Chinese University Prognostic Index Research Articles

A Novel Prognostic Score Based on Artificial Intelligence in Hepatocellular Carcinoma: A Long-Term Follow-Up Analysis.

ObjectiveT cell immunity plays an important role in anti-tumor effects and immunosuppression often leads to the development and relapse of cancer. This study aimed to investigate the effect of T cell numbers on the long-term prognosis of patients with hepatocellular carcinoma (HCC) and construct an artificial neural network (ANN) model to evaluate its prognostic value.MethodsWe enrolled 3,427 patients with HCC at Beijing Ditan Hospital, Capital Medical University, and randomly divided them into two groups of 1,861 and 809 patients as the training and validation sets, respectively. Cox regression analysis was used to screen for independent risk factors of survival in patients with HCC. These factors were used to build an ANN model using Python. Concordance index, calibration curve, and decision curve analysis were used to evaluate the model performance.ResultsThe 1-year, 3-year, 5-year, and 10-year cumulative overall survival (OS) rates were 66.9%, 45.7%, 34.9%, and 22.6%, respectively. Cox multivariate regression analysis showed that age, white blood cell count, creatinine, total bilirubin, γ-GGT, LDH, tumor size ≥ 5 cm, tumor number ≥ 2, portal vein tumor thrombus, and AFP ≥ 400 ng/ml were independent risk factors for long-term survival in HCC. Antiviral therapy, albumin, T cell, and CD8 T cell counts were independent protective factors. An ANN model was developed for long-term survival. The areas under the receiver operating characteristic (ROC) curve of 1-year, 3-year, and 5-year OS rates by ANNs were 0.838, 0.833, and 0.843, respectively, which were higher than those of the Barcelona Clinic Liver Cancer (BCLC), tumor node metastasis (TNM), Okuda, Chinese University Prognostic Index (CUPI), Cancer of the Liver Italian Program (CLIP), Japan Integrated Staging (JIS), and albumin–bilirubin (ALBI) models (P < 0.0001). According to the ANN model scores, all patients were divided into high-, middle-, and low-risk groups. Compared with low-risk patients, the hazard ratios of 5-year OS of the high-risk group were 8.11 (95% CI: 7.0-9.4) and 6.13 (95% CI: 4.28-8.79) (P<0.0001) in the training and validation sets, respectively.ConclusionHigh levels of circulating T cells and CD8 + T cells in peripheral blood may benefit the long-term survival of patients with HCC. The ANN model has a good individual prediction performance, which can be used to assess the prognosis of HCC and lay the foundation for the implementation of precision treatment in the future.

Nomogram for prediction of long-term survival with hepatocellular carcinoma based on NK cell counts

IntroductionAmong all immune cells, natural killer (NK) cells play an important role as the first line of defense against tumor. The purpose of our study is to observe whether the NK cell counts can predict the overall survival of patients with hepatocellular carcinoma (HCC). MethodsTo develop a novel model, from January 2010 to June 2015, HCC patients enrolled in Beijing Ditan hospital were divided into training and validation cohort. Cox multiple regression analysis was used to analyze the independent risk factors for 1-year, 3-year and 5-year overall survival (OS) of patients with HCC, and the nomogram was used to establish the prediction model. In addition, the decision tree was established to verify the contribution of NK cell counts to the survival of patients with HCC. ResultsThe model used in predicting overall survival of HCC included six variables (namely, NK cell counts, albumin (ALB) level, alpha-fetoprotein (AFP) level, portal vein tumor thrombus (PVTT), tumor number and treatment). The C-index of nomogram model in HCC patients predicting 1-year, 3-year and 5-year overall survival was 0.858, 0.788 and 0.782 respectively, which was higher than tumor–lymph node–metastasis (TNM) staging system, Okuda, model for end-stage liver disease (MELD), MELD-Na, the Chinese University Prognostic Index (CUPI) and Japan Integrated Staging (JIS) scores (p < 0.001). The decision tree showed the specific 5-year OS probability of HCC patients under different risk factors, and found that NK cell counts were the third in the column contribution. ConclusionsOur study emphasizes the utility of NK cell counts for exploring interactions between long-term survival of HCC patients and predictor variables.

