Mesenchymal stromal cells protect combined oncolytic and helper-dependent adenoviruses from humoral immunity.

Systemic delivery of oncolytic and immunomodulatory adenoviruses may be required for optimal effects on human malignancies. Mesenchymal stromal cells (MSCs) can serve as delivery systems for cancer therapeutics due to their ability to transport and shield these agents while homing to tumors. We now use MSCs to deliver a clinically validated binary oncolytic and helper-dependent adenovirus combination (CAdVEC) to tumor cells. We show successful oncolysis and helper-dependent virus function in tumor cells even in the presence of plasma from adenovirus-seropositive donors. In both two- and three-dimensional cultures, CAdVEC function is eliminated even at high dilutions of seropositive plasma but is well sustained when CAdVEC is delivered by MSCs. These results provide a robust in vitro model to measure oncolytic and helper-dependent virus spread and demonstrate a beneficial role of using MSCs for systemic delivery of CAdVEC even in the presence of a neutralizing humoral response.

National safety monitoring of vaccines from the Canadian Adverse Events Following Immunization Surveillance System (CAEFISS), 2018-2019.

Background: The Canadian Adverse Events Following Immunization Surveillance System (CAEFISS) is a comprehensive vaccine safety surveillance system that includes both passive and active surveillance of vaccines administered in Canada. This work presents a summary of adverse events following immunization (AEFI) nationally for 2018 and 2019. Methods: Data extracted from CAEFISS included all AEFI reports received by the Public Health Agency of Canada by April 30, 2022, for vaccines marketed in Canada and administered between January 1, 2018, and December 31, 2019. Descriptive statistics were conducted on AEFI reports by type of surveillance program (i.e., active vs. passive), AEFIs, demographics, healthcare utilization, outcome, seriousness of adverse events and type of vaccine. Results: Between 2018 and 2019, 5,875 AEFI reports were received from across Canada. The average annual AEFI reporting rate was 10.9/100,000 doses distributed in Canada for vaccines administered during 2018-2019 and was found to be inversely proportional to age. The majority of reports (91%) were non-serious events, involving vaccination site reactions, rash and allergic events. Overall, there were 511 serious adverse event reports during 2018-2019. Of the serious adverse event reports, the most common primary AEFIs were anaphylaxis followed by seizure. There were no unexpected vaccine safety issues identified or increases in frequency or severity of adverse events. Conclusion: Canada's continuous monitoring of the safety of marketed vaccines during 2018-2019 did not identify any increase in the frequency or severity of AEFIs, previously unknown AEFIs, or areas that required further investigation or research.

Canadian vaccine safety surveillance reports following immunization with seasonal influenza vaccines, 2021-2022.

Background: Seasonal influenza vaccines (SIV) authorized for use in Canada have all undergone rigorous regulatory assessments for safety and effectiveness. Serious adverse events following immunization (AEFI) can occur, though they are rare. Continuous safety surveillance of vaccines during the post-marketing phase is a critical component of vaccination programs. This enables the detection of rare, late onset, or unexpected adverse events. An updated safety summary following the introduction of any new vaccines and/or formulations to immunization programs is necessary for refining the risk-benefit profile of a specific vaccine and maintaining public confidence. Here we provide an updated safety summary for SIVs distributed during the 2021/2022 influenza season from AEFI reports submitted to the Canadian Adverse Event Following Immunization Surveillance System (CAEFISS) and the Canadian Vigilance Database (CVD). Methods: We searched CAEFISS and CVD for individuals who were vaccinated with a SIV between October 1, 2021, and March 31, 2022. Descriptive statistics were calculated, including median age of vaccinated individuals, vaccines co-administered with SIV, and the most frequently reported AEFIs. Crude AEFI reporting rates were calculated by severity of the AEFI report, and SIV-type using doses distributed data. Medical reviews were conducted for reports including death, serious events (or outcomes) after SIV were administered alone, and selected adverse events (i.e., anaphylaxis, Guillain-Barré syndrome, febrile seizures, oculo-respiratory syndrome). Disproportionality analysis was used to identify potential safety signals among SIV and AEFI pairs. Results: There were 448 AEFI reports, with most AEFI classified as non-serious events (84.2%). The majority of reports described vaccination in adults at least 65 years of age (38.6%). The most frequently reported AEFIs were vaccination site pain, urticaria, pyrexia and rash. Medical review of AEFI reports did not find any evidence that reported deaths were related to vaccination with SIV. Among serious reports, nervous system disorders were the most commonly reported medical conditions. A higher number of events related to vaccination errors were also identified using disproportionality analysis. Conclusion: Findings from our analysis of reports to CAEFISS and CVD following vaccination with SIV are consistent with the known safety profile of SIVs distributed during the 2021/2022 influenza season. The majority of reports were non-serious with the most common AEFI symptoms occurring at the vaccination site or systemic symptoms that were self-limiting. The majority of vaccination error reports involved the administration of the vaccine at an inappropriate site, although no serious AEFIs were reported.

