Use of chemotherapy in patients with oesophageal, stomach, colon, rectal, liver, pancreatic, lung, and ovarian cancer: an International Cancer Benchmarking Partnership (ICBP) population-based study.

BACKGROUND: There are few data on international variation in chemotherapy use, despite it being a key treatment type for some patients with cancer. Here, we aimed to examine the presence and size of such variation. METHODS: This population-based study used data from Norway, the four UK nations (England, Northern Ireland, Scotland, and Wales), eight Canadian provinces (Alberta, British Columbia, Manitoba, Newfoundland and Labrador, Nova Scotia, Ontario, Prince Edward Island, and Saskatchewan), and two Australian states (New South Wales and Victoria). Patients aged 15-99 years diagnosed with cancer in eight different sites (oesophageal, stomach, colon, rectal, liver, pancreatic, lung, or ovarian cancer), with no other primary cancer diagnosis occurring from within the 5 years before to 1 year after the index cancer diagnosis or during the study period were included in the study. We examined variation in chemotherapy use from 31 days before to 365 days after diagnosis and time to its initiation, alongside related variation in patient group differences. Information was obtained from cancer registry records linked to clinical or patient management system data or hospital administration data. Random-effects meta-analyses quantified interjurisdictional variation using 95% prediction intervals (95% PIs). FINDINGS: Between Jan 1, 2012, and Dec 31, 2017, of 893 461 patients with a new diagnosis of one of the studied cancers, 111 569 (12·5%) did not meet the inclusion criteria, and 781 892 were included in the analysis. There was large interjurisdictional variation in chemotherapy use for all studied cancers, with wide 95% PIs: 47·5 to 81·2 (pooled estimate 66·4%) for ovarian cancer, 34·9 to 59·8 (47·2%) for oesophageal cancer, 22·3 to 62·3 (40·8%) for rectal cancer, 25·7 to 55·5 (39·6%) for stomach cancer, 17·2 to 56·3 (34·1%) for pancreatic cancer, 17·9 to 49·0 (31·4%) for lung cancer, 18·6 to 43·8 (29·7%) for colon cancer, and 3·5 to 50·7 (16·1%) for liver cancer. For patients with stage 3 colon cancer, the interjurisdictional variation was greater than that for all patients with colon cancer (95% PI 38·5 to 78·4; 60·1%). Patients aged 85-99 years had 20-times lower odds of chemotherapy use than those aged 65-74 years, with very large interjurisdictional variation in this age difference (odds ratio 0·05; 95% PI 0·01 to 0·19). There was large variation in median time to first chemotherapy (from diagnosis date) by cancer site, with substantial interjurisdictional variation, particularly for rectal cancer (95% PI -15·5 to 193·9 days; pooled estimate 89·2 days). Patients aged 85-99 years had slightly shorter median time to first chemotherapy compared with those aged 65-74 years, consistently between jurisdictions (-3·7 days, 95% PI -7·6 to 0·1). INTERPRETATION: Large variation in use and time to chemotherapy initiation were observed between the participating jurisdictions, alongside large and variable age group differences in chemotherapy use. To guide efforts to improve patient outcomes, the underlying reasons for these patterns need to be established. FUNDING: International Cancer Benchmarking Partnership (funded by the Canadian Partnership Against Cancer, Cancer Council Victoria, Cancer Institute New South Wales, Cancer Research UK, Danish Cancer Society, National Cancer Registry Ireland, The Cancer Society of New Zealand, National Health Service England, Norwegian Cancer Society, Public Health Agency Northern Ireland on behalf of the Northern Ireland Cancer Registry, DG Health and Social Care Scottish Government, Western Australia Department of Health, and Public Health Wales NHS Trust).

Trends in management and outcomes of colon cancer in the United States over 15 years: Analysis of the National Cancer Database.

Management of colon cancer has changed over the last few decades. We assessed the trends in management and outcomes using the US National Cancer Database (NCDB). A retrospective analysis of all patients with colonic adenocarcinoma between 2005 and 2019 was conducted. The cohort was divided into three equal time periods: Period 1 (2005-2009), Period 2 (2010-2014), and Period 3 (2015-2019) to examine treatment and outcomes trends. The primary outcome was 5-year overall survival (OS). The study included 923,275 patients. A significant increase in patients with stage IV disease was noted in Period 3 compared to Period 1 (47.9% vs. 27.9%, respectively), whereas a reciprocal reduction was seen in patients with locally advanced disease (stage II: 20.8%-12%; stage III: 14.5%-7.7%). Use of immunotherapy significantly increased from 0.3% to 7.6%. Mean 5-year OS increased (43.6 vs. 42.1 months) despite the increase in metastatic disease and longer time from diagnosis to definitive surgery (7 vs. 14 days). A reduction in 30-day readmission (5.1%-4.2%), 30- (3.9%-2.8%), and 90-day mortality (7.1%-5%) was seen. Laparoscopic and robotic surgery increased from 45.8% to 53.1% and 2.9% to 12.7%, respectively. Median postoperative length of hospital stay decreased by 2 days. Rate of positive resection margins (7.2%-6%) and median number of examined lymph nodes (14-16) also improved. Minimally invasive surgery and immunotherapy for colon cancer significantly increased in recent years. Patient outcomes including OS improved over time.

