Abstract

BackgroundExtrahepatic metastasis is the independent risk factor of poor survival of primary hepatic carcinoma (PHC), and most occurs in the chest and abdomen. Currently, there is still no available method to predict thoracoabdominal extrahepatic metastasis in PHC. In this study, a novel nomogram model was developed and validated for prediction of thoracoabdominal extrahepatic metastasis in PHC, thereby conducted individualized risk management for pretreatment different risk population.MethodsThe nomogram model was developed in a primary study that consisted of 330 consecutive pretreatment patients with PHC. Large-scale datasets were extracted from clinical practice. The nomogram was based on the predictors optimized by data dimension reduction through Lasso regression. The prediction performance was measured by the area under the receiver operating characteristic (AUROC), and calibrated to decrease the overfit bias. Individualized risk management was conducted by weighing the net benefit of different risk population via decision curve analysis. The prediction performance was internally and independently validated, respectively. An independent-validation study using a separate set of 107 consecutive patients.ResultsFour predictors from 55 high-dimensional clinical datasets, including size, portal vein tumor thrombus, infection, and carbohydrate antigen 125, were incorporated to develop a nomogram model. The nomogram demonstrated valuable prediction performance with AUROC of 0.830 (0.803 in internal-validation, and 0.773 in independent-validation, respectively), and fine calibration. Individual risk probability was visually scored. Weighing the net benefit, threshold probability was classified for three-independent risk population, which was < 19.9%, 19.9–71.8% and > 71.8%, respectively. According to this classification, pretreatment risk management was based on a treatment-flowchart for individualized clinical decision-making.ConclusionsThe proposed nomogram is a useful tool for pretreatment risk management of thoracoabdominal extrahepatic metastasis in PHC for the first time, and may handily facilitate timely individualized clinical decision-making for different risk population.

Highlights

  • Extrahepatic metastasis is the independent risk factor of poor survival of primary hepatic carcinoma (PHC), and most occurs in the chest and abdomen

  • Primary hepatic carcinoma (PHC), including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), is one of the commonest cancers leading to death worldwide

  • Extrahepatic metastasis is the independent predictor of poor survival of PHC [4], and the most frequent metastatic sites occur in chest and abdomen, [5, 6] including lungs, lymph nodes, bones, adrenal glands, gastrointestinal tract, and pleuroperitoneum

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Summary

Introduction

Extrahepatic metastasis is the independent risk factor of poor survival of primary hepatic carcinoma (PHC), and most occurs in the chest and abdomen. Several biomarkers had been proposed as predictors, such as alpha-fetoprotein (AFP) mRNA, glypican-3, CK19, CD44, and vascular endothelial growth factor [7,8,9] Their pragmatic value remains controversial so that they still not serve for the clinical applications. The most valuable diagnostic strategy are comprehensive scanning of medical imaging and regular monitoring These workups are costly, complicated, timeconsuming, and probably unnecessary for majority which may not benefit more than tumor treatments after essential examination. It is necessary to conduct risk prediction for thoracoabdominal extrahepatic metastasis in PHC, in order to facilitate the individualized clinical risk management for different pretreatment population

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