Relative Efficacies of Interventions to Improve the Quality of Screening-Related Colonoscopy: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND & AIMS: Significant variability exists in colonoscopy quality indicators, including adenoma detection rate (ADR). We synthesized evidence from randomized trials in a network meta-analysis on interventions to improve colonoscopy quality. METHODS: We included trials from database inceptions to September 25, 2023, of patients undergoing screening-related colonoscopy and presented efficacies of interventions within domains (periprocedural parameters, endoscopist-directed interventions, intraprocedural techniques, endoscopic technologies, distal attachment devices, and additive substances) compared to standard colonoscopy. The primary outcome was ADR. We used a Bayesian random-effects model using Markov-chain Monte Carlo simulation, with 10,000 burn-ins and 100,000 iterations. We calculated odds ratios with 95% credible intervals and present surface under the cumulative ranking (SUCRA) curves. RESULTS: We included 124 trials evaluating 37 interventions for the primary outcome. Nine interventions resulted in statistically significant improvements in ADR compared to standard colonoscopy (9-minute withdrawal time, dual observation, water exchange, i-SCAN [Pentax Ltd], linked color imaging, computer-aided detection, Endocuff [Olympus Corp], Endocuff Vision [Olympus Corp], and oral methylene blue). Dual observation (SUCRA, 0.84) and water exchange (SUCRA, 0.78) ranked highest among intraprocedural techniques; i-SCAN (SUCRA, 0.95), linked color imaging (SUCRA, 0.85), and computer-aided detection (SUCRA, 0.78) among endoscopic technologies; WingCap (A&A Medical Supply LLC) (SUCRA, 0.87) and Endocuff (SUCRA, 0.85) among distal attachment devices and oral methylene blue (SUCRA, 0.94) among additive substances. No interventions improved detection of advanced adenomas, and only narrow-band imaging improved detection of serrated lesions (odds ratio, 2.94; 95% credible interval, 1.46-6.25). CONCLUSIONS: Several interventions are effective in improving adenoma detection and overall colonoscopy quality, many of which are cost-free. These results can inform endoscopists, unit managers, and endoscopy societies on relative efficacies.

The association between neighborhood-level income and cancer stage at diagnosis and survival in Alberta.

BACKGROUND: Socioeconomic status (SES) is associated with a range of health outcomes, including cancer diagnosis and survival. However, the evidence for this association is inconsistent between countries with and without single-payer health care systems. In this study, the relationships between neighborhood-level income, cancer stage at diagnosis, and cancer-specific mortality in Alberta, Canada, were evaluated. METHODS: The Alberta Cancer Registry was used to identify all primary cancer diagnoses between 2010 and 2020. Average neighborhood income was determined by linking the Canadian census to postal codes and was categorized into quintiles on the basis of income distribution in Alberta. Multivariable multinomial logistic regression was used to model the association between income quintile and stage at diagnosis, and the Fine-Gray proportional subdistribution hazards model was used to estimate the association between SES and cancer-specific mortality. RESULTS: Out of the 143,818 patients with cancer included in the study, those in lower income quintiles were significantly more likely to be diagnosed at stage III (odds ratio [OR], 1.07; 95% CI [confidence interval], 1.06-1.09) or IV (OR, 1.12; 95% CI, 1.11-1.14) after adjusting for age and sex. Lower income quintiles also had significantly worse cancer-specific survival for breast, colorectal, liver, lung, non-Hodgkin lymphoma, oral cavity, pancreas, and prostate cancers. CONCLUSIONS: Disparities were observed in cancer outcomes across neighborhood-level income groups in Alberta, which demonstrates that health inequities by SES exist in countries with single-payer health care systems. Further research is needed to better understand the underlying causes and to develop strategies to mitigate these disparities.

Association between treatment and improvements in overall survival of patients with advanced/metastatic non-small cell lung cancer since 2011: A study in the United States, Canada, and Germany using retrospective real-world databases.

