Using nomogram of the Barcelona Clinic Liver Cancer system for treatment selection in patients with stage C hepatocellular carcinoma.

BACKGROUND: The nomogram of the Barcelona Clinic Liver Cancer (BCLC) for hepatocellular carcinoma (HCC) has been used for outcome prediction. Patients with BCLC stage C HCC often undergo anti-cancer therapy against current treatment guidelines in real world practice. We aimed to use the nomogram to provide guidance on treatment selection for BCLC stage C patients. METHODS: A total of 1317 patients with stage C HCC were retrospectively analyzed and divided into four groups by nomogram points. One-to-one matched pairs between patients receiving different treatments were generated by the propensity score with matching model within these groups. Survival analysis was performed by Kaplan-Meier method with log-rank test. RESULTS: Patients with higher nomogram points were more often treated with targeted or supportive therapies (p <  0.001). Patients receiving targeted or supportive therapies had a decreased survival compared to patients undergoing aggressive treatments (surgical resection, ablation, transarterial chemo-embolization or transplantation) across all four groups (p <  0.001). After matching for baseline differences in the propensity model, patients receiving different treatments had comparable age, gender, etiology of liver disease, tumor burden, severity of cirrhosis and performance status. Survival analyses were re-performed and disclosed that patients with nomogram points < 15 had better overall outcome after aggressive treatments (p <  0.05). For patients with nomogram points > 15, there was no significant difference in survival between patients receiving two different treatment strategies. CONCLUSIONS: The nomogram of BCLC system is a feasible tool to help stage C HCC patients to select primary anti-cancer treatment in pursuance of better overall survival.

Metastasis in patients with hepatocellular carcinoma: Prevalence, determinants, prognostic impact and ability to improve the Barcelona Clinic Liver Cancer system.

BACKGROUND & AIM: Patients with hepatocellular carcinoma and metastasis are classified as advanced or terminal stage by the Barcelona Clinic Liver Cancer system. This study investigates the prevalence, determinants, and prognostic effect of metastasis and its ability to improve the Barcelona Clinic Liver Cancer system. METHODS: A total of 3414 patients were enrolled. The Kaplan-Meier and Cox regression methods were used to determine survival predictors. Akaike information criterion was used to compare the prognostic performance of staging systems. RESULTS: There were 357 (10%) patients having extrahepatic metastasis at the time of diagnosis. Metastases were associated with old age, alcoholism, hepatitis B, poorer liver function, higher α-foetoprotein level and larger tumour burden (all P < .05). Vascular invasion was associated with metastasis regardless of total tumour volume, and higher α-foetoprotein level and multiple tumours were associated with metastasis in patients with smaller tumour volume (all P < .05). Patients with both vascular invasion and metastasis had significantly worse outcome compared to patients with either vascular invasion or metastasis (P < .05). In the Cox proportional model, the co-existence of vascular invasion and metastasis was an independent predictor of decreased survival (P < .05). Re-allocating 181 Barcelona Clinic Liver Cancer stage C patients with both vascular invasion and metastasis into stage D was associated with lower Akaike information criterion, indicating enhanced prognostic power of the Barcelona Clinic Liver Cancer. CONCLUSIONS: Metastasis is not uncommon, and is strongly associated with tumoural factors and poor long-term survival in hepatocellular carcinoma. Modification of the Barcelona Clinic Liver Cancer system based on vascular invasion and metastasis may further improve its predictive accuracy in advanced stage patients.

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

BACKGROUND AND AIM: 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. METHODS: Between 2002 and 2014, consecutive 3182 HCC patients were enrolled to follow up their survival. The area under receiver-operator-characteristic curve (AUC) was calculated to test the discriminatory powers over 1-year, 3-year, and 5-year survival. RESULTS: Significant survival differences were found across all ALBI and PALBI grades (both P < 0.001). The majority (73%) of patients were CTP class A. Within CTP class A, ALBI revealed two prognostic groups while PALBI segregated three prognostic groups. The PABLI grade also identified three different survival groups for patients undergoing resection, ablation, and chemoembolization. Both ALBI and PALBI grade were capable of discerning survival among different HCC stages. The PALBI grade had significantly higher AUC compared with CTP classification and ALBI grade at 1, 3, and 5 years. For CTP class A patients, the PALBI grade was also associated with significantly higher AUC compared with ALBI grade at 1-year and 3-year intervals. The MELD score has the lowest AUC compared with other systems. CONCLUSIONS: Both ALBI and PALBI grade are adequate models to assess liver dysfunction in HCC. The PALBI grade is consistently better in all patients, in patients with minimally decreased liver function, and in patients receiving different aggressive therapies.

