger age at CRC diagnosis in the CRCSA cohort, we hypothesised that comorbidity may be less prevalent and have little impact on CRC survival. To determine the prevalence of comorbidity and whether comorbidity adversely affects overall survival (OS) of CRC patients. Patients enrolled in the CRCSA study between January 2016 and July 2018 were included. The cohort comprised a convenience sample of adults with histologically confirmed CRC, treated at the University of the Witwatersrand Academic Teaching Hospital Complex. Demographic, clinical and histological variables were collected at baseline and participants were followed up for OS. The Charlson comorbidity index (CCI) scoring system was used to classify participants as 'no comorbidity' (CCI score 0) and '1 or more comorbidities' (CCI score ≥1). A descriptive analysis of the cohort was undertaken, while survival across comorbidity groups was compared by the Kaplan-Meier method and Cox proportional hazards (PH) regression models. Multivariable Cox PH regression was performed to examine the effect of comorbidity on survival (unadjusted) and then adjusted for variables. There were 424 participants, and the mean (standard deviation) age was 56.6 (14.1) years (range 18 - 91). Only 19.1% of participants had ≥1 comorbidities, of which diabetes mellitus was most frequent (12.3%), followed by chronic obstructive pulmonary disease (4.7%) and cardiovascular disease (3.1%). There was no significant difference in unadjusted and adjusted risk of death for the group with ≥1comorbidities compared with those with no comorbidity. However, an incidental finding showed a significantly increased risk of death for those receiving potentially curative treatment later than 40 days after CRC diagnosis. In the CRCSA cohort from Johannesburg, comorbidity is uncommon, with no significant adverse effect on OS. If potentially curative treatment is initiated within 40 days of CRC diagnosis, OS could be improved. To fully understand the epidemiology of CRC in SA, population-based registries are essential, and future research should aim to identify health system failures that lead to delays in intervention beyond 40 days in patients with CRC.

Covering the Cover

Covering the Cover

Brain metastases in newly diagnosed colorectal cancer: a population-based study.

BackgroundPopulation-based incidence evaluations and prognosis assessments of brain metastasis (BM) at diagnosis of colorectal cancer (CRC) are lacking. Our study sought to determine the incidence of BM in CRC patients, median survival of patients with BM, and the risk factors of BM in CRC.Patients and methodsPatients diagnosed with CRC were identified using the Surveillance, Epidemiology, and End Results database. Multivariable logistic and Cox regression analyses were performed to identify predictors of the presence of BM at CRC diagnosis and the factors associated with poor survival. Kaplan–Meier analysis was used to estimate the survival difference between subgroups.ResultsWe identified 170,793 adult patients diagnosed with CRC between 2010 and 2013. From these patients, we identified 401 patients with BM at the time of CRC diagnosis, which represents 0.23% of the entire patient CRC cohort and 1.3% of the patients with metastatic disease to any site. Median survival of patients with BM was 7.0 months, and the survival could increase to 15.59 months if there was no metastasis to other organs. We found that extracranial metastases number, tumor site, and pathology type were associated with BM at CRC diagnosis.ConclusionThe findings of this study indicate the incidence and prognosis for patients with BM at the time of CRC diagnosis. Our findings lend support for positive treatment for BM without metastasis to other organs.

Statin consumption as a risk factor for developing colorectal cancer: a retrospective case study

BackgroundStatins are the backbone of lipid-lowering therapy and are among the most commonly prescribed drugs in the elderly population in Sweden today. Colorectal cancer is the second most common cancer in men and women, after prostate and breast cancer, respectively, with a median age of 72 years at diagnosis. Statins induce mitochondrial damage leading to accumulation of reactive oxygen species in the cell. Reactive oxygen species can cause mutations in mitochondrial as well as nuclear DNA leading to the development of cancer. Our hypothesis was that statins increase the risk for colorectal cancer.MethodsA case study was performed on consecutive cases of colorectal cancer diagnosed at Norrlands University Hospital (NUS) in Umeå between 2012 and 2015 (n = 325). Patients diagnosed with diabetes mellitus type II (DM II n = 65) were excluded in the primary endpoint analysis (occurrence of colorectal cancer). As control, three databases were used to create an age-matched population in order to calculate the proportion of inhabitants using statins in the county of Västerbotten, Sweden. A secondary endpoint was cancer-specific survival among our study group of colorectal cancer patients, including those with DM II, investigating whether there was a difference if the patient was a ‘recent’ statin user or not at the time of diagnosis.ResultsStatin use at the time of colorectal cancer diagnosis in the study group was 23.8%. The corresponding figure in an age-matched population in Västerbotten was 24.6%. Using a one-proportional one-sided z test, there was no significant difference between these (23.8%, 95% CI 18.6–29.0%, p = 0.601). When comparing groups 20–64 years of age, the difference was greater with recent statin use in 17.8% in the study population and 11.9% in Västerbotten (17.8%, 95% CI 9.0–26.6%, p = 0.059). When considering cancer-specific survival, no significant difference in survival was seen when comparing ‘former/never’ statin users as reference category with ‘recent’ users diagnosed with colorectal cancer (HR 1.39, 95% CI 0.89–2.16).ConclusionsNo significant increase in risk for developing colorectal cancer among patients (type II diabetics excluded) medicated with statins was found. We found no correlation between ‘recent’ statin use at the time of diagnosis and cancer-specific survival.

