Continuation of fluoropyrimidine treatment with S-1 after cardiotoxicity on capecitabine- or 5-fluorouracil-based therapy in patients with solid tumours: a multicentre retrospective observational cohort study

Background: Capecitabine- or 5-fluorouracil (5-FU)-based chemotherapy is widely used in many solid tumours, but is associated with cardiotoxicity. S-1 is a fluoropyrimidine with low rates of cardiotoxicity, but evidence regarding the safety of switching to S-1 after 5-FU- or capecitabine-associated cardiotoxicity is scarce. Patients and methods: This retrospective study (NCT04260269) was conducted at 13 centres in 6 countries. The primary endpoint was recurrence of cardiotoxicity after switch to S-1-based treatment due to 5-FU- or capecitabinerelated cardiotoxicity: clinically meaningful if the upper boundary of the 95% confidence interval (CI; by competing risk) is not including 15%. Secondary endpoints included cardiac risk factors, diagnostic work-up, treatments, outcomes, and timelines of cardiotoxicity. Results: Per protocol, 200 patients, treated between 2011 and 2020 [median age 66 years (range 19-86); 118 (59%) males], were included. Treatment intent was curative in 145 (73%). Initial cardiotoxicity was due to capecitabine (n ¼ 170), continuous infusion 5-FU (n ¼ 22), or bolus 5-FU (n ¼ 8), which was administered in combination with other chemotherapy, targeted agents, or radiotherapy in 133 patients. Previous cardiovascular comorbidities were present in 99 (50%) patients. Cardiotoxic events (n ¼ 228/200) included chest pain (n ¼ 125), coronary syndrome/ infarction (n ¼ 69), arrhythmia (n ¼ 22), heart failure/cardiomyopathy (n ¼ 7), cardiac arrest (n ¼ 4), and malignant hypertension (n ¼ 1). Cardiotoxicity was severe or life-threatening in 112 (56%) patients and led to permanent capecitabine/5-FU discontinuation in 192 (96%). After switch to S-1, recurrent cardiotoxicity was observed in eight (4%) patients (95% CI 2.02-7.89, primary endpoint met). Events were limited to grade 1-2 and occurred at a median of 16 days (interquartile range 7-67) from therapy switch. Baseline ischemic heart disease was a risk factor for recurrent cardiotoxicity (odds ratio 6.18, 95% CI 1.36-28.11). Conclusion: Switching to S-1-based therapy is safe and feasible after development of cardiotoxicity on 5-FU- or capecitabine-based therapy and allows patients to continue their pivotal fluoropyrimidine-based treatment.</p

Echocardiography protocol for early detection of cardiac dysfunction in childhood cancer survivors in the multicenter DCCSS LATER 2 CARD study: design, feasibility, and reproducibility

Background Cardiotoxicity is a well-known side effect after anthracyclines and chest radiotherapy in childhood cancer survivors (CCS). The DCCSS LATER 2 CARD (cardiology) study includes evaluation of echocardiographic measurements for early identification of CCS at highest risk of developing heart failure. This paper describes the design, feasibility, and reproducibility of the echocardiography protocol.Methods Echocardiograms from CCS and sibling controls were prospectively obtained at the participating centers and centrally analyzed. We describe the image acquisition, measurement protocol, and software-specific considerations for myocardial strain analyses. We report the feasibility of the primary outcomes of systolic and diastolic function, as well as reproducibility analyses in 30 subjects.Results We obtained 1,679 echocardiograms. Biplane ejection fraction (LVEF) measurement was feasible in 91% and 96% of CCS and siblings, respectively, global longitudinal strain (GLS) in 80% and 91%, global circumferential strain (GCS) in 86% and 89%, and >= 2 diastolic function parameters in 99% and 100%, right ventricle free wall strain (RVFWS) in 57% and 65%, and left atrial reservoir strain (LASr) in 72% and 79%. Intra-class correlation coefficients for inter-observer variability were 0.85 for LVEF, 0.76 for GLS, 0.70 for GCS, 0.89 for RVFWS and 0.89 for LASr. Intra-class correlation coefficients for intra-observer variability were 0.87 for LVEF, 0.82 for GLS, 0.82 for GCS, 0.85 for RVFWS and 0.79 for LASr.Conclusion The DCCSS LATER 2 CARD study includes a protocolized echocardiogram, with feasible and reproducible primary outcome measurements. This ensures high-quality outcome data for prevalence estimates and for reliable comparison of cardiac function parameters.Diabetes mellitus: pathophysiological changes and therap

