Prognostic factors for survival in patients with hepatocellular carcinoma after radiofrequency ablation]

BACKGROUND/AIMS: Currently there is no consensus on which staging system is the best in predicting the survival of patients with hepatocellular carcinoma (HCC). The aim of this study was to identify independent factors to predict survival and to compare 4 available prognostic staging systems in patients with early HCC after radiofrequency ablation. METHODS: We retrospectively studied 100 Korean patients with early HCC. Prognostic factors for survival were analysed by univariate and multivariate analysis using the Kaplan-Meier method and Cox proportional hazard regression models. Okuda, Cancer of the Liver Italian Program (CLIP), TNM and Japanese integrated staging score (JIS score) were evaluated before the treatments. RESULTS: Overall survival rates of 12, 24 and 36 months were 89%, 76%, and 64% respectively and the mean survival duration was 45 months. Multivariable analysis showed that albumin, total bilirubin and size of tumor were independent prognostic factors. Multivariate analysis showed that TNM and JIS score staging systems were significant staging systems for the prediction of prognosis. CONCLUSIONS: Both TNM and JIS score are more effective than the Okuda and CLIP staging systems in stratifying patients into different risk groups with early HCC. However, JIS score gives better prediction of prognosis in patients with HCC after radiofrequency ablation.     

Modified Japan Integrated Staging is currently the best available staging system for hepatocellular carcinoma patients who have undergone hepatectomy

Background We previously reported the effectiveness of the modified Cancer of the Liver Italian Program (CLIP) score in hepatocellular carcinoma (HCC) staging. To determine the best predictive staging system for HCC patients, we conducted a comparative analysis of prognosis using multivariate analysis in 230 Japanese HCC patients following hepatic resection. Methods We compared overall survival as predicted by different staging systems: the tumor node metastasis (TNM) system by the Liver Cancer Study Group of Japan, the Japan Integrated Staging (JIS) score (Japanese TNM and Child-Pugh classification), the modified JIS score using liver damage grade, the CLIP score, and our modified CLIP score using protein induced by vitamin K absence or the antagonist II (PIVKA-II). Results By a univariate analysis the PIVKA-II level (cut-off level, 400 mAU/ml) was significantly associated with patient survival (P = 0.031); however, alpha-fetoprotein level was not related to survival. Liver damage grade was significantly associated with patient survival (P = 0.039), although Child-Pugh classification was not related to survival. Univariate analysis showed that prediction of survival, according to disease stage, was better with the modified JIS score than with the TNM system, CLIP, modified CLIP, or JIS score. Multivariate analysis showed the modified JIS score showed the best ability to predict overall survival according to disease stage (Hazard ratio, 1.77; P = 0.002), and its Akaike information criteria statistic was the lowest (634.3). Conclusions The modified JIS score, a staging system that combines tumor factors and hepatic function, is a better predictor of prognosis than other systems in HCC patients who have undergone hepatic resection.     

Comparison of four current staging systems for Chinese patients with hepatocellular carcinoma undergoing curative resection: Okuda, CLIP, TNM and CUPI

Background and Aim: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. However, there is no general consensus as to which staging system is the most reliable for predicting the survival of patients with HCC. The aims of this study were to compare commonly‐used staging systems in a cohort of Chinese HCC patients undergoing curative resection. Methods: From January 1991 to June 2002, 234 Chinese patients undergoing curative resection for HCC from one medical center were evaluated. All patients were classified by the Okuda, Cancer of the Liver Italian Program (CLIP), tumor node metastasis (TNM) (6th edition) and the Chinese University Prognostic Index (CUPI) staging systems. Survival curves were calculated using the Kaplan–Meier method and were examined using log‐rank testing. The overall predictive power for patient survival with each staging system was evaluated by the area under the receiver operating characteristic (ROC) curve. Results: The overall median survival of the entire cohort was 24.9 months (95% confidence interval (CI) 18.15–31.65 months) and the estimated survival rates at 1, 3, and 5 years were 69.66% ± 3.01%, 41.02% ± 3.31%, and 29.08% ± 3.55%, respectively. In our patient cohort, the log‐rank test demonstrated that the TNM and Okuda staging systems gave better results than the other staging systems in the prognosis stratification. The prognostic predictive powers of the TNM staging for survival, evaluated by ROC curve areas, was also superior. Conclusions: For HCC patients undergoing curative resection, the TNM staging system (6th edition) proved the best for prognostic stratification and prognosis prediction.     