Age at diagnosis for lung, colon, breast and prostate cancers: An international comparative study.

Differences in the average age at cancer diagnosis are observed across countries. We therefore aimed to assess international variation in the median age at diagnosis of common cancers worldwide, after adjusting for differences in population age structure. We used IARC's Cancer Incidence in Five Continents (CI5) Volume XI database, comprising cancer diagnoses between 2008 and 2012 from population-based cancer registries in 65 countries. We calculated crude median ages at diagnosis for lung, colon, breast and prostate cancers in each country, then adjusted for population age differences using indirect standardization. We showed that median ages at diagnosis changed by up to 10 years after standardization, typically increasing in low- and middle-income countries (LMICs) and decreasing in high-income countries (HICs), given relatively younger and older populations, respectively. After standardization, the range of ages at diagnosis was 12 years for lung cancer (median age 61-Bulgaria vs 73-Bahrain), 12 years for colon cancer (60-the Islamic Republic of Iran vs 72-Peru), 10 years for female breast cancer (49-Algeria, the Islamic Republic of Iran, Republic of Korea vs 59-USA and others) and 10 years for prostate cancer (65-USA, Lithuania vs 75-Philippines). Compared to HICs, populations in LMICs were diagnosed with colon cancer at younger ages but with prostate cancer at older ages (both pLMICS-vs-HICs < 0.001). In countries with higher smoking prevalence, lung cancers were diagnosed at younger ages in both women and men (both pcorr < 0.001). Female breast cancer tended to be diagnosed at younger ages in East Asia, the Middle East and Africa. Our findings suggest that the differences in median ages at cancer diagnosis worldwide likely reflect population-level variation in risk factors and cancer control measures, including screening.

What can hospital emergency admissions prior to cancer diagnosis tell us about socio-economic inequalities in cancer diagnosis? Evidence from population-based data in England.

BACKGROUND: More deprived cancer patients are at higher risk of Emergency Presentation (EP) with most studies pointing to lower symptom awareness and increased comorbidities to explain those patterns. With the example of colon cancer, we examine patterns of hospital emergency admissions (HEAs) history in the most and least deprived patients as a potential precursor of EP. METHODS: We analysed the rates of hospital admissions and their admission codes (retrieved from Hospital Episode Statistics) in the two years preceding cancer diagnosis by sex, deprivation and route to diagnosis (EP, non-EP). To select the conditions (grouped admission codes) that best predict emergency admission, we adapted the purposeful variable selection to mixed-effects logistic regression. RESULTS: Colon cancer patients diagnosed through EP had the highest number of HEAs than all the other routes to diagnosis, especially in the last 7 months before diagnosis. Most deprived patients had an overall higher rate and higher probability of HEA but fewer conditions associated with it. CONCLUSIONS: Our findings point to higher use of emergency services for non-specific symptoms and conditions in the most deprived patients, preceding colon cancer diagnosis. Health system barriers may be a shared factor of socio-economic inequalities in EP and HEAs.

Pulmonary Metastasis as the First Site of Metastasis After Curative Surgery for Colon Cancer: Incidence and Risk Factors According to the TNM Stage.

