Evaluation of the treatment related acute and chronic cardiotoxicity in children with cancer

SUMMARYEVALUATION OF THE TREATMENT RELATED ACUTE & CHRONICCARDIOTOXICITY IN CHILDREN WITH CANCERAim:Cardiotoxicity is one of the most important side effects of anticancer treatment.Although anthracyclines are the major cause of cardiotoxicity in children with cancer, theyremain as one of the most frequently used agents because of their excellent antitumouractivity. There are some other risk factors that may also induce cardiac side effects such assex and age of patients at diagnosis, pre-existing hearth disease, other cardiotoxicchemotherapeutic agents, doses and administration schedule of these agents, mediastinalradiotherapy and surgery that effects the heart. The aim of this study was to retrospectivelyevaluate the oncologic treatment related acute and chronic cardiotoxicity in 18 years oldpatients with the diagnosis of lymphoma and solid tumor whose diagnosis, treatment andfollow-up have been done at the Pediatric Oncology department of Dokuz Eylul University,Faculty of Medicine during the last ten years.Patients and methods:From January 01, 1996 to January 01, 2006, 330 consecutive patients 18 years ofage with the diagnosis of lymphoma and solid tumors who were diagnosed at Dokuz EylulUniversity Faculty of Medicine Department of Pediatric Oncology were analized. Patientswere analized, and patients who received anthracyclines, and/or received radiotherapy to theheart, and/or performed minor/major surgery that effects the heart were included to this study.Patients who diagnosed and treated at another center and who hadn?t detailed medical reportfor that period were excluded. Hospital medical records and Pediatric Oncology Departmentreports and cardiologic examination records of Pediatric Cardiology department were analizedfor all patients. Medical history and family history of patients were assessed for existent heartdisease, acute myocardial infarction at early ages and coronary artery diseases.Findings:Total of 330 patients were evaluated, 109 (33%) of them received oncologic treatmentthat had cardiotoxicity risk, and 7 of them were excluded because of they hadn?t detailed4medical report, 102 of them were included to this study.The sex distribution of patients (n:102) included to this study was as following: 37(36%) patients were female and 65 (65%) patients were male, the median age of diagnosiswas 10 years (0-18 y). Forty-six (45%) patients had lymphoma, and 56 (55%) patients haddiagnosis of solid tumor. The median follow up time of patients was 3,7 years (1mos-11years). Only two (2%) patients had existent heart disease at the time of diagnosis, and 11patients had positive family history for heart disease. All 102 patients received anthracyclineincluding chemotherapy, and the cumulative doses of anthracyclines were not exceeded thelimit values in all 102 patients. Additionally 27 (26%) patients received mediastinalradiotherapy, 11 (11%) patients received pulmonary radiotherapy, and minor/major surgerythat effects the heart was performed in 10 (10%) patients. Major cardiac surgery wasperformed in only one patient among 102 patients, and any cardiotoxicity has not beenobserved yet.Cardiac examination findings were attainable in 86% of patients at the time ofdiagnosis, and 86% of them were normal, 14% of them had cardiac murmur whose 92% wereevaluated as a functional murmur. Cardiac involvement was found only in one patient (8%)which was related to the primary disease.Cardiotoxicity was detected in 14 (14%) patients. The median diagnosis age of these14 patients was 11 years (1-17 y), and male to female ratio was 1:1. The rate ofcardiotoxicity was found 19% in females, 11% in males. Twenty-nine percent of this patientshad Hodgkin lymphoma. There is no history of heart disease in these patients. Family historywas positive in only one patient in this group. The cumulative doses of anthracyclines werenot exceeded the limit values in all 14 patients. Intravenous infusion durations ofanthracyclines were one hour in five, 4 hours in 8, and 48 hours in one patient. Three patientshad received mediastinal RT, and one patient had received pulmonary radiotherapy in thiscardiotoxicity group. Surgical intervention (thoracotomy and lymph node biopsy) wasperformed in only one patient in cardiotoxicity group. Four patients had acute, 8 patients hadchronic, and two patients had acute and chronic cardiotoxicities. The median follow up timeof patients with cardiotoxicity was 4,4 years (3 - 91 mos). One patient who had chroniccardiotoxicity and positive family history died suddenly in her bed.The acute myocarditis-pericarditis syndrome, cardiomyopathy, congestive heartfailure were not detected in any patient included to this study. Follow-up for cardiotoxicityhad been made by physical examination, chest radiography, ECG and ECO examinations in5all patients. Exercise testing, radionuclide angiography, endomyocardial biopsy were not donein any patient.Results:Anthracyclines are the most potent cardiotoxic agents that take place in chemotherapyprotocols of lymphomas and malignant solid tumors during childhood. Although there is a lotof attempt for prevention and early definition of cardiotoxicity; patients are exposed with thisdose limiting side effect presently. The 5 years survival rate was 61% in this young patientpopulation. Patients without cardiotoxicity in this study group have a great risk of latecardiotoxicity during follow-up. Cardiotoxicity is one of the leading non-tumoral deathreasons in pediatric oncology patient survivors. Patients who receive chemotherapy includinganthracyclines and/or other treatments that might effect cardiac functions should be followed- up carefully, cardiotoxicity should be detected early.Key words: Anthracycline, Radiotherapy, Surgery, Cardiotoxicity, Childhood6