BACKGROUND: This study aimed to describe treatment patterns and overall survival (OS) in patients with advanced non-small cell lung cancer (aNSCLC) in three countries between 2011 and 2020. METHODS: Three databases (US, Canada, Germany) were used to identify incident aNSCLC patients. OS was assessed from the date of incident aNSCLC diagnosis and, for patients who received at least a first line of therapy (1LOT), from the date of 1LOT initiation. In multivariable analyses, we analyzed the influence of index year and type of prescribed treatment on OS. FINDINGS: We included 51,318 patients with an incident aNSCLC diagnosis. The percentage of patients treated with a 1LOT differed substantially between countries, whereas the number of patients receiving immunotherapies/targeted treatments increased over time in all three countries. Median OS from the date of incident diagnosis was 9.9 months in the United States vs. 4.1 months in Canada. When measured from the start of 1LOT, patients had a median OS of 10.7 months in the United States, 10.9 months in Canada, and 10.9 months in Germany. OS from the start of 1LOT improved in all three countries from 2011 to 2020 by approximately 3 to 4 months. CONCLUSIONS: Observed continuous improvement in OS among patients receiving at least a 1LOT from 2011 to 2020 was likely driven by improved care and changes in the treatment landscape. The difference in the proportion of patients receiving a 1LOT in the observed countries requires further investigation.

Incidence, Predictors, and Outcomes of Clinically Significant Post-ERCP Bleeding: a Contemporary Multi-center Study.

BACKGROUND AIMS: Clinically significant post-endoscopic retrograde cholangiopancreatography (ERCP) bleeding (CSPEB) is common. Contemporary estimates of risk are lacking. We aimed to identify risk factors for and outcomes following CSPEB. METHODS: We analyzed multi-center prospective ERCP data between 2018-2023 with 30-day follow-up. The primary outcome was CSPEB, defined as hematemesis, melena, or hematochezia resulting in: hemoglobin drop ≥20 g/L or transfusion and/or endoscopy to evaluate suspected bleeding, and/or unplanned healthcare visitation and/or prolongation of existing admission. Firth logistic regression was employed. P-values <0.05 were significant, with odds ratios (ORs) and 95% confidence intervals reported. RESULTS: CSPEB occurred following 129 (1.5%) of 8,517 ERCPs (mean onset 3.2 days), with 110 of 4,849 events (2.3%) occurring following higher-risk interventions (sphincterotomy, sphincteroplasty, pre-cut sphincterotomy, and/or needle-knife access). CSPEB patients required endoscopy and transfusion in 86.0% and 53.5% of cases, respectively, with three cases (2.3%) being fatal. P2Y12 inhibitors were held for a median of 4 days (IQR 4) prior to higher-risk ERCP. Following higher-risk interventions, P2Y12 inhibitors (OR 3.33, 1.26-7.74), warfarin (OR 8.54, 3.32-19.81), dabigatran (OR 13.40, 2.06-59.96), rivaroxaban (OR 7.42, 3.43-15.24) and apixaban (OR 4.16, 1.99-8.20) were associated with CSPEB. Significant intraprocedural bleeding post sphincterotomy (OR 2.32, 1.06-4.60), but not post sphincteroplasty, was also associated. Concomitant cardiorespiratory events occurred more frequently within 30 days following CSPEB (OR 12.71, 4.75-32.54). CONCLUSIONS: Risks of antiplatelet-related CSPEB may be underestimated by endoscopists based on observations of suboptimal holding before higher-risk ERCP. Appropriate periprocedural antithrombotic management is essential and could represent novel quality initiative targets.

Next Generation Weight Loss Drugs for the Prevention of Cancer?

Background: Western populations are losing the battle over healthy weight management, and excess body weight is a notable cancer risk factor at the population level. There is ongoing interest in pharmacological interventions aimed at promoting weight loss, including GLP-1 receptor agonists (GLP-1RA), which may be a useful tool to stem the rising tide of obesity-related cancers. Purpose: To investigate the potential of next generation weight loss drugs (NGWLD) like GLP-1RA in population-level chemoprevention.Research Design: We used the OncoSim microsimulation tool to estimate the population-level reductions in obesity and the potentially avoidable obesity-related cancers in Canada over the next 25 years.Results: We estimated a total of 71 281 preventable cancers by 2049, with 36 235 and 35 046 cancers prevented for females and males, respectively. Among the 327 254 total projected cancer cases in 2049, 1.3% are estimated to be preventable through intervention with NGWLD.Conclusions: Pharmacologic intervention is not the ideal solution for the obesity-related cancer crisis. However, these agents and subsequent generations provide an additional tool to rapidly reduce body weight and adiposity in populations that have been extremely challenging to reduce weight with standard diet and exercise approaches. Additional research is needed around approaches to prevent initial weight gain and maintain long-term weight loss.