Ultralow-dose binary oncolytic/helper-dependent adenovirus promotes antitumor activity in preclinical and clinical studies.

We show that a binary oncolytic/helper-dependent adenovirus (CAdVEC) that both lyses tumor cells and locally expresses the proinflammatory cytokine IL-12 and PD-L1 blocking antibody has potent antitumor activity in humanized mouse models. On the basis of these preclinical studies, we treated four patients with a single intratumoral injection of an ultralow dose of CAdVEC (NCT03740256), representing a dose of oncolytic adenovirus more than 100-fold lower than used in previous trials. While CAdVEC caused no significant toxicities, it repolarized the tumor microenvironment with increased infiltration of CD8 T cells. A single administration of CAdVEC was associated with both locoregional and abscopal effects on metastases and, in combination with systemic administration of immune checkpoint antibodies, induced sustained antitumor responses, including one complete and two partial responses. Hence, in both preclinical and clinical studies, CAdVEC is safe and even at extremely low doses is sufficiently potent to induce significant tumor control through oncolysis and immune repolarization.

HydrAd: A Helper-Dependent Adenovirus Targeting Multiple Immune Pathways for Cancer Immunotherapy.

For decades, Adenoviruses (Ads) have been staple cancer gene therapy vectors. Ads are highly immunogenic, making them effective adjuvants. These viruses have well characterized genomes, allowing for substantial modifications including capsid chimerism and therapeutic transgene insertion. Multiple generations of Ad vectors have been generated with reduced or enhanced immunogenicity, depending on their intended purpose, and with increased transgene capacity. The latest-generation Ad vector is the Helper-dependent Ad (HDAd), in which all viral coding sequences are removed from the genome, leaving only the cis-acting ITRs and packaging sequences, providing up to 34 kb of transgene capacity. Although HDAds are replication incompetent, their innate immunogenicity remains intact. Therefore, the HDAd is an ideal cancer gene therapy vector as its infection results in anti-viral immune stimulation that can be enhanced or redirected towards the tumor via transgene expression. Co-infection of tumor cells with an oncolytic Ad and an HDAd results in tumor cell lysis and amplification of HDAd-encoded transgene expression. Here, we describe an HDAd-based cancer gene therapy expressing multiple classes of immunomodulatory molecules to simultaneously stimulate multiple axes of immune pathways: the HydrAd. Overall, the HydrAd platform represents a promising cancer immunotherapy agent against complex solid tumors.

Myocarditis and/or pericarditis risk after mRNA COVID-19 vaccination: A Canadian head to head comparison of BNT162b2 and mRNA-1273 vaccines.

