Medical interventions for treating anthracycline-induced symptomatic and asymptomatic cardiotoxicity during and after treatment for childhood cancer

Anthracyclines are frequently used chemotherapeutic agents for childhood cancer that can cause cardiotoxicity during and after treatment. Although several medical interventions in adults with symptomatic or asymptomatic cardiac dysfunction due to other causes are beneficial, it is not known if the same treatments are effective for childhood cancer patients and survivors with anthracycline-induced cardiotoxicity. To compare the effect of medical interventions on anthracycline-induced cardiotoxicity in childhood cancer patients or survivors with the effect of placebo, other medical interventions or no treatment. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2011, issue 1), MEDLINE/PubMed (1949 to May 2011) and EMBASE/Ovid (1980 to May 2011) for potentially relevant articles. We additionally searched reference lists of relevant articles, conference proceedings and ongoing trial databases. Randomised controlled trials (RCTs) or controlled clinical trials (CCTs) comparing the effectiveness of medical interventions to treat anthracycline-induced cardiotoxicity with either placebo, other medical interventions or no treatment. Two review authors independently performed the study selection. One review author performed the data extraction and 'Risk of bias' assessments which were checked by another review author. We identified two RCTs. One trial (135 patients) compared enalapril with placebo in childhood cancer survivors with asymptomatic anthracycline induced cardiac dysfunction. The other trial (68 patients) compared a two-week treatment of phosphocreatine with a control treatment (vitamin C, ATP, vitamin E, oral coenzyme Q10) in leukaemia patients with anthracycline-induced cardiotoxicity. Both studies had methodological limitations.The RCT on enalapril showed no (statistically) significant differences in overall survival, mortality due to heart failure, development of clinical heart failure and quality of life between treatment and control group. A post-hoc analysis showed a decrease (i.e. improvement) in one measure of cardiac function (left ventricular end systolic wall stress (LVESWS): -8.62% change) compared with placebo (+1.66% change) in the first year of treatment (P = 0.036), but not afterwards. Patients treated with enalapril had a higher risk of dizziness or hypotension (RR 7.17, 95% CI 1.71 to 30.17) and fatigue (Fisher's exact test, P = 0.013).The RCT on phosphocreatine found no differences in overall survival, mortality due to heart failure, echocardiographic cardiac function and adverse events between treatment and control group. For the effect of enalapril in childhood cancer survivors with asymptomatic cardiac dysfunction, only one RCT is available. Although there is some evidence that enalapril temporarily improves one parameter of cardiac function (LVESWS), it is unclear whether it improves clinical outcomes. Enalapril was associated with a higher risk of dizziness or hypotension and fatigue. Clinicians should weigh the possible benefits with the known side-effects of enalapril in childhood cancer survivors with asymptomatic anthracycline-induced cardiotoxicity.For the effect of phosphocreatine in childhood cancer patients with anthracycline-induced cardiotoxicity, only one RCT is available. Limited data with a high risk of bias showed no significant difference between phosphocreatine and control treatment on echocardiographic function and clinical outcomes.We did not identify any RCTs or CCTs studying other medical interventions for symptomatic or asymptomatic cardiotoxicity in childhood cancer patients or survivors.High-quality studies should be performe

Body mass index and annual increase of body mass index in long-term childhood cancer survivors; relationship to treatment

Evaluation of body mass index (BMI) at final height (FH) and annual BMI increase in adult childhood cancer survivors (CCS) after treatment with anthracyclines, platinum, and/or radiotherapy. BMI (weight/heightA(2)) was calculated retrospectively from diagnosis until FH. The prevalence of underweight (BMI < 18.5 kg/m(2)) and overweight (BMI a parts per thousand yenaEuro parts per thousand 25 kg/m(2))/obesity (BMI a parts per thousand yenaEuro parts per thousand 30 kg/m(2)) at FH was compared with age-matched controls. The association between underweight/overweight at FH and treatment was assessed by multivariate logistic regression. Annual BMI increase after treatment was assessed by multilevel analysis. Analyses were adjusted for age and underweight/overweight at diagnosis, and age at FH. At FH the prevalence of overweight had not increased, while CCS experienced more underweight as compared to controls (14% vs. 4%, P < 0.001). Overweight at FH was associated with cranial/craniospinal radiotherapy (CRT; OR, 2.23; 95% CI, 1.17-4.26) and underweight at FH with anthracyclines > 300 mg/m(2) (OR, 2.84; 95% CI, 1.33-6.06). Annual BMI increase was +0.47 (0.34-0.60) kg/m(2)/year. In CCS, the annual BMI increase was greater in those with CRT a parts per thousand yenaEuro parts per thousand 30 Gy as compared with those with less or no CRT (+0.15 kg/m(2)/year [0.04-0.25 kg/m(2)/year], P = 0.008) and smaller in those with a higher cumulative anthracycline dose (-0.03 kg/m(2)/year [-0.05 to -0.0005 kg/m(2)/year] per 100 mg/m(2), P = 0.046). After treatment with anthracyclines, platinum, and/or radiotherapy, CRT-treated survivors have more overweight at FH, and a greater annual BMI increase, while anthracycline-treated survivors have more underweight at FH and a lower annual BMI increase

