Radiation dose and long term risk of cardiac pathology following radiotherapy and anthracyclin for a childhood cancer

Purpose: To determine the cardiac status in children 15 years (yrs) or more after a solid tumour treatment. Patients and Methods: Of the 447 patients, 229 were fully studied and 218 were not. The following cardiac evaluation was proposed to all the 447 consecutive patients: (1) cardiac Doppler US by one of two expert cardiologists; (2) cardiac rhythm and conduction abnormalities including 24-h holter ECG; (3) ¹³¹I-mIBG myocardial scintigraphy; (4) serum brain natriuretic peptide levels at rest; (5) an exercise test with VO ²max measurement. The radiation dose delivered to 7 points in the heart was estimated for all patients who had received radiotherapy. Results: Cardiac disorder was diagnosed in 89 evaluated patients (39%) including 24 heart failures and 65 other asymptomatic cardiac diseases. When adjusting on potential confounders, cardiac disorder and cardiac failure risks were respectively linear (ERR at 1 Gy: 26%) and linear-quadratic (ERR at 1 Gy: 19%) functions of the average radiation dose received to the heart. No interaction between cumulative dose of adriamycin and average radiation dose was evidenced for cardiac disorders, but the ERR/Gy of cardiac failure was higher for patients receiving less than 350 mg/m ² of Adriamycin. Conclusion: Long term heart pathologies are probably one of the major iatrogenic risks encored by patients who survived a childhood cancer. This study strongly emphasizes the need to limit the heart irradiation during radiotherapy, particularly, for patients who also received or were susceptible to later received adriamycin.