Prognostic staging system for hepatocellular carcinoma (CLIP score): its value and limitations,and a proposal for a new staging system,the Japan Integrated Staging Score (JIS score)

A clinical staging system for cancer patients provides guidance for patient assessment and making therapeutic decisions. It is useful in deciding whether to treat a patient aggressively, and in avoiding the overtreatment of patients who would not tolerate the treatment or patients whose life expectancy rules out any chance of treatment. Clinical staging is also an essential tool for comparison between groups in therapeutic trials and for comparison between different studies. The current classifications most commonly used for hepatocellular carcinoma (HCC) are the Okuda stages, the Child-Pugh staging system, tumor node metastasis (TNM) staging, and the Cancer of the Liver Italian Program (CLIP) score. Among these, the CLIP score is currently the most commonly used integrated staging score, including both tumor stage and liver disease stage. Although the CLIP score has been well validated by many authors in terms of its prognostic value in HCC patients, this score has some problems and limitations when applied to currently diagnosed HCC patients, who are diagnosed in the early stage of disease. First, the CLIP score can discriminate score 0- to 3-patient populations, but it is not able to discriminate score 4- to 6-patient groups. Second, the definition of tumor morphology in the best prognostic group is too advanced, i.e., uninodular and a tumor extent of less than 50% of the liver. As a result, the prognosis of the CLIP system best prognostic group is not so good. In other words, this system cannot identify the best prognostic group who would benefit from curative and aggressive treatment. Third, nearly 80% of the patient population is classified as having a CLIP score of 0–2, as confirmed by many studies, which shows poor stratification ability. In contrast, a new staging system based on the Liver Cancer Study Group of Japan (LCSGJ), the Japan Integrated Staging (JIS) score is currently proposed in Japan. This staging system combines Child-Pugh grade (grade A, score 0; grade B, score 1; grade C, score 2) and TNM staging by the LCSGJ criteria (stage I, score 0; stage II, score 1; stage III, score 2; stage IV, score 3). The stratification ability of the JIS scoring system is much better than that of the CLIP scoring system. The JIS scoring system also performed better than the CLIP scoring system in selecting the best prognostic patient group. The cumulative 10-year survival rates of the best prognostic groups in the CLIP staging system (CLIP score 0) and JIS staging system (JIS score 0) were 23% and 65%, respectively (P < 0.01). All scoring systems arise as a compromise between simplicity and discriminatory ability. We confirmed that the JIS score increases predictive efficacy, while remaining simple compared with the CLIP score. Because the JIS score is quite easily obtained and is objective, we strongly propose it for widespread use as a prognostic staging system for HCC in clinical practice. Received: December 19, 2002 / Accepted: December 19, 2002 Reprint requests to: M. Kudo     

Comparison of seven prognostic staging systems in patients who undergo hepatectomy for hepatocellular carcinoma

BACKGROUND/AIMS: Various staging systems containing both the tumor and liver function factors for hepatocellular carcinoma (HCC) have been proposed. The aim of this study was to evaluate the appropriate staging system in patients received hepatic resection for HCC. METHODOLOGY: The prognosis of the 235 patients who had undergone hepatectomy in these 15 years were analyzed according to the 7 staging systems, the Cancer of the Liver Italian Program (CLIP) score, the Barcelona Clinic Liver Cancer (BCLC) staging, the Groupe d'Etude et de Traitment du Carcinome Hépatocellulaire (GETCH) classification, the Chinese University Prognostic Index (CUPI) grade, the Japan Integrated Staging (JIS) score, modified JIS (mJIS) score, and Tokyo score. The capabilities to differentiate the postoperative survival between the neighboring score in each staging system were examined. Statistical analyses of the log-rank test, linear trend test, likelihood ratio (LR) test, Akaike Information Criteria (AIC), and Harrels' c-index were used. RESULTS: The patients were widely distributed in the most of the staging system with the exceptions of GETCH classification and CUPI grade where almost all patients were classified to only the two groups. CLIP, JIS, mJIS, and Tokyo scores significantly differentiated the postoperative survival rate between 2 or 3 neighboring scores, whereas other staging systems only did between one. Statistical evaluations of prognostic stratification by the LR test, AIC, and Harrels' c-index showed that the JIS score system was the best among the 7 staging systems. CONCLUSIONS: JIS score is the best staging system for HCC in patients who undergo hepatectomy.     

