The Adenoma Prevention with Celecoxib Trial examined the efficacy and safety of the cyclooxygenase (Cox)-2 inhibitor, celecoxib, for sporadic colorectal adenoma prevention in patients at high risk ...for colorectal cancer. The trial randomized 2,035 subjects to receive either placebo, celecoxib 200 mg twice daily, or celecoxib 400 mg twice daily. The primary study safety and efficacy analyses involved 3 years of treatment. The results showed significant antitumor effect but also indicated increased cardiovascular adverse events in patients treated with celecoxib compared with placebo. A total of 933 patients participated in an extension of the Adenoma Prevention with Celecoxib Trial, with a planned total treatment and surveillance duration of 5 years. Study medication was stopped early, resulting in a median treatment duration of 3.1 years for those with a year 5 colonoscopy. Patients treated on the placebo arm had a cumulative adenoma incidence of 68.4% over 5 years of observation. This figure was 59.0% (P < 0.0001) for those receiving low-dose celecoxib, and 60.1% (P < 0.0001) for those receiving high-dose celecoxib. The cumulative incidence of advanced adenomas over 5 years was 21.3% of those taking placebo, 12.5% (P < 0.0001) of those taking low dose celecoxib and 15.8% (P < 0.0001) of those taking high-dose celecoxib. Investigator reported treatment emergent adverse events were similar across all treatment groups for categories including renal and hypertensive events and gastrointestinal ulceration and hemorrhage events. For a category composed of cardiovascular and thrombotic events, the risk relative to placebo was 1.6 (95% confidence interval, 1.0, 2.5) for those using 200 mg twice daily celecoxib and 1.9 (95% confidence interval, 1.2, 3.1) for those using 400 mg twice daily celecoxib. Secondary analysis showed an interaction between a baseline history of atherosclerotic heart disease and study drug use with respect to cardiovascular and thrombotic adverse events (P = 0.004). These results confirm the inhibitory effect of celecoxib on colorectal adenoma formation, and provide additional safety data indicating an elevated risk for cardiovascular and thrombotic adverse events, particularly for patients with preexisting atherosclerotic heart disease.
To ensure that National Institutes of Health-funded research is relevant to the population's needs, specific emphasis on proportional representation of minority/sex groups into National Cancer ...Institute (NCI) cancer centers' clinical research programs is reported to the NCI.
EMPaCT investigators at 5 regionally diverse comprehensive cancer centers compared data reported to the NCI for their most recent Cancer Center Support Grant competitive renewal to assess and compare the centers' catchment area designations, data definitions, data elements, collection processes, reporting, and performance regarding proportional representation of race/ethnicity and sex subsets.
Cancer centers' catchment area definitions differed widely in terms of their cancer patient versus general population specificity, levels of specificity, and geographic coverage. Racial/ethnic categories were similar, yet were defined differently, across institutions. Patients' socioeconomic status and insurance status were inconsistently captured across the 5 centers.
Catchment area definitions and the collection of patient-level demographic factors varied widely across the 5 comprehensive cancer centers. This challenged the assessment of success by cancer centers in accruing representative populations into the cancer research enterprise. Accrual of minorities was less than desired for at least 1 racial/ethnic subcategory at 4 of the 5 centers. Institutions should clearly and consistently declare their primary catchment area and the rationale and should report how race/ethnicity and sex are defined, determined, collected, and reported. More standardized, frequent, consistent collection, reporting, and review of these data are recommended, as is a commitment to collecting socioeconomic data, given that socioeconomic status is a primary driver of cancer disparities in the United States.
Germline mutations in the tumor suppressor
(
) define Familial Adenomatous Polyposis (FAP), the genetic predisposition to developing adenomatous polyps. Recent sequencing of FAP adenomas have ...challenged established dogma that
mutations alone represent the adenoma mutational landscape because recurrent somatic mutations in non-WNT pathway genes were also discovered. In particular, one of these novel genes,
, presented E20K and E70K mutations that are predicted to be deleterious
. We utilized zebrafish embryos to determine if these mutations affect
function and perform novel biology in an APC-dependent pathway
. Human
(
) and
mRNA injection rescued zebrafish
knockdown lordosis phenotype while
did not. In the FAP
zebrafish model, we show that
, but not retinoic acid, regulates
expression. Injection of
and
, but not
, to homozygous
zebrafish initiated gut differentiation while
knockdown in wildtype embryos led to decreased intestinal development and differentiation. Finally, targeted sequencing of 37 additional FAP adenomas revealed
mutations in 20% of these samples. Overall, our work supports a mechanism where
regulates
and that overall
perturbation could work in concert with germline
mutations in advancing adenomas to a more transformed state prior to progression to adenocarcinoma.
Hereditary non-polyposis colorectal cancer is almost always associated with microsatellite instability, so what is the best way to identify the disorder at an early-stage, and what should the next ...step be in preventing the development of colorectal cancer? Different clinical and molecular diagnostic guidelines have recently been proposed in the context of recent scientific advances, but how are these criteria interpreted and modified across the world?