Projected estimates of cancer in Canada in 2024.

BACKGROUND: Cancer surveillance data are essential to help understand where gaps exist and progress is being made in cancer control. We sought to summarize the expected impact of cancer in Canada in 2024, with projections of new cancer cases and deaths from cancer by sex and province or territory for all ages combined. METHODS: We obtained data on new cancer cases (i.e., incidence, 1984-2019) and deaths from cancer (i.e., mortality, 1984-2020) from the Canadian Cancer Registry and Canadian Vital Statistics Death Database, respectively. We projected cancer incidence and mortality counts and rates to 2024 for 23 types of cancer, overall, by sex, and by province or territory. We calculated age-standardized rates using data from the 2011 Canadian standard population. RESULTS: In 2024, the number of new cancer cases and deaths from cancer are expected to reach 247 100 and 88 100, respectively. The age-standardized incidence rate (ASIR) and mortality rate (ASMR) are projected to decrease slightly from previous years for both males and females, with higher rates among males (ASIR 562.2 per 100 000 and ASMR 209.6 per 100 000 among males; ASIR 495.9 per 100 000 and ASMR 152.8 per 100 000 among females). The ASIRs and ASMRs of several common cancers are projected to continue to decrease (i.e., lung, colorectal, and prostate cancer), while those of several others are projected to increase (i.e., liver and intrahepatic bile duct cancer, kidney cancer, melanoma, and non-Hodgkin lymphoma). INTERPRETATION: Although the overall incidence of cancer and associated mortality are declining, new cases and deaths in Canada are expected to increase in 2024, largely because of the growing and aging population. Efforts in prevention, screening, and treatment have reduced the impact of some cancers, but these short-term projections highlight the potential effect of cancer on people and health care systems in Canada.

Text analysis framework for identifying mutations among non-small cell lung cancer patients from laboratory data.

BACKGROUND: Laboratory data can provide great value to support research aimed at reducing the incidence, prolonging survival and enhancing outcomes of cancer. Data is characterized by the information it carries and the format it holds. Data captured in Alberta's biomarker laboratory repository is free text, cluttered and rouge. Such data format limits its utility and prohibits broader adoption and research development. Text analysis for information extraction of unstructured data can change this and lead to more complete analyses. Previous work on extracting relevant information from free text, unstructured data employed Natural Language Processing (NLP), Machine Learning (ML), rule-based Information Extraction (IE) methods, or a hybrid combination between them. METHODS: In our study, text analysis was performed on Alberta Precision Laboratories data which consisted of 95,854 entries from the Southern Alberta Dataset (SAD) and 6944 entries from the Northern Alberta Dataset (NAD). The data covers all of Alberta and is completely population-based. Our proposed framework is built around rule-based IE methods. It incorporates topics such as Syntax and Lexical analyses to achieve deterministic extraction of data from biomarker laboratory data (i.e., Epidermal Growth Factor Receptor (EGFR) test results). Lexical analysis compromises of data cleaning and pre-processing, Rich Text Format text conversion into readable plain text format, and normalization and tokenization of text. The framework then passes the text into the Syntax analysis stage which includes the rule-based method of extracting relevant data. Rule-based patterns of the test result are identified, and a Context Free Grammar then generates the rules of information extraction. Finally, the results are linked with the Alberta Cancer Registry to support real-world cancer research studies. RESULTS: Of the original 5512 entries in the SAD dataset and 5017 entries in the NAD dataset which were filtered for EGFR, the framework yielded 5129 and 3388 extracted EGFR test results from the SAD and NAD datasets, respectively. An accuracy of 97.5% was achieved on a random sample of 362 tests. CONCLUSIONS: We presented a text analysis framework to extract specific information from unstructured clinical data. Our proposed framework has shown that it can successfully extract relevant information from EGFR test results.

Outcomes and Healthcare Utilization Among New Persistent Opioid Users and Nonopioid Users After Curative-intent Surgery for Cancer.

