The impact of elevated cumulative anthracycline dose on cardiac repolarization changes in children with cancer: a prospective study

Abstract

Aim: We aimed to prospectively interpret the cardiac repolarization changes with 12-lead electrocardiography (ECG) in children with cancer who were treated with anthracycline drugs. Materials and Methods: A total of 53 patients with cancer treated with anthracycline were enrolled in the study. During 6 months follow-up, standard 12-lead ECG was performed at basal, 1st, 4th, and 24th hours after first dose of anthracycline treatment, at the time of 120mg/m2 cumulative anthracycline dose and 240mg/m2 of cumulative anthracycline dose in same patients, respectively. P dispersion(PWd), QT dispersion(QTd), corrected QT dispersion(QTcd), Tp-e interval, Tp-e/QT and Tp-e/QTc ratio were obtained from 12-lead ECG. The patients were classified into three groups according to increasing cumulative anthracycline doses: Group1: first dose(n=53), Group2:120 mg/m2(n=53), Group3:240 mg/m2(n=53). Results: The median age was 48 months(range 9-192 months). While PWd, QTd, QTcd, and Tp-e interval were significantly increased during first 24 hours of the first dose (p<0.001, p=0.005, p=0.041, p=0.016, respectively), Tp-e/QT and Tp-e/QTc ratios were significantly altered during first 24 hours of 120mg/m2 cumulative dose of anthracycline treatment(p<0.001). Any changes in 12-lead ECG were not significantly at 240mg/m2 cumulative dose. However, it was detected that all variables were affected according to each increased anthracycline cumulative dose despite it was not statistically significant. Conclusions: ECG parameters such as PWd, QTd, QTcd, Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios are useful for detecting subclinical cardiac abnormality and acute anthracycline toxicity during both uses of single-dose anthracycline and increased anthracycline doses. These parameters may also predict arrhythmias in patients with cancer.

Keywords

• Childhood cancer
• anthracyclines
• cardiac toxicity
• dispersion

Artan kümülatif antrasiklin dozunun kanserli çocuklarda kardiyak repolarizasyon değişikliklerine etkisi: prospektif bir çalışma

Öz

Amaç: Antrasiklin kemoterapisi ile tedavi edilen kanserli çocuklarda kardiyak repolarizasyon değişikliklerini 12 derivasyonlu elektrokardiyografi (EKG) ile değerlendirmeyi amaçladık. Gereç ve yöntem: Çalışmaya antrasiklin ile tedavi edilen kanserli toplam 53 hasta çalışmaya dahil edildi. Bu hastalara 12 derivasyonlu EKG ile antrasiklin tedavisinin ilk dozu, 120 mg/m2 kümülatif dozu ve 240 mg/m2 kümülatif dozu verilir ikenki her doz uygulaması sırasında ilaç verilmeden hemen önce, ilaç verildikten sonraki 1., 4. Ve 24. Saatteki EKG’leri çekildi. Bu EKG’lerden P dispersiyonu (PWd), QT dispersiyonu (QTd), düzeltilmiş QT dispersiyonu (QTcd), Tp-e aralığı, Tp-e / QT ve Tp-e / QTc oranı hesaplandı. Hastalar artan kümülatif antrasiklin dozlarına göre üç gruba ayrıldı: Grup 1: ilk doz (n = 53), Grup 2: 120 mg / m2 (n = 53), Grup 3: 240 mg / m2 (n = 53). Bulgular: Ortanca yaş 48 ay (aralık 9-192 ay) idi. İlk dozun ilk 24 saatinde PWd, QTd, QTcd ve Tp-e değişkenleri anlamlı olarak artış gösterdiği saptandı. (sırasıyla p <0,001, p = 0,005, p = 0,041, p = 0,016). 120mg / m2 kümülatif antrasiklin tedavisinin ilk 24 saatinde ise Tp-e/QT and Tp-e/QTc oranları istatistiksel anlamlı olarak değişiklik gösterdi (p <0.001). 240 mg / m2 kümülatif antrasiklin dozunda ise herhangi bir anlamlı değişiklik saptanmadı. Ancak istatistiksel olarak anlamlı olmamakla birlikte, artan her antrasiklin kümülatif dozuna göre disperisyon değişkenlerinde uzama, Tp-e / QT ve Tp-e / QTc oranlarında ise azalma olduğu belirlendi. Sonuç: PWd, QTd, QTcd, Tp-e aralığı, Tp-e / QT ve Tp-e / QTc oranları gibi EKG değişkenleri, hem tek doz antrasiklin hem de artan antrasiklin kullanımı sırasında subklinik kardiyak anormalliği ve akut antrasiklin toksisitesini saptamak için yararlı olduğunu saptadık. Bu parametreler değerlendirildiğinde kanserli hastalarda aritmileri de belirlemede önemli olacaktır.

Anahtar Kelimeler

• Çocukluk çağı kanseri
• antrasiklinler
• kardiyak toksisite
• dispersiyon

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