RESUMO
Cancer therapy-related cardiac dysfunction (CTRCD), which commonly includes left ventricular dysfunction and heart failure, is the main adverse effect of anticancer therapy. In recent years several candidate genes studies and genome-wide association studies have identified common genetic variants associated with CTRCD, but evidence remains limited and few genetic variants are robust. A genome-wide meta-analysis of CTRCD was performed with 852 oncology patients receiving cancer therapy. DNA samples were genotyped and imputed to perform a GWAS meta-analysis for case-control (N = 852 (380 cases and 472 controls) and extreme phenotypes (N = 618 (78 cases and 472 controls) looking for genetic variants that predispose to CTRCD. The results were validated in a replicate cohort of 1,191 oncology patients (245 cases and 946 controls). Functional mapping of the replicated loci was then performed. The meta-analysis showed 9 and 17 loci suggestively associated (P-value < 1 × 10-5) with CTRCD in case-control and extreme phenotypes analyses, respectively. The 3q28 locus (rs rs7652759, P = 5.64 × 10-6) in the case-control analysis was the strongest signal, with up to 64 SNPs above the suggestive significance threshold. The rs7652759, an intergenic variant between TPRG1 and TP63 genes, was the only variant validated in the replication cohort (P-value = 0.01). Functional mapping of this significant locus revealed up to 5 new genes potentially involved in the CTRCD. We identified the intergenic region near TP63 as a novel CTRCD susceptibility locus. In the future, the genotyping of these markers could be considered in new CTRCD risk scores to improve preventive strategies in cardio-oncology.
Assuntos
Estudo de Associação Genômica Ampla , Neoplasias , Polimorfismo de Nucleotídeo Único , Proteínas Supressoras de Tumor , Humanos , Proteínas Supressoras de Tumor/genética , Neoplasias/genética , Neoplasias/tratamento farmacológico , Feminino , Masculino , Predisposição Genética para Doença , Fatores de Transcrição/genética , Estudos de Casos e Controles , DNA Intergênico/genética , Pessoa de Meia-Idade , Idoso , Mapeamento CromossômicoRESUMO
AIMS: To develop quality indicators (QIs) for the evaluation of the prevention and management of cancer therapy-related cardiovascular toxicity. METHODS AND RESULTS: We followed the European Society of Cardiology (ESC) methodology for QI development which comprises (i) identifying the key domains of care for the prevention and management of cancer therapy-related cardiovascular toxicity in patients on cancer treatment, (ii) performing a systematic review of the literature to develop candidate QIs, and (iii) selecting of the final set of QIs using a modified Delphi process. Work was undertaken in parallel with the writing of the 2022 ESC Guidelines on Cardio-Oncology and in collaboration with the European Haematology Association, the European Society for Therapeutic Radiology and Oncology and the International Cardio-Oncology Society. In total, 5 main and 9 secondary QIs were selected across five domains of care: (i) Structural framework, (ii) Baseline cardiovascular risk assessment, (iii) Cancer therapy related cardiovascular toxicity, (iv) Predictors of outcomes, and (v) Monitoring of cardiovascular complications during cancer therapy. CONCLUSION: We present the ESC Cardio-Oncology QIs with their development process and provide an overview of the scientific rationale for their selection. These indicators are aimed at quantifying and improving the adherence to guideline-recommended clinical practice and improving patient outcomes.
Assuntos
Cardiologia , Neoplasias , Humanos , Indicadores de Qualidade em Assistência à Saúde , Oncologia , Neoplasias/terapiaRESUMO
PURPOSE: The aim of the current survey was to describe the functioning of cardio-oncology (C-O) units in Spain. METHODS: All members of the Spanish Society of Cardiology pertaining to scientific communities related to C-O received questionnaires on the existence of specific programs at their institutions. A second, more extensive questionnaire was sent to the centers which reported C-O organization. RESULTS: We identified 56 centers with C-O programs of which 32 (62.5%) replied to the extended questionnaire. 28% of all centers reported having a multidisciplinary unit involving specialists in several areas. More than 80% of the centers developed surveillance protocols locally adapted which included advanced echocardiographic techniques (68%) or troponin (82%). CONCLUSIONS: The number of institutions with C-O programs is still limited but higher than reported in a survey in 2017. Development of multidisciplinary units of C-O should be promoted to improve the cardiovascular health of cancer patients.