OBJECTIVE: The aim of the study was to compare the health outcomes and resource use of cancer patients who were new persistent opioid users with those who were not, after undergoing curative intent surgery for cancer. BACKGROUND: Little is known about long-term health outcomes (overdose, mortality) and resource utilization of new persistent opioid users among cancer patients undergoing curative-intent surgery. METHODS: This retrospective cohort study included all adults with a diagnosis of solid cancers who underwent curative-intent surgery during the study period (2011-2015) in Alberta, Canada and were opioid-naïve before surgery, with a follow-up period until December 31, 2019. The key exposure, "new persistent opioid user," was defined as a patient who was opioid-naive before surgery and subsequently filled at least 1 opioid prescription between 60 and 180 days after surgery. The primary outcome was opioid overdose that occurred within 3 years of surgery. All-cause death, noncancer caused death, and department visit (yes vs. no), and hospitalization (yes vs. no) in the follow-up periods were also included as outcomes. RESULTS: In total, 19,219 patients underwent curative intent surgery with a median follow-up of 47 months, of whom 1530 (8.0%) were identified as postoperative new persistent opioid users. In total, 101 (0.5%) patients experienced opioid overdose within 3 years of surgery. Compared with nonopioid users, new persistent opioid users experienced a higher rate of opioid overdose (OR = 2.37, 95% CI: 1.44-3.9) within 3 years of surgery. New persistent opioid use was also associated with a greater likelihood of being hospitalized (OR = 2.03, 95% CI: 1.76-2.33) and visiting an emergency room (OR = 1.83, 95% CI: 1.62-2.06) in the first year after surgery, and a higher overall (HR = 1.28, 95% CI: 1.1-1.49) and noncancer caused mortality (HR = 1.33, 95% CI: 1.12-1.58), when compared with nonopioid users. CONCLUSION: Postoperative new persistent opioid use among cancer patients undergoing curative-intent surgery is associated with subsequent opioid overdose, worse survival, and more health resource utilization.

Development and Validation of a Prognostic Risk Model for Patients with Advanced Melanoma Treated with Immune Checkpoint Inhibitors.

BACKGROUND: Risk stratification tools for patients with advanced melanoma (AM) treated with immune checkpoint inhibitors (ICI) are lacking. We identified a new prognostic model associated with overall survival (OS). PATIENTS AND METHODS: A total of 318 treatment naïve patients with AM receiving ICI were collected from a multi-centre retrospective cohort study. LASSO Cox regression identified independent prognostic factors associated with OS. Model validation was carried out on 500 iterations of bootstrapped samples. Harrel's C-index was calculated and internally validated to outline the model's discriminatory performance. External validation was carried out in 142 advanced melanoma patients receiving ICI in later lines. RESULTS: High white blood cell count (WBC), high lactate dehydrogenase (LDH), low albumin, Eastern Cooperative Oncology Group (ECOG) performance status ≥1, and the presence of liver metastases were included in the model. Patients were parsed into 3 risk groups: favorable (0-1 factors) OS of 52.9 months, intermediate (2-3 factors) OS 13.0 months, and poor (≥4 factors) OS 2.7 months. The C-index of the model from the discovery cohort was 0.69. External validation in later-lines (N = 142) of therapy demonstrated a c-index of 0.65. CONCLUSIONS: Liver metastases, low albumin, high LDH, high WBC, and ECOG≥1 can be combined into a prognostic model for AM patients treated with ICI.

Time spent in the sun and the risk of developing non-Hodgkin lymphoma: a Canadian cohort study.