Pancreatic, Gastric, and other Gastrointestinal Cancers

According to 2009 estimates from the American Cancer Society, cancers originating in the gastrointestinal tract rank second in both incidence and cancer-related deaths. One in four deaths in the United States is caused by cancer, with 25% of cancer-related deaths caused by gastrointestinal (GI) malignancies; more than 50% of these deaths are caused by cancer of the pancreas, stomach, esophagus, liver, or biliary tract. Recent advances in molecular biology, medical genetics, and imaging and endoscopic techniques, as well as the development of antitumor agents, have significantly altered the approaches to the prevention, diagnosis, and treatment of GI cancers. The chapter covers esophageal, gastric, pancreatic, hepatocellular, biliary tract, and anal cancers, as well as GI stromal tumors and gastric lymphoma. Coverage of all cancers includes diagnosis and treatment; various sections include information on epidemiology, etiology, risk factors, screening and prevention, molecular mutations, pathogenesis, and/or metastatic disease. Figures depict a barium esophagogram showing squamous cell carcinoma; imaging of esophageal cancer, gastric cancer, and pancreatic cancer; a pedigree of a family with inactivation of germline mutation of E-cadherin; hereditary gastric cancer; gastric cancer survival rates after gastrectomy; axial T1-weighted magnetic resonance imaging (MRI) showing cancer of the pancreatic head; and T1- and T2-weighted MRIs of intrahepatic bile duct carcinoma. Tables provide information on new cases and mortality from GI cancer in 2009; guidelines for diagnosis and surveillance of Barrett esophagus; the declining incidence of gastric cancer in Japan, Slovenia, and the United States; TNM staging of gastric cancer, pancreatic cancer, and hepatocellular carcinoma; the incidence of familial pancreatic carcinoma; molecular mutations involved in pancreatic cancer; staging of pancreatic intraepithelial neoplasia; and the Chinese University Prognostic Index. This review contains 9 figures, 39 tables, and 173 references. Keywords: biliary cancer, carcinoma, endoscopic, esophageal, gastric, hepatic, lesions, lymphoma, malignant, mutations

Pancreatic, Gastric, and other Gastrointestinal Cancers

According to 2009 estimates from the American Cancer Society, cancers originating in the gastrointestinal tract rank second in both incidence and cancer-related deaths. One in four deaths in the United States is caused by cancer, with 25% of cancer-related deaths caused by gastrointestinal (GI) malignancies; more than 50% of these deaths are caused by cancer of the pancreas, stomach, esophagus, liver, or biliary tract. Recent advances in molecular biology, medical genetics, and imaging and endoscopic techniques, as well as the development of antitumor agents, have significantly altered the approaches to the prevention, diagnosis, and treatment of GI cancers. The chapter covers esophageal, gastric, pancreatic, hepatocellular, biliary tract, and anal cancers, as well as GI stromal tumors and gastric lymphoma. Coverage of all cancers includes diagnosis and treatment; various sections include information on epidemiology, etiology, risk factors, screening and prevention, molecular mutations, pathogenesis, and/or metastatic disease. Figures depict a barium esophagogram showing squamous cell carcinoma; imaging of esophageal cancer, gastric cancer, and pancreatic cancer; a pedigree of a family with inactivation of germline mutation of E-cadherin; hereditary gastric cancer; gastric cancer survival rates after gastrectomy; axial T1-weighted magnetic resonance imaging (MRI) showing cancer of the pancreatic head; and T1- and T2-weighted MRIs of intrahepatic bile duct carcinoma. Tables provide information on new cases and mortality from GI cancer in 2009; guidelines for diagnosis and surveillance of Barrett esophagus; the declining incidence of gastric cancer in Japan, Slovenia, and the United States; TNM staging of gastric cancer, pancreatic cancer, and hepatocellular carcinoma; the incidence of familial pancreatic carcinoma; molecular mutations involved in pancreatic cancer; staging of pancreatic intraepithelial neoplasia; and the Chinese University Prognostic Index. This review contains 9 figures, 39 tables, and 173 references. Keywords: biliary cancer, carcinoma, endoscopic, esophageal, gastric, hepatic, lesions, lymphoma, malignant, mutations

Evaluation of survival of patients with hepatocellular carcinoma: A comparative analysis of prognostic systems