BACKGROUND: Canadian and international data suggest the risk of myocarditis and/or pericarditis is elevated during the week after mRNA COVID-19 vaccination, particularly in younger age groups, in males, and after second doses. OBJECTIVES: This article examines whether there is a product-specific difference in the risk for myocarditis and/or pericarditis between the two mRNA vaccines administered in Canada: BNT162b2 (Pfizer-BioNTech Comirnaty) and mRNA-1273 (Moderna Spikevax). MATERIALS AND METHODS: Reporting rates of myocarditis and/or pericarditis were calculated from reports received by the Canadian Adverse Events Following Immunization Surveillance System from December 2020-March 2022. Excess cases and attributable incidence among individuals aged 18-39 were estimated for each vaccine in comparison with background rates from 2015 to 2019. Head-to-head comparisons used Poisson regression, conditioned on week of vaccine administration, to estimate rate ratios for the week after mRNA-1273 vaccination versus the week after BNT162b2, by age and sex as well as overall. Analyses were restricted to May 30-March 13, 2021, when heightened media awareness was unlikely to have affected reporting rates for the two products differentially. RESULTS: In 18-29 year-old males who received a second dose of mRNA COVID-19 vaccine, attributable risk of myocarditis and/or pericarditis was found to be 5.69 (95% CI: 4.07 - 7.95; p < 0.001) times higher among mRNA-1273 recipients (n = 106) as compared to BNT162b2 recipients (n = 33). In the same group, Poisson regression modelling estimated that the risk of myocarditis and/or pericarditis was 4.72 (p-value = <0.001) times higher after mRNA-1723 compared to BNT162b2 vaccination. CONCLUSIONS: The risk of myocarditis and/or pericarditis is higher after mRNA-1723 vaccination than BNT162b2 vaccination in those aged 18-39 years, especially in males aged 18-29 years, where the risk is several times higher.

Comparison of Routine Hematology, Coagulation, and Clinical Chemistry Parameters of Cynomolgus Macaques of Mauritius Origin With Cynomolgus Macaques of Cambodia, China, and Vietnam Origin.

Cynomolgus macaques (Macaca fascicularis) are commonly used in safety assessment and as translational models for drug development. Recent supply chain pressures, exportation bans, and increased demand for drug safety assessment studies exacerbated by the COVID-19 pandemic have prompted the investigation of utilizing macaques of different geographic origin in preclinical toxicity studies. This study compares routine hematology, coagulation, and clinical chemistry endpoints of 3 distinct subpopulations of mainland Asia origin (Cambodia, China, and Vietnam) with Mauritius origin macaques compiling results of 3,225 animals from 123 regulatory toxicology studies conducted at North American and European Union contract research organization facilities between 2016 and 2019. Results were generally similar amongst the subpopulations compared in this study. Few notable differences in hematology test results and several minor differences in serum biochemistry and coagulation test results were identified when 3 distinct subpopulations of mainland Asia origin macaques were compared with Mauritius origin macaques. Our findings support the use of different origin macaques in drug development programs; however, emphasizes the importance of maintaining consistency in geographic origin of animals within a study.

Current development in adenoviral vectors for cancer immunotherapy.

Adenoviruses are well characterized and thus easily modified to generate oncolytic vectors that directly lyse tumor cells and can be "armed" with transgenes to promote lysis, antigen presentation, and immunostimulation. Oncolytic adenoviruses (OAds) are safe, versatile, and potent immunostimulants in patients. Since transgene expression is restricted to the tumor, adenoviral transgenes overcome the toxicities and short half-life of systemically administered cytokines, immune checkpoint blockade molecules, and bispecific T cell engagers. While OAds expressing immunostimulatory molecules ("armed" OAds) have demonstrated anti-tumor potential in preclinical solid tumor models, the efficacy has not translated into significant clinical outcomes as a monotherapy. However, OAds synergize with established standards of care and novel immunotherapeutic agents, providing a multifaceted means to address complexities associated with solid tumors. Critically, armed OAds revitalize endogenous and adoptively transferred immune cells while simultaneously enhancing their anti-tumor function. To properly evaluate these novel vectors and reduce the gap in the cycle between bench-to-bedside and back, improving model systems must be a priority. The future of OAds will involve a multidimensional approach that provides immunostimulatory molecules, immune checkpoint blockade, and/or immune engagers in concert with endogenous and exogenous immune cells to initiate durable and comprehensive anti-tumor responses.

But What's Your Partner Up to? Associations Between Relationship Quality and Pornography Use Depend on Contextual Patterns of Use Within the Couple.