Early Interval Colorectal Cancer in the Inflammatory Bowel Disease Population: Is There a Role for Risk Stratification?

Introduction: Current guidelines recommend starting colorectal cancer (CRC) surveillance in patients with inflammatory bowel disease (IBD) 8-10 years after symptom-onset. Recent European studies report that the incidence of CRC preceding the 8-10-year recommendation ranges from 12-42%. We aimed to describe the frequency of early interval CRC in a United States IBD cohort and to identify risk factors for early interval CRC. Methods: We performed a case-control study of IBD patients diagnosed with CRC from 2005-2016. We compared characteristics of patients with early interval CRC (diagnosis of CRC within 8 years of IBD symptom-onset) to those with standard interval CRC. Statistical analysis was performed using chisquared and Fisher's exact test for categorical variables and Student's t-test or Wilcoxon Rank Sum test for continuous variables as appropriate. A multivariable logistic regression was performed controlling for all variables with a P-value <0.15. Results: 96 patients with IBD and CRC were identified. 12 (12.5%) patients developed CRC within 8 years of IBD symptom-onset (Figure 1). Patients with an early-interval CRC were older at IBD symptom-onset (mean 44.8 vs. 30.5 years; P=0.002) and slightly younger at the time of CRC diagnosis (mean 47.2 v. 55.2 years; P=0.078) than those with standard interval CRC. Active smoking was also associated with early interval CRC (27.3% v. 5.1%) (P=0.036). Patients with a history of systemic corticosteroid use (8.3% v 40.5%; P=0.051) and oral 5-aminosalicylic acid use (25.0% v. 60.7%; P=0.020) were less likely to have an early interval CRC. On multivariate logistic regression, when controlling for age at CRC diagnosis, age at IBD symptom-onset, gender, 5-aminosalicylic acid use, and smoking, both younger age at CRC diagnosis (odds ratio [OR] 0.57; 95% CI 0.35 - 0.91) and older age at IBD symptom-onset (OR 1.79; 95% CI 1.10-2.92) remain significant predictors of early interval CRC (Table 1).Figure: Frequency of Colorectal Cancer By Duration of Inflammatory Bowel Disease Symptoms.Table: Table. Predictors of Early Interval Colorectal Cancer Among Patients with Inflammatory Bowel DiseaseConclusion: A substantial number of patients with IBD develop CRC prior to the currently recommended timeframe for initiation of CRC surveillance. Risk stratifying patients based on predictors would allow us to individualize CRC surveillance for patients with IBD. Future studies should focus on developing a clinical tool that can be used to individualize the timing of CRC surveillance for this at-risk population. A multicenter study would allow us to better generalize our results as well as validate our predictors.

Influence of NSAID Use Among Colorectal Cancer Survivors on Cancer Outcomes.

Colorectal cancer (CRC) is the third most common cancer diagnosed in men and women in the United States. Given the availability of effective screening, most tumors are found early enough to offer patients substantial long-term survival. Thus there is a resulting significant population of CRC survivors for whom modifiable risk factors for recurrence and survival would be of interest. We conducted a population-based retrospective cohort study among patients enrolled in 2 large Midwestern health plans for which claims data, including pharmacy fill data, and medical record data were available. Men and women who were 40 years of age or older at the time of CRC diagnosis with disease less than stage IV and no history of Crohn disease, ulcerative colitis, and irritable bowel syndrome were included. CRC cases diagnosed between January 1, 1990 and December 31, 2000 were included if they met the inclusion criteria. Adjusted Cox proportional hazard models were used with exposure modeled as a time-dependent covariate. We assessed progression-free survival, defined as an aggressive polyp or invasive disease, and overall survival. After adjustment for age at diagnosis, sex, race, body mass index, stage, side of initial tumor, and tumor histology, we found that current users of nonsteroidal anti-inflammatory drugs had a 3-fold decreased risk of recurrence and a >7-fold decreased risk of death. Our results are statistically significant with P-values <0.05. Our results suggest that current use of nonsteroidal anti-inflammatory drugs provides significant improvements in CRC outcomes.

