Background/Objectives: No reliable noninvasive biomarkers are available to predict RT-induced cardiotoxicity. Because the pericardial sac is a fast responder to cardiac injury, we investigated whether RT-induced radiographic pericardial changes might serve as early imaging biomarkers for late cardiotoxicity. Methods: We performed a retrospective study of 476 patients (210 males, 266 females; median age, 69 years; median follow-up, 26.7 months) treated with chemo-RT for small cell and non-small cell lung cancers at one single institution from 2009 to 2020. The heart and its 4 mm outmost layer (representing the pericardial sac) were contoured on standard-of-care baseline CTs. Six-month post-RT follow-up CTs were deformably registered on the baseline CTs. Data were harmonized for the effect of contrast. We labeled voxels as Fat, Fluid, Heme, Fibrous, and Calcification using Hounsfield units (HUs). We studied pericardial HU-change histograms as well as volume change and voxel-based mass change in each tissue composition. Results: Pericardial HU-change histograms had skewed distributions with a mean that was significantly correlated with mean pericardial dose. Voxels within Fluid, Heme, and Fibrous had mass changes consistent with the dose. In Kaplan–Meier curves, Fibrous and Heme volume changes (translating into thickening and effusion), Fat mass change, mean doses to heart and pericardium, history of cardiac disease, and being male were significantly associated with shorter survival, whereas thickening and effusion were significantly associated with shorter time to a post-RT cardiovascular disease diagnosis. Conclusions: Pericardium composition distribution has dose-dependent changes detectable on standard-of-care CTs at around 6 months post-RT and may serve as surrogate markers for clinically relevant cardiotoxicity. The findings should be validated with additional research.
背景/目的：目前尚无可靠的无创生物标志物可用于预测放疗（RT）诱发的心脏毒性。鉴于心包囊对心脏损伤反应迅速，本研究探讨放疗引起的影像学心包改变是否可作为晚期心脏毒性的早期影像生物标志物。方法：我们对2009年至2020年间在同一机构接受放化疗治疗的476例小细胞及非小细胞肺癌患者（男性210例，女性266例；中位年龄69岁；中位随访时间26.7个月）进行回顾性研究。在标准基线CT图像上勾画心脏及其外4mm层（代表心包囊）。将放疗后6个月随访CT通过形变配准与基线CT对齐，并对造影剂影响进行数据校正。基于亨氏单位（HU）将体素标记为脂肪、液体、血性、纤维及钙化组织。我们分析了心包HU变化直方图，以及各组织成分的体积变化和基于体素的质量变化。结果：心包HU变化直方图呈偏态分布，其均值与心包平均剂量显著相关。液体、血性及纤维组织内的体素质量变化与剂量具有一致性。Kaplan-Meier曲线显示：纤维与血性组织体积变化（对应增厚与积液）、脂肪质量变化、心脏与心包平均剂量、心脏病史及男性性别与较短生存期显著相关，而心包增厚与积液与放疗后心血管疾病诊断时间缩短显著相关。结论：放疗后约6个月时，标准CT可检测到心包成分分布存在剂量依赖性改变，这些改变可能作为临床相关心脏毒性的替代标志物。该发现尚需进一步研究验证。
CT-Based Pericardial Composition Change as an Imaging Biomarker for Radiation-Induced Cardiotoxicity
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