Progression-free survival as a surrogate endpoint for overall survival in patients with relapsed or refractory multiple myeloma.

OBJECTIVES: The goal of the research was to assess the quantitative relationship between median progression-free survival (PFS) and median overall survival (OS) specifically among patients with relapsed/refractory multiple myeloma (RRMM) based on published randomized controlled trials (RCTs). METHODS: Two bibliographic databases (PubMed and Embase, 1970-2017) were systematically searched for RCTs in RRMM that reported OS and PFS, followed by an updated search of studies published between 2010 and 2022 in 3 databases (Embase, MEDLINE, and EBM Reviews, 2010-2022). The association between median PFS and median OS was assessed using the nonparametric Spearman rank and parametric Pearson correlation coefficients. Subsequently, the quantitative relationship between PFS and OS was assessed using weighted least-squares regression adjusted for covariates including age, sex, and publication year. Study arms were weighted by the number of patients in each arm. RESULTS: A total of 31 RCTs (56 treatment arms, 10,450 patients with RRMM) were included in the analysis. The average median PFS and median OS were 7.1 months (SD 5.5) and 28.1 months (SD 11.8), respectively. The Spearman and Pearson correlation coefficients between median PFS and median OS were 0.80 (P < 0.0001) and 0.79 (P < 0.0001), respectively. In individual treatment arms of RRMM trials, each 1-month increase in median PFS was associated with a 1.72-month (95% CI 1.26-2.17) increase in median OS. CONCLUSION: Analysis of the relationship between PFS and OS incorporating more recent studies in RRMM further substantiates the use of PFS to predict OS in RRMM.

Performance of the fecal immunochemical test for colorectal cancer and advanced neoplasia in individuals under age 50.

The increased demand for colonoscopy combined with increased incidence of colorectal cancer (CRC) among younger populations presents a need to determine FIT performance among individuals in this age group. We conducted a systematic review to assess test performance characteristics of FIT in detecting CRC and advanced neoplasia in younger age populations. A search through December 2022 identified published articles assessing the sensitivity and specificity of FIT for advanced neoplasia or CRC among populations under age 50. Following the search, 3 studies were included in the systematic review. Sensitivity to detect advanced neoplasia ranged from 0.19 to 0.36 and specificity between 0.94 and 0.97 and the overall sensitivity and specificity were 0.23 (0.17-0.30) and 0.96 (0.94-0.98), respectively. Two studies that assessed these metrics in multiple age categories found similar sensitivity and specificity across all age groups 30-49. Sensitivity and specificity to detect CRC was assessed in one study and found no significant differences by age groups. These results suggest that FIT performance may be lower for younger individuals compared to those typically screened for CRC. However, there were few studies available for analysis. Given increasing recommendations to expand screening in younger age groups, more research is needed to determine whether FIT is an adequate screening tool in this population.

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.

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.

Projected estimates of cancer in Canada in 2022.

BACKGROUND: Regular cancer surveillance is crucial for understanding where progress is being made and where more must be done. We sought to provide an overview of the expected burden of cancer in Canada in 2022. METHODS: We obtained data on new cancer incidence from the National Cancer Incidence Reporting System (1984-1991) and Canadian Cancer Registry (1992-2018). Mortality data (1984-2019) were obtained from the Canadian Vital Statistics - Death Database. We projected cancer incidence and mortality counts and rates to 2022 for 22 cancer types by sex and province or territory. Rates were age standardized to the 2011 Canadian standard population. RESULTS: An estimated 233 900 new cancer cases and 85 100 cancer deaths are expected in Canada in 2022. We expect the most commonly diagnosed cancers to be lung overall (30 000), breast in females (28 600) and prostate in males (24 600). We also expect lung cancer to be the leading cause of cancer death, accounting for 24.3% of all cancer deaths, followed by colorectal (11.0%), pancreatic (6.7%) and breast cancers (6.5%). Incidence and mortality rates are generally expected to be higher in the eastern provinces of Canada than the western provinces. INTERPRETATION: Although overall cancer rates are declining, the number of cases and deaths continues to climb, owing to population growth and the aging population. The projected high burden of lung cancer indicates a need for increased tobacco control and improvements in early detection and treatment. Success in breast and colorectal cancer screening and treatment likely account for the continued decline in their burden. The limited progress in early detection and new treatments for pancreatic cancer explains why it is expected to be the third leading cause of cancer death in Canada.

