Zhan Gouling, Cao Peiguo, Peng Honghua
Department of Oncology, Third Xiangya Hospital, Central South University, Changsha 410013, China.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2023 Oct 28;48(10):1546-1560. doi: 10.11817/j.issn.1672-7347.2023.230040.
Hepatocellular carcinoma (HCC) prognosis involves multiple clinical factors. Although nomogram models targeting various clinical factors have been reported in early and locally advanced HCC, there are currently few studies on complete and effective prognostic nomogram models for stage IV HCC patients. This study aims to creat nomograms for cancer-specific survival (CSS) in patients at stage IV of HCC and developing a web predictive nomogram model to predict patient prognosis and guide individualized treatment.
Clinicopathological information on stage IV of HCC between January, 2010 and December, 2015 was collected from the Surveillance, Epidemiology, and End Results (SEER) database. The patients at stage IV of HCC were categorized into IVA (without distant metastases) and IVB (with distant metastases) subgroups based on the presence of distant metastasis, and then the patients from both IVA and IVB subgroups were randomly divided into the training and validation cohorts in a 7꞉3 ratio. Univariate and multivariate Cox regression analyses were used to analyze the independent risk factors that significantly affected CSS in the training cohort, and constructed nomogram models separately for stage IVA and stage IVB patients based on relevant independent risk factors. Two nomogram's accuracy and discrimination were evaluated by receiver operator characteristic (ROC) curves and calibration curves. Furthermore, web-based nomogram models were developed specifically for stage IVA and stage IVB HCC patients by R software. A decision analysis curve (DCA) was used to evaluate the clinical utility of the web-based nomogram models.
A total of 3 060 patients were included in this study, of which 883 were in stage IVA, and 2 177 were in stage IVB. Based on multivariate analysis results, tumor size, alpha-fetoprotein (AFP), T stage, histological grade, surgery, radiotherapy, and chemotherapy were independent prognostic factors for patients with stage IVA of HCC; and tumor size, AFP, T stage, N stage, histological grade, lung metastasis, surgery, radiotherapy, and chemotherapy were independent prognostic factors for patients with stage IVB HCC. In stage IVA patients, the 3-, 6-, 9-, 12-, 15-, and 18-month areas under the ROC curves for the training cohort were 0.823, 0.800, 0.772, 0.784, 0.784, and 0.786, respectively; and the 3-, 6-, 9-, 12-, 15-, and 18-month areas under the ROC curves for the validation cohort were 0.793, 0.764, 0.739, 0.773, 0.798, and 0.799, respectively. In stage IVB patients, the 3-, 6-, 9-, and 12-month areas under the ROC curves for the training cohort were 0.756, 0.750, 0.755, and 0.743, respectively; and the 3-, 6-, 9-, and 12-month areas under the ROC curves for the validation cohort were 0.744, 0.747, 0.775, and 0.779, respectively; showing that the nomograms had an excellent predictive ability. The calibration curves showed a good consistency between the predictions and actual observations.
Predictive nomogram models for CSS in stage IVA and IVB HCC patients are developed and validated based on the SEER database, which might be used for clinicians to predict the prognosis, implement individualized treatment, and follow up those patients.
肝细胞癌(HCC)的预后涉及多个临床因素。尽管针对早期和局部晚期HCC的各种临床因素的列线图模型已有报道,但目前针对IV期HCC患者完整有效的预后列线图模型的研究较少。本研究旨在创建IV期HCC患者癌症特异性生存(CSS)的列线图,并开发一个基于网络的预测列线图模型,以预测患者预后并指导个体化治疗。
收集2010年1月至2015年12月期间来自监测、流行病学和最终结果(SEER)数据库的IV期HCC的临床病理信息。根据远处转移情况,将IV期HCC患者分为IVA(无远处转移)和IVB(有远处转移)亚组,然后将IVA和IVB亚组的患者按7∶3的比例随机分为训练队列和验证队列。采用单因素和多因素Cox回归分析,分析训练队列中显著影响CSS的独立危险因素,并根据相关独立危险因素分别为IVA期和IVB期患者构建列线图模型。通过受试者操作特征(ROC)曲线和校准曲线评估两个列线图的准确性和区分度。此外,使用R软件专门为IVA期和IVB期HCC患者开发基于网络的列线图模型。采用决策分析曲线(DCA)评估基于网络的列线图模型的临床实用性。
本研究共纳入3060例患者,其中IVA期883例,IVB期2177例。基于多因素分析结果,肿瘤大小、甲胎蛋白(AFP)、T分期、组织学分级、手术、放疗和化疗是IVA期HCC患者的独立预后因素;肿瘤大小、AFP、T分期、N分期、组织学分级、肺转移、手术、放疗和化疗是IVB期HCC患者的独立预后因素。在IVA期患者中,训练队列的ROC曲线下3、6、9、12、15和18个月的面积分别为0.823、0.800、0.772、0.784、0.784和0.786;验证队列的ROC曲线下3、6、9、12、15和18个月的面积分别为0.793、0.764、0.739、0.773、0.798和0.799。在IVB期患者中,训练队列的ROC曲线下3、6、9和12个月的面积分别为0.756, 0.750, 0.755和0.743;验证队列的ROC曲线下3、6、9和12个月的面积分别为0.744、0.747、0.775和0.779,表明列线图具有良好的预测能力。校准曲线显示预测值与实际观察值之间具有良好的一致性。
基于SEER数据库开发并验证了IVA期和IVB期HCC患者CSS的预测列线图模型,可用于临床医生预测预后、实施个体化治疗及对这些患者进行随访。