PURPOSE: The objective was to explore the relationship of sun behavior patterns with the risk of developing non-Hodgkin lymphoma (NHL). METHODS: Sun behavior information from Alberta's Tomorrow Project, CARTaGENE, and Ontario Health Study were utilized. The relationship between time in the sun during summer months and risk of NHL was assessed using Cox proportional hazard models with age as the time scale and adjustment for confounders. Cohorts were analyzed separately and hazard ratios (HR) pooled with random effects meta-analysis. Joint effects of time in the sun and use of sun protection were examined. Patterns of exposure were explored via combinations of weekday and weekend time in the sun. RESULTS: During an average follow-up of 7.6 years, 205 NHL cases occurred among study participants (n = 79,803). Compared to < 30 min daily in the sun, we observed HRs of 0.84 (95% CI 0.55-1.28) for 30-59 min, 0.63 (95% CI 0.40-0.98) for 1-2 h, and 0.91 (95% CI 0.61-1.36) for > 2 h. There was suggestive evidence that > 2 h was protective against NHL with use of sun protection, but not without it. Compared to < 30 min daily, moderate exposure (30 min to 2 h on weekdays or weekend) was associated with a lower risk of NHL (HR 0.63, 95% CI 0.43-0.92), while intermittent (< 30 min on weekdays and > 2 h on weekends) and chronic (> 2 h daily) were not. CONCLUSION: This study provides evidence of a protective effect of moderate time spent in the sun on NHL risk.

Long-term projections of cancer incidence and mortality in Canada: The OncoSim All Cancers Model.

Using the OncoSim All Cancers Model, we estimated the annual cancer incidence, mortality and cancer management costs in Canada from 2020 to 2040. Incidence for each cancer type was estimated from logistic regression analyses of the Canadian Cancer Registry (1992-2017), with province/territory, sex, five-year age groups and year as covariates. Deaths were estimated by sex and tumour site for cancers diagnosed between 2000 and 2017 (deaths to the end of 2017). The total cost of a cancer type was the sum of costs for individuals across four phases of cancer care. The projections presented in this study were generated based on a simulation of 32 million cases. The OncoSim All Cancers Model projects a 40% increase in the overall number of incident cancer cases from 2020 to 2040. The number of the four most commonly diagnosed cancers in Canada (breast, colorectal, lung, and prostate) are projected to increase annually. The overall number of cancer deaths is projected to increase by 44% from 2020 to 2040. More cancer deaths are projected in males than in females. The age-standardized mortality rate is expected to remain relatively stable over time. Overall cancer management costs are projected to increase from $20.6B in 2020 to $31.4B in 2040. Due mainly to an aging population and population growth in Canada, we estimate that cancer incidence, mortality and cancer management costs will increase considerably between 2020 and 2040. These results highlight the importance of planning for increasing investment and capacity in cancer control.

Impact of the COVID-19 pandemic on cancer diagnoses, stage and survival in Alberta.

BACKGROUND: The COVID-19 pandemic is suspected to have affected cancer care and outcomes among patients in Canada. In this study, we evaluated the impact of the state of emergency period during the COVID-19 pandemic (Mar. 17 to June 15, 2020) on cancer diagnoses, stage at diagnosis and 1-year survival in Alberta. METHODS: We included new diagnoses of the 10 most prevalent cancer types from Jan. 1, 2018, to Dec. 31, 2020. We followed patients up to Dec. 31, 2021. We used interrupted time series analysis to examine the impact of the first COVID-19-related state of emergency in Alberta on the number of cancer diagnoses. We used multivariable Cox regression to compare 1-year survival of the patients who received a diagnosis during 2020 after the state of emergency with those who received a diagnosis during 2018 and 2019. We also performed stage-specific analyses. RESULTS: We observed significant reductions in diagnoses of breast cancer (incidence rate ratio [IRR] 0.67, 95% confidence interval [CI] 0.59-0.76), prostate cancer (IRR 0.64, 95% CI 0.56-0.73) and colorectal cancer (IRR 0.64, 95% CI 0.56- 0.74) and melanoma (IRR 0.57, 95% CI 0.47-0.69) during the state of emergency period compared with the period before it. These decreases largely occurred among early-stage rather than late-stage diagnoses. Patients who received a diagnosis of colorectal cancer, non-Hodgkin lymphoma and uterine cancer in 2020 had lower 1-year survival than those diagnosed in 2018; no other cancer sites had lower survival. INTERPRETATION: The results from our analyses suggest that health care disruptions during the COVID-19 pandemic in Alberta considerably affected cancer outcomes. Given that the largest impact was observed among early-stage cancers and those with organized screening programs, additional system capacity may be needed to mitigate future impact.

Data Challenges for Externally Controlled Trials: Viewpoint.