BACKGROUND: The lungs are one of the most common sites for colon cancer metastasis. A few studies reported that approximately 2% to 10% of patients with colon cancer developed pulmonary metastasis. However, among these studies, patient characteristics were heterogeneous, and information on pulmonary metastasis incidence by the TNM stage was scarce. OBJECTIVE: This study evaluated the incidence of pulmonary metastasis in colon cancer without synchronous metastasis treated with radical surgery and identified risk factors for pulmonary metastasis according to the TNM stage. DESIGN AND SETTINGS: This retrospective study included all patients with colon cancer without metastasis who underwent radical surgery for primary tumor at Samsung Medical Center between January 2007 and December 2016. PATIENTS: A total of 4889 patients who underwent radical surgery for stage I and III colon cancer were included. MAIN OUTCOME MEASURES: The main outcome measures were the incidence of pulmonary metastasis and overall survival. RESULTS: A total of 156 patients (3.2%) were diagnosed with pulmonary metastasis after a median of 16 months from the time of radical surgery for colon cancer to detection of pulmonary metastasis. The pulmonary metastasis incidence rate by the TNM stage was 0.5% in stage I, 1.6% in stage II, and 6% in stage III. Risk factors for pulmonary metastasis were preoperative CEA >5 ng/mL, cancer obstruction, N stage, vascular invasion, perineural invasion, and adjuvant chemotherapy for primary colon cancer in multivariable analysis. LIMITATION: This was a retrospective single-center study. CONCLUSIONS: Preoperative CEA >5 ng/mL, cancer obstruction, pN stage, vascular invasion, perineural invasion, and receiving adjuvant chemotherapy for primary colon cancer were risk factors for pulmonary metastasis in colon cancer. Therefore, patients with risk factors for pulmonary metastasis should be recommended for intensive follow-up to detect lung metastases. See Video Abstract . METSTASIS PULMONAR EN EL PRIMER SITIO TRAS CIRUGA CURATIVA DEL CNCER DE COLON INCIDENCIA Y FACTORES DE RIESGO SEGN ESTADIO TNM: ANTECEDENTES:Los pulmones son uno de los sitios más comunes de metástasis del cáncer de colon. Algunos estudios informaron que aproximadamente entre el 2% y el 10% de los pacientes con cáncer de colon desarrollaron metástasis pulmonar. Sin embargo, entre estos estudios, las características de los pacientes fueron heterogéneas y la información sobre la incidencia de metástasis pulmonares según el estadio TNM fue escasa.OBJETIVO:Este estudio evaluó la incidencia de metástasis pulmonar en cáncer de colon sin metástasis sincrónica tratada con cirugía radical e identificó factores de riesgo para metástasis pulmonar según el estadio TNM.DISEÑO Y AJUSTES:Este estudio retrospectivo incluyó a todos los pacientes con cáncer de colon sin metástasis que se sometieron a cirugía radical por tumor primario en el Samsung Medical Center entre enero de 2007 y diciembre de 2016.PACIENTES:Se incluyó un total de 4.889 pacientes sometidos a cirugía radical por cáncer de colon en estadio I-III.PRINCIPALES MEDIDAS DE RESULTADO:Las principales medidas de resultado fueron la incidencia de metástasis pulmonar y la supervivencia general.RESULTADOS:Un total de 156 pacientes (3,2%) fueron diagnosticados con metástasis pulmonar con una duración media de 16 meses desde el momento de la cirugía radical por cáncer de colon hasta la detección de la metástasis pulmonar. La tasa de incidencia de metástasis pulmonares por estadio TNM fue del 0,5% en el estadio I, del 1,6% en el estadio II y del 6% en el estadio III. Los factores de riesgo de metástasis pulmonar fueron CEA preoperatorio superior a 5 ng/ml, obstrucción por cáncer, estadio N, invasión vascular, invasión perineural y quimioterapia adyuvante para el cáncer de colon primario en un análisis multivariable.LIMITACIÓN:Este fue un estudio retrospectivo de un solo centro.CONCLUSIÓN:CEA preoperatorio superior a 5 ng/ml, obstrucción por cáncer, estadio pN, invasión vascular, invasión perineural y recibir quimioterapia adyuvante para el cáncer de colon primario fueron factores de riesgo de metástasis pulmonar en el cáncer de colon. Por lo tanto, se debe recomendar un seguimiento intensivo a los pacientes con factores de riesgo de metástasis pulmonares para detectar metástasis pulmonares. (Traducción-Dr Yolanda Colorado ).

Diverticulosis, Adenomas, and Cancer in the Colon: A Systematic Review and Meta-Analysis of Endoscopic Studies.

GOALS: To perform a systematic review and meta-analysis of endoscopic studies to evaluate an association between diverticulosis and neoplastic lesions in the colon. BACKGROUND: Some epidemiological observations suggest an association between diverticulosis and adenoma/cancer in the colon. However, an increased risk of colon neoplastic lesions in diverticulosis subjects was found to be increased in some studies, but not in others, puzzling data interpretation. STUDY: From the retrieved studies, prevalence of adenomas, advanced adenomas, cancer or neoplasia (advanced adenoma or cancer) was compared between subjects with or without diverticulosis, and comparisons in subgroups were also performed. RESULTS: Data of 26 studies with a total of 419,623 patients were eventually considered, including 27,092 patients with diverticulosis. Data analysis found a statistically significant association between diverticulosis and adenomas (OR: 1.88; 95% CI: 1.50-2.25), advanced adenomas (OR: 1.49; 95% CI: 1.02-2.16), and neoplasia (OR: 1.50; 95% CI: 1.11-2.02), but not with cancer alone (OR: 1.01; 95% CI: 0.70-1.47). These associations were confirmed in the subgroup analyses, by considering Caucasian and Asian populations, prospective and retrospective studies, screening or symptoms settings, and between good or fair quality studies. CONCLUSIONS: A statistically significant association between diverticulosis and adenomas, advanced adenomas and neoplasia, but not with cancer alone was found. However, the strength of association seems to be insufficient to impact on clinical practice.

