Chia-Yang Hsu

A new prognostic model for hepatocellular carcinoma based on total tumor volume: The Taipei Integrated Scoring system

BACKGROUND & AIMS The currently used staging systems for hepatocellular carcinoma (HCC) are not satisfactory. The optimal prognostic model for HCC is still under intense debate. This study aimed to propose a new staging system for HCC based on total tumor volume (TTV) and to compare it with the currently used systems. METHODS A total of 2030 HCC patients undergoing different treatment strategies were retrospectively analyzed. TTV was defined as the sum of the volume of each tumor [(4/3)x3.14x(radius of tumor in cm)(3)]. The discriminatory ability of the TTV-based staging system and the four current systems, including the Barcelona Clinic Liver Cancer, Cancer of the Liver Italian Program (CLIP), Japan Integrated Staging system, and Tokyo system, was examined by comparing the Akaike information criterion (AIC) using the Cox proportional hazards model. RESULTS A higher TTV correlated well with the decreased survival in HCC patients (p<0.001). Among the 12 TTV-based staging systems, the TTV-Child-Turcotte-Pugh (CTP)-alpha-fetoprotein (AFP) combination provided the lowest AIC value. The TTV-CTP-AFP model consistently showed a better prognostic ability in comparison to the current four staging systems. In 936 HCC patients receiving curative treatment, the TTV-CTP-AFP model provided the second best predictive accuracy following the CLIP score. Alternatively, in 1094 patients undergoing non-curative treatment, the TTV-CTP-AFP model exhibited the smallest AIC value. CONCLUSIONS TTV may be a feasible tumoral prognostic predictor for HCC. In this single-hospital study that included patients with early to advanced cancer stages, the TTV-CTP-AFP model provides the best prognostic ability among 12 TTV-based and currently used staging systems.

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.

Selecting an optimal staging system for hepatocellular carcinoma: comparison of 5 currently used prognostic models.

Selecting an appropriate staging system is crucial to predict the outcome of patients with hepatocellular carcinoma (HCC). The optimal prognostic model for HCC is under intense debate. This study investigated the prognostic ability of the 5 currently used staging systems, Barcelona Clinic Liver Cancer (BCLC), Cancer of the Liver Italian Program (CLIP), Japan Integrated Scoring (JIS) system, tumor‐node‐metastasis (TNM), and Tokyo score, for HCC.

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.

Comparison of radiofrequency ablation and transarterial chemoembolization for hepatocellular carcinoma within the Milan criteria: a propensity score analysis.

Radiofrequency ablation (RFA) and transarterial chemoembolization (TACE) are used to treat hepatocellular carcinoma (HCC). This study was designed to compare the long‐term survival of HCC patients within the Milan criteria who underwent RFA or TACE. In all, 315 RFA patients and 215 TACE patients with HCC within the Milan criteria were analyzed. Propensity scores were generated to select matched patients. For the propensity model, 101 patients were selected from each arm of the study. Independent prognostic predictors were determined with the Cox proportional hazards model. The long‐term survival was significantly better for the RFA group in the univariate survival analysis (P = 0.048). In the Cox model, the following were identified as independent predictors of poor prognosis (TACE was not): age > 69 years (P = 0.026), serum α‐fetoprotein level > 20 ng/mL (P = 0.003), ascites (P < 0.001), Eastern Cooperative Oncology Group performance status ≥ 1 (P = 0.004), total tumor volume (TTV) > 8.2 cm3 (P = 0.020), and vascular invasion (P = 0.023). With similar baseline patient characteristics generated in the propensity score model, there was no significant difference in the long‐term survival rates of the 2 groups of patients. A subgroup analysis showed that among patients with a TTV < 11 cm3, the RFA group had significantly better long‐term survival than the TACE group (P = 0.032). In conclusion, TACE and RFA lead to comparable long‐term survival rates for HCC patients within the Milan criteria. Patients with a smaller TTV (<11 cm3) are likely to benefit more from RFA treatment. Further studies are needed to compare RFA and TACE in patients with early‐stage cancers. Liver Transpl 17:556–566, 2011.

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.

Comparison of the model for end-stage liver disease (MELD), MELD-Na and MELDNa for outcome prediction in patients with acute decompensated hepatitis

BACKGROUND AND AIM The model for end-stage liver disease (MELD) is used to predict the outcome of patients with cirrhosis. Incorporation of serum sodium (Na) into MELD may further increase its prognostic ability. Two Na-containing MELD models, MELD-Na and MELDNa, were proposed to enhance the prognostic ability. This study compared the predictive accuracy of these models for acute decompensated hepatitis. METHODS We investigated the outcome of 182 patients with acute decompensated hepatitis. RESULTS Twenty (11%) patients died at 3 months. The MELD-Na and MELDNa both had significantly higher area under the receiver operating characteristic curve (AUC) in comparison to MELD (MELD-Na: 0.908, MELDNa: 0.895, MELD: 0.823, p=0.004 and 0.001, respectively). Among 96 patients without specific antiviral treatment, the MELD-Na and MELDNa consistently had significantly higher AUC than the MELD (MELD-Na: 0.901, MELDNa: 0.882, MELD: 0.810, p=0.008 and 0.004, respectively). Three independent indicators, pre-existing cirrhosis (odds ratio [OR]: 5.67, 95% confidence interval [CI]: 1.72-18.7), serum albumin<3.7 g/dL (OR: 5.68, 95% CI: 1.18-27.03) and serum sodium (Na)<138 mequiv./L (OR: 10.0, 95% CI: 2.08-47.62), were associated with 3-month mortality. CONCLUSION MELD-Na and MELDNa provide better prognostic accuracy than the MELD for patients with acute decompensated hepatitis. The adequacy of liver reserve determines the outcome of 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.

Diabetes mellitus as an independent prognostic predictor and its association with renal dysfunction in patients with hepatocellular carcinoma.

Background: Patients with hepatocellular carcinoma (HCC) often have coexisting cirrhosis, which may predispose to the development of diabetes mellitus (DM). Diabetic HCC patients may have renal insufficiency and a subsequent worse outcome. This study investigated the interaction between DM, cirrhosis and renal dysfunction and the impact of these factors on HCC.