Sorensen K, Levitt G, Sebag-Montefiore D, Bull C, Sullivan I
Department of Haematology/Oncology, Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom.
J Clin Oncol. 1995 Jul;13(7):1546-56. doi: 10.1200/JCO.1995.13.7.1546.
To study late cardiac function in a single diagnostic group (children with Wilms' tumor) with good long-term survival; to compare patients treated with anthracyclines (doxorubicin) with patients treated without anthracyclines and with a normal child/adolescent group; and to examine the risk factors involved in late cardiac dysfunction.
Echocardiographic studies were performed on 97 Wilms' tumor patients treated with anthracyclines (mean cumulative dose, 303 mg/m2) with a mean follow-up time of 7.1 years, on 39 Wilms' tumor patients treated without anthracyclines with a mean follow-up time of 8.9 years, and on 50 normal subjects. Left ventricular (LV) dimensions, end systolic wall stress (a measure of afterload), and load-dependent and -independent measures of contractility were compared between groups. Potential risk factors, including age at diagnosis, follow-up duration, sex, pubertal status, cardiac irradiation, dose-intensity, and cumulative dose of anthracyclines, were studied by multivariate analysis.
Twenty-five percent of the anthracycline-treated group showed cardiac abnormalities. All but one of these patients had increased LV afterload. Risk factors for increased afterload were anthracycline cumulative dose (P < .05) and anthracycline dose-intensity (P < .02). Wilms' tumor patients treated without anthracyclines had thickened LV walls compared with normal subjects (P < .05).
Total dose and dose-intensity of anthracycline were risk factors for increased LV afterload in long-term Wilms' tumor survivors treated on standard protocols. The increase in afterload accounted for reduced LV shortening, whereas contractility was rarely abnormal. The new finding that Wilms' tumor survivors who do not receive anthracyclines have mild LV hypertrophy may provide some protection against anthracycline-induced cardiotoxic effects.
研究具有良好长期生存率的单一诊断组(肾母细胞瘤患儿)的晚期心脏功能;比较接受蒽环类药物(阿霉素)治疗的患者与未接受蒽环类药物治疗的患者以及正常儿童/青少年组;并检查晚期心脏功能障碍的危险因素。
对97例接受蒽环类药物治疗(平均累积剂量为303mg/m²)且平均随访时间为7.1年的肾母细胞瘤患者、39例未接受蒽环类药物治疗且平均随访时间为8.9年的肾母细胞瘤患者以及50例正常受试者进行了超声心动图研究。比较了各组之间的左心室(LV)尺寸、收缩末期壁应力(后负荷的一种测量指标)以及与负荷相关和无关的收缩性测量指标。通过多变量分析研究了潜在危险因素,包括诊断时的年龄、随访持续时间、性别、青春期状态、心脏照射、剂量强度以及蒽环类药物的累积剂量。
接受蒽环类药物治疗的组中有25%出现心脏异常。除1例患者外,所有这些患者的左心室后负荷均增加。后负荷增加的危险因素是蒽环类药物累积剂量(P<.05)和蒽环类药物剂量强度(P<.02)。与正常受试者相比,未接受蒽环类药物治疗的肾母细胞瘤患者左心室壁增厚(P<.05)。
在按照标准方案治疗的长期肾母细胞瘤幸存者中,蒽环类药物的总剂量和剂量强度是左心室后负荷增加的危险因素。后负荷增加导致左心室缩短减少,而收缩性很少异常。未接受蒽环类药物治疗的肾母细胞瘤幸存者有轻度左心室肥厚这一新发现可能为预防蒽环类药物引起的心脏毒性作用提供一些保护。