Prognostic nomogram for patients with hepatocellular carcinoma underwent adjuvant transarterial chemoembolization following curative resection

Abstract

Adjuvant transarterial chemoembolization (TACE) is a major option for postoperative hepatocellular carcinoma (HCC) patients with recurrence risk factors. However, individualized predictive models for subgroup of these patients are limited. This study aimed to develop a prognostic nomogram for patients with HCC underwent adjuvant TACE following curative resection.A cohort comprising 144 HCC patients who received adjuvant TACE following curative resection in the Zhongshan Hospital were analyzed. The nomogram was formulated based on independent prognostic indicators for overall survival (OS). The performance of the nomogram was evaluated by the concordance index (C-index), calibration curve, and decision curve analysis (DCA) and compared with the conventional staging systems. The results were validated in an independent cohort of 86 patients with the same inclusion criteria.Serum alpha-fetoprotein (AFP), hyper-sensitive C-reactive protein (hs-CRP), incomplete tumor encapsulation, and double positive staining of Cytokeratin 7 and Cytokeratin 19 on tumor cells were identified as independent predictors for OS. The C-indices of the nomogram for OS prediction in the training cohort and validation cohort were 0.787 (95%CI 0.775-0.799) and 0.714 (95%CI 0.695-0.733), respectively. In both the training and validation cohorts, the calibration plot showed good consistency between the nomogram-predicted and the observed survival. Furthermore, the established nomogram was superior to the conventional staging systems in terms of C-index and clinical net benefit on DCA.The proposed nomogram provided an accurate prediction on risk stratification for HCC patients underwent adjuvant TACE following curative resection.

Figure 1

Prognostic nomogram for hepatocellular carcinoma patients underwent adjuvant transarterial chemoembolization after curative hepatectomy. To use the nomogram, first, a vertical line is drawn from the factor axis to the point scale to determine the number of points for each factor. Second, sum these numbers and locate it on the axis of the total points. Finally, draw a downward line from the axis of the total points to the survival axes to calculate the 2-year and 3-year survival probabilities. AFP = alpha-fetoprotein; CK7 = Cytokeratin 7; CK19 = Cytokeratin 19; hs-CRP = hyper-sensitive C-reactive protein.

Figure 2

The calibration plots for predicting OS of patients at (A) 2 years and (B) 3 years in the training cohort; predicting OS of patients at (C) 2 years and (D) 3 years in the validation cohort. Nomogram-predicted probability of survival is plotted on the x-axis; observed survival is plotted on the y-axis. OS = overall survival.

Figure 3

Decision curve analysis for the nomogram and the conventional staging systems, including the BCLC staging system, the AJCC 7th edition and the CLIP score. The nomogram is compared with the conventional staging systems in terms of 2-year (A for training cohort; C for validation cohort) and 3-year OS (B for training cohort; D for validation cohort), respectively. Dashed lines: clinical net benefits across a range of threshold probabilities; the horizontal solid black line: to assume no patients will experience the event; the solid gray line: to assume all patients will experience the event. On decision curve analysis, the nomogram yielded superior clinical net benefit compared with the conventional staging systems across a range of threshold probabilities. AJCC = American Joint Committee on Cancer, BCLC = Barcelona Clinic Liver Cancer, CLIP = the Cancer Liver of the Italian Program, OS = overall survival.

Figure 4

Kaplan–Meier survival curves for HCC patients with BCLC B stage who received adjuvant transarterial chemoembolization following curative resection stratified by total points calculated by the nomogram in the training cohort (A) and validation cohort (B). BCLC B patients with nomogram-calculated total points > 5 were associated with significant unfavorable OS compared with patients whose total points  ≤ 5. BCLC = Barcelona Clinic Liver Cancer, HCC = hepatocellular carcinoma.