Development and Validation of a New Prognostic System for Patients with Hepatocellular Carcinoma.

BACKGROUND: Prognostic assessment in patients with hepatocellular carcinoma (HCC) remains controversial. Using the Italian Liver Cancer (ITA.LI.CA) database as a training set, we sought to develop and validate a new prognostic system for patients with HCC. METHODS AND FINDINGS: Prospective collected databases from Italy (training cohort, n = 3,628; internal validation cohort, n = 1,555) and Taiwan (external validation cohort, n = 2,651) were used to develop the ITA.LI.CA prognostic system. We first defined ITA.LI.CA stages (0, A, B1, B2, B3, C) using only tumor characteristics (largest tumor diameter, number of nodules, intra- and extrahepatic macroscopic vascular invasion, extrahepatic metastases). A parametric multivariable survival model was then used to calculate the relative prognostic value of ITA.LI.CA tumor stage, Eastern Cooperative Oncology Group (ECOG) performance status, Child-Pugh score (CPS), and alpha-fetoprotein (AFP) in predicting individual survival. Based on the model results, an ITA.LI.CA integrated prognostic score (from 0 to 13 points) was constructed, and its prognostic power compared with that of other integrated systems (BCLC, HKLC, MESIAH, CLIP, JIS). Median follow-up was 58 mo for Italian patients (interquartile range, 26-106 mo) and 39 mo for Taiwanese patients (interquartile range, 12-61 mo). The ITA.LI.CA integrated prognostic score showed optimal discrimination and calibration abilities in Italian patients. Observed median survival in the training and internal validation sets was 57 and 61 mo, respectively, in quartile 1 (ITA.LI.CA score ≤ 1), 43 and 38 mo in quartile 2 (ITA.LI.CA score 2-3), 23 and 23 mo in quartile 3 (ITA.LI.CA score 4-5), and 9 and 8 mo in quartile 4 (ITA.LI.CA score > 5). Observed and predicted median survival in the training and internal validation sets largely coincided. Although observed and predicted survival estimations were significantly lower (log-rank test, p < 0.001) in Italian than in Taiwanese patients, the ITA.LI.CA score maintained very high discrimination and calibration features also in the external validation cohort. The concordance index (C index) of the ITA.LI.CA score in the internal and external validation cohorts was 0.71 and 0.78, respectively. The ITA.LI.CA score's prognostic ability was significantly better (p < 0.001) than that of BCLC stage (respective C indexes of 0.64 and 0.73), CLIP score (0.68 and 0.75), JIS stage (0.67 and 0.70), MESIAH score (0.69 and 0.77), and HKLC stage (0.68 and 0.75). The main limitations of this study are its retrospective nature and the intrinsically significant differences between the Taiwanese and Italian groups. CONCLUSIONS: The ITA.LI.CA prognostic system includes both a tumor staging-stratifying patients with HCC into six main stages (0, A, B1, B2, B3, and C)-and a prognostic score-integrating ITA.LI.CA tumor staging, CPS, ECOG performance status, and AFP. The ITA.LI.CA prognostic system shows a strong ability to predict individual survival in European and Asian populations.

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.

Surgical Resection is Better than Transarterial Chemoembolization for Patients with Hepatocellular Carcinoma Beyond the Milan Criteria: A Prognostic Nomogram Study.

