Zhang Yu-Liang, Liu Zi-Rong, Liu Zhi, Bai Yi, Chi Hao, Chen Da-Peng, Zhang Ya-Min, Cui Zi-Lin
First Central Clinical College, Tianjin Medical University, Tianjin 300070, China.
Department of Hepatobiliary Surgery, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin 300192, China.
World J Gastrointest Oncol. 2024 Mar 15;16(3):844-856. doi: 10.4251/wjgo.v16.i3.844.
Hepatocellular carcinoma (HCC) is one of the most common types of cancers worldwide, ranking fifth among men and seventh among women, resulting in more than 7 million deaths annually. With the development of medical technology, the 5-year survival rate of HCC patients can be increased to 70%. However, HCC patients are often at increased risk of cardiovascular disease (CVD) death due to exposure to potentially cardiotoxic treatments compared with non-HCC patients. Moreover, CVD and cancer have become major disease burdens worldwide. Thus, further research is needed to lessen the risk of CVD death in HCC patient survivors.
To determine the independent risk factors for CVD death in HCC patients and predict cardiovascular mortality (CVM) in HCC patients.
This study was conducted on the basis of the Surveillance, Epidemiology, and End Results database and included HCC patients with a diagnosis period from 2010 to 2015. The independent risk factors were identified using the Fine-Gray model. A nomograph was constructed to predict the CVM in HCC patients. The nomograph performance was measured using Harrell's concordance index (C-index), calibration curve, receiver operating characteristic (ROC) curve, and area under the ROC curve (AUC) value. Moreover, the net benefit was estimated decision curve analysis (DCA).
The study included 21545 HCC patients, of whom 619 died of CVD. Age (< 60) [1.981 (1.573-2.496), < 0.001], marital status (married) [unmarried: 1.370 (1.076-1.745), = 0.011], alpha fetoprotein (normal) [0.778 (0.640-0.946), = 0.012], tumor size (≤ 2 cm) [(2, 5] cm: 1.420 (1.060-1.903), = 0.019; > 5 cm: 2.090 (1.543-2.830), < 0.001], surgery (no) [0.376 (0.297-0.476), < 0.001], and chemotherapy(none/unknown) [0.578 (0.472-0.709), < 0.001] were independent risk factors for CVD death in HCC patients. The discrimination and calibration of the nomograph were better. The C-index values for the training and validation sets were 0.736 and 0.665, respectively. The AUC values of the ROC curves at 2, 4, and 6 years were 0.702, 0.725, 0.740 in the training set and 0.697, 0.710, 0.744 in the validation set, respectively. The calibration curves showed that the predicted probabilities of the CVM prediction model in the training set the validation set were largely consistent with the actual probabilities. DCA demonstrated that the prediction model has a high net benefit.
Risk factors for CVD death in HCC patients were investigated for the first time. The nomograph served as an important reference tool for relevant clinical management decisions.
肝细胞癌（HCC）是全球最常见的癌症类型之一，在男性中排名第五，在女性中排名第七，每年导致超过700万人死亡。随着医学技术的发展，HCC患者的5年生存率可提高到70%。然而，与非HCC患者相比，HCC患者由于接受潜在的心脏毒性治疗，心血管疾病（CVD）死亡风险往往增加。此外，CVD和癌症已成为全球主要的疾病负担。因此，需要进一步研究以降低HCC患者幸存者的CVD死亡风险。
确定HCC患者CVD死亡的独立危险因素，并预测HCC患者的心血管死亡率（CVM）。
本研究基于监测、流行病学和最终结果数据库进行，纳入诊断时间为2010年至2015年的HCC患者。使用Fine-Gray模型确定独立危险因素。构建列线图以预测HCC患者的CVM。使用Harrell一致性指数（C指数）、校准曲线、受试者操作特征（ROC）曲线和ROC曲线下面积（AUC）值来衡量列线图性能。此外，通过决策曲线分析（DCA）估计净效益。
该研究纳入了21545例HCC患者，其中619例死于CVD。年龄（<60岁）[1.981（1.573 - 2.496），<0.001]、婚姻状况（已婚）[未婚：1.370（1.076 - 1.745），=0.011]、甲胎蛋白（正常）[0.778（0.640 - 0.946），=0.012]、肿瘤大小（≤2 cm）[（2，5]cm：1.420（1.060 - 1.903），=0.019；>5 cm：2.090（1.543 - （此处原文有误，应为2.830），<0.001]、手术（未进行）[0.376（0.297 - 0.476），<0.001]以及化疗（无/未知）[0.578（0.472 - 0.709），<0.001]是HCC患者CVD死亡的独立危险因素。列线图的区分度和校准效果较好。训练集和验证集的C指数值分别为0.736和0.665。训练集在2年、4年和6年时ROC曲线的AUC值分别为0.702、0.725、0.740，验证集分别为0.697、0.710、0.744。校准曲线显示，训练集和验证集中CVM预测模型的预测概率与实际概率基本一致。DCA表明预测模型具有较高的净效益。
首次对HCC患者CVD死亡的危险因素进行了研究。列线图可作为相关临床管理决策的重要参考工具。
