Cardio-toxicity in childhood cancer survivors “Cure is not enough”

Abstract

Background According to the latest publication of data by the German Children's cancer registry (DKKR), the 5-year survival rate for children aged under 15 years is estimated with 85%. Since 1980, 47,650 patients have been documented (1). Attention is drawn towards cardiac or cardiovascular sequelae in childhood cancer survivors. Accordingly, this topic was covered in adult cancer survivor studies leading to the ESC position paper on cardiac toxicity, quoted in the subtitle mentioned above (2). There are publications on chemotherapy-induced cardiotoxicity (mainly anthracycline-associated) and additional risk factors. Also radiation, chronic disease, combination of chemotherapies and the introduction of new drugs need to be considered (3). Furthermore, asymptomatic (subclinical) or symptomatic cardiac events have to be distinguished (4). Asymptomatic ventricular dysfunction has been reported to be as high as 57% (5,6). The appearance of cardiomyopathy is reported from 2.8% to 29%, mostly in accordance to the dose of anthracyclines (7,8). Several population based registries or studies were reporting on late term problems of childhood cancer survivors and cardiovascular sequelae. The British Childhood Cancer Survivor Study (BCCSS) (9) represented a cohort of 34,489 5-year survivors of childhood cancer diagnosed between 1940 and 2006. They counted 181 cardiac deaths, a number 3.4 times higher than expected. In the group of participants of age 60 years and older, cardiac disease was present in 22% and vascular sequelae in 15% of the cases. Surprisingly, the mortality was highest among the patients diagnosed between 1980 and 1989. The Euro2K cohort followed 4,567 2-year survivors

Dexrazoxane Treatments Limits Subclinical Cardiac Dysfunction in Childhood Acute Lymphoblastic Leukemia Survivors Exposed to Doxorubicin Treatments

“…To highlight these underlying mechanisms, it would have been interesting to consider the important markers of cardiotoxicity, such as BNP and NT-proBNP markers,48,49 in addition to the echocardiograph assessment 50. This is an important topic because it has been reported that survivors have a considerably increased risk for premature cardiovascular diseases such as congestive heart failure 51,52. Protection strategies must continue to be prescribed, whereas exercise training should be implemented in pediatric oncology to slow survivors’ cardiotoxicity 53,54.…”

“…50 This is an important topic because it has been reported that survivors have a considerably increased risk for premature cardiovascular diseases such as congestive heart failure. 51,52 Protection strategies must continue to be prescribed, whereas exercise training should be implemented in pediatric oncology to slow survivors' cardiotoxicity. 53,54 It has been reported that a good cardiorespiratory fitness level is associated with cardiac health in childhood ALL survivors.…”

Pulmonary Hypertension as a Complication of Pediatric Cancer

“… 48 However up to 57% of pediatric patients have asymptomatic ventricular dysfunction. 49 Risk factors for cardiotoxicity include use of anthracyclines at a young age (<4 years), high cumulative dose for age (≥200 mg/m 2 for age <1 year and ≥300 mg/m 2 for >1 year old), concurrent use of radiation therapy, and female gender. 48 , 49 Cardiotoxicity manifests as left or right ventricular systolic or diastolic dysfunction.…”

“… 49 Risk factors for cardiotoxicity include use of anthracyclines at a young age (<4 years), high cumulative dose for age (≥200 mg/m 2 for age <1 year and ≥300 mg/m 2 for >1 year old), concurrent use of radiation therapy, and female gender. 48 , 49 Cardiotoxicity manifests as left or right ventricular systolic or diastolic dysfunction. 50 Because of the risk of cardiotoxicity, echocardiography is obtained frequently with treatment and every 5 years after low dose anthracycline ± radiation therapy (<15 gray) exposure and every 2 years with high dose (>250 mg/m 2 ) or whenever a higher dose (>15 gray) of radiation therapy is used.…”

Construction of a Nomogram Risk Prediction Model for Acute Cardiotoxicity Associated with Anthracycline Drugs in Pediatric Hematological Tumors: a retrospective cohort study in China

“…Research has shown that compared to normal individuals, childhood cancer survivors have a 5-15 fold increased risk of congestive heart failure, and once diagnosed, the 5-year survival rate is less than 50% [10] . Tumor combined with cardiovascular disease or cardiovascular complications induced by anticancer treatment have become the main cause of incidence rate and mortality/non cancerous death of child cancer survivors [11][12][13][14] . Therefore, early identi cation of high-risk children, successful screening and early treatment of children with cardiac damage are of great signi cance.…”