Yun-Hsuan Lee

Performance status in patients with hepatocellular carcinoma: Determinants, prognostic impact, and ability to improve the Barcelona Clinic Liver Cancer system

Performance status is included in the Barcelona Clinic Liver Cancer (BCLC) system for hepatocellular carcinoma (HCC). Few studies specifically evaluated the role of performance status in patients with HCC. This study investigated its distribution, determinants, and prognostic impact, aiming to improve the performance of the BCLC system. A total of 2,381 HCC patients were enrolled. Performance status was determined according to the Eastern Cooperative Oncology Group scale. The prognostic ability of the original and three modified BCLC systems in HCC patients was compared by the Akaike information criterion (AIC). There were 60, 17, 11, 8, and 4% of patients who were classified as performance status 0, 1, 2, 3, and 4, respectively. A worse performance status significantly correlated with age, alcoholism, hypoalbuminemia, hyperbilirubinemia, renal insufficiency, hyponatremia, and prothrombin time prolongation (all P < 0.001). Larger tumor burden, poorer residual liver function, more frequent vascular invasion, and diabetes mellitus were also observed in patients with worse performance status (all P < 0.001). Patients with poorer performance status more often received best supportive care (P < 0.001). In the Cox proportional hazards model, performance status was an independent prognostic predictor and the long‐term survival tended to be worse in patients with progressively poor performance status (all P < 0.05). Reassigning patients with performance status 0 or 1 to stage B provided the lowest AIC among the four BCLC‐based staging systems.

Prognosis of hepatocellular carcinoma: Assessment of eleven staging systems

BACKGROUND & AIMS Multiple staging systems have been proposed for hepatocellular carcinoma (HCC). However there is no consensus regarding which system provides the best prognostic accuracy. We aimed to investigate the performance of 11 currently used HCC staging systems. METHODS Between 2002 and 2013, a large prospective dataset of 3182 HCC patients were enrolled. The baseline characteristics and staging information were collected. Independent predictors of survival were identified. Homogeneity and corrected Akaike information criterion (AICc) were compared between each system. RESULTS The median follow-up duration was 17months. Independent predictors of adverse outcome were serum albumin <3.5g/dl, bilirubin ⩾1mg/dl, creatinine ⩾1mg/dl, alpha-fetoprotein ⩾20ng/ml, alkaline phosphatase ⩾200IU/L, presence of ascites, multiple tumor nodules, maximal tumor size >5cm, presence of vascular invasion, presence of extrahepatic metastasis, and poor performance status (all p<0.001). Significant differences in survival were found across all stages of the 11 systems except between Hong Kong Liver Cancer stage IV and V, Japan Integrated Staging score 4 and 5, and Tokyo score 5 through 8. The Cancer of the Liver Italian Program (CLIP) score was associated with the highest homogeneity and lowest AICc value in the entire cohort. In subgroup analysis, the CLIP score was also superior in patients with hepatitis B- or hepatitis C-related HCC and in patients receiving curative or non-curative treatments. CONCLUSIONS The CLIP staging system is stable and consistently the best prognostic model in all patients and in patients with different viral etiology and treatment strategy.

Surgical Resection Versus Radiofrequency Ablation for Single Hepatocellular Carcinoma ≤ 2 cm in a Propensity Score Model.

Objectives:To evaluate the efficacy of surgical resection (SR) and radiofrequency ablation (RFA) for single hepatocellular carcinoma (HCC) 2 cm or less. Background:The optimal management for Barcelona Clínic Liver Cancer (BCLC) very early-stage HCC is undetermined. Methods:Between 2002 and 2013, a total of 237 (SR, 109; RFA, 128) patients with BCLC very early-stage HCC were enrolled. Their overall survival (OS) and recurrence-free survival (RFS) were compared. Propensity score matching analysis identified 79 matched pairs of patients to compare outcomes. Results:At baseline, patients with SR were younger and had larger tumors (both P < 0.05). The 5-year OS rates were 81% versus 76% (P = 0.136), whereas 5-year RFS rates were 49% versus 24% (P < 0.001) for SR and RFA groups, respectively. In the propensity model, the baseline variables were well balanced between 2 groups. Surgical resection was significantly associated with better OS and RFS compared with RFA; the 5-year OS rates were 80% versus 66% (P = 0.034), and 5-year RFS rates were 48% versus 18% (P < 0.001) for SR and RFA groups, respectively. The Cox proportional hazards model identified RFA as an independent predictor for mortality and tumor recurrence in the propensity model (hazard ratio, 2.120 and 2.421, respectively; both P < 0.05). Patients with recurrent HCC had inferior prognosis compared with patients without recurrence (P = 0.001). However, the survival after recurrence was similar between patients initially treated with SR or RFA (P = 0.415). Conclusions:Surgical resection provides better long-term OS and RFS compared with RFA in patients with BCLC very early-stage HCC. Surgical resection should be considered as the first-line treatment for these patients.