Endocuff Vision improves adenoma detection rate in a large screening-related cohort.

Background and study aims Endocuff Vision (ECV) increases adenoma detection rate (ADR) in randomized clinical trials; however, observational effectiveness data are lacking. We evaluated the effectiveness, safety, and practical aspects of ECV use in a large screening-related real-world cohort. Patients and methods In this observational study, patients undergoing screening-related colonoscopy from November 2018 to April 2019 comprised the baseline period, and those undergoing it from June to November 2019 comprised the ECV period, where ECV use was discretionary. The primary outcome was ADR, compared: 1) between ECV use and standard colonoscopy across both periods; and 2) between time periods. Secondary outcomes included indication-specific ADR, sessile serrated ADR (SSADR), cecal intubation rate (CIR), procedure times, patient comfort scores, and sedation use. Multilevel logistic regression was performed, yielding adjusted odds ratios (AOR) with 95 % confidence intervals (CIs). Results In 15,814 colonoscopies across both time periods, ADR was 46.7 % with standard colonoscopy and 54.6 % when ECV was used ( P  < 0.001). Endoscopists used ECV in 77.6 % of procedures in the ECV period, during which overall ADR rose to 53.2 % compared to 46.3 % in the baseline period ( P  < 0.001). ECV use was significantly associated with higher ADR (AOR 1.24, 95 % CI 1.10 to 1.40) after adjusting for relevant covariates including time period. ECV use did not result in lower CIR, longer procedure time, increased sedation use, or poorer comfort scores. Conclusions ECV use is associated with improved ADR without negatively impacting other key procedure and patient-related factors. Future studies should evaluate the cost-effectiveness of incorporating ECV into routine screening-related practice.

Estimating the future cancer management costs attributable to modifiable risk factors in Canada.

OBJECTIVES: An estimated 33-37% of incident cancers in Canada are attributable to modifiable risk factors. Interventions targeting these risk factors would minimize the substantial health and economic burdens Canadians face due to cancer. We estimate the future health and economic burden of cancer in Canada by incorporating data from the Canadian Population Attributable Risk of Cancer (ComPARe) study into OncoSim, a web-based microsimulation tool. METHODS: Using the integrated OncoSim population attributable risk and population impact measures, we evaluated risk factor-targeted intervention scenarios implemented in 2020, assuming the targeted risk factor prevalence reduction would be achieved by 2032 with a 12-year latency period. RESULTS: We estimate that smoking will be the largest contributor to cancer-related costs, with a cost of CAD $44.4 billion between 2032 and 2044. An estimated CAD $3.3 billion of the cost could be avoided with a 30% reduction in smoking prevalence by 2022. Following smoking, the next highest cancer management costs are associated with inadequate physical activity and excess body weight, accounting for CAD $10.7 billion ($2.7 billion avoidable) and CAD $9.8 billion ($3.2 billion avoidable), respectively. Avoidable costs for other risk factors range from CAD $90 million to CAD $2.5 billion. CONCLUSION: Interventions targeting modifiable cancer risk factors could prevent a substantial number of incident cancer cases and billions of dollars in cancer management costs. With limited budgets and rising costs in cancer care in Canada, these simulation models and results are valuable for researchers and policymakers to inform decisions and prioritize and evaluate intervention programs.

