Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing, 100015, China.
Department of Hepatobiliary Surgery, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing, 100015, China.
Hepatol Int. 2020 Jul;14(4):567-576. doi: 10.1007/s12072-020-10046-w. Epub 2020 Jun 18.
Disease progression is an important factor affecting the long-term survival in hepatocellular carcinoma (HCC). The progression-free survival (PFS) has been used as a surrogate endpoint for overall survival (OS) in many solid tumors. However, there were few models to predict the PFS in HCC patients. This study aimed to explore the prognostic factors that affect the PFS in HCC and establish an individualized prediction model.
We included 2890 patients with hepatitis B-related HCC hospitalized at Beijing Ditan Hospital, Capital Medical University and randomly divided into training and validation cohort. Cox multivariate regression was used to analyze independent risk factors affecting the 1-year PFS of HCC, and an artificial neural networks (ANNs) model was constructed. C-index, calibration curve, and decision curve analysis were used to evaluate the performance of the model.
The median survival time was 26.2 m (95% CI: 24.08-28.32) and the 1-year PFS rate was 52.3% in whole study population. Cox multivariate regression showed smoking history, tumor number ≥ 2, tumor size ≥ 5 cm, portal vein tumor thrombus, WBC, NLR, γ-GGT, ALP, and AFP ≥ 400 ng/mL were risk factors for 1-year progression-free survival, while albumin and CD4 T cell counts were protective factors in HCC patients. A prediction model for 1-year PFS was constructed ( https://lixuan.me/annmodel/myg-v3/ ). The ANNs model's ability to predict 1-year PFS had an area under the receiver operating characteristic curve (AUROC) of 0.866 (95% CI 0.848-0.884) in HCC patients, which was higher than predicted by TNM, BCLC, Okuda, CLIP, CUPI, JIS, and ALBI scores (p < 0.0001). In addition, the ANNs model could also estimate the probability of 1-year OS and presented a higher AUROC value, 0.877 (95% CI 0.858-0.895), than those other models. All patients were divided into high-, medium-, and low-risk groups, according to the ANNs model scores. Compared with the hazard ratios (HRs) of PFS and OS in low-risk group, those in the high-risk group were 26.42 (95% CI 18.74-37.25; p < 0.0001) and 11.26 (95% CI 9.11-13.93; p < 0.0001), respectively.
The ANNs model has good individualized prediction performance and may be helpful to evaluate the probability of progression-free survival in HCC during clinical practice.
疾病进展是影响肝细胞癌(HCC)长期生存的重要因素。无进展生存期(PFS)已被许多实体瘤用作总生存期(OS)的替代终点。然而,很少有模型可以预测 HCC 患者的 PFS。本研究旨在探讨影响 HCC PFS 的预后因素,并建立个体化预测模型。
我们纳入了 2890 例在北京地坛医院、首都医科大学附属医院住院的乙型肝炎相关 HCC 患者,并随机分为训练队列和验证队列。采用 Cox 多因素回归分析影响 HCC 患者 1 年 PFS 的独立危险因素,并构建人工神经网络(ANNs)模型。采用 C 指数、校准曲线和决策曲线分析评估模型性能。
全研究人群的中位生存时间为 26.2 个月(95%CI:24.08-28.32),1 年 PFS 率为 52.3%。Cox 多因素回归显示,吸烟史、肿瘤数目≥2 个、肿瘤大小≥5cm、门静脉癌栓、白细胞计数、中性粒细胞与淋巴细胞比值、γ-谷氨酰转移酶、碱性磷酸酶、甲胎蛋白≥400ng/ml 是影响 HCC 患者 1 年无进展生存的危险因素,而白蛋白和 CD4 T 细胞计数是 HCC 患者的保护因素。构建了 1 年 PFS 预测模型(https://lixuan.me/annmodel/myg-v3/)。ANNs 模型预测 HCC 患者 1 年 PFS 的能力的受试者工作特征曲线(ROC)下面积(AUROC)为 0.866(95%CI 0.848-0.884),高于 TNM、BCLC、Okuda、CLIP、CUPI、JIS 和 ALBI 评分的预测(p<0.0001)。此外,ANNs 模型还可以估计 1 年 OS 的概率,其 AUC 值为 0.877(95%CI 0.858-0.895),高于其他模型。根据 ANNs 模型评分,将所有患者分为高、中、低风险组。与低风险组的 PFS 和 OS 风险比(HR)相比,高风险组的 HR 分别为 26.42(95%CI 18.74-37.25;p<0.0001)和 11.26(95%CI 9.11-13.93;p<0.0001)。
ANNs 模型具有良好的个体化预测性能,可能有助于在临床实践中评估 HCC 患者的无进展生存概率。