Hereditary colorectal cancer syndromes: American Society of Clinical Oncology Clinical Practice Guideline endorsement of the familial risk-colorectal cancer: European Society for Medical Oncology Clinical Practice Guidelines.

To provide recommendations on prevention, screening, genetics, treatment, and management for people at risk for hereditary colorectal cancer (CRC) syndromes. The American Society of Clinical Oncology (ASCO) has a policy and set of procedures for endorsing clinical practice guidelines that have been developed by other professional organizations. The Familial Risk-Colorectal Cancer: European Society for Medical Oncology Clinical Practice Guideline published in 2013 on behalf of the European Society for Medical Oncology (ESMO) Guidelines Working Group in Annals of Oncology was reviewed for developmental rigor by methodologists, with content and recommendations reviewed by an ASCO endorsement panel. The ASCO endorsement panel determined that the recommendations of the ESMO guidelines are clear, thorough, and based on the most relevant scientific evidence. The ASCO panel endorsed the ESMO guidelines and added a few qualifying statements. Approximately 5% to 6% of patient cases of CRC are associated with germline mutations that confer an inherited predisposition for cancer. The possibility of a hereditary cancer syndrome should be assessed for every patient at the time of CRC diagnosis. A diagnosis of Lynch syndrome, familial adenomatous polyposis, or another genetic syndrome can influence clinical management for patients with CRC and their family members. Screening for hereditary cancer syndromes in patients with CRC should include review of personal and family histories and testing of tumors for DNA mismatch repair deficiency and/or microsatellite instability. Formal genetic evaluation is recommended for individuals who meet defined criteria.

Detection of colorectal cancer (CRC) by urinary volatile organic compound analysis.

Colorectal cancer (CRC) is a leading cause of cancer related death in Europe and the USA. There is no universally accepted effective non-invasive screening test for CRC. Guaiac based faecal occult blood (gFOB) testing has largely been superseded by Faecal Immunochemical testing (FIT), but sensitivity still remains poor. The uptake of population based FOBt testing in the UK is also low at around 50%. The detection of volatile organic compounds (VOCs) signature(s) for many cancer subtypes is receiving increasing interest using a variety of gas phase analytical instruments. One such example is FAIMS (Field Asymmetric Ion Mobility Spectrometer). FAIMS is able to identify Inflammatory Bowel disease (IBD) patients by analysing shifts in VOCs patterns in both urine and faeces. This study extends this concept to determine whether CRC patients can be identified through non-invasive analysis of urine, using FAIMS. 133 patients were recruited; 83 CRC patients and 50 healthy controls. Urine was collected at the time of CRC diagnosis and headspace analysis undertaken using a FAIMS instrument (Owlstone, Lonestar, UK). Data was processed using Fisher Discriminant Analysis (FDA) after feature extraction from the raw data. FAIMS analyses demonstrated that the VOC profiles of CRC patients were tightly clustered and could be distinguished from healthy controls. Sensitivity and specificity for CRC detection with FAIMS were 88% and 60% respectively. This study suggests that VOC signatures emanating from urine can be detected in patients with CRC using ion mobility spectroscopy technology (FAIMS) with potential as a novel screening tool.

Cancer‐associated autoantibodies to MUC1 and MUC4—A blinded case–control study of colorectal cancer in UK collaborative trial of ovarian cancer screening

Recent reports suggest that autoantibodies directed to aberrantly glycosylated mucins, in particular MUC1 and MUC4, are found in patients with colorectal cancer. There is, however, limited information on the autoantibody levels before clinical diagnosis, and their utility in cancer screening in the general population. In our study, we have generated O-glycosylated synthetic MUC1 and MUC4 peptides in vitro, to mimic cancer-associated glycoforms, and displayed these on microarrays. The assay’s performance was tested through an initial screening of serum samples taken from patients at the time of colorectal cancer diagnosis and healthy controls. Subsequently, the selected biomarkers were evaluated in a blinded nested case–control study using stored serum samples from among the 50,640 women randomized to the multimodal arm of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), where women gave annual blood samples for several years. Cases were 97 postmenopausal women who developed colorectal cancer after recruitment and were age-matched to 97 women without any history of cancer. MUC1-STn and MUC1-Core3 IgG autoantibodies identified cases with 8.2 and 13.4% sensitivity, respectively, at 95% specificity. IgA to MUC4 glycoforms were unable to discriminate between cases and controls in the UKCTOCS sera. Additional analysis was undertaken by combining the data of MUC1-STn and MUC1-Core3 with previously generated data on autoantibodies to p53 peptides, which increased the sensitivity to 32.0% at 95% specificity. These findings suggest that a combination of antibody signatures may have a role as part of a biomarker panel for the early detection of colorectal cancer.