Discrimination value of the new western prognostic system (CLIP score) for hepatocellular carcinoma in 662 Japanese patients. Cancer of the Liver Italian Program

To reliably estimate the prognoses of patients with hepatocellular carcinoma (HCC), both liver function and tumor-related factors should be accounted for. However, there are few worldwide staging systems that assess prognostic value in the context of selecting individual patients for randomized stratification in therapeutic and clinical trials. We investigated the value of known prognostic systems and verified the usefulness of the new scoring system proposed by the Cancer of the Liver Italian Program (CLIP), as determined from 662 Japanese patients. A retrospective analysis of the HCC diagnoses at 4 Japanese institutions from 1990 and 1998 was performed. Overall survival was the only end point used in the analysis. Discriminatory ability and predictive power of the CLIP score were compared with those of Okuda stage and AJCC TNM stage. Compared with the Okuda and AJCC staging systems, the CLIP score's enhanced discriminatory capacity, which was tested by the linear trend test and Harrels' c-index, revealed a class of patients with an impressively more favorable prognosis and another class with a relatively shorter life expectancy. Moreover, the likelihood ratio test showed that the CLIP score had additional homogeneity of survival within each score above that of the Okuda stage or the AJCC stage. This was true for 3 subgroups of patients who received surgery, transcatheter arterial chemoembolizations, and percutaneous ethanol injections. Collectively, these findings indicate that the CLIP score has the highest stratification ability with regard to prognosis in patients with HCC. The CLIP score could be used internationally to stratify randomization groups in therapeutic and clinical trials.     

Prospective validation of the Eastern Staging in predicting survival after surgical resection for patients with hepatocellular carcinoma: a multicenter study from China

BackgroundThe Eastern Staging System, which was specially developed for patients undergoing surgical resection for hepatocellular carcinoma (HCC), has been proposed for more than ten years. To prospectively validate the predictive accuracy of the Eastern staging on long-term survival after HCC resection.MethodsPatients who underwent hepatectomy for HCC from 2011 to 2020 at 10 Chinese hospitals were identified from a prospectively collected database. The survival predictive accuracy was evaluated and compared between the Eastern Staging with six other staging systems, including the JIS, BCLC, Okuda, CLIP, 8th AJCC TNM, and HKLC staging.ResultsAmong 2365 patients, the 1-, 3-, and 5-year overall survival rates were 84.2%, 64.5%, and 52.6%, respectively. Among these seven staging systems, the Eastern staging was associated with the best monotonicity of gradients (linear trend χ²: 408.5) and homogeneity (likelihood ratio χ²: 447.3), and the highest discriminatory ability (the areas under curves for 1-, 3-, and 5-year mortality: 0.776, 0.787, and 0.768, respectively). In addition, the Eastern staging was the most informative staging system in predicting survival (Akaike information criterion: 2982.33).ConclusionUsing a large multicenter prospectively collected database, the Eastern Staging was found to show the best predictive accuracy on long-term overall survival in patients with resectable HCC than the other 6 commonly-used staging systems.     