BACKGROUND: The clinical outcomes in hepatocellular carcinoma (HCC) patients receiving surgical resection (SR) or transarterial chemoembolization (TACE) are diverse. This study aimed to develop a nomogram to predict individualized survival risk in patients with HCC beyond the Milan criteria undergoing aggressive treatments (SR and TACE). METHODS: A total of 1009 patients were enrolled in the study and randomly grouped into derivation (n = 505) and validation sets (n = 504). The multivariate Cox proportional hazards model was used to select significant prognostic predictors from the derivation set to generate the nomogram. The performance of the nomogram was evaluated by discrimination (concordance index) and calibration tests. RESULTS: Serum albumin <3.8 g/dL, α-fetoprotein ≥400 ng/mL, TACE, vascular invasion, multiple tumors, and tumor volume ≥200 cm(3) were associated with poor survival in the multivariate Cox model (all p < 0.05). A nomogram with a scale of 0-47 was developed with these six variables, and the predicted survival rates at 1 and 3 years were calculated. The derivation set with bootstrapping (B = 100) had a good concordance index of 0.694 [95% confidence interval (CI) 0.68-0.708]. Discrimination test in the validation set provided a concordance index of 0.71 (95 % CI 0.697-0.722), and the calibration plots well-matched the 45-degree line for 1- and 3-year survival prediction. The respective survival for patients undergoing SR or TACE could be predicted based on the nomogram across different risk scores. CONCLUSIONS: This easy-to-use nomogram may accurately predict survival at 1 and 3 years for individual HCC patients beyond the Milan criteria, and provide quantitative survival advantage of SR over TACE.

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

BACKGROUND & AIMS: 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. METHODS: A total of 3179 patients were randomly grouped into derivation (n = 2119) and validation (n = 1060) sets. The multivariate Cox proportional hazards model was used to generate the nomogram from tumour burden, cirrhosis and performance status (PS). The performance of the nomogram was evaluated by concordance indices and calibration tests. RESULTS: Beta coefficients from the Cox model were used to assign nomogram points to different degrees of tumour burden, Child-Turcotte-Pugh classification and PS. A nomogram with a scale of 0-26 was developed and the predicted survival rates at 3 and 5 years were calculated. The derivation set had a concordance index of 0.766 (95% confidence interval [CI]: 0.686-0.838); and the validation set showed a concordance index of 0.775 (95% CI: 0.607-0.909). The calibration plots were close to the 45-degree line for 3- and 5-year survival prediction of BCLC stages 0-C patients in both derivation and validation groups. For BCLC stage D patients, calibration plots in both groups showed deviation from the 45-degree line for 3- and 5-year prediction. CONCLUSIONS: This study provides quantitative evidence to support the prognostic ability of BCLC system. This straightforward and easy-to-use nomogram may accurately predict the survival at 3 and 5 years for individual HCC patient except for BCLC stage D patients.

Survival Benefit of Liver Transplantation Versus Resection for Hepatocellular Carcinoma: Impact of MELD Score.

BACKGROUND: We sought to measure the impact of model for end stage liver disease (MELD) score, tumor staging, and microvascular invasion (MVI) on the relative survival benefit of liver transplantation (LT) versus liver resection (LR) for hepatocellular carcinoma (HCC). METHODS: The study population comprised 1,106 HCC patients with cirrhosis undergoing LR from one Eastern (n = 424) and two Western (n = 682) surgical units. Exclusion criteria were very large (>10 cm) tumors, macrovascular invasion, and metastases. We identified three tumor stages: stage I (within Milan, n = 806), stage II (beyond Milan within Up-to-7, n = 123), and stage III (beyond Milan and Up-to-7, n = 177). Patient survival after LR was compared to that predicted after LT by the Metroticket calculator in relationship with staging, MVI, and MELD score using Monte Carlo simulation. RESULTS: Two hundred eighty-three patients (26 %) with a MELD score of ≥10 had an acceptable 5-year survival after LR of 47 %, while that of patients with a low MELD score was 67 % (p < 0.0001). Mean 5-year LT benefit was -4.50 months (95 % confidence interval [CI] -4.73 to -4.27) for patients with a MELD score of <10, and 0.81 months (95 % CI 0.58 to 1.04) for those with a MELD score of ≥10. MELD score and MVI were the strongest predictors of transplant survival benefit. LT reached a survival benefit, versus LR only in HCC patients with a MELD score of ≥10 and without MVI (3.08 months, 95 % CI 2.78 to 3.39), whatever the tumor stage. CONCLUSIONS: LT proved to be harmful in patients with resectable HCC with a low MELD score (<10) or with aggressive tumors (with MVI). As a result of a shortage of donors, only selected resectable tumors with a MELD score of ≥10 should be considered for transplantation.

Aggressive therapeutic strategies improve the survival of hepatocellular carcinoma patients with performance status 1 or 2: a propensity score analysis.