The preferred evidence of a large randomized controlled trial is difficult to adopt in scenarios, such as rare conditions or clinical subgroups with high unmet needs, and evidence from external sources, including real-world data, is being increasingly considered by decision makers. Real-world data originate from many sources, and identifying suitable real-world data that can be used to contextualize a single-arm trial, as an external control arm, has several challenges. In this viewpoint article, we provide an overview of the technical challenges raised by regulatory and health reimbursement agencies when evaluating comparative efficacy, such as identification, outcome, and time selection challenges. By breaking down these challenges, we provide practical solutions for researchers to consider through the approaches of detailed planning, collection, and record linkage to analyze external data for comparative efficacy.

Risk Factors for Early-Onset Colorectal Cancer: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Despite the widespread increase in the incidence of early-onset colorectal cancer (EoCRC), the reasons for this increase remain unclear. The objective of this study was to determine risk factors for the development of EoCRC. METHODS: We conducted a systematic literature review and meta-analysis of studies examining non-genetic risk factors for EoCRC, including demographic factors, comorbidities, and lifestyle factors. Random effects meta-analyses were conducted for risk factors that were examined in at least three studies. Heterogeneity was investigated using the Q-test and I2 statistic. RESULTS: From 3304 initial citations, 20 studies were included in this review. Significant risk factors for EoCRC included CRC history in a first-degree relative (RR 4.21, 95% CI 2.61-6.79), hyperlipidemia (RR 1.62, 95% CI 1.22-2.13), obesity (RR 1.54, 95% CI 1.01-2.35), and alcohol consumption (high vs. non-drinkers) (RR 1.71, 95% CI 1.62-1.80). While smoking was suggestive as a risk factor, the association was not statistically significant (RR 1.35, 95% CI 0.81-2.25). With the exception of alcohol consumption, there was considerable heterogeneity among studies (I2 > 60%). Other potential risk factors included hypertension, metabolic syndrome, ulcerative colitis, chronic kidney disease, dietary factors, sedentary behaviour, and occupational exposure to organic dusts, but these were only examined in one or two studies. CONCLUSIONS: The results of this study advance the understanding of the etiology of EoCRC. High-quality studies conducted on generalizable populations and that comprehensively examine risk factors for EoCRC are required to inform primary and secondary prevention strategies.

Association Between Endoscopist Specialty and Colonoscopy Quality: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Colonoscopy quality indicators provide measurable assessments of performance, but significant provider-level variations exist. We performed a systematic review and meta-analysis to assess whether endoscopist specialty is associated with adenoma detection rate (ADR) - the primary outcome - or cecal intubation rate, adverse event rates, and post-colonoscopy colorectal cancer rates. METHODS: We searched EMBASE, Google Scholar, MEDLINE, and the Cochrane Central Registry of Controlled Trials from inception to December 14, 2020. Two reviewers independently screened titles and abstracts. Citations underwent duplicate full-text review, with disagreements resolved by a third reviewer. Data were abstracted in duplicate. The DerSimonian and Laird random effects model was used to calculate pooled odds ratios (ORs) with respective 95% confidence intervals (CIs). Risk of bias was assessed using Risk of Bias in Non-randomised Studies of Interventions. RESULTS: Of 11,314 citations, 36 studies representing 3,500,832 colonoscopies were included. Compared with colonoscopies performed by gastroenterologists, those by surgeons were associated with lower ADRs (OR, 0.81; 95% CI, 0.74-0.88) and lower cecal intubation rates (OR, 0.76; 95% CI, 0.63-0.92). Compared with colonoscopies performed by gastroenterologists, those by other (non-gastroenterologist, non-surgeon) endoscopists were associated with lower ADRs (OR, 0.91; 95% CI, 0.87-0.96), higher perforation rates (OR, 3.02; 95% CI, 1.65-5.51), and higher post-colonoscopy colorectal cancer rates (OR, 1.23; 95% CI, 1.14-1.33). Substantial to considerable heterogeneity existed for most analyses, and overall certainty in the evidence was low according to the Grading of Recommendations, Assessment, Development, and Evaluations framework. CONCLUSION: Colonoscopies performed by surgeons or other endoscopists were associated with poorer quality metrics and outcomes compared with those performed by gastroenterologists. Targeted quality improvement efforts may be warranted.

