Validation of prognostic impact of ADV score for resection of hepatocellular carcinoma: analysis using Korea Liver Cancer Registry Database

Abstract

Purpose: We aimed to validate the prognostic predictive power of ADV score (α-FP-des-γ-carboxyprothrombin [DCP]-tumor volume [TV] score, calculated as α-FP [ng/mL] × DCP [mAU/mL] × TV [mL] and expressed in log₁₀) for predicting patient survival after resection of hepatocellular carcinoma (HCC).

Methods: This study included 1,390 patients with HCC registered in the Korea Liver Cancer Registry. Patients underwent hepatic resection between 2008 and 2012 and were followed up until December 2016. They were divided into 4 groups according to the number of tumors and preoperative treatment.

Results: There was no significant correlation among α-FP, DCP, and TV values (r² ≤ 0.04, P < 0.001). In group 1 with single treatment-naive tumor (n = 1,154), patient stratification with postoperative ADV 1log-interval and cutoffs of 5log, 7log, and 10log showed great prognostic contrast (P < 0.001). In group 2 with multiple treatment-naive tumors (n = 170), patient stratification with postoperative ADV 1log-interval and above-mentioned 3 cutoffs also showed great prognostic contrast (P < 0.001). In group 3 (n = 50) and group 4 (n = 16) with preoperative-treated tumors, patient stratification with postoperative ADV 1log-interval and above-mentioned 3 cutoffs showed noticeable prognostic contrast (P ≤ 0.031). Preoperative ADV score based on preoperative findings also showed great prognostic contrast in 1,106 patients preoperatively diagnosed as having single treatment-naive tumor (P < 0.001). Confining patients to tumor-node-metastasis stages I and II (n = 1,072) as well as Barcelona Clinic Liver Cancer stage 0 and A (n = 862), postoperative ADV cutoffs showed further prognostic stratification.

Conclusion: This validation study strongly suggests that ADV score is an integrated surrogate marker for postresection prognosis in patients with HCC.

Keywords: Biology; Carcinogenesis; Hepatitis B; Hepatocellular carcinoma; Recurrence.

Fig. 1. Comparison of overall patient survival curves according to the number of tumors and preoperative treatment for hepatocellular carcinoma. Group 1, naive single tumor group; group 2, naive multiple tumor group; group 3, treated single tumor group; group 4, treated multiple tumor group.

Fig. 2. Two-dimensional scatter plots for the correlation of α-FP, des-γ-carboxy prothrombin (DCP), and tumor volume (TV). (A) DCP vs. α-FP. (B) TV vs. α-FP. (C) TV vs. DCP.

Fig. 3. Comparison of overall patient survival curves in group 1 patients. (A) Comparison according to the postoperative ADV scores of 1log intervals. (B) Comparison in 4 subgroups with cutoffs of 5log, 7log, and 10log. ADV score, α-FP-des-γ-carboxyprothrombin-tumor volume score.

Fig. 4. Comparison of overall patient survival curves in group 2 patients. (A) Comparison according to the postoperative ADV scores of 1log intervals. (B) Comparison in 4 subgroups with cutoffs of 5log, 7log, and 10log. ADV score, α-FP-des-γ-carboxyprothrombin-tumor volume score.

Fig. 5. Comparison of overall patient survival curves. (A, B) Comparison according to the postoperative ADV scores of 1log intervals and in 4 subgroups with cutoffs of 5log, 7log, and 10log in group 3 patients. (C, D) Comparison according to the postoperative ADV scores of 1log intervals and in 4 subgroups with cutoffs of 5log, 7log, and 10log in group 4 patients. ADV score, α-FP-des-γ-carboxyprothrombin-tumor volume score.

Fig. 6. Comparison of overall patient survival curves according to the preoperative ADV score based on preoperative findings. (A) Comparison according to the preoperative ADV scores of 1log intervals. (B) Comparison in 4 subgroups with cutoffs of 5log, 7log, and 10log. ADV score, α-FP-des-γ-carboxyprothrombin-tumor volume score.

Fig. 7. Comparison of overall patient survival curves according to the tumor staging system and postoperative ADV score in group 1 and 2 patients. (A) Comparison according to the TNM staging system. (B) After confining patients to TNM stages I and II: comparison of 4 subgroups with postoperative ADV cutoffs of 5log, 7log, and 10log in group 3 patients. (C) Comparison according to Barcelona Clinic Liver Cancer (BCLC) stage. (D) After confining patients to BCLC stage 0 and A: comparison of 4 subgroups with postoperative ADV cutoffs of 5log, 7log, and 10log in group 3 patients. ADV score, α-FP-des-γ-carboxyprothrombin-tumor volume score.