RéSUMé: OBJECTIFS: Il est estimé que de 33 % à 37 % des cancers incidents au Canada sont imputables à des facteurs de risque modifiables. Des interventions ciblant ces facteurs de risque réduiraient le fardeau sanitaire et économique considérable du cancer dans la population canadienne. Nous avons estimé le futur fardeau sanitaire et économique du cancer au Canada en intégrant les données de l'étude ComPARe (Canadian Population Attributable Risk of Cancer) dans l'outil de microsimulation en ligne OncoSim. MéTHODE: À l'aide des indicateurs d'impact dans la population et du risque attribuable dans la population intégrés dans OncoSim, nous avons évalué des scénarios d'intervention mis en œuvre en 2020 axés sur les facteurs de risque, en partant de l'hypothèse que la réduction de la prévalence des facteurs de risque ciblés serait atteinte d'ici 2032 avec une période de latence de 12 ans. RéSULTATS: Nous estimons que le tabagisme sera le facteur qui contribuera le plus aux coûts du cancer, avec un coût de 44,4 milliards $ CA entre 2032 et 2044. Il est estimé qu'une part de 3,3 milliards $ CA de ce coût pourrait être évitée en réduisant de 30 % la prévalence du tabagisme d'ici 2022. Après le tabagisme, les coûts de prise en charge du cancer les plus élevés sont associés à l'inactivité physique et au surpoids, qui représentent respectivement 10,7 milliard $ CA (dont 2,7 milliards $ évitables) et 9,8 milliards $ CA (dont 3,2 milliards $ évitables). Les coûts évitables pour d'autres facteurs de risque vont de 90 millions $ CA à 2,5 milliards $ CA. CONCLUSION: Des interventions ciblant les facteurs de risque de cancer modifiables pourraient prévenir un nombre considérable de cas de cancers incidents et épargner des milliards de dollars en coûts de prise en charge du cancer. Avec les budgets serrés et la hausse des coûts des soins du cancer au Canada, ces modèles de simulation et leurs résultats permettent aux chercheurs et aux responsables des politiques d'éclairer les décisions et de hiérarchiser et d'évaluer les programmes d'intervention.

Estimates of future cancer mortality attributable to modifiable risk factors in Canada.

OBJECTIVES: Modifiable lifestyle, environmental, and infectious risk factors associated with cancer impact both cancer incidence and mortality at the population level. Most studies estimating this burden focus on cancer incidence. However, because these risk factors are associated with cancers of disparate mortality rates, the burden associated with cancer incidence could differ from cancer mortality. Therefore, estimating the cancer mortality attributable to these risk factors provides additional insight into cancer prevention. Here, we estimated future cancer deaths and the number of avoidable deaths in Canada due to modifiable risk factors. METHODS: The projected cancer mortality data came from OncoSim, a web-based microsimulation tool. These data were applied to the methodological framework that we previously used to estimate the population attributable risks and the potential impact fractions of modifiable risk factors on Canadian cancer incidence. RESULTS: We estimated that most cancer deaths will be attributed to tobacco smoking with an average of 27,900 deaths annually from 2024 to 2047. If Canada's current trends in excess body weight continue, cancer deaths attributable to excess body weight would double from 2786 deaths in 2024 to 5604 deaths in 2047, becoming the second leading modifiable cause of cancer death. Applying targets to reduce these risk factors, up to 34,600 cancer deaths could be prevented from 2024 to 2047. CONCLUSION: Our simulated results complement our previous findings on the cancer incidence burden since decreasing the overall burden of cancer will be accelerated through a combination of decreasing cancer incidence and improving survival outcomes through improved treatments.

