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.

The primary cilium is a non-motile microtubule-based structure that shares many similarities with the structures of flagella and motile cilia. It is well known that the length of flagella is under stringent control, but it is not known whether this is true for primary cilia. In this study, we found that the length of primary cilia in fibroblast-like synoviocytes, either in log phase culture or in quiescent state, was confined within a range. However, when lithium was added to the culture to a final concentration of 100 mM, primary cilia of synoviocytes grew beyond this range, elongating to a length that was on average approximately 3 times the length of untreated cilia. Lithium is a drug approved for treating bipolar disorder. We dissected the molecular targets of this drug, and observed that inhibition of adenylate cyclase III (ACIII) by specific inhibitors mimicked the effects of lithium on primary cilium elongation. Inhibition of GSK-3beta by four different inhibitors did not induce primary cilia elongation. ACIII was found in primary cilia of a variety of cell types, and lithium treatment of these cell types led to their cilium elongation. Further, we demonstrate that different cell types displayed distinct sensitivities to the lithium treatment. However, in all cases examined primary cilia elongated as a result of lithium treatment. In particular, two neuronal cell types, rat PC-12 adrenal medulla cells and human astrocytes, developed long primary cilia when lithium was used at or close to the therapeutic relevant concentration (1-2 mM). These results suggest that the length of primary cilia is controlled, at least in part, by the ACIII-cAMP signaling pathway.

Recent analyses in the United States have shown an overall decrease in the incidence of colorectal cancer despite contrasting increases in younger age groups. We examined whether these cohort trends are occurring in Canada. Age-specific trends in colon and rectal cancer incidence in Canada from the National Cancer Incidence Reporting System (1969-1992) and the Canadian Cancer Registry (1992-2012) were analyzed. We estimated annual percent changes (APC) with the Joinpoint Regression Program from the Surveillance Epidemiology, and End Results Program. Birth cohort effects were estimated using 5-year groups starting in 1888. Age-specific prevalence of class I, II and III obesity in Canada was examined from the National Population Health Survey (1994-2001) and the Canadian Community Health Survey (2001-2011). The reductions in CRC incidence among Canadians are limited to older populations. While reductions among younger age groups (20-29year olds (yo), 30-39yo and 40-50yo) were observed between 1969 and 1995, rates have returned to and surpassed historical levels (APCs 20-29yo colon cancer=6.24%, APCs 20-29yo rectal cancer=1.5%). Recent birth cohorts (1970-1990) have the highest incidence rate ratios ever recorded. Ecologic trends in obesity prevalence among these birth cohorts in Canada are suggestive of an impact on increasing incidence trends. Furthermore, obesity prevalence estimates suggest that these trends may continue to increase justifying further examination of the etiologic associations and biological impacts of excess adipose tissue among younger populations. While population-based screening of younger age groups deserves careful consideration, these concerning observed trends warrant public health action to address the growing obesity epidemic.

Background Although adolescent and young adult (AYA) cancers represent a unique spectrum of malignancies, epidemiological studies of cancer incidence often group AYAs together with younger or older populations, obscuring patterns specific to this population. Methods We examined AYA cancer incidence trends in 41 countries over a 15-year period using the CI5plus database. Truncated age-standardized incidence rates were calculated and the annual percentage change was assessed, with statistical significance corresponding to a 95% confidence interval that does not include zero. Results From 1998 to 2012, the 41 included countries contributed a total of 1 846 588 cancer cases and 3.1 billion person-years among AYAs. Although statistically significant increases in the overall cancer burden were observed in 23 countries, the magnitude varied considerably, with the greatest increase in incidence observed in South Korea (annual percentage change2002–2012 = 8.5%, 95% confidence interval = 7.6% to 9.4%) due to thyroid cancer. Notable trends included sharp increases in the incidence of obesity-related malignancies among AYAs; indeed, statistically significant increases were observed among AYAs for 10 of 11 and 9 of 11 obesity-related cancer sites in the US and UK, respectively, with at least five obesity-related cancers statistically significantly increasing in Canada, Japan, South Korea, Australia, and the Netherlands. Other striking trends were noted for thyroid and testicular cancer, with statistically significantly increasing rates observed in 33 and 22 countries, respectively, whereas statistically significant declines in incidence were observed for smoking-related cancers, cervical cancer, and Kaposi sarcoma in many countries. Conclusions Our results highlight the future health-care needs related to treatment as well as the urgency for public health initiatives that can mitigate the increasing burden of cancer in AYAs.

Purpose: To prescribe different physical activity (PA) intensities using activity trackers to increase PA, reduce sedentary time, and improve health outcomes among breast cancer survivors. The maintenance effect of the interventions on study outcomes was also assessed. Methods: The Breast Cancer and Physical Activity Level pilot trial randomized 45 breast cancer survivors to a home-based, 12-wk lower (300 min•wk−1 at 40%-59% of HR reserve) or higherintensity PA (150 min•wk−1 at 60%-80% of HR reserve), or no PA intervention/control. Both intervention groups received Polar A360® activity trackers. Study outcomes assessed at baseline, 12 and 24 wk included PA and sedentary time (ActiGraph GT3X+), health-related fitness (e.g., body composition, cardiopulmonary fitness/VO2max), and patient-reported outcomes (e.g., quality of life). Intention-to-treat analyses were conducted using linear mixed models and adjusted for baseline outcomes. Results: Increases in moderate-vigorous intensity PA (least squares adjusted group difference [LSAGD], 0.6; 95% confidence interval [CI], 0.1-1.0) and decreases in sedentary time (LSAGD, −1.2; 95% CI, −2.2 to −0.2) were significantly greater in the lowerintensity PA group versus control at 12 wk. Increases in VO2max at 12 wk in both interventions groups were significantly greater than changes in the control group (lower-intensity PA group LSAGD, 4.2; 95% CI, 0.5-8.0 mL•kg−1•min−1; higher-intensity PA group LSAGD, 5.4; 95% CI, 1.7-9.1mL•kg−1•min−1). Changes in PA and VO2max remained at 24wk, but differences between the intervention and control groups were no longer statistically significant. Conclusions: Increases in PA time and cardiopulmonary fitness/VO2max can be achieved with both lower-and higher-intensity PA interventions in breast cancer survivors. Reductions in sedentary time were also noted in the lower-intensity PA group.

Our study demonstrates the in vitro and in vivo efficacy of on-target JAK2/STAT3 inhibition in heterogeneous BTSC lines that closely emulate the genomic and tumorigenic characteristics of human GBM.

Key Points Question Is the incidence of colorectal cancer among younger adults still increasing in Canada? Findings This cohort study used data from comprehensive Canadian national cancer registries and included all 688 515 incident colorectal cancers diagnosed from 1969 to 2015. The incidence of colorectal cancer among younger adults increased from 2006 to 2015 among men with an annual percentage change of 3.47% and from 2010 to 2015 among women with an annual percentage change of 4.45%. Meaning These results provide evidence that the increased incidence of colorectal cancer among younger adults in Canada is continuing and possibly accelerating.

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