Echocardiographic surveillance for asymptomatic late-onset anthracycline cardiomyopathy in childhood cancer survivors

Background

The optimal frequency of echocardiographic surveillance in asymptomatic childhood cancer survivors exposed to anthracyclines has not been established. We evaluated the effectiveness of performing surveillance echocardiograms according to the Children's Oncology Group's (COG) Long‐Term Follow‐Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers in survivors ≥1 year from concluding therapy.

Methods

We reviewed all children treated at our institution with anthracycline chemotherapy from 1995 to 2003. We assessed the frequency of abnormal echocardiograms according to risk groups defined in the COG guidelines, and evaluated the risk factors for an abnormal echocardiogram using Cox proportional hazards modeling.

Results

At least one echocardiogram was completed by 469/603 (77.8%) eligible survivors. Mean diagnosis age was 7.7 (SD = 4.6) years. Mean cumulative doxorubicin‐equivalent dose was 205 mg/m² (SD = 115). Survivors completed 1,013 echocardiograms (median = 2, range = 1–10) beyond 1 year after concluding therapy. Seventy‐nine (16.8%) survivors had an abnormal echocardiogram at a median of 2.9 years (range 0.01–9.8) from 1 year after concluding therapy. Anthracycline dose >300 mg/m² (hazard ratio [HR] 3.00; 95% CI 1.51–5.98), age 1–4 years at treatment (HR 1.89; 95% CI 1.08–3.31) and radiation to a field involving the heart (HR 1.73; 95% CI 1.08–2.76) predicted an increased risk of an abnormal echocardiogram; however, even survivors in the lower COG risk groups demonstrated abnormalities.

Conclusion

Periodic echocardiographic surveillance in childhood cancer survivors can yield abnormalities that require further evaluation. Abnormalities may become evident as early as 1 year after the conclusion of therapy and can impact even those survivors considered to be at low risk. Pediatr Blood Cancer 2011; 57: 467–472. © 2011 Wiley‐Liss, Inc.     

Prevalence and predictors of anthracycline cardiotoxicity in children treated for acute myeloid leukaemia: retrospective cohort study in a single centre in the United Kingdom

Background

Anthracycline cardiomyopathy is of concern in children treated for acute myeloid leukaemia (AML), but there are few data on the incidence and natural history of cardiotoxicity after AML treatment in the United Kingdom, where regimens have included high anthracycline exposure.

Procedure

Prevalence and predictors of cardiotoxicity were retrospectively reviewed in 124 children treated on the MRC AML 10 and AML 12 trials in a single, large centre from November 1987 to September 2004. Subclinical cardiotoxicity was defined as a shortening fraction of less than 28% and clinical cardiomyopathy as evidence of heart failure, and both were classified as late cardiotoxicity 1 year after completing first line therapy.

Results

Cumulative survival was 61% at 10 years. The prevalence of early and late cardiotoxicity was 13.7% (95%‐CI: 8.2–22.0%) and 17.4% (95%‐CI: 10.9–26.8%), respectively. Early cardiotoxicity was a strong predictor (OR = 9.18; 95%‐CI: 2.10–40.11; P < 0.005) and children who received salvage therapy following relapse showed a trend towards increased late cardiotoxicity (OR = 3.53; 95%‐CI: 0.86–14.48; P < 0.08). Subclinical cardiotoxicity resolved spontaneously in all but one case, but clinical cardiomyopathy always required continuing therapy. Two children died of cardiomyopathy and six remained on medical therapy.

Conclusions

Anthracycline cardiotoxicity remains a major concern for survivors of childhood AML and correlates with early cardiotoxicity and treatment intensity. Long‐term follow‐up is required to fully determine the outcome for children with subclinical cardiotoxicity. Pediatr Blood Cancer 2011;56:625–630. © 2011 Wiley‐Liss, Inc.     