Adult Height and Risk of Colorectal Cancer: A Pooled Analysis of 10 Population-based Cohort Studies in Japan.

BACKGROUND: While tall stature has been linked to an increase in the risk of colorectal cancer (CRC), its association with cancer in the colorectum and its subsites remains unclear among Asians. METHODS: We conducted a pooled analysis of 10 population-based cohort studies among adults in Japan. Each study estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC incidence associated with adult height were estimated using Cox proportional hazards regression with adjustment of the same set of covariates were then pooled to estimate summary HRs incidence using random-effect models. RESULTS: We identified 9,470 CRC incidences among 390,063 participants during 5,672,930 person-years of follow-up. Men and women with tall stature had a higher risk of CRC and colon cancer. HRs for CRC, colon cancer, and distal colon cancer for the highest versus lowest height categories were 1.23 (95% CI, 1.07-1.40), 1.22 (95% CI, 1.09-1.36), and 1.27 (95% CI, 1.08-1.49), respectively, in men and 1.21 (95% CI, 1.09-1.35), 1.23 (95% CI, 1.08-1.40), and 1.35 (95% CI, 1.003-1.81), respectively, in women. The association with proximal colon cancer and rectal cancer was less evident in both sexes. CONCLUSION: This pooled analysis confirms the link between tall stature and a higher risk of CRC and colon cancer (especially distal colon) among the Japanese and adds evidence to support the use of adult height to identify those at a higher risk of CRC.

Cancer of colon, rectum and anus: the rising burden of disease worldwide from 1990 to 2019.

BACKGROUND: Previous studies suggest that trends of cancer of colon, rectum and anus (CRA) incidence and mortality have been decreasing in recent decades. However, the trends are not uniform across age groups. This study aimed to assess the trends of the cancer of CRA burden worldwide. METHODS: A descriptive study was carried out with a joinpoint regression analysis using the database of the Global Burden of Disease study. RESULTS: About 2.2 million new cases of cancer of CRA were diagnosed in the world in 2019, whereby cancer of CRA caused ~1.1 million deaths. Globally, the incidence trend in both sexes together was increasing in 1990-2019, while the mortality trend was decreasing. The highest rise both in incidence and mortality was observed in the East Asia region (by 3.6% per year and by 1.4% per year, respectively) and the Andean Latin America region (by 2.7% per year and by 1.2% per year, respectively). However, of particular concern is the significant increase in the incidence (by 1.7% per year) and mortality (by 0.5% per year) from cancer of CRA in people aged 15-49. CONCLUSIONS: Unfavorable trends in cancer of CRA in the young require more attention in management plans.

Distinct Driver Pathway Enrichments and a High Prevalence of TSC2 Mutations in Right Colon Cancer in Chile: A Preliminary Comparative Analysis.

Colorectal cancer (CRC) is the second leading cause of cancer deaths globally. While ethnic differences in driver gene mutations have been documented, the South American population remains understudied at the genomic level, despite facing a rising burden of CRC. We analyzed tumors of 40 Chilean CRC patients (Chp) using next-generation sequencing and compared them to data from mainly Caucasian cohorts (TCGA and MSK-IMPACT). We identified 388 mutations in 96 out of 135 genes, with TP53 (45%), KRAS (30%), PIK3CA (22.5%), ATM (20%), and POLE (20%) being the most frequently mutated. TSC2 mutations were associated with right colon cancer (44.44% in RCRC vs. 6.45% in LCRC, p-value = 0.016), and overall frequency was higher compared to TCGA (p-value = 1.847 × 10-5) and MSK-IMPACT cohorts (p-value = 3.062 × 10-2). Limited sample size restricts definitive conclusions, but our data suggest potential differences in driver mutations for Chilean patients, being that the RTK-RAS oncogenic pathway is less affected and the PI3K pathway is more altered in Chp compared to TCGA (45% vs. 25.56%, respectively). The prevalence of actionable pathways and driver mutations can guide therapeutic choices, but can also impact treatment effectiveness. Thus, these findings warrant further investigation in larger Chilean cohorts to confirm these initial observations. Understanding population-specific driver mutations can guide the development of precision medicine programs for CRC patients.