BACKGROUND: Targeted therapy or chemotherapy is suggested as standard treatment for hepatocellular carcinoma (HCC) patients with performance status (PS) 1-2 according to the Barcelona Clinic Liver Cancer (BCLC) system. The underlying rationales have not been fully studied. METHODS: This study enrolled 2,620 HCC patients. One-to-one matched pairs between HCC patients receiving aggressive anti-HCC treatments (resection, transplantation, ablation, and transarterial chemoembolization) and those receiving targeted therapy or chemotherapy or best supportive care were generated by using the propensity score with a matching model. Survival analysis was performed with the Kaplan-Meier method and the log-rank test. Mortality risk was calculated with the Cox proportional hazards model. RESULTS: Of 793 patients with PS 1-2, 64 % received aggressive anti-HCC treatments against the suggestion of the BCLC system. The patients receiving aggressive anti-HCC treatments had significantly milder cirrhosis, a smaller tumor burden, and better long-term survival than the patients undergoing targeted therapy or chemotherapy or best supportive care (all p < 0.05). With the use of propensity scores, 166 pairs of matched HCC patients with PS 1-2 were selected from different treatment groups. After matching, patients were comparable in age, gender, severity of cirrhosis, tumor burden, and prevalence of diabetes mellitus (all p > 0.05) at baseline. In the propensity score model, patients with PS 1-2 undergoing aggressive anti-HCC treatments had significantly better long-term survival (p < 0.0001). The adjusted hazard ratio of the choice for targeted therapy or chemotherapy or best supportive care to the choice for aggressive anti-HCC treatments was 2.028 (p < 0.0001). CONCLUSIONS: According to the findings, HCC patients with PS 1-2 should consider aggressive anticancer treatments if no contraindication is noted. Adjustment of the BCLC treatment allocation is needed to enhance its prognostic accuracy.

Surgical resection versus transarterial chemoembolization for BCLC stage C hepatocellular carcinoma.

BACKGROUND: Sorafenib is the only recommended treatment for patients with Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC). We aimed to compare surgical resection (SR) and transarterial chemoembolization (TACE) for advanced (BCLC stage C) HCC patients. METHODS: A total of 264 and 389 advanced HCC patients received SR and TACE, respectively. Among them, 163 matched pairs of patients were identified from each treatment arm by propensity score matching analysis to compare long-term survival. RESULTS: Of all patients, the SR group had better liver functional reserve than the TACE group. In the matched propensity model, the baseline characteristics were similar between patients receiving SR and TACE. SR provided significantly better long-term survival than TACE in all patients and in patients selected in the propensity model (both P < 0.001). In the Cox proportional hazards model, patients receiving TACE had a 2.393-fold increased risk of mortality compared with patients receiving SR (95% confidence interval: 1.610-3.556, P < 0.001). CONCLUSIONS: SR provides significantly better long-term survival than TACE in patients with BCLC stage C HCC, and should be an integral part in the management of advanced HCC. Multidisciplinary approaches for these patients and further amendment to the BCLC classification scheme are required.

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.

Active Treatments Prolong the Survival in Patients With Hepatocellular Carcinoma and Performance Status 3 or 4: A Propensity Score Analysis.

GOALS AND BACKGROUNDS: Best supportive care is suggested as the standard treatment for hepatocellular carcinoma (HCC) patients with performance status (PS) 3-4 by the Barcelona Clinic Liver Cancer (BCLC) system. To investigate the rationale of treatment allocation. STUDY: A total of 2660 HCC patients were reviewed. One-to-one matched pairs between PS 3 and 4 patients receiving supportive care and anti-HCC treatments were generated by using the propensity score with matching model. The survival analysis was performed with the Kaplan-Meier method and log-rank test. The hazard ratio was calculated with the Cox proportional hazards model. RESULTS: Among 328 patients with PS 3-4, 38% of patients received active anti-HCC treatments against the BCLC system. Compared with patients undergoing supportive care, patients receiving anti-HCC treatments more often had milder cirrhosis, smaller tumor burden, and lower serum α-fetoprotein levels (all P<0.05). Patients undergoing supportive care had significantly decreased survival (P<0.0001). With propensity scores, 101 pairs of similar HCC patients with PS 3-4 were selected from different treatment groups. They were comparable in age, sex, etiologies of liver disease, severity of cirrhosis, tumor burden, and prevalence of diabetes mellitus (all P>0.05) at baseline. In the matching model, patients with PS 3-4 undergoing supportive care had significantly shortened survival with an adjusted hazard ratio of 4.711 (confidence interval: 3.041-7.297, P<0.0001). CONCLUSIONS: Over one-third of patients with PS 3-4 receive active anti-HCC treatments against the BCLC allocation algorithm in this study. Active anticancer therapies rather than best supportive care should be performed if there is no apparent contraindication.