Late effects of cancer treatment. Studies in children and young adults

This thesis deals with the topic of iatrogenic late effects of childhood and adolescent cancer treatment. Although the treatment of children and adolescents with cancer has been increasingly successful over the last few decades, the aggressive treament modalities needed to achieve this improvement may produce adverse late effects that interfere with quality of life or even may be life-treatening. The pattern of late effects includes a variety of mild and severe morbidity. Zie: Summary

The effect of cyclic loads on bond

The purpose of this investigation was to study the effect of load history on the behavior of axially reinforced concrete prisms. The six test specimens were divided into three pairs in which one specimen was tested under repeated tension, and the other under repeated tension and compression loading. A test apparatus was designed to enable the use of a standard hydraulic testing machine to apply the tension and compression loads; The strain along the bar and the total deformation of the specimens were continuously recorded. The main factors studied were the effect of the peak stress level, the effect of repeated cycles and the effect of repeated tension loads versus repeated tension and compression loads. The strain distribution, the bond stresses, the residual and total elongations, the crack width and the stiffness of the concrete prism were the main items discussed

Cochrane Review: Medical interventions for treating anthracycline-induced symptomatic and asymptomatic cardiotoxicity during and after treatment for childhood cancer

Background: Anthracyclines are frequently used chemotherapeutic agents for childhood cancer that can cause cardiotoxicity during and after treatment. Although several medical interventions in adults with symptomatic or asymptomatic cardiac dysfunction due to other causes are beneficial, it is not known if the same treatments are effective for childhood cancer patients and survivors with anthracycline-induced cardiotoxicity. Objectives: To compare the effect of medical interventions on anthracycline-induced cardiotoxicity in childhood cancer patients or survivors with the effect of placebo, other medical interventions or no treatment. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2011, issue 1), MEDLINE/PubMed (1949 to May 2011) and EMBASE/Ovid (1980 to May 2011) for potentially relevant articles. We additionally searched reference lists of relevant articles, conference proceedings and ongoing trial databases. Selection criteria: Randomised controlled trials (RCTs) or controlled clinical trials (CCTs) comparing the effectiveness of medical interventions to treat anthracycline-induced cardiotoxicity with either placebo, other medical interventions or no treatment. Data collection and analysis: Two review authors independently performed the study selection. One review author performed the data extraction and 'Risk of bias' assessments which were checked by another review author. Main results: We identified two RCTs. One trial (135 patients) compared enalapril with placebo in childhood cancer survivors with asymptomatic anthracycline induced cardiac dysfunction. The other trial (68 patients) compared a two-week treatment of phosphocreatine with a control treatment (vitamin C, ATP, vitamin E, oral coenzyme Q10) in leukaemia patients with anthracycline-induced cardiotoxicity. Both studies had methodological limitations. The RCT on enalapril showed no (statistically) significant differences in overall survival, mortality due to heart failure, development of clinical heart failure and quality of life between treatment and control group. A post-hoc analysis showed a decrease (i.e. improvement) in one measure of cardiac function (left ventricular end systolic wall stress (LVESWS): -8.62% change) compared with placebo (+1.66% change) in the first year of treatment (P = 0.036), but not afterwards. Patients treated with enalapril had a higher risk of dizziness or hypotension (RR 7.17, 95% CI 1.71 to 30.17) and fatigue (Fisher's exact test, P = 0.013). The RCT on phosphocreatine found no differences in overall survival, mortality due to heart failure, echocardiographic cardiac function and adverse events between treatment and control group. Authors' conclusions: For the effect of enalapril in childhood cancer survivors with asymptomatic cardiac dysfunction, only one RCT is available. Although there is some evidence that enalapril temporarily improves one parameter of cardiac function (LVESWS), it is unclear whether it improves clinical outcomes. Enalapril was associated with a higher risk of dizziness or hypotension and fatigue. Clinicians should weigh the possible benefits with the known side-effects of enalapril in childhood cancer survivors with asymptomatic anthracycline-induced cardiotoxicity. For the effect of phosphocreatine in childhood cancer patients with anthracycline-induced cardiotoxicity, only one RCT is available. Limited data with a high risk of bias showed no significant difference between phosphocreatine and control treatment on echocardiographic function and clinical outcomes. We did not identify any RCTs or CCTs studying other medical interventions for symptomatic or asymptomatic cardiotoxicity in childhood cancer patients or survivors. High-quality studies should be performed. Plain Language Summary: Treatment for cardiac problems caused by anthracycline chemotherapy for childhood cancer Anthracyclines are anti-cancer drugs that are used in the treatment of different types of childhood cancer. An important adverse effect of anthracyclines is damage to the heart that can lead to asymptomatic (without complaints) or symptomatic (with complaints) cardiac problems during and after cancer treatment. There are several drugs available to treat other types of cardiac problems in adults, but it is not known if these drugs are beneficial in treating cardiac problems caused by anthracyclines in childhood cancer patients and survivors. If a physician is confronted with a childhood cancer patient or survivor with anthracycline-induced cardiac problems, he or she should be able to make an informed decision to treat this patient based on high-quality evidence about the beneficial and adverse effects of the treatment options. We searched for and summarised studies that evaluated drugs for treating anthracycline-induced cardiac problems in childhood cancer patients and survivors. We identified two randomised studies evaluating two different drugs in two different types of patients. One of these drugs, an ACE-inhibitor (enalapril), had a short-term beneficial effect on heart function in survivors of childhood cancer with asymptomatic cardiac problems caused by anthracyclines compared with placebo. However, the drug had no significant beneficial effect on other important outcomes and was associated with side effects such as dizziness and fatigue. This study was of reasonable/good quality. The other study was of low quality and found no effect of a short treatment with phosphocreatine in childhood leukaemia patients with symptomatic or asymptomatic cardiac problems compared with a control treatment with vitamin C, ATP, vitamin E, and oral coenzyme Q10. No definitive conclusions can be made about treatment options for anthracycline-induced cardiac problems in childhood cancer patients and survivors. High-quality studies are necessary to show if there are drugs that improve heart function in these patients