Bragatston study protocol: a multicentre cohort study on automated quantification of cardiovascular calcifications on radiotherapy planning CT scans for cardiovascular risk prediction in patients with breast cancer

Introduction Cardiovascular disease (CVD) is an important cause of death in breast cancer survivors. Some breast cancer treatments including anthracyclines, trastuzumab and radiotherapy can increase the risk of CVD, especially for patients with pre-existing CVD risk factors. Early identification of patients at increased CVD risk may allow switching to less cardiotoxic treatments, active surveillance or treatment of CVD risk factors. One of the strongest independent CVD risk factors is the presence and extent of coronary artery calcifications (CAC). In clinical practice, CAC are generally quantified on ECGtriggered cardiac CT scans. Patients with breast cancer treated with radiotherapy routinely undergo radiotherapy planning CT scans of the chest, and those scans could provide the opportunity to routinely assess CAC before a potentially cardiotoxic treatment. The Bragatston study aims to investigate the association between calcifications in the coronary arteries, aorta and heart valves (hereinafter called ‘cardiovascular calcifications’) measured automatically on planning CT scans of patients with breast cancer and CVD risk. Methods and analysis In a first step, we will optimise and validate a deep learning algorithm for automated quantification of cardiovascular calcifications on planning CT scans of patients with breast cancer. Then, in a multicentre cohort study (University Medical Center Utrecht, Utrecht, Erasmus MC Cancer Institute, Rotterdam and Radboudumc, Nijmegen, The Netherlands), the association between cardiovascular calcifications measured on planning CT scans of patients with breast cancer (n≈16 000) and incident (non-)fatal CVD events will be evaluated. To assess the added predictive value of these calcifications over traditional CVD risk factors and treatment characteristics, a case-cohort analysis will be performed among all cohort members diagnosed with a CVD event during follow-up (n≈200) and a random sample of the baseline cohort (n≈600). Ethics and dissemination The Institutional Review Boards of the participating hospitals decided that the Medical R

The necessity of drawing up the annual production plan and the importance of establishment crop structure for next agricultural year

Planning represents establishment and substantiate the objectives, accomplish tasks and necessary resources for appropriate period plan ( of perspective, annual, quarterly, monthly). Drawing up annual production plan into a ferm is required primarily for evolution or involution recorded by economical phenomenes, which directly determines the operation of the farm. After determining the annual production plan can establish structures and cultures for the next agricultural year using modeling and simulation methods. Following the application of modeling and simulation methods in a farm resulting optimal dimensions of business operations with profit maximization in terms of economic efficiency increased

Diagnostic tools for early detection of cardiac dysfunction in childhood cancer survivors: Methodological aspects of the Dutch late effects after childhood cancer (LATER) cardiology study

Background: Cancer therapy-related cardiac dysfunction and heart failure are major problems in long-term childhood cancer survivors (CCS). We hypothesize that assessment of more sensitive echo- and electrocardiographic measurements, and/or biomarkers will allow for improved recognition of patients with cardiac dysfunction before heart failure develops, and may also identify patients at lower risk for heart failure. Objective: To describe the methodology of the Dutch LATER cardiology study (LATER CARD). Methods: The LATER CARD study is a cross-sectional study in long-term CCS treated with (potentially) cardiotoxic cancer therapies and sibling controls. We will evaluate 1) the prevalence and associated (treatment related) risk factors of subclinical cardiac dysfunction in CCS compared to sibling controls and 2) the diagnostic value of echocardiography including myocardial strain and diastolic function parameters, blood biomarkers for cardiomyocyte apoptosis, oxidative stress, cardiac remodeling and inflammation and ECG or combinations of them in the surveillance for cancer therapy-related cardiac dysfunction. From 2017 to 2020 we expect to include 1900 CCS and 500 siblings. Conclusions: The LATER CARD study will provide knowledge on different surveillance modalities for detection of cardiac dysfunction in long-term CCS at risk for heart