Background and aimThere are several prognostic systems that address different aspects of the patient and the tumour and can guide the management of patients with hepatocellular carcinoma (HCC). This study aimed to evaluate and compare the eight staging systems for a group of patients in a public service in Brazil.MethodsPatients with HCC were retrospectively analysed between 2000 and 2012. The prognostic systems Okuda, The Cancer of the Liver Italian Program (CLIP), the Chinese University Prognostic Index (CUPI), Groupe d'Etude et de Traitément du Carcinome Hepatocellulaire (GRETCH), the modified TNM-based Japan Integrated Score (JIS) combined with alpha-fetoprotein and Child-Turcotte-Pugh (CTP), the TNM system, and the Barcelona Clinic Liver Cancer Classification (BCLC) were applied to these patients and compared through model fit measurements, likelihood scores, and the Akaike Information Criterion (AIC).ResultsA total of 247 patients were studied. The average survival time was 60 months. The TNM, Okuda, CLIP, GRETCH, modified JIS, and BCLC systems were well correlated with one another and individually important to the prediction of survival among the patients studied. However, in the statistical analysis, the CUPI delivered the best predictive performance (AIC = 566; log-likelihood = -281,240).ConclusionAlthough the CUPI system was demonstrated to be the most appropriate HCC staging system for the studied population, the choice of an ideal system is a controversial subject, and future studies with larger numbers of patients are necessary for the validation of the CUPI system as the method of choice for other populations.

Validation and ranking of seven staging systems of hepatocellular carcinoma.

The aim of the present study was to evaluate the ability of seven staging systems to predict 3- and 6-month and cumulative survival rates of patients with advanced hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). Data were collected from 220 patients with HBV-associated HCC who did not receive any standard anticancer treatment. Participants were patients at The Third Affiliated Hospital of Sun Yat-sen University from September 2008 to June 2010. The participants were classified according to the Chinese University Prognostic Index (CUPI), the Cancer of the Liver Italian Program (CLIP), Japan Integrated Staging (JIS), China Integrated Score (CIS) systems, Barcelona Clinic Liver Cancer (BCLC), Okuda and tumor-node-metastasis (TNM) staging systems at the time of diagnosis and during patient follow-up. The sensitivity and specificity of the predictive value of each staging system for 3- and 6-month mortality were analyzed by relative operating characteristic (ROC) curve analysis with a non-parametric test being used to compare the area under curve (AUC) of the ROC curves. In addition, log-rank tests and Kaplan-Meier estimator survival curves were applied to compare the overall survival rates of the patients with HCC defined as advanced using the various staging systems, and the Akaike information criterion (AIC) and likelihood ratio tests (LRTs) were used to evaluate the predictive value for overall survival in patients with advanced HCC. Using univariate and multivariate Cox's model analyses, the factors predictive of survival were also identified. A total of 220 patients with HBV-associated HCC were analyzed. Independent prognostic factors identified by multivariate analyses included tumor size, α-fetoprotein levels, blood urea nitrogen levels, the presence or absence of portal vein thrombus, Child-Pugh score and neutrophil count. When predicting 3-month survival, the AUCs of CLIP, CIS, CUPI, Okuda, TNM, JIS and BCLC were 0.806, 0.772, 0.751, 0.731, 0.643, 0.754 and 0.622, respectively. When predicting 6-month survival, the AUCs of CLIP, CIS, CUPI, Okuda, TNM, JIS and BCLC were 0.828, 0.729, 0.717, 0.692, 0.664, 0.746 and 0.575, respectively. For 3-month mortality, the prognostic value of CLIP ranked highest, followed by CIS; for 6-month mortality, the prognostic value of CLIP also ranked highest, followed by JIS. No significant difference between the AUCs of CLIP and CIS (P>0.05) in their predictive value for 3-month mortality was observed. The AUC of CLIP was significantly higher compared with that of the other staging systems (P<0.05) for predicting 6-month mortality. The χ2 values from the LRTs of CLIP, CIS, CUPI, Okuda, TNM, JIS and BCLC were 75.6, 48.4, 46.7, 36.0, 21.0, 46.8 and 7.24, respectively. The AIC values of CLIP, CIS, CUPI, Okuda, TNM, JIS and BCLC were 1601.5, 1632.3, 1629.9, 1641.1, 1654.8, 1627.4 and 1671.1, respectively. CLIP exhibited the highest χ2 value and lowest AIC value, indicating that CLIP has the highest predictive value of cumulative survival rate. In the selected patients of the present study, CLIP was the staging system best able to predict 3- and 6-month and overall survival rates. CIS ranked second in predicting 3-month mortality.