Global application of National Comprehensive Cancer Network resource-stratified guidelines for systemic treatment of colon cancer: a population-based, customisable model for cost, demand, and procurement.

BACKGROUND: Resource-stratified guidelines (RSGs) can inform systemic treatment decisions in the face of limited resources. The objective of this study was to develop a customisable modelling tool to predict the demand, cost, and drug procurement needs of delivering National Comprehensive Cancer Network (NCCN) RSG-based systemic treatment for colon cancer. METHODS: We developed decision trees for first-course systemic therapy for colon cancer based on the NCCN RSGs. Decision trees were merged with data from the Surveillance, Epidemiology, and End Results programme, the International Agency for Research on Cancer's GLOBOCAN 2020 national estimates for colon cancer incidence, country-level income data, and data on drug costs from Redbook (USA), the Pharmaceutical Benefits Scheme (Australia), and the Management Sciences for Health 2015 International Medical Products price guide to estimate global treatment needs and costs, and forecast drug procurement. Simulations and sensitivity analyses were used to explore the effect of scaling up services globally and the effect of alternative stage distributions on treatment demand and cost. We generated a customisable model, in which estimates can be tailored to local incidence, epidemiological, and costing data. FINDINGS: First-course systemic therapy is indicated in 608 314 (53·6%) of 1 135 864 colon cancer diagnoses in 2020. Indications for first-course systemic therapy are projected to rise to 926 653 in 2040; the indications in 2020 might be as high as 826 123 (72·7%), depending on stage distribution assumptions. Adhering to NCCN RSGs, patients with colon cancer in low-income and middle income countries (LMICs) would constitute 329 098 (54·1%) of 608 314 global systemic therapy demands, but only 10% of global expenditure on systemic therapies. The total cost of NCCN RSG-based first-course systemic therapy for colon cancer in 2020 would be between about US$4·2 and about $4·6 billion, depending on stage distribution. If all patients with colon cancer in 2020 were treated according to maximal resources, global expenditure on systemic therapy for colon cancer would rise to around $8·3 billion. INTERPRETATION: We have developed a customisable model that can be applied at global, national, and subnational levels to estimate systemic treatment needs, forecast drug procurement, and calculate expected drug costs on the basis of local data. This tool can be used to plan resource allocation for colon cancer globally. FUNDING: None.

The burden of colon cancer attributable to modifiable factors-The Norwegian Women and Cancer Study.

Colon cancer is the second most frequently diagnosed cancer in women in Norway, where incidence rates of colon cancer increased 3-fold between 1955 and 2014, for unknown reasons. We aimed to assess the burden of colon cancer attributable to modifiable risk factors in Norwegian women using the data from the Norwegian Women and Cancer (NOWAC) study. Self-reported information from 35 525 women from the NOWAC study were available. These included the following exposures: smoking status, alcohol consumption, body mass index, physical activity, intake of calcium, fibers, and red and processed meat. Colon cancer cases were identified from the Cancer Registry of Norway. A parametric piecewise constant hazards model was used to estimate the strength of exposure-cancer associations. Population attributable fractions with 95% confidence intervals (CIs) were calculated considering competing risk of death. The fraction of incident colon cancer attributable to ever smoking was 18.7% (95% CI 4.7%-30.6%), low physical activity 10.8% (95% CI -0.7% to 21.0%), alcohol consumption 14.5% (95% CI -2.8% to 28.9%), and low intake of calcium 10.0% (95% CI -7.8% to 24.8%). A small proportion of colon cancer cases was attributable to combined intake of red and processed meat over 500 g/week, overweight/obesity, and low intake of fibers. Jointly, these seven risk factors could explain 46.0% (95% CI 23.0%-62.4%) of the colon cancer incidence burden. Between 23% and 62% of the colon cancer burden among women in Norway was attributable to modifiable risk factors, indicating an important preventive potential of a healthy lifestyle.

Antibodies to oral pathobionts and colon cancer risk in the CLUE I cohort study.