It is commonly assumed that exposure to pornography harms relationships because pornography changes the way that individuals think, feel, and behave in problematic ways. In the current research, we contribute to a small but growing body of work that challenges this assumption by carefully scrutinizing the relational context of pornography use. In contrast to dominant theoretical explanations in this field, we argue that at least some of the apparent negative "impacts" of pornography use on relationship quality may reflect partner dissimilarity in pornography use behavior rather than the consequences of exposure to such materials. Moreover, we further examine a particular type of pornography use - shared use with a partner - which previous evidence suggests may be positively associated with relationship quality. To this end, we sought to test whether dyadic patterns of pornography use, and related attributes, were associated with sexual and relationship satisfaction in two cross-sectional (N 1 = 200; N 3 = 207) and two longitudinal (N 2 = 77; N 4 = 277) samples of heterosexual couples. Across these samples, we found consistent evidence that partners who watch pornography together report higher relationship and sexual satisfaction than partners who do not, and notably, this association was not moderated by gender. Independent of this association, we also found evidence of a similarity-dissimilarity effect, such that the solitary pornography use of one partner was negatively associated with their own relationship and sexual satisfaction, but only in cases where their romantic partners used little or no pornography alone. Further consideration of several correlates of pornography use established comparable patterns of results for dissimilarity in attitudes toward pornography, erotophobia-erotophilia, sexual preferences, and sex drive. Importantly, only dissimilarity in sex drive statistically accounted for dissimilarity in solitary pornography use, suggesting that differences in sex drive may be implicated in the associations between pornography use and relationship quality. These findings demonstrate that links between pornography use and relationship health are partially a function of different dyadic patterns of pornography use within couples and do not always suggest relational harm.

Oncolytic adeno-immunotherapy modulates the immune system enabling CAR T-cells to cure pancreatic tumors.

High expression levels of human epidermal growth factor receptor 2 (HER2) have been associated with poor prognosis in patients with pancreatic adenocarcinoma (PDAC). However, HER2-targeting immunotherapies have been unsuccessful to date. Here we increase the breadth, potency, and duration of anti-PDAC HER2-specific CAR T-cell (HER2.CART) activity with an oncolytic adeno-immunotherapy that produces cytokine, immune checkpoint blockade, and a safety switch (CAdTrio). Combination treatment with CAdTrio and HER2.CARTs cured tumors in two PDAC xenograft models and produced durable tumor responses in humanized mice. Modifications to the tumor immune microenvironment contributed to the antitumor activity of our combination immunotherapy, as intratumoral CAdTrio treatment induced chemotaxis to enable HER2.CART migration to the tumor site. Using an advanced PDAC model in humanized mice, we found that local CAdTrio treatment of primary tumor stimulated systemic host immune responses that repolarized distant tumor microenvironments, improving HER2.CART anti-tumor activity. Overall, our data demonstrate that CAdTrio and HER2.CARTs provide complementary activities to eradicate metastatic PDAC and may represent a promising co-operative therapy for PDAC patients.

Clinical CAR-T Cell and Oncolytic Virotherapy for Cancer Treatment.

Immunotherapy has recently garnered success with the induction of clinical responses in tumors, which are traditionally associated with poor outcomes. Chimeric antigen receptor T (CAR-T) cells and oncolytic viruses (OVs) have emerged as promising cancer immunotherapy agents. Herein, we provide an overview of the current clinical status of CAR-T cell and OV therapies. While preclinical studies have demonstrated curative potential, the benefit of CAR-T cells and OVs as single-agent treatments remains limited to a subset of patients. Combinations of different targeted therapies may be required to achieve efficient, durable responses against heterogeneous tumors, as well as the microenvironment. Using a combinatorial approach to take advantage of the unique features of CAR-T cells and OVs with other treatments can produce additive therapeutic effects. This review also discusses ongoing clinical evaluations of these combination strategies for improved outcomes in treatment of resistant malignancies.

Validation of Canproj for projecting Canadian cancer incidence data. / Validation de Canproj pour les projections de données sur l'incidence du cancer au Canada.

