Longitudinal Change in Cardiac Function After Doxorubicin and Dexrazoxane: A Report From Children's Oncology Group ALTE11C2.

IF 44.7 1区医学 Q1 ONCOLOGY

Journal of Clinical Oncology Pub Date : 2026-10-01 Epub Date: 2026-08-06 DOI:10.1200/JCO-26-00260

Erin M Mobley, David R Doody, Steven D Colan, Sanjeev Aggarwal, Richard Aplenc, Saro H Armenian, K Scott Baker, Smita Bhatia, Louis S Constine, David R Freyer, Lisa M Kopp, Wendy M Leisenring, Nao Sasaki, Lynda M Vrooman, Barbara L Asselin, Cindy L Schwartz, Eric J Chow, Steven E Lipshultz

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引用次数: 0

Abstract

Purpose: Dexrazoxane has been associated with preservation of left ventricular (LV) systolic function in relatively small studies of long-term childhood cancer survivors. What remains less clear is whether this association is also seen in larger populations over time and what effect dexrazoxane has on cardiomyopathy screening recommendations.

Methods: We analyzed echocardiographic data from participants who received doxorubicin treatment and were enrolled on Children's Oncology Group protocols P9404, P9425, P9426, P9754, and Dana Farber Cancer Institute protocol 95-01. Except for P9754, all protocols featured up-front 1:1 random assignment with dexrazoxane administered uniformly as an intravenous bolus before doxorubicin (10:1 mg/m² dexrazoxane:doxorubicin dose). Blinded central echocardiogram remeasurements were used when possible; otherwise, data were abstracted from institutional reports. Differences and associations by ± dexrazoxane were estimated using generalized estimating equations and Cox proportional hazard models, adjusting for age, sex, doxorubicin dose, chest radiotherapy, and echocardiogram data type.

Results: Among 895 patients (mean follow-up, 5.9 years, 230 with ≥10-year follow-up; median doxorubicin dose, 360 mg/m²; 51% dexrazoxane-exposed) with evaluable echocardiograms (n = 2,279; 1,581 centrally remeasured; 698 report only), preserved LV systolic function was observed in patients treated with dexrazoxane (z-score difference 0.4 [95% CI, 0.2 to 0.5]) versus without. Dexrazoxane was also associated with decreased hazards of reduced LV function (fractional shortening <30% or ejection fraction <50%) occurring after 1 (0.58 [95% CI, 0.41 to 0.82]) and 5 years (0.54 [95% CI, 0.31 to 0.93]) postdiagnosis. Finally, dexrazoxane appeared to decrease the incidence of reduced LV function among those classified by current cardiomyopathy screening guidelines as high risk to rates like a lower-risk group (from 40 to 21.8 events/1,000 person-years; P = .001).

Conclusion: Dexrazoxane exerts a significant doxorubicin cardioprotective effect on LV systolic function long term and may reduce screening needs.

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阿霉素和右拉唑烷治疗后心功能的纵向变化：来自儿童肿瘤组ALTE11C2的报告。

目的：在相对较小的长期儿童癌症幸存者研究中，Dexrazoxane与左心室（LV）收缩功能的保存有关。目前尚不清楚的是，随着时间的推移，这种关联是否也在更大的人群中出现，以及dexrazoxane对心肌病筛查建议有何影响。方法：我们分析了接受阿霉素治疗的参与者的超声心动图数据，这些参与者参加了儿童肿瘤组方案P9404、P9425、P9426、P9754和Dana Farber癌症研究所方案95-01。除P9754外，所有方案均采用预先1:1随机分配，在阿霉素之前均匀静脉注射右唑嗪（10:1 mg/m2右唑嗪：阿霉素剂量）。在可能的情况下使用盲法中心超声心动图重新测量；否则，数据是从机构报告中摘录的。使用广义估计方程和Cox比例风险模型，调整年龄、性别、阿霉素剂量、胸部放疗和超声心动图数据类型，估计±右唑嗪的差异和关联。结果：在895例超声心动图可评估的患者（平均随访5.9年，230例随访≥10年；阿霉素中位剂量为360 mg/m2； 51%的患者暴露于右唑嗪中）（n = 2279；中心重新测量1581例；仅报告698例）中，右唑嗪治疗与未治疗的患者左室收缩功能保持（z评分差0.4 [95% CI， 0.2至0.5]）。右唑嗪还与左室功能降低的风险降低相关（分数缩短P = .001）。结论：右拉唑烷对左室收缩功能具有明显的长期心脏保护作用，可减少筛查需求。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Clinical Oncology 医学-肿瘤学

CiteScore

41.20

自引率

2.20%

发文量

8215

审稿时长

2 months

期刊介绍： The Journal of Clinical Oncology serves its readers as the single most credible, authoritative resource for disseminating significant clinical oncology research. In print and in electronic format, JCO strives to publish the highest quality articles dedicated to clinical research. Original Reports remain the focus of JCO, but this scientific communication is enhanced by appropriately selected Editorials, Commentaries, Reviews, and other work that relate to the care of patients with cancer.