Diagnosing Preclinical Cardiac Dysfunction in Swiss Childhood Cancer Survivors: Protocol for a Single-Center Cohort Study

Abstract

Background Cardiovascular disease is the leading nonmalignant cause of late deaths in childhood cancer survivors. Cardiovascular disease and cardiac dysfunction can remain asymptomatic for many years, but eventually lead to progressive disease with high morbidity and mortality. Early detection and intervention are therefore crucial to improve outcomes. Objective In our study, we aim to assess the prevalence of preclinical cardiac dysfunction in adult childhood cancer survivors using conventional and speckle tracking echocardiography; determine the association between cardiac dysfunction and treatment-related risk factors (anthracyclines, alkylating agents, steroids, cardiac radiation) and modifiable cardiovascular risk factors (abdominal obesity, hypertension); investigate the development of cardiac dysfunction longitudinally in a defined cohort; study the association between cardiac dysfunction and other health outcomes like pulmonary disease, endocrine disease, renal disease, quality of life, fatigue, strength and endurance, and physical activity; and gain experience conducting a clinical study of childhood cancer survivors that will be extended to a national, multicenter study of cardiac complications. Methods For this retrospective cohort study, we will invite ≥5-year childhood cancer survivors who were treated at the University Children's Hospital Bern, Switzerland with any chemotherapy or cardiac radiation since 1976 and who are ≥18 years of age at the time of the study for a cardiac assessment at the University Hospital Bern. This includes 544 childhood cancer survivors, of whom about half were treated with anthracyclines and/or cardiac radiation and half with any other chemotherapy. The standardized cardiac assessment includes a medical history focusing on signs of cardiovascular disease and its risk factors, a physical examination, anthropometry, vital parameters, the 1-minute sit-to-stand test, and echocardiography including 2-dimensional speckle tracking. Results We will invite 544 eligible childhood cancer survivors (median age at the time of the study, 32.5 years; median length of time since diagnosis, 25.0 years) for a cardiac assessment. Of these survivors, 300 (55%) are at high risk, and 244 (45%) are at standard risk of cardiac dysfunction. Conclusions This study will determine the prevalence of preclinical cardiac dysfunction in Swiss childhood cancer survivors, inform whether speckle tracking echocardiography is more sensitive to cardiac dysfunction than conventional echocardiography, and give a detailed picture of risk factors for cardiac dysfunction. The results will help improve primary treatment and follow-up care of children with cancer. Trial Registration ClinicalTrials.gov NCT03790943; https://clinicaltrials.gov/ct2/show/NCT03790943 International Registered Report Identifier (IRRID) DERR1-10.2196/17724

Reduced lower body muscular strength and endurance among childhood cancer survivors measured by 1-minute sit-to-stand test

“…34 [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] 62 (39) 55 ( 35 27 [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] 141 (42) 74 (22) 18 ( 5 29 [21][22][23][24][25][26][27][28][29][30][31][32][33][34] 62 (35) 48 (27) 13…”

“…Our study is part of the Swiss CardioOnco study, which investigates cardiovascular health among adult CCS in a routine care set-up. The study protocol has been published (22). The CardioOnco study was initiated in 2016 as a single-center study at the University Hospital Inselspital in Bern, Switzerland.…”

“…A dedicated study nurse performed anthropometric measurements to obtain survivor BMI and waist-hip ratio. We measured hip circumference at the widest circumference over the buttocks and waist circumference at the midpoint between the lower margin of the lowest rib and the top of the iliac crest while participants stood with both feet tight together with a measuring tape (22). We applied the World Health Organization cut-off points to classify BMI as underweight (<18.5kg/m 2 ), normal weight (18.5-24.9kg/m 2 ), overweight (25.0-29.9kg/m 2 ), and obesity (≥ 30kg/m 2 ) (27); we also classi ed abdominal obesity (waist-to-hip ratio of ≥0.90 in men and ≥0.85 in women) (28).…”

Cohort-based association study of germline genetic variants with acute and chronic health complications of childhood cancer and its treatment: Genetic Risks for Childhood Cancer Complications Switzerland (GECCOS) study protocol

“…This large base cohort will allow selection of specific treatment exposures to create homogenous samples for specific genotype–phenotype associations. Several studies are planned or ongoing to assess long-term complications in a standardised way in Switzerland (eg, cardiac outcomes) 69 which will improve quality of outcome assessments that can be used for the GECCOS study. Outcomes for health conditions that have been less investigated, like pulmonary complications, are also being collected and will be used in the GECCOS study.…”

Prevalence and factors associated with cancer-related fatigue in Swiss adult survivors of childhood cancer

“…Our study is part of the CardioOnco study investigating cardiovascular health among adult CCS set up within routine care in a cardio-oncology clinic. Detailed information about the CardioOnco study design is available [ 10 ]. It was initiated in 2016 as a single-center study involving Pediatric Hematology and Oncology and Pediatric and Adult Cardiology at the University Hospital Bern, Inselspital, in Switzerland.…”