Leerink Jan M, van der Pal Helena J H, Kremer Leontien C M, Feijen Elizabeth A M, Meregalli Paola G, Pourier Milanthy S, Merkx Remy, Bellersen Louise, van Dalen Elvira C, Loonen Jacqueline, Pinto Yigal M, Kapusta Livia, Mavinkurve-Groothuis Annelies M C, Kok Wouter E M
Amsterdam UMC, University of Amsterdam, Heart Center, Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands.
Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
JACC CardioOncol. 2021 Mar 16;3(1):62-72. doi: 10.1016/j.jaccao.2020.11.013. eCollection 2021 Mar.
In childhood cancer survivors (CCS) at risk for heart failure, echocardiographic surveillance recommendations are currently based on anthracyclines and chest-directed radiotherapy dose. Whether the ejection fraction (EF) measured at an initial surveillance echocardiogram can refine these recommendations is unknown.
The purpose of this study was to assess the added predictive value of EF at >5 years after cancer diagnosis to anthracyclines and chest-directed radiotherapy dose in CCS, for the development of left ventricular dysfunction with an ejection fraction <40% (LVD40).
Echocardiographic surveillance was performed in 299 CCS from the Emma Children's Hospital in the Netherlands. Cox regression models were built including cardiotoxic cancer treatment exposures with and without EF to estimate the probability of LVD40 at 10-year follow-up. Calibration, discrimination, and reclassification were assessed. Results were externally validated in 218 CCS.
Cumulative incidences of LVD40 at 10-year follow-up were 3.7% and 3.6% in the derivation and validation cohort, respectively. The addition of EF resulted in an integrated area under the curve increase from 0.74 to 0.87 in the derivation cohort and from 0.72 to 0.86 in the validation cohort (likelihood ratio p < 0.001). Reclassification of CCS without LVD40 improved significantly (noncase continuous net reclassification improvement 0.50; 95% confidence interval [CI]: 0.40 to 0.60). A predicted LVD40 probability ≤3%, representing 75% of the CCS, had a negative predictive value of 99% (95% CI: 98% to 100%) for LVD40 within 10 years. However, patients with midrange EF (40% to 49%) at initial screening had an incidence of LVD40 of 11% and a 7.81-fold (95% CI: 2.07- to 29.50-fold) increased risk of LV40 at follow-up.
In CCS, an initial surveillance EF, in addition to anthracyclines and chest-directed radiotherapy dose, improves the 10-year prediction for LVD40. Through this strategy, both the identification of low-risk survivors in whom the surveillance frequency may be reduced and a group of survivors at increased risk of LVD40 could be identified.
在有心力衰竭风险的儿童癌症幸存者（CCS）中，目前超声心动图监测建议是基于蒽环类药物和胸部定向放疗剂量。癌症诊断后5年以上时测量的射血分数（EF）是否能优化这些建议尚不清楚。
本研究的目的是评估癌症诊断后5年以上时EF对CCS中蒽环类药物和胸部定向放疗剂量的额外预测价值，以预测射血分数<40%（LVD40）的左心室功能障碍的发生情况。
对荷兰艾玛儿童医院的299例CCS进行了超声心动图监测。构建了包含有和没有EF的心脏毒性癌症治疗暴露情况的Cox回归模型，以估计10年随访时LVD40的概率。评估了校准、区分度和重新分类情况。在218例CCS中对结果进行了外部验证。
在推导队列和验证队列中，10年随访时LVD40的累积发生率分别为3.7%和3.6%。加入EF后，推导队列的曲线下综合面积从0.74增加到0.87，验证队列从0.72增加到0.86（似然比p<0.001）。无LVD40的CCS的重新分类有显著改善（非病例连续净重新分类改善0.50；95%置信区间[CI]：0.40至0.60）。预测的LVD40概率≤3%（占CCS的75%）对10年内LVD40的阴性预测值为99%（95%CI：98%至100%）。然而，初始筛查时EF处于中等范围（40%至49%）的患者，LVD40的发生率为11%，随访时发生LV40的风险增加7.81倍（95%CI：2.07至29.50倍）。
在CCS中，除了蒽环类药物和胸部定向放疗剂量外，初始监测EF可改善对LVD40的10年预测。通过这种策略，既可以识别出监测频率可能降低的低风险幸存者，也可以识别出LVD40风险增加的一组幸存者。