Echocardiographic quantification of regional right ventricular systolic function

In this thesis we addressed the currently available imaging modalities to evaluate RV function and morphology, the role echocardiographic deformation imaging could have for this assessment, and explored its technical traits. Quantifcation of regional RV function is currently lacking, while it is of clinical relevance in order to establish the risk of a patients for ventricular arrhythmias. We have shown that defornation imaging is a feasable tool to acomplish this end. The questions related to the physiological right and left ventricular (LV) remodeling in the athletes’ heart were addressed in Part 2, where the functional and morphological adaptations in response to long term endurance training were studied. The RV shows marked dialation with a moderate reduction in regional, but not global function. LV function remains preserved as well. Diastolic parameters in both ventricles showed no differences between atheltes and non-athletes. Finally, the role of echocardiographic deformation imaging in pathological RV remodeling was studied in Part 3. The clinical applicability of this technique in the evaluation and diagnostic process of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) was explored with respect to the detection of subtle functional abnormalities in both the RV and the LV. The main findings were that deformation imaging is the single best test to detect functional abnormalities in the RV, and even detects subtle abnormalties in asymptomatic mutation carriers. Furtheremore, LV abnormalties (a prognostic infavorable sign) were also detected in a large number of patients, while this was not seen by routine evaluation

Intraperitoneal antineoplastic drug delivery: experience with a cyclophosphamide, vincristine and prednisolone protocol in cats with malignant lymphoma

In this retrospective study, the efficacy and safety were examined for an intraperitoneal chemotherapy protocol-cyclophosphamide, vincristine and prednisolone (IP-COP) in 26 cats with malignant lymphoma. Certainly in cats fiercely resisting IV administration the IP route is a more practical method, safer for the administrator and less stressful for the cat. Complete remission (CR) rate was 76.9% (n=20). Median duration of first remission was 421 days. Estimated 1- and 2-year disease free period were 67.1 and 48.0%, respectively. Median duration of survival was 388 days and estimated overall 1- and 2-year survival periods were 54.7 and 46.9% respectively. Young cats had a more favourable prognosis. Reaching CR was essential for long-term survival. No specific IP-related adverse events (AE) were seen. AE were generally scored as mild and were not excessively abundant. These results indicate that the IP route is a safe and effective alternative for the administration of COP protocol chemotherapeutics

Deformation imaging to assess global and regional effects of cardiac regenerative therapy in ischaemic heart disease : A systematic review

Currently, left ventricular ejection fraction (LVEF) is the most common endpoint in cardiovascular stem cell therapy research. However, this global measure of cardiac function might not be suitable to detect the regional effects sorted by this therapy and is hampered by high operator variability and loading dependency. Deformation imaging might be more accurate in detecting potential regional functional improvements by cardiac regenerative therapy. The aim of this systematic review is to provide a comprehensive overview of current literature on the value of deformation imaging in cardiac regenerative therapy. A systematic review of current literature available on PubMed, Embase, and Cochrane databases was performed regarding both animal and patient studies in which deformation imaging was used to study cardiac cell therapy. After critical appraisal, outcomes regarding study design, type of cell therapy, procedural characteristics, outcome measure, method for measuring strain, and efficacy on both LVEF and deformation parameters were depicted. A total of 30 studies, 15 preclinical and 15 clinical, were included for analysis. Deformation outcomes improved significantly in 14 out of 15 preclinical studies and in 10 out of 15 clinical studies, whereas LVEF improved in 12 and 4 articles, respectively. Study designs and used deformation outcomes varied significantly among the included papers. Six studies found a positive effect on deformation outcomes without LVEF improvement. Hence, deformation imaging seems at least equal, and perhaps superior, to LVEF measurement in the assessment of cardiac regenerative therapy. However, strategies varied substantially and call for a standardized approach