Prognosis of hepatocellular carcinoma in anti-HCV positive cirrhotic patients: a single-centre comparison amongst four different staging systems

BACKGROUND: Epidemiological studies have foreseen an increase in the incidence of hepatocellular carcinoma (HCC) in the near future and it is estimated that this trend will mostly affect hepatitis C virus (HCV) positive cirrhotic patients. Therefore, accuracy of HCC staging is an important clinical issue. AIM: To investigate the prognostic usefulness of a series of newly proposed HCC prognostic systems such as the Cancer of the Liver Italian Program (CLIP) score, the Groupe d'Etude et de Traitement du Carcinome Hépatocellulaire (GRETCH) model and the Barcelona Clinic Liver Cancer (BCLC) staging classification when compared with the usefulness of a known staging system such as the Okuda staging system in a group of anti-HCV positive cirrhotic patients with HCC seen at a single centre. METHODS: Okuda stage, CLIP score, GRETCH model and BCLC stages were retrospectively computed in 81 anti-HCV positive cirrhotic patients with HCC. We evaluated and compared the ability of these methods to assess survival prognosis. RESULTS: As of December 2001, 51 patients had died and overall median survival was 18 months. All the staging systems were able to identify various patient subgroups with different survival. The CLIP score, the GRETCH model and the BCLC staging classification were better at characterizing the 1-year prognosis of the patients when compared with the Okuda staging system, whilst the 3-year prognostic evaluation was improved only by using the CLIP score or the BCLC staging classification. CONCLUSIONS: The prognostic value and usefulness of the CLIP score, the GRETCH model and the BCLC staging classification was reproduced in a single-centre analysis of anti-HCV positive HCC cirrhotic patients. These scores provided a prognostic assessment of our patients which is superior to what was obtained by the Okuda staging system.     

肝细胞癌四种临床分期系统预后判断和治疗指导价值的比较

目的 比较4个分期系统[巴塞罗那临床肝癌分期标准(BCLC)、日本综合分期积分(JIS)、意大利肝癌评分(CLIP)和国内分期]对中国肝癌患者预后判断和对治疗方案选择的指导意义.方法 回顾性分析2001年至2002年复旦大学附属中山医院收治的861例初发肝细胞癌患者的临床资料,分别按4个分期系统分期或评分,比较各期患者的生存情况以及不同治疗方案对其生存的影响.结果 在判断预后方面,BCLC、JIS和国内分期系统的各分期间生存率差异均有统计学意义;而在CLIP分期的一些评分间的生存率差异无统计学意义.在指导治疗方面,BCLC C期,CLIP 3、4分以及国内分期ⅢA期的患者接受手术治疗与接受肝动脉化学治疗栓塞(TACE)和(或)肝动脉栓塞(TAE)治疗的生存率差异无统计学意义;而比这些更早期的患者接受手术治疗的生存率优于接受TACE和(或)TAE治疗的生存率.结论 BCLC、JIS和国内分期系统在判断预后方面适用于中国患者;但仅国内分期和BCLC分期同时兼备了判断预后和指导治疗两方面的作用.     

A new classification for hepatocellular carcinoma with portal vein tumor thrombus

Background/purpose

We aimed to correlate the survival of patients with hepatocellular carcinoma (HCC) with macroscopic portal vein tumor thrombus (PVTT) who underwent partial hepatectomy with or without portal thrombectomy with our PVTT classification. Currently, different staging systems for HCC are widely used in clinical practice. However, they lack the refinement in giving prognosis and guiding surgical treatment once macroscopic PVTT is present.

Methods

A retrospective study was carried out, in a single tertiary center, from January 2001 to December 2004 on 441 patients who underwent partial hepatectomy with or without portal thrombectomy for HCC with macroscopic PVTT. Overall survival was examined to determine whether it was correlated with our PVTT classification, and with the TNM staging, Cancer of the Liver Italian Program (CLIP) scoring system, and the Japan Integrated Staging (JIS) scoring system.