Non-communicable chronic diseases (NCDs) are the single greatest threat to global public health and national prosperity. Populations around the world are rapidly aging and experiencing an increase in ...the incidence of age-associated diseases such as cancer, heart disease and Alzheimer’s. By 2025, approximately 1.2 billion individuals will be 60 years of age or older. The world population has also experienced economic development and modernization which have improved the quality of life for many, but which have also enabled increasing adoption of unhealthy lifestyles. Notably, approximately 10% of the global population is now considered obese and at least one billion people worldwide use tobacco. DOI: http://dx.doi.org/10.21149/spm.v58i2.7776
Growing premature mortality because of cancer is an increasing public health concern in all countries. This article reviews 10 years of the International Cancer Control Partnership (ICCP) considering ...the themes of National Cancer Control Plan (NCCP) support, technical assistance, governance, and the renewed momentum of global calls to action. ICCP has provided key resources for the cancer community by hosting a portal with national cancer control and noncommunicable disease (NCD) plans, strategies, guidelines, and key implementation guides for a growing community of best practices. ICCP partners have responded to the changing needs of country planners, adjusting technical guidance as needs evolve from planning to implementation at the national level with an associated shift to peer-to-peer learning and knowledge exchange. The ICCP offer to assist countries in cancer planning continues to be relevant as countries focus on implementation of global initiatives for breast, cervical, and childhood cancers. These initiatives are important to drive priority actions and a systems approach in the emerging road map on NCDs-a message that will be supported by a second global review of NCCPs in 2023. This is critical for driving national action in all countries on cancer and other NCDs in line with global health commitments made for 2030 and adopted by the United Nations General Assemblies. ICCP sees robust systems and financial planning for implementation, monitoring, and evaluation of NCCPs and protection from cancer-related catastrophic expenditure, as critical to longer-term sustainability and success. ICCP calls for national policymakers to prioritize integration of cancer prevention and control into emerging universal health care approaches, including pandemic preparedness/health system resilience and calls for an equity focus in new NCCPs.
Background/aims:
Trust is the cornerstone of clinical trial recruitment and retention. Efforts to decrease barriers and increase clinical trial participation among diverse populations have yielded ...modest results. There is an urgent need to better understand the complex interactions between trust and clinical trial participation. The process of trust-building has been a focus of intense research in the business community. Yet, little has been published about trust in oncology clinical trials or the process of building trust in clinical trials. Both clinical trials and business share common dimensions. Business strategies for building trust may be transferable to the clinical trial setting. This study was conducted to understand and utilize contemporary thinking about building trust to develop an Integrated Model of Trust that incorporates both clinical and business perspectives.
Methods:
A key word–directed literature search of the PubMed, Medline, Cochrane, and Google Search databases for entries dated between 1 January 1985 and 1 September 2015 was conducted to obtain information from which to develop an Integrated Model of Trust.
Results:
Successful trial participation requires both participants and clinical trial team members to build distinctly different types of interpersonal trust to effect recruitment and retention. They are built under conditions of significant emotional stress and time constraints among people who do not know each other and have never worked together before. Swift Trust and Traditional Trust are sequentially built during the clinical trial process. Swift trust operates during the recruitment and very early active treatment phases of the clinical trial process. Traditional trust is built over time and operates during the active treatment and surveillance stages of clinical trials. The Psychological Contract frames the participants’ and clinical trial team members’ interpersonal trust relationship. The “terms” of interpersonal trust are negotiated through the psychological contract. Contract renegotiation occurs in response to cyclical changes within the trust relationship throughout trial participation.
Conclusion:
The Integrated Model of Trust offers a novel framework to interrogate the process by which diverse populations and clinical trial teams build trust. To our knowledge, this is the first model of trust-building in clinical trials that frames trust development through integrated clinical and business perspectives. By focusing on the process, rather than outcomes of trust-building diverse trial participants, clinical trials teams, participants, and cancer centers may be able to better understand, measure, and manage their trust relationships in real time. Ultimately, this may foster increased recruitment and retention of diverse populations to clinical trials.
We analyzed the association between meat intake, heterocyclic amines (HCAs) and bladder cancer (BC) risk in a large case‐control study comprised of 884 BC cases and 878 healthy controls, recruited ...from 1999 to 2009. Epidemiologic and dietary data were collected via an in‐person interview. Compared to the lowest quartile of red meat intake, the odds ratios (ORs) for the second, third and fourth quartiles were 1.17 (95% CI: 0.87–1.58), 1.47 (95% CI: 1.09–1.99) and 1.95 (95% CI: 1.41–2.68), respectively, (p‐for trend <0.001). In a subset of participants with intakes of HCAs available, compared with those with the lowest quartile of intake, the ORs for the second, third and fourth quartiles were 1.47 (95% CI: 0.60–3.64), 2.58 (95% CI: 1.09–6.11) and 3.32 (95% CI: 1.37–8.01), respectively, (p for trend <0.001). In cumulative analysis of SNPs in the pathway, compared with subjects carrying 0–4 unfavorable genotypes, subjects carrying 5 and 6 or more unfavorable genotypes were at 1.60‐fold (95% CI: 1.20–2.12) and 2.37‐fold (95% CI: 1.82–3.10) increased risk, respectively. Moreover, subjects carrying six or more unfavorable genotypes and whose red meat intake was in the highest quartile were at 5.09‐fold increased risk (95% CI: 2.89–8.96; p < 0.001). These results strongly support that high red meat intake, high intake of HCAs and carrying high number of unfavorable genotypes in the HCA metabolic pathways are associated with increased risk of BC in the study population.
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