左旋肉碱监测及防治蒽环类抗生素心脏毒性作用

目的 分析急性淋巴细胞白血病患儿血浆游离肉碱浓度的变化与蒽环类药物的关系,同时探讨补充左旋肉碱改善蒽环类药物心脏毒性的疗效.方法 急性淋巴细胞白血病缓解期42例患儿,根据入院时化疗是否含有蒽环类药物分为非蒽环类化疗组(1组)及蒽环类化疗组,后者又分为蒽环类化疗未补充肉碱组(2组)及蒽环类化疗补充肉碱组(3组).每组14例.所有患儿均在化疗后第3天接受常规支持治疗或左旋肉碱治疗,疗程共10 d.监测3组患儿用药前、中、后的血浆游离肉碱浓度及心肌酶、超声心动图、心电图各项指标.另将1组及3组患儿合并后按照蒽环类药物累积量分为蒽环类药物低累积量组(Ⅰ组<150ms/m2)及高累积量组(Ⅱ组≥150mg/m2),分别比较各项监测指标.结果 1组患儿左旋肉碱浓度及心电图异常率较3组患儿低,差异有统计学意义.2组与3组所有指标差异无统计学意义.Ⅰ组肉碱浓度明显高于Ⅱ组,心电图异常率亦较Ⅱ组增高,差异有统计学意义.结论 使用蒽环类抗生素短期内可能使左旋肉碱浓度代偿性增高,同时左旋肉碱浓度与蒽环类药物累积量呈负相关,监测其下降程度可以比超声心动图更早反映患儿出现慢性心肌损害的可能性.     

Randomized Phase II Study of Two Doses of Pixantrone in Patients with Metastatic Breast Cancer (NCCTG N1031, Alliance)

BackgroundAnthracycline use in metastatic breast cancer (MBC) is hindered by cumulative exposure limits and risk of cardiotoxicity. Pixantrone, a novel aza-anthracenedione with structural similarities to mitoxantrone and anthracyclines, is theorized to exhibit less cardiotoxicity, mainly due to lack of iron binding. We conducted a randomized phase II study to evaluate the efficacy and safety of 2 dosing schedules of pixantrone in patients with refractory HER2-negative MBC.MethodsIntravenous pixantrone was administered at 180 mg/m² every 3 weeks (group A) versus 85 mg/m² on days 1, 8, and 15 of a 28-day cycle (group B). Primary endpoint was objective response rate (ORR) and secondary endpoints included progression-free survival (PFS), median 6-month PFS, overall survival (OS), safety, quality of life, and serial assessment of circulating tumor cells. A 20% ORR was targeted as sufficient for further testing of pixantrone in this patient population.ResultsForty-five patients were evaluable, with 2 confirmed partial responses in group A and 1 in group B. The trial was terminated due to insufficient activity. Overall median PFS and OS were 2.8 (95% confidence interval [CI]: 2.0-4.1) and 16.8 (95% CI: 8.9-21.6) months, respectively. Notable overall grade 3-4 adverse events were the following: neutrophil count decrease (62%), fatigue (16%), and decrease in ejection fraction (EF) (4%).ConclusionPixantrone has insufficient activity in the second- and third-line MBC setting. It appears, however, to have limited cardiotoxicity. (ClinicalTrials.gov ID: {"type":"clinical-trial","attrs":{"text":"NCT01086605","term_id":"NCT01086605"}}NCT01086605).     

小金片联合NX方案治疗紫杉类及蒽环类耐药晚期乳腺癌的临床研究

目的 观察小金片联合NX化疗方案(长春瑞滨联合卡培他滨)治疗紫杉类及蒽环类耐药晚期乳腺癌的临床效果.方法 选取2019年1月—2020年1月南阳市第二人民医院收治的100例紫杉类及蒽环类耐药晚期乳腺癌患者,根据信封抽签法分为对照组和治疗组,每组各50例.对照组给予NX化疗方案治疗,第1、8天静脉滴注酒石酸长春瑞滨注射液...     

右丙亚胺对蒽环类药物所致急性白血病儿童心脏毒性防治作用的临床观察

目的探讨急性白血病（AL）儿童中右丙亚胺（DZR）对蒽环类药物（ANT）所致心脏毒性的防治作用。方法观察40例急性白血病患儿,在ANT化疗时合用DZR前后临床表现和心电图、超声心动图、心肌酶谱的变化。结果ANT使用前有心电图异常者,使用ANT时合用DZR,有2例损害持续时间较长,其余均在1个月内恢复正常;ANT累积≥300mg·m^-2再进行化疗时,DZR组心电图异常发生率较对照组明显降低,与对照组比较差异有统计学意义（P〈0．01）。7例AL患儿第1次使用ANT就联合使用DZR,在其后的多次心电图等检查中未发现心脏损害,与同期患儿未使用DZR者比较,显示了良好的心脏保护作用。无一例充血性心力衰竭和其他严重心脏意外的发生。结论DZR对ANT所致急性白血病儿童心脏毒性的发生有一定的防护作用,并且对已经形成的损害有一定的修复作用。     