ALBI and PALBI grade predict survival for HCC across treatment modalities and BCLC stages in the MELD Era

The severity of liver dysfunction in hepatocellular carcinoma (HCC) is often estimated with Child–Turcotte–Pugh (CTP) classification or model for end‐stage liver disease (MELD) score. We aim to investigate the performance of albumin‐bilirubin (ALBI) and platelet‐albumin‐bilirubin (PALBI) grade, which are recently reported to be simple and objective measurements for liver reserve in HCC.

Vascular invasion in hepatocellular carcinoma: prevalence, determinants and prognostic impact.

Goals/Background: Macrovascular invasion (MaVI) is often detected by radiologic imaging in hepatocellular carcinoma (HCC) patients and may affect their long-term survival. We aimed to investigate the prevalence, determinants, and prognostic impact of MaVI in patients with HCC receiving curative and noncurative therapies. Study: A total of 2654 HCC patients in a single center were identified. The risk factors and prognostic determinants of MaVI were determined. Results: A total of 928 (35%) patients had MaVI. Old age, lower serum &agr;-fetoprotein level, higher serum sodium level, good performance status, smaller total tumor volume, and better liver functional reserve were significantly associated with a lower risk for VI. In the Cox proportional hazards model, patients with lower serum albumin level, higher serum bilirubin and &agr;-fetoprotein level, worse performance status, the presence of ascites, and MaVI independently predicted a decreased long-term survival in patients undergoing both curative and noncurative treatments. In addition, lower sodium level and larger tumor size were independently associated with a poor outcome in the noncurative treatment group. Of the patients with MaVI, the 1-year survival rates for patients receiving surgical treatment, local ablation, transarterial chemoembolization, and supportive care were 83%, 75%, 57%, and 24%, respectively (P<0.001). Conclusions: MaVI represents a distinct tumor phenotype of HCC and is associated with younger age, aggressive tumor behavior, poor liver functional reserve, and poor performance status. It adversely affects the survival of HCC patients independent of treatment strategy. Intensive anticancer therapy should be proposed to achieve a better long-term survival for the at-risk patients.

When to Perform Surgical Resection or Radiofrequency Ablation for Early Hepatocellular Carcinoma?: A Nomogram-guided Treatment Strategy

AbstractRadiofrequency ablation (RFA) is indicated for early-stage hepatocellular carcinoma (HCC), but the comparative efficacy between RFA and surgical resection (SR) is inconclusive. We aim to develop a prognostic nomogram for predicting recurrence-free survival (RFS) after RFA. We also evaluate the possibility of using nomogram in improving treatment algorithm.We retrospectively enrolled 836 patients with Barcelona Clínic Liver Cancer very-early/early-stage HCC receiving SR or RFA. A visually-orientated nomogram was constructed with Cox proportional hazards model, and number and size of tumor, platelet count, albumin level, and model for end-stage liver disease score were included. The concordance index of the nomogram was 0.69.Radiofrequency ablation patients were stratified into low and high-risk groups by the median of nomogram scores. The RFS and overall survival (OS) of 2 risk groups were compared with SR patients with propensity score matching analysis. SR provided better RFS and OS compared with high-risk (nomogram score ≥9.8) RFA patients in the propensity model. The 5-year RFS rates were 36% versus 11%, whereas the 5-year OS rates were 74% versus 60% for SR and high-risk RFA groups, respectively (both P < 0.05). However, SR was associated with better RFS (5-year RFS rates 41% vs 29%), but similar OS (5-year OS rates 80% vs 81%), compared with low-risk (nomogram score <9.8) RFA patients in the propensity model (P < 0.05 and P > 0.05, respectively).In conclusion, this user-friendly nomogram offers individualized recurrence risk estimation and stratification for early HCC patients receiving curative RFA. The nomogram can be integrated into current treatment algorithm. SR should be considered the first-line treatment for high-risk patients to achieve better long-term survival.

Radiofrequency ablation is better than surgical resection in patients with hepatocellular carcinoma within the Milan criteria and preserved liver function: a retrospective study using propensity score analyses.

