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Table 1 Sex-related differences in anthracycline-induced cardiomyopathy in pediatric cancer patients

From: Clinical and preclinical evidence of sex-related differences in anthracycline-induced cardiotoxicity

Pediatric studies Number of patients Age at diagnosis in years Follow-up Anthracycline cumulative dose Major conclusion/comments
Silber et al. [20] 150 0.23–21, mean 9.5 years 0.09–18 years, average 4.7 50–750 mg/m2
Mean = 307 mg/m2
Female sex was a significant risk factor for cardiac abnormality (OR = 3.2)
Lipshultz et al. [21] 120 0.6–28.9 2–14.6 244–550 mg/m2
Median = 390 and 395 mg/m2 for osteogenic sarcoma and acute lymphoblastic leukemia, respectively
Female sex was an independent risk factor for cardiac abnormality after DOX therapy.
Krischer et al. [26] 6493 < 1 year to > 15 years 1 year From < 99 mg/m2 to > 500 mg/m2
No specific doses were stated
Female sex increased the risk of anthracycline-associated cardiotoxicity (RR = 1.9)
Review of protocols records
Ewer et al. [27] 113 1–17
Mean, 10.6;
Median, 11
4–180 months 113–506 mg/m2
Mean = 341 mg/m2
More girls than boys developed cardiac dysfunction (not statistically significant, small sample size)
Green et al. [28] 2710 < 16 Up to 20 years 59–691 mg/m2 Females are at 4 times higher risk of congestive heart failure after
Review of medical records
Pein et al. [34] 229 0–21 > 15 years 40–600 mg/m2
Mean = 344 mg/m2
Sex was not a significant risk factor
Van Dalen et al. [35] 830 0.1–18.0 years, median 8.7 years 0.01–28.4 years, median 7.1 years 15–900 mg/m2
Mean = 288 mg/m2
Median = 280 mg/m2
Sex was not a significant risk factor for clinical heart failure (female RR = 1.46, 95% CI 0.62–3.43 p value = 0.39)
Review of medical records/registry charts
Hudson et al. [36] 217 5 years 3–21.7 years 25–510 mg/m2
Median = 202 mg/m2
Sex was not a significant risk factor for abnormal non-invasive cardiac testing
Armstrong et al. [29] 20,483 0–20 years > 5 years NA Female sex was a risk factor for mortality due to cardiac disease (RR = 1.4).
Reviewing of national death index and death certificates
Mulrooney et al. [10] 14,358 0–20 > 5 years NA Female sex was a risk factor for congestive heart failure (HR = 1.4)
Retrospective cohort study
Lipshultz et al. [30] 66 (out of 100 enrolled patients) Mean age 7.8 years 5 years 300 mg/m2 Reduction in left ventricular fractional shortening was significantly greater in DOX-treated girls than boys
Rathe et al. [37] 80 0.8–13.4
Median of 4 years
1.1– 20.6
Median of 8.2 years
120–300 mg/m2 Sex was not a significant risk factor for subclinical decline in cardiac function (less than 300 mg/m2 DOX)
Longitudinal follow-up
Amigoni et al. [31] 62 0–13 6–19 years 120–280 mg/m2
Mean = 228 mg/m2
Left ventricular mass and dimensions were reduced only in female ALL survivors (less than 300 mg/m2 DOX)
Andolina et al. [38] 308 < 1 year to > 5 years ≥ 5 years Mean = 210 mg/m2
Median = 190 mg/m2
Sex was not a significant risk factor
Retrospective medical record and echocardiography review
Van der Pal et al. [39] 525 9 ≥ 5 years 33–720 mg/m2
Median = 250 mg/m2
Sex was not a significant risk factor
Brouwer et al. [40] 277 ≤ 20 years
Median 8.8
5–31 years
Median 18.2
50–600 mg/m2
Median = 183 mg/m2
Female sex was protective from diastolic dysfunction (OR = 0.3). Sex was not a risk factor for systolic dysfunction
Vandecruys et al. [18] 37 0.2–12.2
Median 4.8
10.6–18.3
Median 13.3
180–240 mg/m2 Subclinical echocardiographic abnormalities were found more frequently in male ALL survivors who had received less than 250 mg/m2 DOX
Toro-Salazar et al. [32] 46 Mean of 11 ± 5.1 2.5–26.9 200–600 mg/m2
Mean = 328 mg/m2
Higher extracellular volume was detected in female than in male survivors who had received 200 mg/m2 or more
Ylanen et al. [41] 62 0–13.8 4.9–18 80–419 mg/m2
Median = 222 mg/m2
There was a trend toward a male predominance among those with abnormal left ventricular ejection fraction and those with abnormal right ventricular ejection fraction
Tham et al. [33] 30 7–19 years 7.6 ± 4.5 80–375 mg/m2
Mean = 197.2 mg/m2
Higher non-contrast myocardial T1 and extra-cellular volume (ECV) was observed in female subjects