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.

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.

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 active and passive tobacco smoking in Canada.

Although previous studies have examined the burden of cancer attributable to tobacco smoking, updated estimates are needed given the dramatic changes in smoking behaviours over the last 20 years. In this study, we estimate the proportion of cancer cases in 2015 attributable to past tobacco smoking and passive exposure in Canada and the proportion of cancers in the future that could be prevented through the implementation of interventions targeted at reducing tobacco use. Data from the Canadian Community Health Survey (2003) were used to estimate the prevalence of active tobacco smoking and passive exposure. Population attributable risk estimates were employed to estimate the proportion of cancers attributable to tobacco in 2015. The prevalence of active tobacco smoking and passive exposure was projected to 2032 and cancer incidence was projected from 2016 to 2042 to estimate the future burden of cancer attributable to tobacco. In 2003, 30% and 24% of Canadians were former and current smoker, respectively and 24% had been exposed to tobacco smoke in the past. We estimated that 17.5% (32,655 cases; 95% CI: 31,253-34,034) of cancers were attributable to active tobacco smoking and 0.8% (1408 cases; 95% CI: 1048-1781) to passive tobacco exposure in never smokers. Between 41,191 and 50,696 cases of cancer could be prevented by 2042 under various prevention scenarios. By decreasing passive tobacco exposure by 10-50%, between 730 and 3650 cancer cases could be prevented by 2042. Strategies focused on reducing the prevalence of tobacco smoking are crucial for cancer control in Canada.

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.

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 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.

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.

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.

Measures of excess body weight and anthropometry among adult Albertans: cross-sectional results from Alberta's tomorrow project cohort.

BACKGROUND: Excess body weight during adulthood has been consistently associated with all-cause mortality, cardiovascular disease, and cancer at multiple sites among other chronic diseases. We describe the prevalence of excess body weight and abdominal obesity reported by participants enrolled in Alberta's Tomorrow Project (ATP). METHODS: ATP is a geographically-based cohort study conducted among adults aged 35-69 years from across the province of Alberta. Participants completed anthropometric measures and health and lifestyle questionnaires at enrolment. Overweight and obese were categorized as a body mass index (BMI) of 25.0-29.9 kg/m2 and ≥30 kg/m2, respectively. Abdominal obesity was categorized using cut-offs of waist circumference of >94 cm for men and >80 cm for women and waist-tp-hip ratio cut-offs of >0.90 for men and >0.85 for women. RESULTS: BMI and hip and waist circumference data were obtained from 12,062 men and 18,853 women enrolled between 2001 and 2009. Overall, 76.8% of men and 59.5% of women reported a BMI ≥25 kg/m2. The proportions of overweight and obese were significantly higher in older age groups (p < 0.001). In addition, the proportion of participants reporting being overweight and obese was higher among lower education (p < 0.001) and lower income groups (p < 0.001). Overall, approximately two thirds of men and women in ATP cohort reported abdominal obesity. Overweight, obesity and abdominal obesity were all associated with a history of several cardiometabolic chronic conditions including hypertension, heart attack, angina, high cholesterol, stroke and diabetes. CONCLUSION: A large majority of ATP participants were overweight and carried excess abdominal fat. Strategies to improve energy balance among Albertans are encouraged and may have a notable impact on future chronic disease burden.