Goals/Background: Radiofrequency ablation (RFA) and surgical resection (SR) are effective therapies for hepatocellular carcinoma (HCC) within the Milan criteria. We aimed to compare the treatment efficacy according to the liver functional reserve using propensity score analysis. Study: There were 330 and 369 HCC patients within the Milan criteria undergoing SR and RFA, respectively. A total of 147 and 48 pairs of patients with Child-Turcotte-Pugh (CTP) scores=5 and >5, respectively, were matched for analyses. Results: Overall, the 3- and the 5-year survivals were 88% and 76% in the SR group and 80% and 66% in the RFA group, respectively (P=0.006). The SR group had significantly younger patients, a higher male-to-female ratio and hepatitis B infection rate, with a better liver functional reserve and performance status, and a larger tumor burden. In patients with a CTP score of 5, no survival difference was noted between the SR and the RFA groups (P=0.564). In patients with CTP score >5, the SR group had a better long-term survival than the RFA group (P=0.016). After propensity score analysis, the RFA group had a better long-term survival than the SR group in patients with CTP score=5 in the univariate (P=0.024) and the Cox proportional hazards models (hazard ratio: 0.47, P=0.031). Comparable survival results were noted between SR and RFA in patients with CTP score >5 (P=0.15). Conclusions: RFA is a safe procedure with better treatment efficacy than SR in patients with small HCC and a CTP score of 5, and provides effects comparable to SR in patients with CTP score >5. The baseline liver functional reserve may enhance treatment selection for outcome prediction.

Using serum α-fetoprotein for prognostic prediction in patients with hepatocellular carcinoma: what is the most optimal cutoff?

Background and Aims The prognostic ability of α-fetoprotein (AFP) for patients with hepatocellular carcinoma (HCC) was examined by using different cutoff values. The optimal AFP cutoff level is still unclear. Methods A total of 2579 HCC patients were consecutively enrolled in Taiwan, where hepatitis B is the major etiology of chronic liver disease. Four frequently used AFP cutoff levels, 20, 200, 400, 1000 ng/mL, were investigated. One-to-one matched pairs between patients having AFP higher and lower than the cutoffs were selected by using the propensity model. The adjusted hazard ratios of survival difference were calculated with Cox proportional hazards model. Results Patients with a higher AFP level were associated with more severe cirrhosis, more frequent vascular invasion, higher tumor burden and poorer performance status (all p<0.0001). In the propensity model, 4 groups of paired patients were selected, and there was no difference found in the comparison of baseline characteristics (all p>0.05). Patients with AFP <20 ng/mL had significantly better long-term survival than patients with AFP ≧20 ng/mL (p<0.0001), and patients with AFP <400 ng/mL had significantly better overall outcome than patients with AFP ≧400 ng/mL (p = 0.0186). There was no difference of long-term survival between patients divided by AFP levels of 200 and 1000 ng/mL. The adjusted hazard ratios of AFP ≧20 ng/mL and AFP ≧400 ng/mL were 1.545 and 1.471 (95% confidence interval: 1.3–1.838 and 1.178–1.837), respectively. Conclusions This study shows the independently predictive ability of baseline serum AFP level in HCC patients. AFP levels of 20 and 400 ng/mL are considered feasible cutoffs to predict long-term outcome in unselected HCC patients.

Solitary Large Hepatocellular Carcinoma: Staging and Treatment Strategy

Background & Aims Controversies exist on staging and management of solitary large (>5 cm) hepatocellular carcinoma (HCC). This study aims to evaluate the impact of tumor size on Barcelona Clinic Liver Cancer (BCLC) staging and treatment strategy. Methods BCLC stage A and B patients were included and re-classified as single tumor 2–5 cm or up to 3 tumors ≤3 cm (group A; n = 657), single tumor >5 cm (group SL; n = 224), and multiple tumors >3 cm (group B; n = 351). Alternatively, 240 and 229 patients with solitary large HCC regardless of tumor stage received surgical resection (SR) and transarterial chemoembolization (TACE), respectively. The propensity score analysis identified 156 pairs of patients from each treatment arm for survival comparison. Results The survival was significantly higher for group A but was comparable between group SL and group B patients. Of patients with solitary large HCC, the 1-, 3- and 5-year survival rates were 88% versus 74%, 76% versus 44%, and 63% versus 35% between SR and TACE group, respectively (p<0.001). When baseline demographics were adjusted in the propensity model, the respective 1-, 3- and 5-year survival rates were 87% versus 79%, 76% versus 46%, and 61% versus 36% (p<0.001). The Cox proportional hazards model identified TACE with a 2.765-fold increased risk of mortality compared with SR (95% confidence interval: 1.853–4.127, p<0.001). Conclusions Patients with solitary large HCC should be classified at least as intermediate stage HCC. SR provides significantly better survival than TACE for solitary large HCC regardless of tumor stage. Further amendment to the BCLC classification is mandatory.

Nomogram of the Barcelona Clinic Liver Cancer system for individual prognostic prediction in hepatocellular carcinoma

The predictive accuracy of the Barcelona Clinic Liver Cancer (BCLC) staging system on a single patient is not clear. This study aimed to develop a nomogram to predict individualized survival of patients with hepatocellular carcinoma (HCC) based on the BCLC system.