RéSUMé: OBJECTIFS: Les facteurs de risque modifiables associés au cancer (liés au mode de vie, à l'environnement, aux maladies infectieuses) ont des effets à la fois sur l'incidence du cancer et sur la mortalité par cancer à l'échelle de la population. La plupart des études qui estiment ce fardeau portent sur l'incidence du cancer. Cependant, comme les facteurs de risque susmentionnés sont associés à des cancers dont les taux de mortalité sont disparates, le fardeau associé à l'incidence du cancer pourrait différer de la mortalité par cancer. En conséquence, l'estimation de la mortalité par cancer imputable à ces facteurs de risque pourrait éclairer la prévention du cancer. Nous estimons ici les décès futurs par cancer et le nombre de décès évitables au Canada dus à des facteurs de risque modifiables. MéTHODE: Les données projetées sur la mortalité par cancer proviennent d'OncoSim, un outil de microsimulation en ligne. Elles ont été appliquées au cadre méthodologique que nous avions déjà utilisé pour estimer les risques attribuables dans la population et les fractions de l'incidence potentielle des facteurs de risque modifiables sur l'incidence canadienne du cancer. RéSULTATS: Selon nos estimations, entre 2024 et 2047, la plupart des décès par cancer seront imputés au tabagisme, qui causera en moyenne 27 900 décès par année. Si les tendances actuelles au Canada en matière de surpoids se maintiennent, les décès par cancer attribuables au surpoids doubleraient, passant de 2 786 décès en 2024 à 5 604 en 2047, et le surpoids deviendrait la deuxième cause modifiable de décès par cancer. En appliquant des cibles de réduction de ces facteurs de risque, jusqu'à 34 600 décès par cancer pourraient être évités entre 2024 et 2047. CONCLUSION: Les résultats de notre simulation confirment nos constatations antérieures sur le fardeau de l'incidence du cancer, car la diminution du fardeau global du cancer sera accélérée par une combinaison de la diminution de l'incidence du cancer et de l'amélioration des résultats de survie grâce à l'amélioration des traitements.

The impact of episodic screening interruption: COVID-19 and population-based cancer screening in Canada.

BACKGROUND: Population-based cancer screening can reduce cancer burden but was interrupted temporarily due to the COVID-19 pandemic. We estimated the long-term clinical impact of breast and colorectal cancer screening interruptions in Canada using a validated mathematical model. METHODS: We used the OncoSim breast and colorectal cancers microsimulation models to explore scenarios of primary screening stops for 3, 6, and 12 months followed by 6-24-month transition periods of reduced screening volumes. For breast cancer, we estimated changes in cancer incidence over time, additional advanced-stage cases diagnosed, and excess cancer deaths in 2020-2029. For colorectal cancer, we estimated changes in cancer incidence over time, undiagnosed advanced adenomas and colorectal cancers in 2020, and lifetime excess cancer incidence and deaths. RESULTS: Our simulations projected a surge of cancer cases when screening resumes. For breast cancer screening, a three-month interruption could increase cases diagnosed at advanced stages (310 more) and cancer deaths (110 more) in 2020-2029. A six-month interruption could lead to 670 extra advanced cancers and 250 additional cancer deaths. For colorectal cancers, a six-month suspension of primary screening could increase cancer incidence by 2200 cases with 960 more cancer deaths over the lifetime. Longer interruptions, and reduced volumes when screening resumes, would further increase excess cancer deaths. CONCLUSIONS: Interruptions in cancer screening will lead to additional cancer deaths, additional advanced cancers diagnosed, and a surge in demand for downstream resources when screening resumes. An effective strategy is needed to minimize potential harm to people who missed their screening.

Bayesian network modelling study to identify factors influencing the risk of cardiovascular disease in Canadian adults with hepatitis C virus infection.