Medical interventions for treating anthracycline-induced symptomatic and asymptomatic cardiotoxicity during and after treatment for childhood cancer

Background: Anthracyclines are frequently used chemotherapeutic agents for childhood cancer that can cause cardiotoxicity during and after treatment. Although several medical interventions in adults with symptomatic or asymptomatic cardiac dysfunction due to other causes are beneficial, it is not known if the same treatments are effective for childhood cancer patients and survivors with anthracycline-induced cardiotoxicity. Objectives: To compare the effect of medical interventions on anthracycline-induced cardiotoxicity in childhood cancer patients or survivors with the effect of placebo, other medical interventions or no treatment. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2011, issue 1), MEDLINE/PubMed (1949 to May 2011) and EMBASE/Ovid (1980 to May 2011) for potentially relevant articles. We additionally searched reference lists of relevant articles, conference proceedings and ongoing trial databases. Selection criteria: Randomised controlled trials (RCTs) or controlled clinical trials (CCTs) comparing the effectiveness of medical interventions to treat anthracycline-induced cardiotoxicity with either placebo, other medical interventions or no treatment. Data collection and analysis: Two review authors independently performed the study selection. One review author performed the data extraction and 'Risk of bias' assessments which were checked by another review author. Main results: We identified two RCTs. One trial (135 patients) compared enalapril with placebo in childhood cancer survivors with asymptomatic anthracycline induced cardiac dysfunction. The other trial (68 patients) compared a two-week treatment of phosphocreatine with a control treatment (vitamin C, ATP, vitamin E, oral coenzyme Q10) in leukaemia patients with anthracycline-induced cardiotoxicity. Both studies had methodological limitations. The RCT on enalapril showed no (statistically) significant differences in overall survival, mortality due to heart failure, development of clinical heart failure and quality of life between treatment and control group. A post-hoc analysis showed a decrease (i.e. improvement) in one measure of cardiac function (left ventricular end systolic wall stress (LVESWS): -8.62% change) compared with placebo (+1.66% change) in the first year of treatment (P = 0.036), but not afterwards. Patients treated with enalapril had a higher risk of dizziness or hypotension (RR 7.17, 95% CI 1.71 to 30.17) and fatigue (Fisher's exact test, P = 0.013). The RCT on phosphocreatine found no differences in overall survival, mortality due to heart failure, echocardiographic cardiac function and adverse events between treatment and control group. Authors' conclusions: For the effect of enalapril in childhood cancer survivors with asymptomatic cardiac dysfunction, only one RCT is available. Although there is some evidence that enalapril temporarily improves one parameter of cardiac function (LVESWS), it is unclear whether it improves clinical outcomes. Enalapril was associated with a higher risk of dizziness or hypotension and fatigue. Clinicians should weigh the possible benefits with the known side-effects of enalapril in childhood cancer survivors with asymptomatic anthracycline-induced cardiotoxicity. For the effect of phosphocreatine in childhood cancer patients with anthracycline-induced cardiotoxicity, only one RCT is available. Limited data with a high risk of bias showed no significant difference between phosphocreatine and control treatment on echocardiographic function and clinical outcomes. We did not identify any RCTs or CCTs studying other medical interventions for symptomatic or asymptomatic cardiotoxicity in childhood cancer patients or survivors. High-quality studies should be performed