Early-Onset Colorectal Cancer Incidence, Staging, and Mortality in Canada: Implications for Population-Based Screening.

INTRODUCTION: The incidence of early-onset colorectal cancer (eoCRC) has been increasing in North America. Debate remains as to whether the trends by topography, histology, stage, or mortality in this population are amenable to intervention from screening. METHODS: CRC incidence (2000-2017) and mortality (2000-2018) data were obtained from the Canadian Cancer Registry and Vital Statistics. Annual percentage changes (APC) in the incidence (topography and histology) and mortality of eoCRC were estimated using joinpoint regression. Incidence of late-stage CRC (III or IV) versus early-stage CRC (I or II) was compared between the eoCRC (age 20-49 years) and eligible screening (age 50-74 years) groups with Poisson regression. RESULTS: Among women aged 20-49 years, the incidence of CRC significantly increased from 2000 to 2017 in both the distal colon (APC = 1.40) and rectum (APC = 3.00), whereas for men aged 20-49 years, the CRC incidence increased in the proximal colon (APC = 1.10), distal colon (APC = 3.00), and rectum (APC = 3.70). Among both men and women aged 20-49 years, the incidence of nonmucinous adenocarcinomas significantly increased (APC: 1.90 and 2.30, respectively), whereas mucinous adenocarcinomas decreased for women (APC = -1.60) and remained stable for men. Adults aged 30 to 49 years, when diagnosed with CRC, had a significantly higher risk of being diagnosed with a late-stage CRC compared with those in the age group of 50-74 years. Rectal cancer mortality increased from 2000 to 2018 in the eoCRC group (APC for women and men 3.80 and 3.40, respectively). DISCUSSION: Emerging data support future modifications to guidelines on screening for eoCRC in Canada. Further research is required on the effect, cost-effectiveness, and risk prediction for targeted screening within this group.

Lifestyle factors and lung cancer risk among never smokers in the Canadian Partnership for Tomorrow's Health (CanPath).

BACKGROUND: Although smoking is the primary risk factor for lung cancer, 15-25% of lung cancers occur in never smokers. Emerging evidence suggests lifestyle factors are associated with lung cancer risk, but few studies among never smokers exist. METHODS: A case-control study of never smokers within the Canadian Partnership for Tomorrow's Health was conducted. At recruitment, participants provided data on lifestyle, health history and sociodemographic factors. Incident lung cancers were identified through linkage with administrative health records. Cases (n = 190) were matched to controls (n = 760) on age, sex, and follow-up time. Logistic regression analyses, adjusted for matching factors and annual income, were used to identify associations between lifestyle factors and lung cancer risk. RESULTS: Consumption of < 5 servings of fruits and vegetables/day was associated with higher risk of lung cancer (OR 1.50, 95% CI 1.03-2.17). Short or long sleep (≤ 6 or > 9 h/night) was also associated with increased risk of lung cancer (OR 1.52, 95% CI 1.01-2.29). No associations were observed for obesity measures, alcohol consumption, or physical activity. CONCLUSION: Our findings provide evidence of a potential role between sleep, fruits and vegetable consumption, and lung cancer risk in a pan-Canadian, non-smoking population. However, the sample size is modest, and further investigation is needed.

Body Composition and Metabolomics in the Alberta Physical Activity and Breast Cancer Prevention Trial.

