Physical fitness and modifiable cardiovascular disease risk factors in survivors of childhood cancer: A report from the SURfit study

Background: Childhood cancer survivors are at risk for cardiovascular disease (CVD) because of intensive cancer therapies often accompanied by an unhealthy lifestyle. This study was aimed at 1) describing modifiable CVD risk factors in survivors and 2) investigating the association between different aspects of physical fitness and CVD risk factors. Methods: The authors analyzed cross-sectional data from ≥5-year survivors who were 16 years old or younger at their cancer diagnosis and 16 years old or older at the time of the study. Single CVD risk factors (waist circumference, blood pressure, fasting glucose, inverse high-density lipoprotein, and triglycerides), a composite CVD risk score (combined z scores of all CVD risk factors), and metabolic syndrome were evaluated. Physical fitness measures included cardiopulmonary exercise testing (CPET), a handgrip test, and a 1-minute sit-to-stand test (STS). Multivariable logistic regression was used for the association between fitness measures and CVD risk factors, with adjustments made for demographic factors and cancer therapy. Results: This study included 163 survivors with a median age at diagnosis of 7 years and a median age at the time of the study of 28 years. Among those survivors, 27% had a high waist circumference, 32% had high blood pressure, 19% had high triglycerides, 20% had an increased composite CVD risk score, and 10% had metabolic syndrome. A better performance during CPET, handgrip testing, and STS was associated with a lower probability of having a high waist circumference, high triglycerides, and metabolic syndrome. Conclusions: Better aerobic fitness (CPET) and, to a lesser extent, handgrip and STS were associated with fewer CVD risk factors. Further investigations are warranted to investigate which fitness measures should preferably be used to screen survivors to promote physical activity in those with impaired test performance. Lay summary: This study investigated the relationship between physical fitness of adult childhood cancer survivors and their risk factors for cardiovascular disease. Cardiovascular risk factors such as high blood pressure, a high waist circumference, and high blood lipids were frequently found in childhood cancer survivors. Survivors with better physical fitness (measured by a cycling test or simple strength and endurance tests) had a lower chance of having cardiovascular risk factors. This suggests that childhood cancer survivors could benefit from physical activity and general fitness by increasing their physical fitness and possibly decreasing their risk of cardiovascular disease. Keywords: cardiovascular disease; childhood cancer survivors; exercise test; metabolic syndrome; physical fitness

Hémato-oncologie pédiatrique : de la biologie cellulaire aux traitements ciblés et individualisés

Progresses in pediatric oncology over the last decades have been dramatic and allow current cure rates above 80%. There are mainly due to multicentre clinical trials aiming at optimizing chemotherapy protocols as well as local therapies in a stepwise approach. Most of the new anticancer drugs currently in development are based on targeted therapies, directed to specific targets present only in or on tumor cells, like growth factor receptors, mechanisms involved in proliferation, DNA repair, apoptosis, tumor invasion or angiogenesis. Concerning bone marrow transplantation also, new strategic approaches are in advanced development. They aim at reducing treatment induced toxicity and enhancing efficacy at the same time. This short paper would like to point out these new technologies, which should be known by the general practitioner

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

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 outcome. OBJECTIVE In our study, we aim to 1) assess the prevalence of preclinical cardiac dysfunction in adult childhood cancer survivors using conventional and speckle tracking echocardiography, 2) 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), 3) investigate the development of cardiac dysfunction longitudinally in a defined cohort, 4) study the association between cardiac dysfunction and other health outcomes like pulmonary, endocrine, and renal diseases, quality of life, fatigue, strength and endurance, and physical activity, and 5) 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 and/or cardiac radiation since 1976 and who are ≥18 years of age at time of study for a cardiac assessment at the University Hospital Bern. This includes overall 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 an echocardiography including 2-dimensional speckle tracking. RESULTS We will invite 544 eligible childhood cancer survivors for a cardiac assessment with a median age at study of 32.5 years and a median times since diagnosis of 25.0 years. Three hundred survivors (55%) are at high risk and 244 survivors (45%) are at standard risk for cardiac dysfunction. CONCLUSIONS The results of this study will show 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 suffering from cancer. CLINICALTRIAL Prospectively registered in ClinicalTrials.gov, Identifier: NCT03790943, registration

Pulmonary Dysfunction after Treatment for Childhood Cancer: Comparing Multiple-Breath Washout with Spirometry.

