Health Outcomes in Childhood Cancer Survivors: Screening for Anthracycline-Induced Cardiac Toxicity.

Cardiac toxicity secondary to anthracyclines is a significant problem in childhood cancer survivors, and the Children's Oncology Group (COG) has developed a recommended screening protocol for echocardiograms based on age at diagnosis, cumulative anthracycline dose, and chest radiation. The objective of this study was to assess the yield of screening and risk factors for cardiac toxicity in long-term survivors.

A retrospective medical record review was performed for all patients seen in a single institution long-term survivor clinic from 2000 through 2007. Patients eligible for analysis included any patient previously treated with anthracyclines and/or chest radiation; patients with prior cardiac disease were excluded.

370 patients were eligible for analysis; 206 (56%) patients were male, 236 (64%) were white, and 197 (53%) were ≤5 years of age at diagnosis. The most common diagnoses included acute lymphoblastic anemia in 152 (41%) patients and Wilms' tumor in 44 (12%). 360 (97%) patients received anthracyclines, and the median dose received was 190 mg/m². Fifty (14%) patients received radiation to the chest only while an additional 64 (17%) patients received total body irradiation. Overall, 308/370 (83%) patients had received at least one screening echocardiogram with a mean time from diagnosis to latest follow-up of 9.3 years. Younger patients at diagnosis were more likely to be screened during follow-up (p=0.007). All other measured factors were similar between those screened and not screened, including diagnosis, sex, BMI, anthracycline dose, and having received radiation. Of all patients receiving a screening echocardiogram, 24/308 (8%) patients had an abnormal echocardiogram defined as shortening fraction (SF) <28%. By the end of the study period, 9 patients had been placed on cardiac medications for the treatment of cardiac dysfunction identified through screening. Anthracycline dose was associated with a future abnormal echocardiogram; odds ratio (OR) of ever having SF<28% was 9.2 (95% CI: 3.1–27.6) for anthracycline dose ≥250 mg/m². For all patients who had received an echocardiogram and received an anthracycline dose ≥250 mg/m², 20/122 (16%) had a SF<28%; for patients who received an anthracycline dose <250 mg/m², only 4/185 (2%) had a SF<28% (p<0.001). Further, only 1 patient who received a dose <175 mg/m² had a SF<28%. Age, sex, chest radiation, type of anthracycline, history of relapse, and history of stem cell transplant were not associated with an abnormal echocardiogram in univariate analyses. Body mass index (BMI) was calculated from available weight and height data at latest follow-up visit. BMI category was significantly associated with having an abnormal echocardiogram, as currently underweight patients (BMI <5^th%) were more likely to have a SF<28% than their heavier counterparts (p=0.001). For currently underweight patients, 4/12 (33%) had an abnormal echocardiogram with a SF<28%; for all patients in a non-underweight category, only 15/216 (7%) had a SF<28%. This result was significant with an OR of 6.7 (95% CI: 1.8–24.8).

We found anthracycline toxicity to be dependent on dose although not on age, with a significantly increased risk with doses ≥250 mg/m². We also describe a novel association between underweight status and anthracycline-induced cardiac toxicity. Eighty-three percent of patients at our institution are being screened by echocardiography. Our data support the current screening recommendations of the Children's Oncology Group (COG), as 24 patients were identified with decreased cardiac function. Echocardiography is a relatively inexpensive tool to identify patients with late-onset cardiac toxicity and may positively impact the medical care for the growing population of childhood cancer survivors.

No relevant conflicts of interest to declare.