OBJECTIVES: The present study evaluates the extent of association between hepatitis C virus (HCV) infection and cardiovascular disease (CVD) risk and identifies factors mediating this relationship using Bayesian network (BN) analysis. DESIGN AND SETTING: A population-based cross-sectional survey in Canada. PARTICIPANTS: Adults from the Canadian Health Measures Survey (n=10 115) aged 30 to 74 years. PRIMARY AND SECONDARY OUTCOME MEASURES: The 10-year risk of CVD was determined using the Framingham Risk Score in HCV-positive and HCV-negative subjects. Using BN analysis, variables were modelled to calculate the probability of CVD risk in HCV infection. RESULTS: When the BN is compiled, and no variable has been instantiated, 73%, 17% and 11% of the subjects had low, moderate and high 10-year CVD risk, respectively. The conditional probability of high CVD risk increased to 13.9%±1.6% (p<2.2×10-16) when the HCV variable is instantiated to 'Present' state and decreased to 8.6%±0.2% when HCV was instantiated to 'Absent' (p<2.2×10-16). HCV cases had 1.6-fold higher prevalence of high-CVD risk compared with non-infected individuals (p=0.038). Analysis of the effect modification of the HCV-CVD relationship (using median Kullback-Leibler divergence; DKL ) showed diabetes as a major effect modifier on the joint probability distribution of HCV infection and CVD risk (DKL =0.27, IQR: 0.26 to 0.27), followed by hypertension (0.24, IQR: 0.23 to 0.25), age (0.21, IQR: 0.10 to 0.38) and injection drug use (0.19, IQR: 0.06 to 0.59). CONCLUSIONS: Exploring the relationship between HCV infection and CVD risk using BN modelling analysis revealed that the infection is associated with elevated CVD risk. A number of risk modifiers were identified to play a role in this relationship. Targeting these factors during the course of infection to reduce CVD risk should be studied further.

Age-standardized cancer-incidence trends in Canada, 1971-2015.

BACKGROUND: Although cancer incidence over time is well documented in Canada, trends by birth cohort and age group are less well known. We analyzed age- and sex-standardized incidence trends in Canada for 16 major cancer sites and all cancers combined. METHODS: We obtained nationally representative population-based cancer incidence data in Canada between 1971 and 2015 from the National Cancer Incidence Reporting System (1969-1992) and the Canadian Cancer Registry (1992-2015). We analyzed cancer-incidence trends, reported as annual percent change (APC) for each 10-year group from age 20 to 89 years. We also estimated age-adjusted incidence rate ratios from fitted birth cohort models. RESULTS: Across most age categories, the most recent trends show significant decreases in the incidence of cervical (APC -8.8% to -0.33%), lung (men: -7.42% to -0.36%; women: -6.27% to 1.07%), bladder (women: -4.12% to -0.07%; men: -5.13% to -0.38%) and prostate cancer (-11.11% to -1.11%). Significant increasing trends were observed for kidney, thyroid and uterine cancers. Overall incidence has increased among both sexes younger than 50 years of age, with recent increases in pancreatic cancer among men, breast cancer among women and colorectal cancer among both sexes. From the birth cohort analysis, we observed increasing trends in colorectal, liver and prostate cancers among men; kidney cancer and melanoma among women; and thyroid cancer among both sexes. We observed decreasing trends in cervical and ovarian cancers, and in bladder and lung cancers among men. INTERPRETATION: Cancer incidence is decreasing at many sites targeted by primary-prevention efforts, such as smoking cessation and screening programs. Substantial increases in incidence among younger populations are driven by cancers possibly associated with obesity.

The current and future burden of cancer attributable to modifiable risk factors in Canada: Summary of results.

Nearly one in two Canadians are expected to be diagnosed with cancer in their lifetime. However, there are opportunities to reduce the impact of modifiable cancer risk factors through well-informed interventions and policies. Since no comprehensive Canadian estimates have been available previously, we estimated the proportion of cancer diagnosed in 2015 and the future burden in 2042 attributable to lifestyle and environmental factors, and infections. Population-based historical estimates of exposure prevalence and their associated risks for each exposure-cancer site pair were obtained to estimate population attributable risks, assuming the exposures were distributed independently and that the risk estimates were multiplicative. We estimated that between 33 and 37% (up to 70,000 cases) of incident cancer cases among adults aged 30 years and over in 2015 were attributable to preventable risk factors. Similar proportions of cancer cases in males (34%) and females (33%) were attributable to these risk factors. Tobacco smoking and a lack of physical activity were associated with the highest proportions of cancer cases. Cancers with the highest number of preventable cases were lung (20,100), colorectal (9800) and female breast (5300) cancer. If current trends in the prevalence of preventable risk factors continue into the future, we project that by 2042 approximately 102,000 incident cancer cases are expected to be attributable to these risk factors per year, which would account for roughly one-third of all incident cancers. Through various risk reduction interventions, policies and public health campaigns, an estimated 10,600 to 39,700 cancer cases per year could be prevented by 2042.