INTRODUCTION: Cancer projections can provide key information to help prioritize cancer control strategies, allocate resources and evaluate current treatments and interventions. Canproj is a cancer-projection tool that builds on the Nordpred R-package by adding a selection of projection models. The objective of this project was to validate the Canproj R-package for the short-term projection of cancer rates. METHODS: We used national cancer incidence data from 1986 to 2014 from the National Cancer Incidence Reporting System and Canadian Cancer Registry. Cross-validation was used to estimate the accuracy of the projections generated by Canproj and relative bias (RB) was used as validation measure. The Canproj automatic model selection decision tree was also assessed. RESULTS: Five of the six models had mean RB between 5% and 10% and median RB around 5%. For some of the cancer sites that were more difficult to project, a shorter time period improved reliability. The Nordpred model was selected 79% of the time by Canproj automatic model selection although it had the smallest RB only 24% of the time. CONCLUSIONS: The Canproj package was able to provide projections that closely matched the real data for most cancer sites.

Projected estimates of cancer in Canada in 2020.

BACKGROUND: Cancer projections to the current year help in policy development, planning of programs and allocation of resources. We sought to provide an overview of the expected incidence and mortality of cancer in Canada in 2020 in follow-up to the Canadian Cancer Statistics 2019 report. METHODS: We obtained incidence data from the National Cancer Incidence Reporting System (1984-1991) and Canadian Cancer Registry (1992-2015). Mortality data (1984-2015) were obtained from the Canadian Vital Statistics - Death Database. All databases are maintained by Statistics Canada. Cancer incidence and mortality counts and age-standardized rates were projected to 2020 for 23 cancer types by sex and geographic region (provinces and territories) for all ages combined. RESULTS: An estimated 225 800 new cancer cases and 83 300 cancer deaths are expected in Canada in 2020. The most commonly diagnosed cancers are expected to be lung overall (29 800), breast in females (27 400) and prostate in males (23 300). Lung cancer is also expected to be the leading cause of cancer death, accounting for 25.5% of all cancer deaths, followed by colorectal (11.6%), pancreatic (6.4%) and breast (6.1%) cancers. Incidence and mortality rates will be generally higher in the eastern provinces than in the western provinces. INTERPRETATION: The number of cancer cases and deaths remains high in Canada and, owing to the growing and aging population, is expected to continue to increase. Although progress has been made in reducing deaths for most major cancers (breast, prostate and lung), there has been limited progress for pancreatic cancer, which is expected to be the third leading cause of cancer death in Canada in 2020. Additional efforts to improve uptake of existing programs, as well as to advance research, prevention, screening and treatment, are needed to address the cancer burden in Canada.

Modeling the Efficacy of Oncolytic Adenoviruses In Vitro and In Vivo: Current and Future Perspectives.

Oncolytic adenoviruses (OAd) selectively target and lyse tumor cells and enhance anti- tumor immune responses. OAds have been used as promising cancer gene therapies for many years and there are a multitude of encouraging pre-clinical studies. However, translating OAd therapies to the clinic has had limited success, in part due to the lack of realistic pre-clinical models to rigorously test the efficacy of OAds. Solid tumors have a heterogenous and hostile microenvironment that provides many barriers to OAd treatment, including structural and immunosuppressive components that cannot be modeled in two-dimensional tissue culture. To replicate these characteristics and bridge the gap between pre-clinical and clinical success, studies must test OAd therapy in three-dimensional culture and animal models. This review focuses on current methods to test OAd efficacy in vitro and in vivo and the development of new model systems to test both oncolysis and immune stimulatory components of oncolytic adenovirotherapy.

Oncolytic Adenovirus Armed with BiTE, Cytokine, and Checkpoint Inhibitor Enables CAR T Cells to Control the Growth of Heterogeneous Tumors.