Results

With our PVTT classification, the numbers (percentages) of patients with types I, II, III, and IV PVTT were 144 (32.7%), 189 (42.9%), 86 (19.5%), and 22 (5.0%), respectively. The corresponding 1-, 2-, and 3-year overall survival rates for types I to IV PVTT were 54.8, 33.9, and 26.7%; 36.4, 24.9, and 16.9%; 25.9, 12.9, and 3.7%; and 11.1, 0, and 0%, respectively (log-rank of the survival curves P?<?0.0001). Using the TNM system, the majority of patients were classified as stage III (n?=?379 or 85.9%). Similarly, the majority of patients (n?=?388 or 88.0%) were classified as having CLIP scores of 2 (n?=?143, or 32.4%), 3 (n?=?171, or 38.8%), and 4 (n?=?74, or 16.8%). The 1-, 2-, and 3-year overall survivals for these 3 CLIP scores were very similar. Using the JIS score, the majority of patients (n?=?372 or 84.4%) were classified with a JIS score of 2. The 1-, 2-, and 3-year overall survivals of patients with a JIS score of 2 were worse than those of the patients with a JIS score of 1 (this was expected) as well as being worse than those with a JIS score of 3 (this was unexpected). Thus, the latter 3 systems of classification were not refined enough, and they were inadequate for stratifying HCC with macroscopic PVTT treated with partial hepatectomy with or without thrombectomy.

Conclusions

In patients with HCC with macroscopic PVTT treated by partial hepatectomy with or without thrombectomy, our PVTT classification better stratified and predicted prognosis than the TNM staging, CLIP scoring system, and JIS scoring system, which were unrefined and inadequate for this group of patients.     

Staging of hepatocellular carcinoma: assessment of the CLIP,Okuda, and Child-Pugh staging systems in a cohort of 257 patients in Toronto

BACKGROUND: A new staging system for hepatocellular carcinoma (HCC) has recently been reported from Italy (CLIP classification). It combines Child-Pugh staging with tumour criteria: tumour morphology, portal invasion, and alpha fetoprotein levels. AIMS: To validate the use of the CLIP staging in a cohort of HCC patients and compare it with Okuda staging. PATIENTS AND METHODS: A retrospective analysis of patients with HCC diagnosed in the Toronto General Hospital between October 1994 and December 1998. RESULTS: A total of 313 patients were identified; 19 patient with insufficient data and 37 transplant patients were excluded. Hence 257 patients in whom complete data for clinical staging were available were included in the study. The median survival of the cohort was 22.8 months. The CLIP stage 0 group (23.1% of the cohort) and the Okuda stage 1 group (50.7% of the cohort) had a five year survival rate of 67% and 35%, respectively (p<0.02). The CLIP stage 0 criteria more accurately defined patients with a good prognosis. The Okuda classification failed to identify two thirds of the 37 patients with a poor prognosis, who were identified by the CLIP criteria. Patients with a CLIP score > or =4 shared a very poor prognosis (median survival 1-3 months). Further classification above stage 4 was unnecessary. SUMMARY: The CLIP classification for HCC is easy to implement and more accurate than the Okuda classification. Our cohort was different from the CLIP cohort (more hepatitis B) but the results were still consistent.     

Comparison of the usefulness of three staging systems for hepatocellular carcinoma (CLIP, BCLC, and JIS) in Japan

OBJECTIVES: We retrospectively compared the usefulness of three different staging systems for hepatocellular carcinoma (HCC), the Cancer of the Liver Italian Program (CLIP) scoring system, the Barcelona Clinic Liver Cancer (BCLC) classification system, and the Japan Integrated Staging (JIS) system, in terms of patient distribution and survival rates. METHODS: Subjects were 1,508 patients diagnosed as having initial HCC during the period of 1976-2003. The disease was staged in all patients by means of the three staging systems, and the distribution of patients across stages and associated survival rates were compared between systems. In addition, comparisons were made on the basis of the time of diagnosis: 1976-1990 (n = 497) and 1991-2003 (n = 1,011). RESULTS: Patients were evenly distributed across stages within each staging system, and survival rates differed between stages except for BCLC C and D. During the period 1991-2003, when HCCs were smaller at diagnosis, JIS system is in particular yielded even distribution of patient across stages and marked differences in survival rates. CONCLUSIONS: Overall, the CLIP and the JIS scoring systems proved to be suitable for patients in Japan with HCC. The CLIP staging systems proved to be more suitable before 1991. In contrast, the JIS system was the most suitable after 1990, when early detection and early treatment of HCC became common. The JIS system is, therefore, the appropriate system in this era of early detection and treatment of HCC.     