Estimates of the current and future burden of cancer attributable to low fruit and vegetable consumption in Canada.

Low fruit and vegetable consumption is associated with colorectal cancer and may be associated with lung, breast, bladder, pancreatic, ovarian, liver, stomach, esophageal, head and neck cancers. We estimated the current attributable and future avoidable burden of cancer associated with low fruit and vegetable consumption in Canada. Using data on cancer incidence, exposure prevalence and risk effects, we estimated the population attributable risk (PAR) for cancers associated with low fruit and vegetable consumption as well as the future avoidable burden. The prevalence of fruit and vegetable consumption was projected to 2032 and cancer incidence was projected to 2042 to estimate the future potential impact fraction of cancer attributable to low fruit and vegetable consumption. Based on estimates from the Canadian Community Health Survey, the prevalence of low fruit (<4 servings/day) and vegetable (<4 servings/day) consumption in the Canadian population was 80.5% and 86.6%, respectively. The PARs for colorectal cancer associated with low fruit and vegetable consumption were 6.1% (1, 371 cases) and 2.2% (487 cases), respectively. For all incident cancers in 2015, 0.7% and 0.3% were attributable to low fruit and vegetable consumption, respectively. An increase of one serving/week of fruit could prevent 20,710 colorectal cancer cases cumulatively by 2042, and the same increase in vegetable consumption could prevent 10,185 cases. Although more research on the association between fruit and vegetable consumption and cancer risk is needed, our results demonstrate that with reasonable increases in current fruit and vegetable consumption by Canadians, over 30,000 colorectal cancer cases could be prevented by 2042.

The burden of cancer attributable to modifiable risk factors in Canada: Methods overview.

Up-to-date estimates of current and projected future cancer burden attributable to various exposures are essential for planning and implementing cancer prevention initiatives. The Canadian Population Attributable Risk of Cancer (ComPARe) study was conducted to: i) estimate the number and proportion of cancers diagnosed among adults in Canada in 2015 that are attributable to modifiable risk factors and ii) project the future avoidable cancers by 2042 under various intervention targets. We estimated the population attributable risk (with 95% confidence intervals) and the potential impact fraction of cancers associated with selected lifestyle, environmental, and infectious factors. Exposure-specific sensitivity analyses were also completed where appropriate. Several exposures of interest included active and passive smoking, obesity and abdominal adiposity, leisure-time physical inactivity, sedentary behaviour, alcohol consumption, insufficient fruit and vegetable intake, red and processed meat consumption, air pollution (PM2.5, NO2), indoor radon gas, ultraviolet radiation (UVR), hepatitis B and C virus, Helicobacter pylori, Epstein-Barr virus, human papillomavirus, human herpesvirus type 8 and human T-cell lymphotropic virus type 1. We used the 2015 cancer incidence data for 35 cancer sites from the Canadian Cancer Registry and projected cancer incidence to 2042 using historical data from 1983 to 2012. Here, we provide an overview of the data sources and methods used in estimating the current and future cancer burden in Canada. Specific methodologic details for each exposure are included in the individual articles included as part of this special issue.

Estimates of the current and future burden of cancer attributable to red and processed meat consumption in Canada.

