Hahn Ezra, Jiang Haiyan, Ng Angela, Bashir Shaheena, Ahmed Sameera, Tsang Richard, Sun Alexander, Gospodarowicz Mary, Hodgson David
Radiation Medicine Program, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
Biostatistics, Princess Margaret Cancer Centre, University of Toronto, Toronto, Ontario, Canada.
Int J Radiat Oncol Biol Phys. 2017 Aug 1;98(5):1116-1123. doi: 10.1016/j.ijrobp.2017.03.026. Epub 2017 Mar 27.
Mediastinal radiation therapy (RT) for Hodgkin lymphoma (HL) is associated with late cardiotoxicity, but there are limited data to indicate which dosimetric parameters are most valuable for predicting this risk. This study investigated which whole heart dosimetric measurements provide the most information regarding late cardiotoxicity, and whether coronary artery dosimetry was more predictive of this outcome than whole heart dosimetry.
A random sample of 125 HL patients treated with mediastinal RT was selected, and 3-dimensional cardiac dose-volume data were generated from historical plans using validated methods. Cardiac events were determined by linking patients to population-based datasets of inpatient and same-day hospitalizations and same-day procedures. Variables collected for the whole heart and 3 coronary arteries included the following: Dmean, Dmax, Dmin, dose homogeneity, V5, V10, V20, and V30. Multivariable competing risk regression models were generated for the whole heart and coronary arteries.
There were 44 cardiac events documented, of which 70% were ischemic. The best multivariable model included the following covariates: whole heart Dmean (hazard ratio [HR] 1.09, P=.0083), dose homogeneity (HR 0.94, P=.0034), male sex (HR 2.31, P=.014), and age (HR 1.03, P=.0049). When any adverse cardiac event was the outcome, models using coronary artery variables did not perform better than models using whole heart variables. However, in a subanalysis of ischemic cardiac events only, the model using coronary artery variables was superior to the whole heart model and included the following covariates: age (HR 1.05, P<.001), volume of left anterior descending artery receiving 5 Gy (HR 0.98, P=.003), and volume of left circumflex artery receiving 20 Gy (HR 1.03, P<.001).
In addition to higher mean heart dose, increasing inhomogeneity in cardiac dose was associated with a greater risk of late cardiac effects. When all types of cardiotoxicity were evaluated, the whole heart variable model outperformed the coronary artery models. However, when events were limited to ischemic cardiotoxicity, the coronary artery-based model was superior.
霍奇金淋巴瘤（HL）的纵隔放射治疗（RT）与晚期心脏毒性相关，但仅有有限的数据表明哪些剂量学参数对预测这种风险最有价值。本研究调查了哪些全心剂量学测量能提供关于晚期心脏毒性的最多信息，以及冠状动脉剂量学是否比全心剂量学更能预测这一结果。
选取125例接受纵隔RT治疗的HL患者的随机样本，并使用经过验证的方法从历史计划中生成三维心脏剂量 - 体积数据。通过将患者与基于人群的住院患者、当日住院和当日手术数据集相链接来确定心脏事件。为全心和3条冠状动脉收集的变量包括：平均剂量（Dmean）、最大剂量（Dmax）、最小剂量（Dmin）、剂量均匀性、V5、V10、V20和V30。为全心和冠状动脉生成多变量竞争风险回归模型。
记录到44例心脏事件，其中70%为缺血性事件。最佳多变量模型包括以下协变量：全心平均剂量（风险比[HR] 1.09，P = 0.0083）、剂量均匀性（HR 0.94，P = 0.0034）、男性（HR 2.31，P = 0.014）和年龄（HR 1.03，P = 0.0049）。当以任何不良心脏事件作为结局时，使用冠状动脉变量的模型并不比使用全心变量的模型表现更好。然而，仅在缺血性心脏事件的亚分析中，使用冠状动脉变量的模型优于全心模型，且包括以下协变量：年龄（HR 1.05，P < 0.001）、接受5 Gy的左前降支动脉体积（HR 0.98，P = 0.003）和接受20 Gy的左旋支动脉体积（HR 1.03，P < 0.001）。
除了较高的全心平均剂量外，心脏剂量不均匀性增加与晚期心脏效应风险增加相关。当评估所有类型的心脏毒性时，全心变量模型优于冠状动脉模型。然而，当事件仅限于缺血性心脏毒性时，基于冠状动脉的模型更优。