自动心肌运动定量技术评价蒽环类药物致白血病儿童心脏毒性的价值

目的：探讨自动心肌运动定量（a CMQ）技术评价急性淋巴细胞白血病（ALL）儿童使用蒽环类药物化疗后亚临床左室功能损害的价值。方法：选取2021年11月至2022年1月在温州医科大学附属第二医院育英儿童医院采用DVLD方案诱导化疗的30例ALL患儿作为白血病组,在化疗前和化疗3个月后行超声心动图检查。同期选取性别匹配的26例健康者作为对照组。运用常规超声心动图获取左室射血分数（LVEF）、左室短轴缩短率（LVFS）、二尖瓣口舒张早期峰值流速（E）与晚期最大峰值流速（A）比值（E/A）、E与二尖瓣环舒张早期血流峰值（e’）比值（E/e’）、e’与二尖瓣环舒张晚期血流峰值（a’）比值e’/a’。运用aCMQ技术获得两腔心纵向应变（AP2LS）、三腔心纵向应变（AP3LS）、四腔心纵向应变（AP4LS）及整体纵向应变（LVGLS）,左室短轴基底段环向应变（SAXBCS）、左室短轴中间段环向应变（SAXMCS）、左室短轴心尖段环向应变（SAXACS）及整体环向应变（LVGCS）,并进行比较分析。结果：白血病组与对照组年龄差异无统计学意义（P>0.05）;对照组、化疗前组及化疗后组LVEF...     

Cardioprotective effect of Chinese herbal medicine for anthracycline-induced cardiotoxicity in cancer patients: A meta-analysis of prospective studies

Background:To assess the benefits and harmful effects of Chinese herbal medicine (CHM) formulations in preventing anthracyclines (ANT)-induced cardiotoxicity.Method:The Cochrane Library, Pubmed and EMBASE databases were electronically searched for relevant randomized controlled trials (RCTs) published till December 2021 in English or Chinese-language, in addition to manual searches through the reference lists of the selected papers, and the Chinese Conference Papers Database. Data was extracted by 2 investigators independently.Result:Seventeen RCTs reporting 11 different CHMs were included in this meta-analysis. The use of CHM reduced the occurrence of clinical heart failure (RR 0.48, 95% CI 0.39 to 0.60, P < .01) compared to the control group. Data on subclinical heart failure in terms of LVEF values showed that CHM reduced the occurrence of subclinical heart failure (RR 0.47, 95% CI 0.35 to 0.62, P < .01) as well.Conclusion:CHM is an effective and safe cardioprotective intervention that can potentially prevent ANT-induced cardiotoxicity. However, due to the insufficient quality of the included trials, our results should be interpreted with cautious.     

Effect of standard low-dose anthracycline chemotherapy on late congestive heart failure in breast cancer survivors aged between 50 and 59 at diagnosis: A nationwide study

ObjectivesAlthough chemotherapy-induced congestive heart failure (CHF) is a well-known adverse event in cancer survivors, the long-term risk of standard low-dose anthracycline has not yet been reported. This study aimed to investigate the long-term effects of standard anthracycline on late CHF in breast cancer survivors.Materials and methodsA nationwide retrospective cohort study was conducted using the national insurance claims data for nearly 98% of Korean citizens. Between Jan 2010 and Dec 2015, a total of 56,338 newly diagnosed female breast cancer survivors were included.ResultsThe total number of person-years was 199,648 and the incidence rate of late CHF was 3.57 per 1000 person-years. In multivariate analysis according to the subject’s age at diagnosis, only in the 50–59 age group, anthracycline-based [hazard ratio (HR) 1.765, 95% confidence interval (CI) 1.206–2.583] and taxane plus anthracycline-based regimens (HR 1.816, 95% CI 1.192–2.768) significantly increased the risk of late CHF. In the 50–59 age group, standard low-dose anthracycline significantly increased the risk of late CHF (HR 1.627, 95% CI 1.080–2.451) in Cox proportional hazard regression models. In competing risk model with recurrence and in-hospital death as competing risks, standard low-dose anthracycline was a significant risk factor for late CHF [subdistribution hazard ratio (SHR) 1.553, 95% CI 1.029–2.340].ConclusionThis nationwide study showed that standard chemotherapy with low-dose anthracycline is a risk factor for late-onset CHF in breast cancer survivors who were in their 50 s at breast cancer diagnosis. Long-term monitoring of late CHF should be considered in these younger breast cancer survivors.