No single cancer immunotherapy will likely defeat all evasion mechanisms of solid tumors, including plasticity of tumor antigen expression and active immune suppression by the tumor environment. In this study, we increase the breadth, potency, and duration of anti-tumor activity of chimeric antigen receptor (CAR) T cells using an oncolytic virus (OV) that produces cytokine, checkpoint blockade, and a bispecific tumor-targeted T cell engager (BiTE) molecule. First, we constructed a BiTE molecule specific for CD44 variant 6 (CD44v6), since CD44v6 is widely expressed on tumor but not normal tissue, and a CD44v6 antibody has been safely administered to cancer patients. We then incorporated this BiTE sequence into an oncolytic-helper binary adenovirus (CAdDuo) encoding an immunostimulatory cytokine (interleukin [IL]-12) and an immune checkpoint blocker (PD-L1Ab) to form CAdTrio. CD44v6 BiTE from CAdTrio enabled HER2-specific CAR T cells to kill multiple CD44v6+ cancer cell lines and to produce more rapid and sustained disease control of orthotopic HER2+ and HER2-/- CD44v6+ tumors than any component alone. Thus, the combination of CAdTrio with HER2.CAR T cells ensures dual targeting of two tumor antigens by engagement of distinct classes of receptor (CAR and native T cell receptor [TCR]), and significantly improves tumor control and survival.

Childhood maltreatment as a risk factor for cancer: findings from a population-based survey of Canadian adults.

BACKGROUND: Childhood maltreatment (CM) is an established risk factor for various mental and substance use disorders. This study adds to existing evidence that CM may also be a risk factor for cancer. METHODS: Based on data from a sample of 9783 men and 12,132 women from the 2012 Canadian Community Health Survey - Mental Health (CCHS-MH), this analysis explores mediated associations between cancer in adulthood and different levels of exposure to three types of CM-childhood physical abuse (CPA), childhood sexual abuse (CSA), and childhood exposure to intimate partner violence (CEIPV). "Cancer" was defined as an affirmative response to either of these questions: "Do you have cancer?" or "Have you ever been diagnosed with cancer?" The potential mediators were: smoking, depression, alcohol abuse/dependence, life stress, obesity, and physical activity. RESULTS: For women, but not men, having experienced CM was significantly associated with a cancer diagnosis in adulthood, even when effects due to age and socio-demographic characteristics were controlled. Smoking, life stress, depression, and alcohol abuse/dependence reduced the strength of the association between CM and cancer in women. However, most associations remained statistically significant when controlling for effects due to these behavioural and other mediators. Evidence indicated a "dose-response" relationship, in that the likelihood of reporting cancer increased with the number of abuse types (CPA, CSA, CEIPV) reported, and with the severity of CPA. CONCLUSIONS: The analyses suggest an association between CM and cancer in women, even when the effects of known risk factors were taken into account. The association was graded, becoming stronger as CM exposure increased. Implications for the provision of cancer screening and other health care services to women with histories of CM to reduce health disparities are discussed.

Risk of a second cancer in Canadians diagnosed with a first cancer in childhood or adolescence.

BACKGROUND: Second cancers are an adverse outcome experienced by childhood cancer survivors. We quantify the risk and correlates of a second cancer in Canadians diagnosed with a first cancer prior to age 20 years. METHODS: Using death-linked Canadian Cancer Registry data, a population-based cohort diagnosed with a first cancer between 1992 and 2014, prior to age 20 years, were followed for occurrence of a second cancer to the end of 2014. We estimate standardized incidence ratios (SIR), absolute excess risks (AER), cumulative probabilities, and hazard ratios (HR). FINDINGS: 22,635 people contributed 204,309•1 person-years of follow-up. Overall risk of a second cancer was 6•5 (95% CI: 5•8-7•1) times greater than expected resulting in an AER of 16•5 (14•4-18•5) cancers per 10,000 person-years and a 4•8% (3•8%-6•0%) cumulative probability of a second cancer at 22•6 years of follow-up. SIRs decreased with increasing age at diagnosis and time since diagnosis; were larger in more recent calendar periods of diagnosis; and varied by type of first cancer. Large SIRs in the first year after diagnosis and in those diagnosed in 2010-2014 were partly associated with changing registry practices. For the whole cohort, factors associated with the hazard of a second cancer included: being female vs. male [HR = 1•439 (95%CI: 1•179-1•760)]; being diagnosed in 2005-2014 vs. 1992-2004 [2•084 (1•598-2•719)]; having synchronous first cancers [4•814 (2•042-9•509)]; and being diagnosed with certain types of cancer. Factors varied, however, by type of first cancer. INTERPRETATION: Risks of a second cancer are not equally distributed and can be impacted by changes in registry practice and the methods used to define second cancers.