Periodontitis has been associated with an increased risk for gastrointestinal cancers. The objective of our study was to investigate the association of antibodies to oral bacteria and the risk of colon cancer in a cohort setting. Using the CLUE I cohort, a prospective cohort initiated in 1974 in Washington County, Maryland, we conducted a nested case-control study to examine the association of levels of IgG antibodies to 11 oral bacterial species (13 total strains) with risk of colon cancer diagnosed a median of 16 years later (range: 1-26 years). Antibody response was measured using checkerboard immunoblotting assays. We included 200 colon cancer cases and 200 controls matched on age, sex, cigarette smoking status, time of blood draw and pipe or cigar smoking status. Controls were selected using incidence density sampling. Conditional logistic regression models were used to assess the association between antibody levels and colon cancer risk. In the overall analysis, we observed significant inverse associations for 6 of the 13 antibodies measured (P-trends <.05) and one positive association for antibody levels to Aggregatibacter actinomycetemcomitans (ATCC 29523; P-trend = .04). While we cannot rule out a role for periodontal disease in colon cancer risk, findings from our study suggest that a strong adaptive immune response may be associated with a lower risk of colon cancer. More studies will need to examine whether the positive associations we observed with antibodies to A. actinomycetemcomitans reflect a true causal association for this bacterium.

Use of 2-Stage Modeling to Identify How Colorectal Cancer Risk Changes With Period and Cohort.

Colorectal cancer (CRC) incidence rates have decreased among adults aged 50 years or older while increasing in adults under age 50 years. Understanding these trends is challenging because of the multiple related time scales of age, diagnosis period, and birth cohort. We analyzed incidence rates of rectal, distal colon, and proximal colon cancer for individuals aged 20 years or more from the Surveillance, Epidemiology, and End Results Program for diagnosis years 1978-2017. We used a 2-stage generalized linear model to determine age, period, and cohort effects for CRC incidence. We first estimated birth cohort effects among people under age 45 years. We used these results to specify prior distributions for cohort effects in a Bayesian model to estimate period effects among people aged 45 years or more. There was no evidence of period effects for people under age 45 years. Risks of rectal and distal colon cancer increased for later birth cohorts. Compared with the 1943-1952 birth cohort, the 1983-1992 birth cohort had 2.2 times the risk of rectal cancer, 1.9 times the risk of distal colon cancer, and 1.3 times the risk of proximal colon cancer. For people aged ≥45 years, period effects showed declines in CRC risk that were attributable to screening.

Association Between Metabolic Syndrome and the Risk of Colorectal Cancer Diagnosed Before Age 50 Years According to Tumor Location.

BACKGROUND & AIMS: The increasing prevalence of obesity at younger ages is concurrent with an increased earlier-onset colorectal cancer (CRC) (before age 50 years) incidence, particularly left-sided colon cancer. We investigated whether obesity and metabolic syndrome (MetS) are associated with increased earlier-onset CRC risk according to tumor location. METHODS: Our nationwide population-based cohort study enrolled 9,774,081 individuals who underwent health checkups under the Korean National Health Insurance Service from 2009 to 2010, with follow-up until 2019. We collected data on age, sex, lifestyle factors, body mass index (BMI), waist circumference (WC), blood pressure, and laboratory findings. A multivariate Cox proportional hazards regression analysis was performed. RESULTS: A total of 8320 earlier-onset and 57,257 later-onset CRC cases developed during follow-up. MetS was associated with increased earlier-onset CRC (adjusted hazard ratio, 1.20; 95% CI, 1.14-1.27), similar to later-onset CRC (adjusted hazard ratio, 1.19; 95% CI, 1.17-1.21). The adjusted hazard ratios for earlier-onset CRC with 1, 2, 3, 4, and 5 MetS components were 1.07 (95% CI, 1.01-1.13), 1.13 (95% CI, 1.06-1.21), 1.25 (95% CI, 1.16-1.35), 1.27 (95% CI, 1.15-1.41), and 1.50 (95% CI, 1.26-1.79), respectively (P for trend < .0001). We found that higher body mass index and larger waist circumference were significantly associated with increased earlier-onset CRC (P for trend < .0001). These dose-response associations were significant in distal colon and rectal cancers, although not in proximal colon cancers. CONCLUSIONS: MetS and obesity are positively associated with CRC before age 50 years with a similar magnitude of association as people diagnosed after age 50 years. Thus, people younger than 50 years with MetS require effective preventive interventions to help reduce CRC risk.

Impact of Patient Comorbidities on Presentation Stage of Breast and Colon Cancers.

