Development and Validation of Prognostic Nomograms for Hepatocellular Carcinoma After Hepatectomy Based on Inflammatory Markers

Abstract

Zili Hu,1,2,* Yu Yuan,3,* Zhiwen Hu,1,2,* Qingbo Liu,4 Yizhen Fu,1,2 Jingyu Hou,1,2 Xuqi Sun,5 Shaoqiang Li,6 Wenbin Duan,7 Minshan Chen1,2 1Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 2Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 3Department of Respiratory Medicine, the Second Xiangya Hospital, Central South University, Changsha, 510235, People’s Republic of China; 4Department of Hepatobiliary Surgery, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, 528308, People’s Republic of China; 5Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of China; 6Hepatic Pancreatobiliary Surgery Center, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 7Department of Hepatobiliary Surgery, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, 410005, People’s Republic of China*These authors contributed equally to this workCorrespondence: Minshan Chen; Wenbin Duan, Fax ++86-20-87343117 ; +86-20-877557668214, Email [email protected]; [email protected]: The value of lactate dehydrogenase (LDH) compared with other inflammation-based scores in predicting the outcomes of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients after curative resection remains unknown. This study aims to evaluate the predictive value of LDH and develop novel nomograms to predict postoperative recurrence and survival in these patients.Methods: This study retrospectively collected 1560 patients with HBV-related HCC who underwent curative resection from four institutions in China. In total, 924 patients were recruited from our center and randomly divided into the training cohort (n = 616) and internal validation (n = 308) cohorts. Additionally, 636 patients were selected from three other centers as the external validation cohort. The C index of inflammation-based scores was calculated and compared in the training cohort. Novel models were developed according to multivariable Cox regression analysis in the training cohort and validated in the internal and external validation cohorts.Results: LDH showed a higher C-index than other inflammation-based scores for recurrence survival (RFS, 0.60, 95% CI, 0.58– 0.61) and overall survival (OS, 0.65, 95% CI, 0.63– 0.68). The nomograms of RFS and OS were developed based on tumor diameter, macrovascular invasion, AFP, operative hemorrhage, tumor differentiation, tumor number and LDH and achieved a high C-index (0.78, 95% CI, 0.76– 0.79 and 0.81, 95% CI, 0.79– 0.83), which were remarkably higher than the C-indexes of the five conventional HCC staging systems (0.52– 0.62 for RFS and 0.53– 0.67 for OS). The nomograms were validated in the internal validation cohort (0.77 for RFS, 0.78 for OS) and external validation cohort (0.80 for RFS, 0.81 for OS) and performed well-fitted calibration curves.Conclusion: The two nomograms based on inflammatory markers achieved optimal prediction for RFS and OS of patients with HBV-related HCC after hepatectomy.Keywords: hepatocellular carcinoma, hepatectomy, inflammation-based scores, lactate dehydrogenase, nomogram

Keywords

• hepatocellular carcinoma
• hepatectomy
• inflammation-based scores
• lactate dehydrogenase
• nomogram.