Noninvasive Evaluation of Late Anthracycline Cardiac Toxicity in Childhood Cancer Survivors

Abstract

Purpose Childhood cancer survivors treated with anthracyclines and cardiac radiation are at risk for late-onset cardiotoxicity. The purpose of this study was to delineate the relationship between clinical factors and abnormalities of noninvasive cardiac testing (NICT). Patients and Methods Participants were recruited from a long-term follow-up clinic. Study measures comprised physical examination, laboratory evaluation, echocardiogram, and ECG. Mean fractional shortening (FS) and afterload were compared for survivors who did (at risk [AR]) and did not (no risk [NR]) receive potentially cardiotoxic modalities, and with values expected for comparable age- and sex-matched controls. Results The 278 study participants (mean age, 18.1 years; median age, 16.8 years; range, 7.5 to 39.7 years) included 223 survivors AR for cardiotoxicity after treatment with anthracyclines (median dose ± standard deviation [SD], 202 ± 109 mg/m2) and/or cardiac radiation. Mean FS (± SD) was lower for AR (0.33 ± 0.06) compared with NR survivors (0.36 ± 0.05; P = .004) and normative controls (0.36 ± 0.04; P < .001). Mean afterload (± SD) was higher for AR (58 ± 21 g/cm2) compared with NR survivors (46 ± 15 g/cm2; P < .001) and normative controls (48 ± 13 g/cm2; P < .001). The distribution of FS and afterload among NR survivors did not differ from that of controls. After adjustment for age group at diagnosis and time since completion of therapy, anthracycline dose predicted decline in distribution of FS (P < .001) and increase in distribution of afterload (P < .001). Treatment with anthracycline doses ≥ 100 mg/m2 increased the risk of abnormal NICT; survivors who received ≥ 270 mg/m2 had a 4.5-fold excess risk of abnormal NICT (95% CI, 2.1 to 9.6) compared with controls. Conclusion Childhood cancer survivors treated with anthracycline doses ≥ 270 mg/m2 are at greatest risk for abnormalities of FS and afterload.