RESULTS

Patient characteristics

Table 1 presents the baseline characteristics of the derivation cohort (n=208) and the validation cohort (n=101). There were no differences in the baseline characteristics of the derivation and validation cohort. Patients were younger, male predominant and more likely to have a single tumor in both groups. Hepatitis B virus (HBV)-positive patients made up 64.9% of the derivation cohort and 69.3% of the validation cohort, respectively. Compared with the validation set, the derivation set tended to have a high proportion of adjuvant TACE after liver resection.

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Outcomes of CHC patients

Among the entire cohort, the median OS was 18.1 months (range, 1.6–192.5 months). The 1-, 3- and 5-year OS probability was 76.2%, 41.2% and 28.3%, respectively (Figure S1). The median RFS was 11.0 months (range, 1.0 to 192.5). The 1-, 3- and 5-year RFS probability was 48.0%, 37.8% and 28.0%, respectively. Till to the date of last follow-up, 171 (55.3%) patients died and 149 (48.2%) patients encountered tumor relapse. There was no significant difference in the CHC recurrence between two groups (Figure 1).

Predictor selection and construction of the PECAR score

By using univariate analysis, male sex, elevated γ-glutamyl transferase (GGT), bleeding volume, tumor diameter and presence of macrovascular invasion, confirmed with hilar lymphoid metastasis and adjuvant TACE, at the first month after surgery were associated with subsequent CHC recurrence in the derivation cohort (Table 2). On multivariate analysis, the predictors that independently correlated with CHC recurrence included (1) sex, (2) GGT (at the following cutoffs: 0–39.9 and ≥40), (3) macrovascular invasion, (4) hilar lymphoid metastasis and (5) adjuvant TACE. The multivariate model coefficients for these 5 significant variables were transformed into relative points, and then summed to calculate the PECAR score as listed in Table 3. By adding total points for these 5 variables, the individualized PECAR score is calculated (Table 3).

Predictive performance and discrimination

The PECAR score ranged from 0 to 4, with the most common score being 1 and 2 (Table 4). A female patient with CHC after liver resection, no macrovascular invasion, no hilar lymphoid metastasis and the GGT level lower than 40 U/L would have a PECAR score of 0, predicting 1- and 5-year recurrence risk of only 11.1% and 22.2%, respectively. Predicted risk of 1- and 5-year CHC recurrence rose with each point score (Figure 2), such as a patient with a PECAR score of 4 or more, had a predicted 1- and 5-year recurrence risk of 72.7% and 81.8%, respectively. The C-index of PECAR score was 0.651 (95% CI, 0.593–0.710) in the derivation cohort for predicting CHC recurrence compared with AJCC 7^thTNM staging system 0.520 (95% CI, 0.465–0.575). By using the NRI, we found that the PECAR score improved prediction of CHC recurrence after liver resection compared with AJCC 7^th TNM staging system at 1 year (0.194, P=0.002) and 5 years (0.407, P<001) after liver resection.

Validation of the PECAR score

To validate whether the PECAR score would be applicable to other datasets, we conducted an external validation study with 101 CHC patients in the validation group. In the validation cohort, median OS and RFS were 17.0 (1.8, 152.0) and 10.8 (1.0, 152.0) months, respectively. The C-index of the PECAR score for predicting postoperative recurrence was 0.610 (95% CI, 0.524–0.697), while the C-index of AJCC 7^th TNM staging system was 0.598 (95% CI, 0.519–0.678). Similarly, the PECAR score improved the performance of recurrence prediction on CHC compared with AJCC 7^th TNM staging system in the validation cohort (1 year: 0.185, P<0.001; 5 years: 0.425, P=0.03).

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