Table_1_A novel nomogram predicting the early recurrence of hepatocellular carcinoma patients after R0 resection.docx

BackgroundEarly tumor recurrence is one of the most significant poor prognostic factors for patients with HCC after R0 resection. The aim of this study is to identify risk factors of early recurrence, in addition, to develop a nomogram model predicting early recurrence of HCC patients.
MethodsA total of 481 HCC patients after R0 resection were enrolled and divided into a training cohort (n = 337) and a validation cohort (n = 144). Risk factors for early recurrence were determined based on Cox regression analysis in the training cohort. A nomogram incorporating independent risk predictors was established and validated.
ResultsEarly recurrence occurred in 37.8% of the 481 patients who underwent curative liver resection of HCC. AFP ≥ 400 ng/mL (HR: 1.662; P = 0.008), VEGF-A among 127.8 to 240.3 pg/mL (HR: 1.781, P = 0.012), VEGF-A > 240.3 pg/mL (HR: 2.552, P < 0.001), M1 subgroup of MVI (HR: 2.221, P = 0.002), M2 subgroup of MVI (HR: 3.120, P < 0.001), intratumor necrosis (HR: 1.666, P = 0.011), surgical margin among 5.0 to 10.0 mm (HR: 1.601, P = 0.043) and surgical margin < 5.0 mm (HR: 1.790, P = 0.012) were found to be independent risk factors for recurrence-free survival in the training cohort and were used for constructing the nomogram. The nomogram indicated good predictive performance with an AUC of 0.781 (95% CI: 0.729-0.832) and 0.808 (95% CI: 0.731-0.886) in the training and validation cohorts, respectively.
ConclusionsElevated serum concentrations of AFP and VEGF-A, microvascular invasion, intratumor necrosis, surgical margin were independent risk factors of early intrahepatic recurrence. A reliable nomogram model which incorporated blood biomarkers and pathological variables was established and validated. The nomogram achieved desirable effectiveness in predicting early recurrence in HCC patients.

背景：术后早期肿瘤复发是肝细胞癌（HCC）患者接受R0切除（R0 resection）后最显著的不良预后因素之一。本研究旨在明确该人群早期复发的危险因素，并构建可预测其早期复发的列线图（nomogram）模型。
方法：本研究共纳入481例接受R0切除的HCC患者，将其分为训练队列（n=337）与验证队列（n=144）。在训练队列中，基于Cox回归分析确定早期复发的危险因素。构建纳入独立危险因素的列线图模型并进行验证。
结果：481例接受根治性肝切除的HCC患者中，37.8%发生了早期复发。在训练队列中，以下指标被证实为无复发生存期的独立危险因素：甲胎蛋白（AFP）≥400 ng/mL（风险比HR=1.662，P=0.008）、血管内皮生长因子A（VEGF-A）水平为127.8~240.3 pg/mL（HR=1.781，P=0.012）、VEGF-A>240.3 pg/mL（HR=2.552，P<0.001）、微血管侵犯（MVI）M1亚型（HR=2.221，P=0.002）、MVI M2亚型（HR=3.120，P<0.001）、肿瘤内坏死（HR=1.666，P=0.011）、手术切缘宽度为5.0~10.0 mm（HR=1.601，P=0.043）以及手术切缘宽度<5.0 mm（HR=1.790，P=0.012）。基于上述危险因素构建的列线图模型预测性能良好，训练队列与验证队列的受试者工作特征曲线下面积（AUC）分别为0.781（95%置信区间CI：0.729~0.832）与0.808（95%CI：0.731~0.886）。
结论：血清AFP与VEGF-A水平升高、微血管侵犯、肿瘤内坏死及手术切缘状态是早期肝内复发的独立危险因素。本研究构建并验证了一款纳入血液生物标志物与病理变量的可靠列线图模型，该模型在预测HCC患者早期复发方面具有理想的临床效能。