BACKGROUND: While patients with multiple comorbidities may have frequent contact with medical providers, it is unclear whether their healthcare visits translate into earlier detection of cancers, specifically breast and colon cancers. METHODS: Patients diagnosed with stage I-IV breast ductal carcinoma and colon adenocarcinoma were identified from the National Cancer Database and stratified by comorbidity burden, dichotomized as a Charlson Comorbidity Index (CCI) Score of <2 or ≥2. Characteristics associated with comorbidities were analyzed by univariate and multivariate logistic regression. Propensity-score matching was performed to determine the impact of CCI on stage at cancer diagnosis, dichotomized as early (I-II) or late (III-IV). RESULTS: A total of 672,032 patients with colon adenocarcinoma and 2,132,889 with breast ductal carcinoma were included. Patients with colon adenocarcinoma who had a CCI ≥ 2 (11%, n = 72,620) were more likely to be diagnosed with early-stage disease (53% vs. 47%; odds ratio [OR] 1.02, p = 0.017), and this finding persisted after propensity matching (CCI ≥ 2 55% vs. CCI < 2 53%, p < 0.001). Patients with breast ductal carcinoma who had a CCI ≥ 2 (4%, n = 85,069) were more likely to be diagnosed with late-stage disease (15% vs. 12%; OR 1.35, p < 0.001). This finding also persisted after propensity matching (CCI ≥ 2 14% vs. CCI < 2 10%, p < 0.001). CONCLUSIONS: Patients with more comorbidities are more likely to present with early-stage colon cancers but late-stage breast cancers. This finding may reflect differences in practice patterns for routine screening in these patients. Providers should continue guideline directed screenings to detect cancers at an earlier stage and optimize outcomes.

Modeling age-specific incidence of colon cancer via niche competition.

Cancer development is a multistep process often starting with a single cell in which a number of epigenetic and genetic alterations have accumulated thus transforming it into a tumor cell. The progeny of such a single benign tumor cell expands in the tissue and can at some point progress to malignant tumor cells until a detectable tumor is formed. The dynamics from the early phase of a single cell to a detectable tumor with billions of tumor cells are complex and still not fully resolved, not even for the well-known prototype of multistage carcinogenesis, the adenoma-adenocarcinoma sequence of colorectal cancer. Mathematical models of such carcinogenesis are frequently tested and calibrated based on reported age-specific incidence rates of cancer, but they usually require calibration of four or more parameters due to the wide range of processes these models aim to reflect. We present a cell-based model, which focuses on the competition between wild-type and tumor cells in colonic crypts, with which we are able reproduce epidemiological incidence rates of colon cancer. Additionally, the fraction of cancerous tumors with precancerous lesions predicted by the model agree with clinical estimates. The correspondence between model and reported data suggests that the fate of tumor development is majorly determined by the early phase of tumor growth and progression long before a tumor becomes detectable. Due to the focus on the early phase of tumor development, the model has only a single fit parameter, the time scale set by an effective replacement rate of stem cells in the crypt. We find this effective rate to be considerable smaller than the actual replacement rate, which implies that the time scale is limited by the processes succeeding clonal conversion of crypts.

The interaction between liver cirrhosis, infection by Streptococcus bovis, and colon cancer.

Whether cirrhotic patients with Streptococcus bovis bacteremia have an increased risk of colorectal neoplasm is uncertain. A multicentric retrospective cohort study was conducted investigating associations between S. bovis biotype and species, cirrhosis, and colorectal neoplasm. Out of 779 patients with S. bovis bacteremia, 69 (8.7%) had cirrhosis. No differences were found in the prevalence of colorectal neoplasm between cirrhotic and non-cirrhotic patients undergoing colonoscopy. Among cirrhotic patients, prevalence of colorectal neoplasms was higher in S. bovis biotype I (S. gallolyticus) bacteremia (80%) than in S. bovis biotype II (33.3%; p < 0.007). In conclusion, risk of colorectal neoplasm is high among cirrhotic patients with S. gallolyticus bacteremia.

Pre-diagnostic intake of vitamin D and incidence of colorectal cancer by anatomical subsites: the Norwegian Women and Cancer Cohort Study (NOWAC).

According to the World Cancer Research Fund International, vitamin D might decrease the risk of colorectal cancer (CRC). However, less is known about the association with cancers in different subsites of the colon and in the rectum. The aim of this study was to examine associations between pre-diagnostic intake of vitamin D and risk of CRC by anatomical subsites. Data from 95 416 participants in the Norwegian Women and Cancer Cohort Study was included, and vitamin D intake was estimated from two repeated FFQ. Associations between vitamin D intake and incidence of CRC were assessed using multivariable Cox regression. During follow-up, there were 1774 incident cases of CRC. A small but borderline significant inverse association was found for a 5-µg increase in vitamin D intake and risk of CRC (hazard ratio (HR) = 0·97; 95 % CI 0·93, 1·01) and colon cancer (HR = 0·96; 95 % CI 0·91, 1·01). High (≥ 20 µg) compared with low (< 10 µg) vitamin D intake was associated with 17 % borderline significant reduced risk of CRC (HR = 0·83; 95 % CI 0·68, 1·02). Medium (10-19 µg) v. low intake (< 10 µg) was associated with 27 % reduced risk of proximal colon cancer (HR = 0·73; 95 % CI 0·57, 0·94). No significant associations were observed between vitamin D intake and risk of distal colon or rectal cancer. Our study indicates that vitamin D may be differently associated with subsites of the colon. The association between vitamin D intake and proximal colon cancer is novel.

