Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort

Abstract

Objectives To assess the incidence of and risks for congestive heart failure, myocardial infarction, pericardial disease, and valvular abnormalities among adult survivors of childhood and adolescent cancers.Design Retrospective cohort study. Setting 26 institutions that participated in the Childhood Cancer Survivor Study.Participants 14 358 five year survivors of cancer diagnosed under the age of 21 with leukaemia, brain cancer, Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, kidney cancer, neuroblastoma, soft tissue sarcoma, or bone cancer between 1970 and 1986. Comparison group included 3899 siblings of cancer survivors.Main outcome measures Participants or their parents (in participants aged less than 18 years) completed a questionnaire collecting information on demographic characteristics, height, weight, health habits, medical conditions, and surgical procedures occurring since diagnosis. The main outcome measures were the incidence of and risk factors for congestive heart failure, myocardial infarction, pericardial disease, and valvular abnormalities in survivors of cancer compared with siblings. Results Survivors of cancer were significantly more likely than siblings to report congestive heart failure (hazard ratio (HR) 5.9, 95% confidence interval 3.4 to 9.6; P<0.001), myocardial infarction (HR 5.0, 95% CI 2.3 to 10.4; P<0.001), pericardial disease (HR 6.3, 95% CI 3.3 to 11.9; P<0.001), or valvular abnormalities (HR 4.8, 95% CI 3.0 to 7.6; P<0.001). Exposure to 250 mg/m2 or more of anthracyclines increased the relative hazard of congestive heart failure, pericardial disease, and valvular abnormalities by two to five times compared with survivors who had not been exposed to anthracyclines. Cardiac radiation exposure of 1500 centigray or more increased the relative hazard of congestive heart failure, myocardial infarction, pericardial disease, and valvular abnormalities by twofold to sixfold compared to non-irradiated survivors. The cumulative incidence of adverse cardiac outcomes in cancer survivors continued to increase up to 30 years after diagnosis.Conclusion Survivors of childhood and adolescent cancer are at substantial risk for cardiovascular disease. Healthcare professionals must be aware of these risks when caring for this growing population.

Circulatory disease mortality in the Massachusetts tuberculosis fluoroscopy cohort study

“…The mechanisms relevant for lower doses are likely to differ from those relevant at higher (e.g., radiotherapeutic) doses. However, risks in studies of medically-exposed groups, with relevant organ doses usually well above 0.5 Gy, are generally consistent with those in populations exposed at the much lower doses and dose rates discussed above [3][4][5][6]44], suggesting that mechanisms operating at high doses and high dose rates may be similar to those at low doses and dose rates. The fact that the IHD risks using mean heart dose in these high-dose/partial-body exposed groups are similar to the risks in the generally uniformly whole-body-exposed groups using whole-body dose discussed above ( Table 7) also suggests that mean dose to the heart is the most relevant metric for predicting radiation-associated IHD [44].…”

“…We provide the analog of Table 2 using these alternative background models in Table 16. 6 X X sex X X X X X year X X X X X X year 2 X X X X X X X year 3 X X year 4 X year 5 X X X X X year 6 X X X smoking X X X X X X alcohol X X X X X other lung surgery X thoracoplasty X X X X pneumolobectomy study cohort X X X X X tuberculosis type X X X sex 6 X The variables used for each circulatory disease endpoint are indicated by X…”

“…Therapeutic doses of ionizing radiation to the heart and large arteries are associated with various types of circulatory disease [3][4][5][6]. More recently, and controversially, studies on several groups exposed to low-to-moderate doses of radiation have reported excess mortality and morbidity from circulatory diseases, in particular the Life Span Study (LSS) of Japanese atomic bomb survivors [7] and several occupationally exposed cohorts [8].…”

Echocardiographic surveillance for asymptomatic late‐onset anthracycline cardiomyopathy in childhood cancer survivors

“…Consistent with previous studies, cumulative anthracycline dose, radiation to a field that involved the heart, younger age at treatment and female gender were identified as risk factors for abnormal surveillance echocardiograms. Although there is compelling evidence that exposure to anthracycline chemotherapy can cause long-term myocardial dysfunction [10,28], there is no consensus on the indications for periodic cardiac surveillance or on the optimal frequency of this surveillance. Pharmacologic interventions, such as angiotensin converting enzyme (ACE) inhibitors, have been shown to slow the rate of cardiac deterioration in some patients with anthracycline-induced cardiomyopathy, but do not appear to prevent the eventual progression of the disease [29,30].…”

Traditional and novel methods to assess and prevent chemotherapy-related cardiac dysfunction noninvasively

“…2,[10][11][12][13][14]57,69,[77][78][79][80] Children with Hodgkin's disease have been reported to manifest cardiotoxicity early and at low cumulative doses of doxorubicin. 77 The potentially long latency and high cumulative incidence of chronic cardiac dysfunction associated with cancer treatment indicates the need for long-term monitoring of asymptomatic children.…”