Reduction Of Cancer Burden Research Articles

Key issues that need to be considered while revising the current annex of the European Council Recommendation (2003) on cancer screening.

The 2003 European Council recommendation urging the Member States to introduce or scale up breast, cervical and colorectal cancer screening through an organized population-based approach has had a remarkable impact. We argue that the recommendation needs to be updated for at least two sets of reasons. First, some of the current clinical guidelines include new tests or protocols that were not available at the time of the Council document. Some have already been adopted by organized screening programs, such as newly defined age ranges for mammography screening, Human Papillomavirus (HPV)-based cervical cancer screening, fecal immunochemical test (FIT) and sigmoidoscopy for colorectal cancer screening. Second, the outcomes of randomized trials evaluating screening for lung and prostate cancer have been published recently and the balance between harms and benefits needs to be pragmatically assessed. In the European Union, research collaboration and networking to exchange and develop best practices should be regularly supported by the European Commission. Integration between primary and secondary preventive strategies through comprehensive approaches is necessary not only to maximize the reduction in cancer burden but also to control the rising trend of other noncommunicable diseases sharing the same risk factors.

Cancer: Towards a general theory of the target

General theories (GT) are reductionist explications of apparently independent facts. Here, in reviewing the literature, I develop a GT to simplify the cluttered landscape of cancer therapy targets by revealing they cluster parsimoniously according to only a few underlying principles. The first principle is that targets can be only exploited by either or both of two fundamentally different approaches: causality-inhibition, and 'acausal' recognition of some marker or signature. Nonetheless, each approach must achieve both of two separate goals, efficacy (reduction in cancer burden) and selectivity (sparing of normal cells); if the mechanisms are known, this provides a definition of rational treatment. The second principle is target fragmentation, whereby the target may perform up to three categoric functions (cytoreduction, modulation, cytoprotection), potentially mediated by physically different target molecules, even on different cell types, or circulating freely. This GT remains incomplete until the minimal requirements for cure, or alternatively, proof that cure is impossible, become predictable.

Abstract P4-15-01: Cost-effectiveness of pre-implantation genetic diagnosis for BRCA mutation carriers

Abstract Introduction: Management of BRCA mutation carriers is very expensive due to preventive surgeries and/or screening tests, as well as greater likelihood of cancer treatment. The related cancer burden and costs continue from generation to generation. One relatively new option for male or female BRCA mutation carriers, who wish to have children, is pre-implantation genetic diagnosis (PGD) of in vitro fertilized embryos. PGD eliminates the mutation from the descendants of these carriers. The purpose of this study was to model the cost-effectiveness of PGD. Methods: We developed a Markov Model using TreeAge Pro 2016 and compared incidence of cancers, cancers-related death, costs, quality adjusted life-years (QALY), and incremental cost-effectiveness ratio (ICER) in the 2nd generation associated with conventional management of BRCA mutation carriers vs. PGD using a U.S. third-party payer's perspective with a lifetime horizon at a discount rate of 3% per year. In the model, health states were implemented to reflect the natural history of breast and ovarian cancer for women, and prostate cancer (and breast cancer in BRCA2 mutation carriers) for men. Model data were obtained from published literature. Costs were determined from published data and insurance payment schedules. Results: Our preliminary results show that for BRCA1 mutation carriers, the PGD with IVF strategy is associated with an increase of 0.29 QALYs and costs an additional $292.68 per person, translating to an ICER of $1,014.25/QALY when compared with “No PGD”, making it highly cost-effective. For BRCA2 mutation carriers, the PGD with IVF strategy is associated with an increase of 0.17 QALYs and costs an additional $4,916.88 per person, translating to an ICER of $28,436.10/QALY when compared with “No PGD”, making it cost-effective. Table 1StrategyCost ($)Incr Cost ($)Eff (QALY)Incr Eff (QALY)Incr C/E ($/QALY) BRCA 1 No PGD323,347.22 28.41 PGD323,639.89292.6828.70.291,014.25BRCA 2 No PGD318,723.02 28.52 PGD323,639.894,916.8828.70.1728,436.10 Conclusion: PGD for both BRCA1 and BRCA2 mutation carriers reduces cancer burden, increases QALYs and, is very cost-effective in the 2nd generation cohort, making this an attractive option from the perspectives of patients and public payers. Our estimates are conservative because the cost-effectiveness of PGD will likely improve further if subsequent generations are included in the model, given the expected further reduction in cancer burden and associated cost-savings in subsequent generations. Citation Format: Lipton JH, Wong WWL, Warner E, Greenblatt EM, Lee EK, Chan KKW. Cost-effectiveness of pre-implantation genetic diagnosis for BRCA mutation carriers [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-15-01.