Exploring the complexity and spectrum of racial/ethnic disparities in colon cancer management.

BACKGROUND: Colorectal cancer is a leading cause of morbidity and mortality across U.S. racial/ethnic groups. Existing studies often focus on a particular race/ethnicity or single domain within the care continuum. Granular exploration of disparities among different racial/ethnic groups across the entire colon cancer care continuum is needed. We aimed to characterize differences in colon cancer outcomes by race/ethnicity across each stage of the care continuum. METHODS: We used the 2010-2017 National Cancer Database to examine differences in outcomes by race/ethnicity across six domains: clinical stage at presentation; timing of surgery; access to minimally invasive surgery; post-operative outcomes; utilization of chemotherapy; and cumulative incidence of death. Analysis was via multivariable logistic or median regression, with select demographics, hospital factors, and treatment details as covariates. RESULTS: 326,003 patients (49.6% female, 24.0% non-White, including 12.7% Black, 6.1% Hispanic/Spanish, 1.3% East Asian, 0.9% Southeast Asian, 0.4% South Asian, 0.3% AIAE, and 0.2% NHOPI) met inclusion criteria. Relative to non-Hispanic White patients: Southeast Asian (OR 1.39, p < 0.01), Hispanic/Spanish (OR 1.11 p < 0.01), and Black (OR 1.09, p < 0.01) patients had increased odds of presenting with advanced clinical stage. Southeast Asian (OR 1.37, p < 0.01), East Asian (OR 1.27, p = 0.05), Hispanic/Spanish (OR 1.05 p = 0.02), and Black (OR 1.05, p < 0.01) patients had increased odds of advanced pathologic stage. Black patients had increased odds of experiencing a surgical delay (OR 1.33, p < 0.01); receiving non-robotic surgery (OR 1.12, p < 0.01); having post-surgical complications (OR 1.29, p < 0.01); initiating chemotherapy more than 90 days post-surgery (OR 1.24, p < 0.01); and omitting chemotherapy altogether (OR 1.12, p = 0.05). Black patients had significantly higher cumulative incidence of death at every pathologic stage relative to non-Hispanic White patients when adjusting for non-modifiable patient factors (p < 0.05, all stages), but these differences were no longer statistically significant when also adjusting for modifiable factors such as insurance status and income. CONCLUSIONS: Non-White patients disproportionately experience advanced stage at presentation. Disparities for Black patients are seen across the entire colon cancer care continuum. Targeted interventions may be appropriate for some groups; however, major system-level transformation is needed to address disparities experienced by Black patients.

Influence of the COVID-19 pandemic on the timing of surgical triage, tumor stage, and therapy of patients with colon carcinoma.

PURPOSE: With the onset of the COVID pandemic in Germany in March 2020, far-reaching restrictions were imposed that limited medical access for patients. Screening examinations such as colonoscopies were greatly reduced in number. As rapid surgical triage after diagnosis is prognostic, our hypothesis was that pandemic-related delays would increase the proportion of advanced colon cancers with an overall sicker patient population. METHODS: A total of 204 patients with initial diagnosis of colon cancer were analyzed in this retrospective single-center study between 03/01/2018 and 03/01/2022. Control group (111 patients, pre-COVID-19) and the study group (93 patients, during COVID-19) were compared in terms of tumor stages, surgical therapy, complications, and delays in the clinical setting. The data were presented either as absolute numbers or as median for constant data. RESULTS: A trend towards more advanced tumor stages (T4a p = 0.067) and a significant increase of emergency surgeries (p = 0.016) with higher rates of ileus and perforation (p = 0.004) as well as discontinuity resections (p = 0.049) during the pandemic could be observed. Delays in surgical triage after endoscopic diagnosis were seen during the 2nd lockdown (02/11/20-26/12/20; p = 0.031). CONCLUSION: In summary, the results suggest delayed treatment during the COVID-19 pandemic, with the infection pattern of COVID appearing to have a major impact on the time between endoscopic diagnosis and surgical triage/surgery. Adequate care of colon cancer patients is possible even during a pandemic, but it is important to focus on structured screening and tight diagnosis to treatment schedules in order to prevent secondary pandemic victims.