Assuntos
Institutos de Câncer/organização & administração , Serviço Hospitalar de Cardiologia/organização & administração , Pesquisas sobre Atenção à Saúde/estatística & dados numéricos , Oncologia/organização & administração , Neoplasias/terapia , Institutos de Câncer/estatística & dados numéricos , Serviço Hospitalar de Cardiologia/estatística & dados numéricos , Humanos , Oncologia/estatística & dados numéricos , Desenvolvimento de Programas , EspanhaRESUMO
INTRODUCTION: The number of patients who have a cardiac implantable electronic device (CIEDs) that undergo a course of radiotherapy is increasing due to the ageing population. The majority of clinical studies only evaluate any CIED malfunction at the end of a course of irradiation or in a case of there being symptoms of possible malfunction. As a result, little data has been collected on CIED status acquired during an active course of irradiation. MATERIAL AND METHODS: We aimed to evaluate the correct functioning of a CIED during a course of radiotherapy. So, a retrospective analysis was made of all patients having CIEDS in a single institution during their course of radiotherapy. All CIEDs were systematically checked before and during the course of radiotherapy according to the risk of device failure and patient dependence. RESULTS: Data was analysed from 56 patients (43 men, 13 women) with a mean age of 78.2 years, of whom 87.5% of the patients carried a pacemaker (PM), the 39% of the patients were PM dependent, and the remaining patients carried an implantable cardioverter-defibrillator (ICD). An observable dose of irradiation was evident in only 10 cases. 69.1% of the CIEDs were checked daily and the remainder were checked weekly. During the radiotherapy course, 82% of the patients did not complain of any cardiological event. The CIED of five patients experienced an increase in the threshold and, in another case, a sudden reduction in the duration of the battery was reported. Another patient with a CIED experienced a cardiac insufficiency episode triggered by a ventricular tachycardia. CONCLUSION: In conclusions, although adverse clinical events from exposure of a CIED to irradiation are rare, they can appear in any group of risk. No dose-dependency was observed on the malfunction of the CIED.
Assuntos
Desfibriladores Implantáveis , Análise de Falha de Equipamento , Neoplasias/radioterapia , Marca-Passo Artificial , Radioterapia Conformacional/métodos , Idoso , Idoso de 80 Anos ou mais , Desfibriladores Implantáveis/estatística & dados numéricos , Feminino , Seguimentos , Cardiopatias/terapia , Humanos , Masculino , Marca-Passo Artificial/estatística & dados numéricos , Dosagem Radioterapêutica , Radioterapia Conformacional/efeitos adversos , Radioterapia de Intensidade Modulada , Estudos RetrospectivosRESUMO
BACKGROUND: There is an increasing number of patients with cardiac implantable electronic devices (CIED), either pacemakers or defibrillators, who are receiving a course of radiotherapy. Several guidelines have been published by national societies, but no Spanish national guidelines for management of these patients have been published. More importantly, national clinical practice regarding these patients is not standardised. MATERIALS AND METHODS: Members of the Spanish Breast Cancer Radiation Oncology Group (GEORM in Spanish) were surveyed through an online questionnaire on behalf of the Spanish radiation oncology departments. RESULTS: Only 39.3% of the Spanish radiation oncology departments have policies aimed at CIED carrier patients. Regardless of that, 96.4% of those who responded to the survey refer these patients to their Cardiology department before the start of the course of radiotherapy, and 17.8% of respondents said to manipulate the CIED without any cardiology department direction. A wide range of responses was obtained related to concepts such as "distance from the irradiation field to the CIED" or "safe accumulated doses". CONCLUSIONS: Our results demonstrate the need for national guidelines for CIED patients and the need to promote educational activities addressed to standardise clinical management of these patients in the radiation oncology departments.