The risk of cancer in kidney transplant recipients may be reduced in those maintained on everolimus and reduced cyclosporine

Kidney transplant recipients are at a high risk of developing cancers after transplantation. Switching from calcineurin inhibitors to sirolimus has been shown to prevent secondary nonmelanoma skin cancer but whether everolimus with reduced exposure to calcineurin inhibitors has similar anti-cancer effects remains unknown. Therefore, we compared the risk of incident cancer over seven years of follow-up among kidney transplant recipients randomized to everolimus plus reduced exposure cyclosporine versus mycophenolate sodium and standard exposure cyclosporine. Using the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA), we assessed the seven-year risk of incident cancer and other graft outcomes among a subgroup of recipients who had participated in the A2309 study using adjusted Cox proportional hazard models. Of 95 recipients, 66 were randomized to everolimus (1.5 mg or 3 mg) with reduced cyclosporine and 29 received mycophenolate sodium and standard exposure cyclosporine. Compared to mycophenolate sodium and standard exposure cyclosporine, everolimus treatment was associated with unadjusted hazard ratios of 0.28 (95% confidence interval 0.11-0.74), 0.39 (0.16-0.98) and 0.41 (0.23-0.71), respectively for nonmelanoma skin cancer, non-skin cancers and any cancers. Interestingly, the adjusted hazard ratios were 0.34 (0.13-0.91), 0.35 (0.09-1.25) and 0.32 (0.15-0.71), respectively. There was no association between treatment groups and rejection, graft loss or death. Compared to standard-exposure cyclosporine, everolimus with reduced exposure to cyclosporine may be associated with a reduced risk of cancer, particularly for non-melanoma skin cancer. Thus, if confirmed in larger patient cohorts, de novo use of everolimus with reduced exposure to calcineurin inhibitors may enable a reduction in cancer burden after transplantation.

Identification of microscopic ovarian tumor foci utilizing a novel imaging device in a murine ovarian cancer model: An opportunity to improve optimal cytoreduction

Objectives: In patients with advanced ovarian cancer, resection of all gross residual disease is associated with a significant improvement in survival. Disease remaining either as infiltrative or microscopic tumor deposits is a challenge to identify. Detection of this disease during cytoreductive surgery may lead to a more thorough reduction of cancer burden. We evaluated the performance of a fluorescent molecular imaging agent, LUM015 (Lumicell, Wellesley, MA), which is activated by cathepsin enzymes in the tumor, and a wide field-of-view imaging device (Lumicell) to detect sub-millimeter residual cancer clusters in an mouse model for ovarian cancer.