Red meat and processed meat have been consistently associated with an increased risk of colorectal, stomach, pancreatic cancer and esophageal cancer (processed meat only). The purpose of this analysis was to estimate the current attributable and future avoidable burden of cancer related to red and processed meat consumption in Canada. We estimated the population attributable risk of cancer separately for red meat consumption (beef, lamb, and pork, excluding processed meat) and processed meat consumption (sausage and bacon) incorporating current cancer incidence data, relative risks, and exposure prevalence. We also estimated the future avoidable burden of cancer from 2015 to 2042 for Canada and by province using the potential impact fraction associated with various potential intervention scenarios intended to reduce consumption, ranging from a decrease of 0.2 servings/week to 2.0 servings/week among the adult Canadian population aged 20 and over. The estimated mean red meat consumption in the Canadian population in 2007 to 2011 was approximately 3.2 times per week. In addition, Canadians consume an average of 1.2 times of processed meat per week. In 2015, an estimated 5.9% of associated cancers and 0.9% of all cancers were attributable to red meat consumption. An estimated 4.5% of associated cancers and 0.7% of all cancers were attributable to processed meat consumption. A mean decrease of 0.5 servings/week of red meat or processed meat could prevent about 8700 or 16,600 cancer cases, respectively, between 2015 and 2042. In conclusion, a small but meaningful cancer burden is associated with red and processed meat consumption. Interventions aimed at reducing consumption at the population level have the potential in the prevention of many cancers in Canada.

Estimates of the current and future burden of cancer attributable to alcohol consumption in Canada.

Alcohol consumption is associated with elevated risk of oropharyngeal, laryngeal, esophageal, colon, rectal, breast, liver, pancreatic and stomach cancers. The purpose of this analysis was to provide national and provincial estimates of the number and proportion of cancers attributable to alcohol consumption in Canada and to project the numbers of potentially avoidable cancers using possible intervention scenarios. We estimated the population attributable risk (PAR) for cancers associated with alcohol consumption levels (drinks/day) using: i) relative risks obtained from the World Cancer Research Fund/(WCRF) reports or meta-analyses, ii) alcohol consumption (prevalence) data from the 2003 Canadian Community Health Survey, and iii) cancer incidence data from the 2015 Canadian Cancer Registry. We used potential impact fractions (PIFs) to estimate the future avoidable cancer burden under four counterfactual scenarios: (1) lowering alcohol consumption to meet the WCRF low risk guidelines, (2) meeting the Canada's Low-Risk Drinking Guidelines, (3) reducing daily intake by one drink/day, and (4) decreasing consumption to 50% of the 2003 levels by 2032. We estimated that 3282 incident cancer cases (5.2% of alcohol-associated cancers and 1.8% of all cancers) diagnosed in Canada in 2015 were attributable to alcohol consumption. At the current consumption levels, alcohol-attributable cancers are expected to increase to 10,122 (8.8% of cases among alcohol-associated cancers) by 2042. Under the best case scenario, reducing alcohol consumption to 50% of 2003 levels by 2032, could prevent 70,261 cases by 2042. Strategies that effectively reduce alcohol consumption at a population level can have a meaningful impact on reducing the cancer burden in Canada.

Estimates of the current and future burden of cancer attributable to excess body weight and abdominal adiposity in Canada.

The increasing prevalence of obesity among Canadians has important implications for newly diagnosed cases of cancer given that excess body weight and abdominal adiposity are known to increase the risk of several cancers. The purpose of this analysis was to estimate the current attributable and future avoidable burden of cancer related to excess body weight and abdominal adiposity among Canadian adults. We estimated the population attributable risk (PAR) for all cancers associated with excess body weight and abdominal adiposity using contemporary cancer incidence, relative risk and exposure prevalence data for body mass index (BMI), waist circumference and waist-to-hip-ratio. Using the partial impact fraction (PIF), we also estimated the future avoidable burden of cancer from 2015 to 2042 in Canada, and by province, through various hypothetical intervention scenarios. In 2003, approximately half (50.5%) of the Canadian population was estimated to be overweight (BMI 25.0-29.9) or obese (BMI ≥30.0), 56.5% to have excess abdominal adiposity and 56.8% with a high waist-to-hip ratio. In 2015, the estimated PARs of all incident cancers associated with excess body weight, excess abdominal adiposity and high waist-to-hip ratio were 7.2%, 8.9% and 10.0%, respectively. If the population BMI could revert to its 1994 distribution, 72,157 associated cancer cases could be prevented cumulatively by 2042. A reduction in excess body weight and abdominal adiposity has the potential to decrease the future cancer burden in Canada substantially, and hence efforts to reverse increasing trends in obesity should be prioritized.