An independent evaluation of modern prognostic scores in a central European cohort of 120 patients with hepatocellular carcinoma

BACKGROUND AND OBJECTIVES: Hepatocellular carcinoma (HCC) is a common cancer worldwide. As prognosis of HCC patients depends not only on tumour extension but also on liver function, TNM staging of HCC is of limited value. The Okuda score incorporating the variables of liver function and tumour extension is used widely. However, among patients with an intermediate Okuda score, survival varies considerably. Several newer scores promise to perform better than the Okuda score in stratifying HCC patients. We therefore tested the ability of several newer scores to predict survival in comparison to the Okuda score in a European cohort of HCC patients. PATIENTS AND METHODS: A total of 120 patients with sufficient follow-up data were identified retrospectively among the 130 patients with HCC first seen between 1997 and 2000 in our department. Child-Pugh score, Okuda score, Vienna survival model for HCC (VISUM-HCC) score, Chevret score, Barcelona clinic liver cancer (BCLC) classification and cancer of the liver Italian programme (CLIP) score were calculated. Survival analysis was performed for all eligible patients stratified according to each scoring system. Receiver operating characteristics analysis was performed using six months survival as the outcome measure. Univariate and stepwise logistic regression analyses were performed to identify prognostic factors. RESULTS: Survival times of HCC patients grouped according to all scores were significantly different. All scores performed similarly to the Okuda score in the receiver operating characteristic analysis. Prognostic factors for survival were albumin concentration and the presence of portal obstruction. CONCLUSION: In our central European cohort, there was no advantage of using the newer scores instead of the Okuda score.     

Prospective validation of the CLIP score: a new prognostic system for patients with cirrhosis and hepatocellular carcinoma. The Cancer of the Liver Italian Program (CLIP) Investigators

Prognosis of patients with cirrhosis and hepatocellular carcinoma (HCC) depends on both residual liver function and tumor extension. The CLIP score includes Child-Pugh stage, tumor morphology and extension, serum alfa-fetoprotein (AFP) levels, and portal vein thrombosis. We externally validated the CLIP score and compared its discriminatory ability and predictive power with that of the Okuda staging system in 196 patients with cirrhosis and HCC prospectively enrolled in a randomized trial. No significant associations were found between the CLIP score and the age, sex, and pattern of viral infection. There was a strong correlation between the CLIP score and the Okuda stage. As of June 1999, 150 patients (76.5%) had died. Median survival time was 11 months, overall, and it was 36, 22, 9, 7, and 3 months for CLIP categories 0, 1, 2, 3, and 4 to 6, respectively. In multivariate analysis, the CLIP score had additional explanatory power above that of the Okuda stage. This was true for both patients treated with locoregional therapy or not. A quantitative estimation of 2-year survival predictive power showed that the CLIP score explained 37% of survival variability, compared with 21% explained by Okuda stage. In conclusion, the CLIP score, compared with the Okuda staging system, gives more accurate prognostic information, is statistically more efficient, and has a greater survival predictive power. It could be useful in treatment planning by improving baseline prognostic evaluation of patients with HCC, and could be used in prospective therapeutic trials as a stratification variable, reducing the variability of results owing to patient selection.     

Validation of a new prognostic staging system for hepatocellular carcinoma: the JIS score compared with the CLIP score

The Japan Integrated Staging score (JIS score), which combines the Child-Turcotte-Pugh classification and tumor-node-metastasis staging, has been proposed as a better prognostic staging system for hepatocellular carcinoma (HCC) than the Cancer of the Liver Italian Program (CLIP) scoring system. In this study, validation was performed among a larger patient population. A total of 4,525 consecutive patients with HCC who had been diagnosed at five institutions were included. Stratification ability, prognostic predictive power, and reproducibility were analyzed and compared with results from the CLIP scoring system. Only 45% (1,951 of 4,525) of all patients were categorized as early stage HCC according to JIS score (0 or 1), whereas 63% (2,878 of 4,525) of the patients were categorized as having a CLIP score of 0 or 1. Significant differences in survival curves were not observed among CLIP scores 3 to 6. In contrast, survival curves showed significant differences among all the JIS scores. The same JIS scoring subgroups showed a similar prognosis, and good internal reproducibility was observed in each of the institutions. Multivariate analysis of the prognosis in all 4,525 patients proved the JIS score to be the best prognostic factor. Furthermore, the Akaike information criteria proved that the JIS scoring system was statistically a better model for predicting outcome than the CLIP scoring system. In conclusion, the stratification ability and prognostic predictive power of the JIS score were much better than that of the CLIP score and were simple to obtain and remember.     

