放疗对曲妥珠单抗心脏毒性的影响

　　曲妥珠单抗治疗HER2阳性乳腺癌患者的心脏毒性发生率较高，左侧乳房放疗也可能增加心脏暴露于辐射的心脏毒性风险。

　　2018年11月26日，施普林格·自然旗下《乳腺癌研究与治疗》在线发表美国哈佛大学医学院、麻省总医院、纽约纪念医院斯隆凯特林癌症中心、查尔斯施密特医学院、埃及亚历山大大学、坦塔大学、艾因夏姆斯大学的研究报告，评估了放疗对乳腺癌患者接受曲妥珠单抗发生心脏毒性的影响。

　　该研究对2000～2014年接受曲妥珠单抗＋化疗＋放疗的220例患者进行回顾分析。左侧乳腺癌放疗计划来自档案。放疗靶区分别勾画心脏、各个房室、冠状动脉左前降支，生成新的剂量体积直方图，分析其连续左心室射血分数。通过费希尔精确性检验，比较左侧和右侧的心脏毒性。通过精算多因素比例风险回归模型分析，将剂量体积直方图数据与预设心脏事件进行关联。

　　结果，左侧病例与右侧病例相比，心律失常发生率显著较高（14.2%比<1%，P<0.001）。左侧10例患者和右侧1例患者出现心脏缺血（P=0.011）。左心室、右心室、冠状动脉左前降支等效均匀剂量与左心室射血分数减少超过10%显著相关（P=0.037、0.023、0.049）。

　　因此，该研究结果表明，左侧乳腺癌患者治疗后的射血分数减少相似。不过，与右侧乳腺癌相比，心脏缺血和心律失常的发生率较高。左心室、右心室、冠状动脉左前降支等效均匀剂量指数可以作为描述心脏放射毒性风险的参数。

Breast Cancer Res Treat. 2018 Nov 26.

Evaluation of radiation-induced cardiac toxicity in breast cancer patients treated with Trastuzumab-based chemotherapy.

Mohamed Abouegylah, Lior Z. Braunstein, Mohamed A. Alm El-Din, Andrzej Niemierko, Laura Salama, Mostafa Elebrashi, Samantha K. Edgington, Kyla Remillard, Brian Napolitano, George E. Naoum, Hoda E. Sayegh, Tessa Gillespie, Mohamed Farouk, Abdelsalam A. Ismail, Alphonse G. Taghian.

Massachusetts General Hospital, Harvard Medical School, Boston, USA; Alexandria University, Alexandria, Egypt; Memorial Sloan Kettering Cancer Center, New York, USA; Tanta University, Tanta, Egypt; Charles E Schmidit COM, (FAU), Boca Raton, USA; Ain Shams University, Cairo, Egypt.

PURPOSE: Patients with Her2-positive breast cancer treated with trastuzumab have higher rates of cardiotoxicity (CT). Left-breast radiation might increase the risk for CT from cardiac exposure to radiation. The goal of our study is to evaluate the contribution of radiotherapy (RT) in the development of CT in breast cancer patients receiving trastuzumab.

METHODS: Two hundred and two patients were treated with RT and trastuzumab from 2000 to 2014. The RT plans for left-side disease were recalled from archives. The heart, each chamber, and left anterior descending artery (LAD) were independently contoured. New dose-volume histograms (DVH) were generated. Their serial left-ventricular ejection fractions (LVEF) were studied. CT for left and right side were compared using Fisher's exact test. The DVH data were correlated with the predefined cardiac events using actuarial Cox regression analysis.

RESULTS: Compared to the right sided, the left-side cases showed statistically significant development of arrhythmia (14.2%) versus (<1%) (p<0.001). Cardiac ischemia was found in 10 patients in left and one patient in right side (p=0.011). The equivalent uniform dose (EUD) to the left ventricle (LV), right ventricle (RV), and LAD was significantly associated with decrease in LVEF by >10% (p=0.037, p=0.023 and p=0.049, respectively).

CONCLUSIONS: Among patients treated for left-sided lesions, there were no significant differences in EF decline. However, there was a higher rate of ischemia and arrhythmia compared to those with right-sided disease. The EUD index of LV, RV, and LAD could be considered as a parameter to describe the risk of radiation-induced CT.

KEYWORDS: Radiotherapy Trastuzumab Cardiotoxicity Dose-volume histograms

DOI: 10.1007/s10549-018-5053-y