RATIONALE Childhood cancer survivors are at risk of long-term pulmonary dysfunction, but we lack sensitive outcome measures to detect early pulmonary damage. OBJECTIVE To assess the ability of nitrogen multiple-breath washout (N2MBW) for detecting pulmonary dysfunction compared to spirometry in long-term survivors of childhood cancer. METHODS We analyzed cross-sectional data from long-term (≥ 5-year) survivors of childhood cancer, aged ≤16 years at cancer diagnosis, ≥16 years at study (assessment period 2015-2019). We categorized survivors by risk: high risk for those having had pulmotoxic chemotherapy, chest radiation, thoracic surgery, and/or hematopoietic stem cell transplantation, and standard risk for other cancer therapies. Primary outcomes were the global lung clearance index (LCI) and acinar ventilation inhomogeneity index (SACIN) from N2MBW, and forced expiratory volume in one second (FEV1) and functional vital capacity (FVC) from spirometry. We calculated z scores for N2MBW and spirometry parameters and compared pulmonary dysfunction between risk groups. Pulmonary dysfunction was defined as z score +1.64 for N2MBW and -1.64 for spirometry. RESULTS We studied 46 survivors, median age at diagnosis 10 years (interquartile range [IQR] 4-14), median age at study 30 years (IQR 25-40). Thirty-seven percent were at high risk and 63% at standard risk for pulmonary dysfunction. LCI and SACIN were higher in the high risk group compared to the standard risk group (mean LCI z scores 2.09, standard deviation [SD] 2.39 vs 0.95, SD 2.81; mean SACIN z scores 2.45, SD 3.29 vs 0.65, SD 2.79). FEV1 and FVC were lower in the high risk compared to the standard risk group (mean FEV1 z scores -0.94, SD 1.39 vs -0.10, SD 1.07; mean FVC z scores -1.14, SD 1.23 vs 0.15, SD 1.61). Overall, LCI, SACIN, FEV1, and FVC were abnormal in 60%, 53%, 33%, and 33% of high risk patients compared to 23%, 21%, 0%, and 4% of standard risk patients. CONCLUSIONS N2MBW identified more cases of pulmonary dysfunction in long-term survivors of childhood cancer than spirometry, even in patients who had cancer therapy not specifically known as being pulmotoxic. N2MBW could be a complementary screening tool for early pulmonary damage after treatment for childhood cancer. Clinical trial registered with ClinicalTrials.gov (NCT02730767)

Fertility preservation in pediatric and adolescent cancer patients in Switzerland: A qualitative cross-sectional survey

Fertility preservation (FP) is an important topic of discussion in the field of oncology, particularly in pediatric oncology. Despite the awareness of severe impact of infertility on quality of life and different guidelines available in this area, the options in FP are not routinely discussed with the pediatric cancer patients and their parents. To the best of our knowledge, this is the first survey report concerned to FP counseling and procedures in pediatric and adolescent cancer patients in Switzerland. This survey was conducted from June 2014 to October 2014 on the counseling and procedures performed between 2009 and 2013; the questionnaire was completed by one of the professional from hematology/oncology centers in Switzerland. Currently, only four out of nine centers have a program for FP. In 2013, 45/301 (15%) patients received FP counseling and 36/301 (12%) underwent an FP procedure. The most commonly performed procedures from 2009 to 2013 were administration of gonadotropin releasing hormone agonist (3%) and cryopreservation of ovarian tissue in females (3%) and cryopreservation of sperms in males (6%); the most frequently cited reason for the absence of FP counseling was lack of time (55%). Therefore, this survey should help to develop and harmonize practices with respect to FP counseling and procedures in Switzerland, and to establish FP as a standard of care during cancer treatment

Physical fitness and modifiable cardiovascular disease risk factors in survivors of childhood cancer: A report from the SURfit study.

BACKGROUND Childhood cancer survivors are at risk for cardiovascular disease (CVD) because of intensive cancer therapies often accompanied by an unhealthy lifestyle. This study was aimed at 1) describing modifiable CVD risk factors in survivors and 2) investigating the association between different aspects of physical fitness and CVD risk factors. METHODS The authors analyzed cross-sectional data from ≥5-year survivors who were 16 years old or younger at their cancer diagnosis and 16 years old or older at the time of the study. Single CVD risk factors (waist circumference, blood pressure, fasting glucose, inverse high-density lipoprotein, and triglycerides), a composite CVD risk score (combined z scores of all CVD risk factors), and metabolic syndrome were evaluated. Physical fitness measures included cardiopulmonary exercise testing (CPET), a handgrip test, and a 1-minute sit-to-stand test (STS). Multivariable logistic regression was used for the association between fitness measures and CVD risk factors, with adjustments made for demographic factors and cancer therapy. RESULTS This study included 163 survivors with a median age at diagnosis of 7 years and a median age at the time of the study of 28 years. Among those survivors, 27% had a high waist circumference, 32% had high blood pressure, 19% had high triglycerides, 20% had an increased composite CVD risk score, and 10% had metabolic syndrome. A better performance during CPET, handgrip testing, and STS was associated with a lower probability of having a high waist circumference, high triglycerides, and metabolic syndrome. CONCLUSIONS Better aerobic fitness (CPET) and, to a lesser extent, handgrip and STS were associated with fewer CVD risk factors. Further investigations are warranted to investigate which fitness measures should preferably be used to screen survivors to promote physical activity in those with impaired test performance. LAY SUMMARY This study investigated the relationship between physical fitness of adult childhood cancer survivors and their risk factors for cardiovascular disease. Cardiovascular risk factors such as high blood pressure, a high waist circumference, and high blood lipids were frequently found in childhood cancer survivors. Survivors with better physical fitness (measured by a cycling test or simple strength and endurance tests) had a lower chance of having cardiovascular risk factors. This suggests that childhood cancer survivors could benefit from physical activity and general fitness by increasing their physical fitness and possibly decreasing their risk of cardiovascular disease