Impact of renal insufficiency on patients with hepatocellular carcinoma undergoing radiofrequency ablation.

BACKGROUND AND AIM: Renal insufficiency (RI) is commonly seen in patients with hepatocellular carcinoma (HCC). We aimed to investigate the impact of RI on the long-term survival of HCC patients undergoing radiofrequency ablation (RFA) and to determine the optimal staging strategy for these patients. METHODS: RI was defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m(2) . A total of 123 and 344 patients with and without RI undergoing RFA, respectively, were enrolled. A one-to-one propensity score matching analysis with preset caliper width was performed. The prognostic ability of four currently used staging systems was compared by the Akaike information criterion (AIC). RESULTS: HCC patients with RI undergoing RFA were older (P < 0.001) and had significantly different baseline characteristics. Of all patients, RI was significantly associated with a decreased long-term survival (P = 0.03). After matching in the propensity model, the baseline characteristics were similar between patients with (n = 92) and without (n = 92) RI. In the propensity model, RI was not significantly associated with a shortened survival (P = 0.273). In the Cox multivariate analysis, Child-Turcotte-Pugh class B or C was identified as the only independent predictor of poor prognosis. Among patients with RI undergoing RFA, the Taipei Integrated Scoring (TIS) system provided the highest homogeneity and lowest AIC value among the currently used staging systems. CONCLUSIONS: The long-term survival of HCC patients undergoing RFA is not affected by RI. The TIS staging system may provide a better prognostic prediction for HCC patients with RI undergoing RFA.

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

UNLABELLED: 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. CONCLUSION: Performance status is strongly associated with both tumoral and cirrhotic factors and accurately predicts long-term survival in HCC patients. Modification of the BCLC system based on performance status may further enhance its prognostic ability in patients with early to advanced cancer stage.

Survival advantage of radiofrequency ablation over transarterial chemoembolization for patients with hepatocellular carcinoma and good performance status within the Milan criteria.

BACKGROUND: Performance status is closely linked with survival in patients with hepatocellular carcinoma (HCC). We evaluated the impact of performance status on patients with small HCC receiving radiofrequency ablation (RFA) versus transarterial chemoembolization (TACE). METHODS: A total of 424 and 282 patients within the Milan criteria undergoing RFA and TACE, respectively, were analyzed. Patients were classified as performance status 0 (n = 516) and performance status ≥1 (n = 190) groups. A propensity-score matching analysis with preset caliper width was used. A total of 167 and 68 matched pairs were selected from patients with a performance status of 0 and ≥1, respectively. RESULTS: Radiofrequency ablation provided significantly better long-term survival than TACE for patients within the Milan criteria (p < 0.01). After being stratified by performance status and matched in the propensity model, the baseline characteristics were similar between the RFA and TACE groups for patients with a performance status of 0 or ≥1. RFA provided significantly better long-term survival than TACE in patients with a performance status of 0 in the propensity model (p < 0.05); TACE was significantly associated with 1.784-fold increased risk of mortality (95 % confidence interval 1.075-2.506) by using the Cox proportional hazards model. TACE was not a significant prognostic predictor in patients with a performance status ≥1 in the propensity model. CONCLUSIONS: For HCC patients within the Milan criteria with a performance status of 0, RFA provides better long-term survival than TACE. RFA should be considered a priority treatment in inoperable HCC patients within the Milan criteria. Performance status is a feasible surrogate marker to enhance treatment allocation.

Surgical resection versus transarterial chemoembolization for hepatocellular carcinoma with portal vein tumor thrombosis: a propensity score analysis.