Comparative performances of staging systems for early hepatocellular carcinoma

Background:

Several staging systems for patients with hepatocellular carcinoma (HCC) have been proposed, but studies of their prognostic accuracy have yielded conflicting conclusions. Stratifying patients with early HCC is of particular interest because these patients may derive the greatest benefit from intervention, yet no studies have evaluated the comparative performances of staging systems in patients with early HCC.

Methods:

A retrospective cohort study was performed using data on 379 patients who underwent liver resection or liver transplantation for HCC at six major hepatobiliary centres in the USA and Europe. The staging systems evaluated were: the Okuda staging system, the International Hepato-Pancreato-Biliary Association (IHPBA) staging system, the Cancer of the Liver Italian Programme (CLIP) score, the Barcelona Clinic Liver Cancer (BCLC) staging system, the Japanese Integrated Staging (JIS) score and the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) staging system, 6th edition. A recently proposed early HCC prognostic score was also evaluated. The discriminative abilities of the staging systems were evaluated using Cox proportional hazards models and the bootstrap-corrected concordance index (c).

Results:

Overall survival of the cohort was 74% at 3 years and 52% at 5 years, with a median survival of 62 months. Most systems demonstrated poor discriminatory ability (P > 0.05 on Cox proportional hazards analysis, c≈ 0.5). However, the AJCC/UICC system clearly stratified patients (P < 0.001, c= 0.59), albeit only into two groups. The early HCC prognostic score also clearly stratified patients (P < 0.001, c= 0.60) and identified three distinct prognostic groups.

Discussion:

The early HCC prognostic score is superior to the AJCC/UICC staging system (6th edition) for predicting the survival of patients with early HCC after liver resection or liver transplantation. Other major HCC staging systems perform poorly in patients with early HCC.     

Prognostic factors for survival in patients with early-intermediate hepatocellular carcinoma undergoing non-surgical therapy: comparison of Okuda, CLIP, and BCLC staging systems in a single Italian centre

BACKGROUND: Several prognostic models have been developed to stage hepatocellular carcinoma (HCC) but there is no general consensus on which is the most reliable. We compared three prognostic indices (Okuda, CLIP, and BCLC scoring systems) in a large series of cirrhotic patients with HCC undergoing non-surgical treatment in terms of their ability to classify patients into different risk groups METHODS: We retrospectively studied 268 Italian patients with HCC. A total of 146 patients were treated with ablation, 132 with percutaneous ethanol injection, and 14 with radiofrequency ablation; 103 underwent transcatheter arterial chemoembolisation and 19 had supportive care alone. Factors determining survival were analysed by univariate and multivariate analysis using the Kaplan-Meier method and Cox proportional hazard regression models. Okuda, CLIP, and BCLC scores evaluated before treatment were applied. RESULTS: Median survival was 25.7 months. In a multivariate analysis, portal vein thrombosis, alpha fetoprotein, total bilirubin, and tumour size were significant predictors of survival. Okuda, CLIP, and BCLC scores were all able to predict survival (p<0.001). They identified two, four, and six risk groups, respectively, with a median survival ranging from 27 to 19 months for Okuda, 30 to 5 months for CLIP, and 43 to 7 months for BCLC. CONCLUSIONS: Both CLIP and BCLC scores were more effective than the Okuda score in stratifying patients into different risk groups with early-intermediate HCC. However, the BCLC scoring system gave a better prediction of prognosis in patients with disease diagnosis at a very early stage.     

