Department of Medicine, Division of Cardiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Department of Radiation Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
Int J Radiat Oncol Biol Phys. 2019 Mar 15;103(4):851-860. doi: 10.1016/j.ijrobp.2018.11.013. Epub 2018 Nov 14.
We characterized the early changes in cardiovascular biomarkers with contemporary thoracic radiation therapy (RT) and evaluated their associations with radiation dose-volume metrics including mean heart dose (MHD), V5, and V30.
In a prospective longitudinal study of 87 patients with breast cancer, lung cancer, or mediastinal lymphoma treated with photon or proton thoracic RT, blood samples were obtained pre-RT and after completion of RT (median, 20 days; interquartile range [IQR], 1-35). High-sensitivity cardiac troponin T, N-terminal pro-B-type natriuretic peptide, placental growth factor (PIGF), and growth differentiation factor 15 (GDF-15) were measured. Associations between MHD, V5 and V30, and biomarker levels and associations between echocardiography-derived measures of cardiac function and biomarker levels were assessed in multivariable linear regression models. Analyses were performed according to the following subgroups: (1) breast cancer alone and (2) lung cancer and lymphoma combined.
The median (IQR) estimates of MHD ranged from 1.3 Gy (0.9-2.4) in breast cancer (n = 60) to 6.8 Gy (5.4-10.2) in mediastinal lymphoma (n = 14) and 8.4 Gy (6.7-16.1) in lung cancer (n = 13) patients (P < .001). There were no significant increases in biomarker levels from pre-RT to post-RT in breast cancer. In lung cancer/lymphoma, PIGF increased from a median (IQR) of 20 ng/L (16-26) to 22 ng/L (16-30) (P = .005), and GDF-15 increased from 1171 ng/L (755-2493) to 1887 ng/L (903-3763) (P = .006). MHD, V5, and V30 were significantly associated with post-RT PIGF and GDF-15 levels in multivariable models. Changes in biomarkers were not significantly associated with changes in echocardiography-derived measures of cardiac function.
Contemporary thoracic RT induces acute abnormalities in vascular and inflammatory biomarkers that are associated with radiation dose-volume metrics, particularly in lung cancer and mediastinal lymphoma. Long-term follow-up studies are needed to determine the impact of these changes on the development of overt cardiac disease.
我们研究了采用现代胸部放射治疗（RT）后的心血管生物标志物的早期变化，并评估了它们与包括平均心脏剂量（MHD）、V5 和 V30 在内的放射剂量-体积指标的相关性。
在一项前瞻性纵向研究中，对 87 例接受光子或质子胸部 RT 治疗的乳腺癌、肺癌或纵隔淋巴瘤患者进行了研究，在 RT 前和 RT 完成后（中位数 20 天；四分位间距 [IQR]，1-35 天）采集血样。检测高敏心肌肌钙蛋白 T、N 端脑利钠肽前体、胎盘生长因子（PIGF）和生长分化因子 15（GDF-15）。采用多变量线性回归模型评估 MHD、V5 和 V30 与生物标志物水平之间的相关性，以及超声心动图心功能测量值与生物标志物水平之间的相关性。根据以下亚组进行分析：（1）单纯乳腺癌和（2）肺癌和淋巴瘤合并。
MHD 的中位数（IQR）估计值范围从乳腺癌（n=60）患者的 1.3 Gy（0.9-2.4）到纵隔淋巴瘤（n=14）患者的 6.8 Gy（5.4-10.2）和肺癌（n=13）患者的 8.4 Gy（6.7-16.1）（P<0.001）。乳腺癌患者从 RT 前到 RT 后，生物标志物水平没有明显升高。在肺癌/淋巴瘤中，PIGF 从 20ng/L（16-26）的中位数（IQR）增加到 22ng/L（16-30）（P=0.005），GDF-15 从 1171ng/L（755-2493）增加到 1887ng/L（903-3763）（P=0.006）。多变量模型显示，MHD、V5 和 V30 与 RT 后 PIGF 和 GDF-15 水平显著相关。生物标志物的变化与超声心动图心功能测量值的变化无显著相关性。
现代胸部 RT 会引起血管和炎症生物标志物的急性异常，这些异常与放射剂量-体积指标相关，特别是在肺癌和纵隔淋巴瘤中。需要进行长期随访研究，以确定这些变化对明显心脏病发展的影响。
