Development and Validation of a Nomogram for Patients Undergoing Transarterial Chemoembolization for Recurrent Hepatocellular Carcinoma After Hepatectomy

Abstract

Purpose: This study aims to establish a prognostic nomogram for patients who underwent transarterial chemoembolization (TACE) for recurrent hepatocellular carcinoma (HCC) after hepatectomy.

Patients and methods: Patients who underwent TACE for recurrent early- and middle-stage HCC after hepatectomy between 2009.01 and 2015.12 were included. Enrolled patients were randomly divided into training (n=345) and validation (n=173) cohorts according to a computer-generated randomized number. Independent factors for overall survival (OS) were determined and included in the nomogram based on the univariate and multivariate analyses of the training group. The nomogram was validated and compared to other prognostic models. Discriminative ability and predictive accuracy were determined using the Harrell C index (C-index), area under the receiver operating characteristic curve (AUROC), and calibration curve.

Results: The final nomogram was established based on four parameters including resection-to-TACE time interval, recurrent tumor diameter, recurrent tumor number, and AFP level. The C-indexes of the nomogram for predicting OS were 0.67 (95% CI 0.63-0.70) and 0.71 (95% CI 0.68-0.74) in the training and validation cohort respectively. The AUROCs for predicting the 1-year, 2-year and 3-year OS based on the nomogram were also superior to those of the other models. The calibration curve for 3-year survival showed a high congruence between the predicted and actual survival probabilities. According to the scores calculated by the nomogram, patients were stratified into three subgroups: high-risk (scoring ≥53 points), middle-risk (scoring ≥26 and <53 points), and low-risk (scoring <26 points) subgroups with a median OS of 10.1 (95% CI 0.63-0.70), 20.3 (95% CI 17.5-22.5) and 47.0 (95% CI 34.2-59.8) months, respectively.

Conclusion: The proposed nomogram served as a new tool to predict individual survival in patients who underwent TACE for recurrent HCC after hepatectomy, with favorable performance and discrimination. For high-risk patients, treatment should be optimized beyond TACE alone based on the nomogram.

Keywords: hepatocellular carcinoma; nomogram; transarterial chemoembolization.

Figure 1

Flowchart of included patients.

Figure 2

Comparison of overall survival between the training cohort and the validation cohort.

Figure 3

Nomogram for predicting overall survival in patients undergoing TACE for post-resection recurrent HCC. The density plots showed the distribution of total points and tumor diameter. The size of the box represented the distribution of category variables. The importance of each variable was ranked according to the standard deviation along nomogram scales. An example of using the nomogram to predict survival probability of a given patient was displayed. The patient received TACE for two recurrent HCC nodules with the largest diameter of 3.5cm 6 months post hepatectomy. AFP was negative before TACE. Red lines and dots were drawn upward to determine the points received by each variable. Another line was drawn from the sum (72.4) of these points on the Total Points axis downward to the survival axes to determine the probability of 1-year(81.0%), 2-year(58.1%) and 3-year(41.2%) survival.

Figure 4

Calibration curve for predicting 3-year survival in the training cohort (upper figure) and the validation cohort (lower figure).

Figure 5

Time-dependent AUROC of different models for predicting overall survival in the training cohort (upper figure) and in the validation cohort (lower figure).

Figure 6

Different risk stratification for overall survival based on the nomogram.