Staging systems in hepatocellular carcinoma

Staging systems are key to predict the prognosis of patients with cancer, to stratify the patients according to prognostic variables in the setting of clinical trials, to allow the exchange of information among researchers, and finally to guide the therapeutic approach. The current knowledge of the disease, however, prevents recommendation of a staging system that can be used world-wide. The conventional staging systems for hepatocellular carcinoma (HCC), such as the Okuda stage or the TNM stage have shown important limitations in classifying patients. Several new systems have been proposed recently, and only three of them have been validated at this point. The BCLC staging classification links the stage of the disease to a specific treatment strategy. The JIS score has been proposed and used in Japan, although it needs Western validation. The CLIP score is used in patients with advanced tumors. Several reasons explain the difficulty in identifying a world-wide system. First, HCC is a complex neoplasm inserted on a pre-neoplastic cirrhotic liver, and thus variables of both diseases leading to death should be taken into account. Second, the disease is very heterogeneous around the world, and this reflects different underlying epidemiological backgrounds and risk factors. Third, HCC is the sole cancer treated by transplantation in a small proportion of patients. Fourth, only around 20% of the cases are currently treated by surgery, thus precluding the wide use of pathology-based systems, such as TNM. Finally, the potential relevance of a molecular signature identified in terms of outcome prediction is unknown, and further research is needed to obtain this valuable biological information that may aid in classifying the patients.     

Prospective validation of the Chinese University Prognostic Index and comparison with other staging systems for hepatocellular carcinoma in an Asian population

Background and Aim: Hepatitis B viral (HBV) infection is the predominant etiology of hepatocellular carcinoma (HCC) in Asia. Our group previously reported a staging system known as the Chinese University Prognostic Index (CUPI) for HCC populations of which HBV infection is the predominant etiology. This study aims to validate CUPI and compare with other published staging systems. Methods: We analyzed a prospective cohort of patients with newly diagnosed HCC from 2003 to 2005. All patients were staged with CUPI, Barcelona Clinic Liver Cancer Classification (BCLC), Cancer of the Liver Italian Program score (CLIP), tumor‐node‐metastasis (TNM) and Okuda systems at diagnosis. They were followed with survival data and the performance of each staging system (in terms of homogeneity, discriminatory ability and monotonicity of gradient) were analyzed and compared. Results: A total of 595 patients (80.2% with chronic HBV infection) were analyzed. The median follow‐up was 41.4 months and the median survival was 6.6 months. Multivariate analyses identified symptomatic disease, ascites, vascular involvement, Child‐Pugh‐stage, alpha‐fetoprotein and treatment to be the independent prognostic factors. CUPI could identify three groups with statistically significant survival difference (P < 0.0001). Both CUPI and CLIP had the most favorable performance in terms of discriminatory ability, homogeneity and monotonicity. CUPI performed the best in predicting 3‐month survival while CLIP performed better in predicting the outcome of 6‐ and 12‐month survival rate. BCLC was inferior to CLIP and CUPI in the overall performance. Conclusion: We have validated CUPI in a population composed of predominant HBV‐related HCC. CUPI is an appropriate staging system for HBV‐related HCC. In patients with advanced HCC, both CUPI and CLIP offer good risk stratification.     

Comparison of seven staging systems in cirrhotic patients with hepatocellular carcinoma in a cohort of patients who underwent radiofrequency ablation with complete response

BACKGROUND AND AIMS: Many staging systems for hepatocellular carcinoma (HCC) have been proposed but the best tool for staging of HCC remains controversial. The aim of the present study was to identify the best staging system evaluating the predictive ability for outcome for each of the seven different staging systems applied in a homogeneous group of patients who underwent percutaneous radiofrequency ablation (RFA). METHODS: We analyzed retrospectively 112 patients with HCC and cirrhosis treated with percutaneous RFA from January, 1998 to April, 2005. Response to treatment after 30 days and for long-term follow-up was evaluated with computed tomography (CT) or magnetic resonance imaging (MRI) and serum alpha-fetoprotein level (AFP). All of the 112 patients were grouped according to each one of the seven different staging systems: Okuda, TNM, BCLC, CLIP, GRETCH, CUPI, JIS. RESULTS: The mean follow-up time of the 112 patients submitted to RFA was 24 months (range 3-92 months) with survival rates at 1, 3, and 5 yr of 82%, 40%, and 18%, respectively. Univariate and multivariate analyses showed that factors related to survival were Child-Pugh score (P相似文献