At-a-glance - Cancer trends in Canada, 1984 to 2015. / Aperçu - Tendances en matière de cancer au Canada, 1984-2015.

Examining incidence trends of all cancers combined in order to understand cancer trends can be misleading, as patterns can vary across individual cancer types. This paper highlights findings on trends over time from Canadian Cancer Statistics 2019, as measured by the annual percent change (APC) of age-standardized incidence rates. Among the results were a recent increase in thyroid cancer in males (APC: 6.4%, 1997-2015), as well as decreases in prostate cancer (APC: -9.1%, 2011-2015) and cervical cancer (APC: -3.3%, 2010-2015).

The incidence of some cancers is changing rapidly in Canada. Recent trends show increasing rates of thyroid cancer in males, drawing attention to the potential impact of overdiagnosis. Prostate cancer incidence is decreasing rapidly, likely reflecting recent changes in screening guidelines.

Les tendances liées à l'incidence de certains cancers évoluent rapidement au Canada. Les tendances récentes révèlent une augmentation des taux d'incidence de cancer de la glande thyroïde chez les hommes, ce qui incite à étudier les répercussions potentielles de surdiagnostic. L'incidence du cancer de la prostate connaît une diminution rapide, ce qui témoigne vraisemblablement des changements récents apportés aux lignes directrices en matière de dépistage.

Recent trends in prostate cancer in Canada.

BACKGROUND: Prostate cancer is the most common type of cancer in Canadian men. Screening recommendations have changed substantially over the last 25 years. Since 2011 (United States) and 2014 (Canada), taskforce guidelines have recommended against screening using the prostate-specific antigen (PSA) test in low-risk men of all ages. This work reports on trends in prostate cancer incidence, mortality, and stage at diagnosis in Canada from 1992 to 2015. DATA AND METHODS: Prostate cancer incidence, mortality, and stage at diagnosis were retrieved from Statistics Canada's Canadian Cancer Registry and Canadian Vital Statistics - Death Database. Joinpoint analysis was used to examine trends over time. RESULTS: The age-standardized incidence rate (ASIR) of prostate cancer peaked in 1993 and 2001, and declined thereafter. From 2011 to 2015, the ASIR declined by 9.3% per year. The age-standardized mortality rate (ASMR) decreased continuously from 1992 to 2015, but fell most rapidly (2.9% per year) after 2001. Data from two provinces show that, from 2005 to 2015, the rate of Stage I and Stage II cancers decreased by 3.2% per year, while the rate of Stage III and Stage IV cancers remained relatively stable. DISCUSSION: Incidence of prostate cancer has declined substantially in recent years. Most of the decline seems to be in localized cases (Stage I and Stage II). Changes in incidence have mirrored changes to PSA screening recommendations. Future work should continue to monitor trends over time at the national level, especially as they relate to screening recommendations.

Advance care planning: the impact of Ceiling of Treatment plans in patients with Coordinate My Care.

OBJECTIVES: The aim of this evaluation is to describe the components and results of urgent care planning in Coordinate My Care (CMC), a digital clinical service for patients with life-limiting illness, for use if a patient is unable to make or express choices. Ceiling of treatment (CoT) plans were created detailing where the patient would like to receive their care and how aggressive medical interventions should be. METHODS: A retrospective service evaluation was completed of all CMC records created between December 2015 and September 2016 (n=6854). CMC records were divided into two cohorts: those with a CoT plan and those without. The factors associated with these cohorts were reviewed including age, diagnosis, resuscitation status and preferences for place of death (PPD). Analysis of the non-mandatory free text section was carried out. RESULTS: Two-thirds of patients had recorded decisions about CoT. Regardless of which CoT option was chosen, for most patients, PPD was home or care home. Patients with a CoT plan were more likely to have a documented resuscitation status. Patients with a CoT were more likely to die in their PPD (82%vs71%, OR 1.79, p<0.0001). A higher proportion of patients with a CoT decision died outside hospital. CONCLUSION: This analysis demonstrates that a substantial proportion of patients are willing to engage in urgent care planning. Three facets of urgent care planning identified include PPD, CoT and resuscitation status.