Abstract CN02-01: Health screening cohort: A new avenue for risk prediction, prevention, and early detection research

Abstract Prospective cohort study is instrumental in assessing cancer risk factors, identifying biomarkers of cancer risk and early detection, and constructing integrative risk prediction model. However, developing a large prospective cohort with longitudinal, repeated questionnaire data and biospecimen collection is often cost-prohibitive. Building upon a large-scale health screening program in Taiwan with existing questionnaire data, medical test results, and biospecimens, we have developed a large prospective health screening cohort – MJ Cohort. MJ Cohort consists of individuals undergoing routine health screening conducted by the MJ Group, the largest health management institution in Asia. Over 600,000 unique participants have been enrolled with detailed baseline questionnaire data collected on demographics, lifestyle factors, occupation, medical history, family history of chronic diseases and cancer, and dietary pattern. Participants undergo a series of medical tests (103 items) for blood, urine, anthropometric measurements, functional tests, and physical examination. Approximately half of all the participants have longitudinal questionnaire data and medical test results. A substantial number of participants also had blood samples collected and stored. We have utilized this unique cohort for a number of research initiatives. For example, we studied the mortality reduction benefits from leisure-time physical activity and found that an average 15 minutes per day of moderate intensity exercise reduced all-cause mortality by 14% and all-cancer mortality by 10%, and gained 3 years in life. Every additional five minutes of daily exercise is predicted to further reduce 2% of all-cause and 1% of all-cancer mortality. We constructed a series of liver cancer risk prediction models, with the highest prediction accuracy, measured as the AUC (area under the ROC curve), reaching 0.933 when combining two simple serum markers of liver function (ALT and AST) with hepatitis infection. However, individuals could substantially reduce their risk by improving their lifestyles, stopping smoking, reducing drinking, becoming physically active, or managing diabetes. We are also using this unique cohort to identify patients at high risk of progression among those with pre-cancerous conditions and to identify biomarkers of aging and dissect the complex relationship of aging-related chronic diseases and cancer. The extensive questionnaire data, medical tests, and existence of strong risk factors and biomarkers will allow us to construct powerful risk prediction models for selected cancers, which will provide evidence-based recommendations for lifestyle and behavioral changes to achieve reduction in cancer burden and identify high-risk individuals and minimally invasive early detection markers for common cancers. The unique and highly efficient infrastructure for participant enrollment, data collection, medical tests, and follow up within the framework of a world-leading health screening center make this cohort extremely cost-efficient. This unique health screening cohort therefore provides an invaluable new avenue for risk prediction, prevention, and early detection research. Citation Format: Xifeng Wu. Health screening cohort: A new avenue for risk prediction, prevention, and early detection research. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr CN02-01.

Cell signaling pathways associated with a reduction in mammary cancer burden by dietary common bean ( Phaseolus vulgaris L.)

Emerging evidence indicates that common bean (Phaseolus vulgaris L.) is associated with reduced cancer risk in human populations and rodent carcinogenesis models. This study sought to identify cancer-associated molecular targets that mediate the effects of bean on cancer burden in a chemically induced rat model for breast cancer. Initial experiments were conducted using a high dietary concentration of bean (60% wt/wt) where carcinoma burden in bean-fed rats was reduced 62.2% (P < 0.001) and histological and western blot analyses revealed that the dominant cellular process associated with reduced burden was induction of apoptosis. Further analysis of mammary carcinomas revealed changes in the phosphorylation states of mammalian target of rapamycin (mTOR) substrates (4E-binding protein 1 and p70S6 kinase) and mTOR regulators adenosine monophosphate-activated protein kinase and protein kinase B (Akt) (P < 0.001). Effects on mTOR signaling in carcinomas were also found at lower dietary concentrations of bean (7.5-30% wt/wt). Liquid chromatography-time of flight-mass spectrometry analysis of plasma provided evidence of altered lipid metabolism consistent with reduced mTOR network activity in the liver (P < 0.001). Plasma concentrations of insulin and insulin-like growth factor-1 were reduced by 36.3 and 38.9%, respectively, (P < 0.001), identifying a link to Akt regulation. Plasma C-reactive protein, a prognostic marker for long-term survival in breast cancer patients, was reduced by 23% (P < 0.001) in bean-fed rats. Identification of a role for the mTOR signaling network in the reduction of cancer burden by dietary bean is highly relevant given that this pathway is deregulated in the majority of human breast cancers.