BACKGROUND: Obesity is correlated with many biomarkers, but the extent to which these correlate with underlying body composition is poorly understood. OBJECTIVES: Our objectives were to 1) describe/compare distinct contributions of fat/lean mass with BMI-metabolite correlations and 2) identify novel metabolite biomarkers of fat/lean mass. METHODS: The Alberta Physical Activity and Breast Cancer Prevention Trial was a 2-center randomized trial of healthy, inactive, postmenopausal women (n = 304). BMI (in kg/m2) was calculated using weight and height, whereas DXA estimated fat/lean mass. Ultra-performance liquid chromatography and mass spectrometry measured relative concentrations of serum metabolite concentrations. We estimated partial Pearson correlations between 1052 metabolites and BMI, adjusting for age, smoking, and site. Fat mass index (FMI; kg/m2) and lean mass index (LMI; kg/m2) correlations were estimated similarly, with mutual adjustment to evaluate independent effects. RESULTS: Using a Bonferroni-corrected α level <4.75 × 10-5,  we observed 53 BMI-correlated metabolites (|r| = 0.24-0.42). Of those, 21 were robustly correlated with FMI (|r| > 0.20), 25 modestly (0.10 ≤ |r| ≤ 0.20), and 7 virtually null (|r| < 0.10). Ten of 53 were more strongly correlated with LMI than with FMI. Examining non-BMI-correlated metabolites, 6 robustly correlated with FMI (|r| = 0.24-0.31) and 2 with LMI (r = 0.25-0.26). For these, correlations for fat and lean mass were in opposing directions compared with BMI-correlated metabolites, in which correlations were mostly in the same direction. CONCLUSIONS: Our results demonstrate how a thorough evaluation of the components of fat and lean mass, along with BMI, provides a more accurate assessment of the associations between body composition and metabolites than BMI alone. Such an assessment makes evident that some metabolites correlated with BMI predominantly reflect lean mass rather than fat, and some metabolites related to body composition are not correlated with BMI. Correctly characterizing these relations is important for an accurate understanding of how and why obesity is associated with disease.

Implications of the United States recommendations for early-age-at-onset colorectal cancer screening in Canada.

The United States Preventive Services Task Force (USPSTF) recently issued an updated recommendation for population-based colorectal cancer (CRC) screening starting at age 45, due to a sustained increase in the incidence of early-age-at-onset CRC (eoCRC). A similar increase in the incidence of eoCRC has been observed in Canada since the early 2000s. However, the inherent differences between the US and Canadian health care systems with many different reimbursement and capacity considerations limit the applicability of the recommendations to the Canadian context. In order to facilitate further discussion around Canadian guidelines and recommendations, several research gaps need to be addressed: 1) a detailed understanding of trends in histology, topography, initial stage at diagnosis, and mortality among eoCRC; 2) a detailed analysis of cost-effectiveness outlining the impacts to the current screening programs with potential harms and benefits; 3) a comprehensive understanding of risk factor profiles that may lead to meaningful recommendations for screening decisions within the 40-49 age group in the absence of wide-spread screening programs; and 4) an evaluation of the effectiveness of current and novel screening tests or biomarkers specifically in the 40-49 age group. In the meantime, we suggest that physicians and patients begin discussions about screening at age 45 by reviewing family history and alerting patients to symptoms of CRC, which may increase screening adherence at age 50. This issue will remain an active area of debate with Canada as a careful laggard in changing recommendations, while attempting to balance system considerations with eoCRC trends and patient outcomes.

The efficacy of chemopreventive agents on the incidence of colorectal adenomas: A systematic review and network meta-analysis.

Colorectal cancer (CRC) is the fourth most common cancer and third leading cause of cancer-related death worldwide. Use of chemopreventive agents (CPAs) to reduce the incidence of precursor colorectal adenomas could lower the future burden of CRC. Many classes of potential CPAs have been investigated. To identify the most effective CPAs, we conducted a systematic review and a network meta-analysis (NMA). An electronic search was performed through August 2020 to identify all randomized controlled trials (RCTs) assessing the efficacy of CPAs in reducing the incidence of colorectal adenomas at the time of surveillance colonoscopy among patients who had previously undergone polypectomy during an index colonoscopy. In total, 33 RCTs were included in the NMA, which was conducted under a Bayesian inference framework. Random effects models were used with adjustment for follow-up length and control group event rates to yield relative risks (RRs) and 95% credible intervals (CrIs). Our full network consisted of 13 interventions in addition to a placebo arm. Of 20,925 included patients, 7766 had an adenoma. Compared to placebo, the combination of difluoromethylornithine (DFMO) + Sulindac (RR 0.24, CrI 0.10-0.55) demonstrated a protective effect, while aspirin had a RR of 0.77 (CrI 0.60-1.00), celecoxib 800 mg had a RR of 0.56 (CrI 0.31-1.01) and metformin had a RR of 0.56 (CrI 0.22-1.39). Our results suggest that select CPAs may be efficacious in preventing the development of adenomas. Further studies are needed to identify those patients most likely to benefit and the minimum effective dosages of CPAs.