BACKGROUND: The long-term survival in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) who received surgical resection (SR) or transarterial chemoembolization (TACE) remains unclear. We compared the efficacy of SR and TACE by using a propensity score analysis. METHODS: A total of 247 and 181 HCC patients with PVTT undergoing SR and TACE, respectively, were evaluated. One hundred eight pairs of matched patients were selected from each treatment arm by using a propensity score analysis. RESULTS: Of all patients, the estimated 1-, 3-, and 5-year survival rates of patients receiving SR and TACE were 85 versus 60 %, 68 versus 42 %, and 61 versus 33 %, respectively (p < 0.001). Patients selected for SR were significantly younger and had better liver functional reserve, performance status, and smaller tumor burden. In the propensity model, the survival benefit of SR remained significant. The estimated 1-, 3-, and 5-year survival rates of patients receiving SR and TACE were 84 versus 71 %, 69 versus 50 %, and 59 versus 35 %, respectively (p = 0.004). The two groups of patients in the propensity score analysis were similar in baseline characteristics. In the Cox proportional hazards model, patients receiving TACE had a 2.044-fold increased risk of mortality compared with patients receiving SR (95 % confidence interval: 1.284-3.252, p = 0.003). CONCLUSIONS: For either unselected patients or patients in the propensity model, SR provides significantly better long-term survival than TACE. SR should be considered as a priority treatment in this subgroup of HCC patients.

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 α-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 α-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.

Performance status enhances the selection of treatment for patients with hepatocellular carcinoma within the milan criteria.

BACKGROUND: Performance status (PS) is closely linked with survival in patients with hepatocellular carcinoma (HCC). We investigated its impact on treatment strategy for small HCC(s). METHODS: A total of 360 and 362 HCC patients within the Milan criteria undergoing surgical resection (SR) and radiofrequency ablation (RFA), respectively, were prospectively enrolled. Patients were classified into PS 0 (n = 558) and PS ≥1 (n = 164) groups. Propensity score analysis was performed, and 168 and 35 matched pairs were selected from patients with PS 0 and ≥1, respectively. RESULTS: The SR group was younger and had a higher male-to-female ratio, higher prevalence of hepatitis B, lower prevalence of hepatitis C, better PS, better liver functional reserve, and larger tumor burden than the RFA group (all p < 0.05). Among patients with PS 0, the SR group was consistently younger, less cirrhotic, and had larger tumor burden (all p < 0.05). The long-term survival was comparable between SR and RFA group in patients with PS 0. After propensity score matching, SR provided significantly better long-term survival than RFA for patients within the Milan criteria classified as PS 0 (p = 0.016); the Cox proportional hazards model showed consistent results. There was no significant difference of overall survival between the SR and RFA group in patients with PS ≥1 before or after propensity score matching (both p > 0.05). CONCLUSIONS: For HCC patients within the Milan criteria and classified as PS 0, SR provides a better long-term survival compared with RFA. Performance status may enhance treatment selection and stratify the risk of survival in these patients.

Hepatocellular carcinoma in uremic patients: is there evidence for an increased risk of mortality?

BACKGROUND AND AIM: The clinical aspects of patients with hepatocellular carcinoma (HCC) undergoing maintenance dialysis are largely unknown. We aimed to investigate the long-term survival and prognostic determinants of dialysis patients with HCC. METHODS: A total of 2502 HCC patients, including 30 dialysis patients and 90 age, sex, and treatment-matched controls were retrospectively analyzed. RESULTS: Dialysis patients more often had dual viral hepatitis B and C, lower serum α-fetoprotein level, worse performance status, higher model for end-stage liver disease (MELD) score than non-dialysis patients and matched controls (P all < 0.05). There was no significant difference in long-term survival between dialysis and non-dialysis patients and matched controls (P = 0.684 and 0.373, respectively). In the Cox proportional hazards model, duration of dialysis < 40 months (hazard ratio [HR]: 6.67, P = 0.019) and ascites (HR: 5.275, P = 0.019) were independent predictors of poor prognosis for dialysis patients with HCC. Survival analysis disclosed that the Child-Turcotte-Pugh (CTP) provided a better prognostic ability than the MELD system. Among the four currently used staging systems, the Japan Integrated Scoring (JIS) system was a more accurate prognostic model for dialysis patients; a JIS score ≥ 2 significantly predicted a worse survival (P = 0.024). CONCLUSIONS: Patients with HCC undergoing maintenance dialysis do not have a worse long-term survival. A longer duration of dialysis and absence of ascites formation are associated with a better outcome in dialysis patients. The CTP classification is a more feasible prognostic marker to indicate the severity of cirrhosis, and the JIS system may be a better staging model for outcome prediction.