Estimates of the current and future burden of cancer attributable to lack of physical activity in Canada.

Physical activity reduces the risk of many cancers, yet the prevalence of inadequate physical activity among Canadians remains high. Here we estimated the current attributable and future avoidable burden of cancer related to inadequate physical activity among Canadian adults. Population attributable risk (PAR) for all cancers associated with inadequate physical activity were estimated using relative risks obtained from comprehensive reports, meta-analyses and pooled analyses. Cancer incidence data were acquired from the Canadian Cancer Registry. Physical activity data were taken from Canadian Community Health Survey (Cycle 2.1, 2003), in which respondents were classified as "physically inactive" (<1.5 kcal/kg/day), "moderately active" (1.5-2.9 kcal/kg/day) or "physically active (≥3.0 kcal/kg/day). We defined "inadequate physical activity" as being either "physically inactive" or "moderately active" to determine the PAR of cancer due to inadequate physical activity. We estimated the future burden of inadequate physical activity using potential impact fractions and a series of intervention scenarios, including 10% to 50% reductions in inadequate physical activity from 2015 to 2042. For 2015, the total attributable burden due to inadequate physical activity for associated cancers was 10.6% and 4.9% for all cancers. A 50% reduction in inadequate physical activity could avoid 39,877 cumulative cases of cancer by 2042. Over 9000 cancer cases in 2015 were estimated to be attributable to inadequate physical activity and 5170 incident cases of cancer could be prevented with increases in physical activity levels by 2042. Policies aimed at increasing physical activity among Canadian could have a meaningful impact for cancer prevention.

Estimates of the current and future burden of cancer attributable to sedentary behavior in Canada.

Leisure-time sedentary behavior is an emerging modifiable risk factor for cancer. We estimated the proportion of cancers attributed to leisure-time sedentary behavior as a separate risk factor from physical activity in Canada for 2015. We projected numbers of future avoidable cancers by 2042 using various assumed levels of reduced leisure-time sedentary behavior in the population. We calculated population attributable risks (PAR) for associated cancers and all-cancers associated with leisure-time sedentary behavior. Our analysis used pooled data on leisure-time sedentary behavior from the Canadian Community Health Survey (CCHS), and incident cancer data from the Canadian Cancer Registry (CCR). Survey respondents were categorized into three levels of leisure-time sedentary behavior, "<3 h/day", "≥3-<6 h/day", and "≥6 h/day". Estimates for the future burden of leisure-time sedentary behavior were calculated using the potential impact fractions framework (PIF) and counterfactual scenarios, from 10% to 50% decreases in leisure-time sedentary behavior. The estimated prevalence of leisure-time sedentary behavior at the highest level (≥6 h/day) in Canada during the 2000s was 9.9% among both sexes combined across age-groups. The total attributable burden due to leisure-time sedentary behavior was estimated to be 10.3% for associated cancers and 6.5% for all-cancers in 2015. A 50% reduction in leisure-time sedentary behavior across the Canadian population could avoid 4054 cancers by 2042. We estimated that over 3000 cancer cases in Canada were attributable to leisure-time sedentary behavior in 2015, and that that 4054 incident cancer cases could be prevented by 2042 with meaningful reductions in leisure-time sedentary behavior.