Nomogram prediction of individual prognosis of patients with hepatocellular carcinoma

BackgroundThe purpose of this study was to develop an effective nomogram capable of estimating the individual survival outcomes of patients with hepatocellular carcinoma (HCC), and compare the predictive accuracy and discriminative ability with other staging systems.MethodsThe nomogram was established based on a retrospective study of 661 patients newly diagnosed with HCC at the Beijing Ditan Hospital (Beijing, China), Capital Medical University, between October 2008 and July 2012. The predictive accuracy and discriminative ability of the previously developed nomogram were assessed by C-index and calibration curves, and were compared to seven current commonly used staging systems. The results were validated, using a bootstrap approach to correct for bias, in a prospective study of 220 patients consecutively enrolled between August 2012 and March 2013.ResultsMultivariate analysis of the primary cohort for survival analysis identified the independent factors to be aspartate aminotransferase, ɣ-glutamyl transpeptidase, white blood cell count, neutrophil-to-lymphocyte ratio, prothrombin activity, α-fetoprotein, tumor number and size, lymph node metastasis, and portal vein involvement, which were all included to build the nomogram. The calibration curve for predicting the probability of survival showed consistency between the nomogram and the actual observation. The C-index of the nomogram was 0.81 (95% confidence interval, 0.79–0.82), which was statistically better than that of the Tumor, Node, Metastasis staging (0.71), Barcelona Clinic Liver Cancer staging (0.77), Okuda (0.62), Japan Integrated Staging (0.73), Cancer of the Liver Italian Program score (0.76), Chinese University Prognostic Index (0.68), and the Groupe d’ Etude et de Traitement du Carcinome Hepatocellulaire Prognostic classification (0.65) (p < 0.001 for all). The results were validated in the prospective validation cohort.ConclusionsThe prognostic nomogram resulted in more accurate individualized risk estimates for overall survival in HCC patients.

Validation of different staging systems for hepatocellular carcinoma in a cohort of 249 patients undergoing radiotherapy.

There is no consensus on predicting prognosis for hepatocellular carcinoma patients undergoing radiotherapy. This study aims to evaluate the validity of different staging systems. Overall, 249 hepatocellular carcinoma patients were evaluated retrospectively. All patients were classified by different staging systems. The cumulative survival rates were calculated using the Kaplan-Meier method, and survival curves were compared using the log-rank test. Harrell's concordance index (c-index) was calculated. The 1-, 3-, and 5-year overall survival rates were 58%, 31% and 20%, respectively. Significant differences in overall survival were observed between stages I and II of the Okuda staging system (p=0.004), between scores of 3 and 4 of Cancer of the Liver Italian Program prognostic score (p=0.009), between Chinese University Prognostic Index low-risk and intermediate-risk groups (p=0.01), between 1 and 2 points of the Japan Integrated Staging score (p=0.037), between stages III and IV of American Joint Committee on Cancer 1997 TNM staging system (p=0.011), between stages II and III of American Joint Committee on Cancer 2002 TNM staging system (p=0.026) and between stages I and II of Guangzhou 2001 staging system (p=0.000). In conclusion, the Okuda staging system, Chinese University Prognostic Index, and Chinese Guangzhou 2001 staging system were more discriminative than the other staging systems in the prognostic stratification for hepatocellular carcinoma patients undergoing radiotherapy.

Novel microvascular invasion-based prognostic nomograms to predict survival outcomes in patients after R0 resection for hepatocellular carcinoma.

To propose a novel histopathological classification system for microvascular invasion (MVI) and to establish nomograms to predict postoperative survival and early tumor recurrence in patients with hepatocellular carcinoma (HCC) after R0 liver resection. The clinicopathological and follow-up data of 686 consecutive patients with HCC who underwent R0 liver resection in our hospital between December 2009 and April 2010 were retrospectively reviewed. A classification system was established based on histological characteristics of MVI. Nomograms were then formulated using a multivariate Cox proportional hazards model to analyze. The results were validated using bootstrap resampling and a new 225-patient validation cohort operated in May and June 2010 at the same institution. A 4-stratification classification system of MVI was established, which satisfactorily determined the risk of survival and early tumor recurrence. Then, an eight-factor nomogram for survival prediction and a seven-factor nomogram for prediction of early tumor recurrence were established. The concordance indices were 0.78 for the survival-prediction nomogram and 0.72 for the recurrence-prediction nomogram. These indices were both significantly higher than the following three commonly used staging systems: tumor-node-metastasis staging system (seventh edition, 0.67/0.65), Japan Integrated Staging System (0.58/0.58) and Chinese University Prognostic Index (0.52/0.51). The calibration curves showed good agreement between predictions by the nomograms and actual survival outcomes. These results were confirmed in the validation cohort. The novel classification system of MVI and the nomograms enabled more accurate predictions of risk of tumor recurrence and overall survival in patients with HCC after R0 liver resection.

A novel risk score (MCCT) to guide decision for treatment of advanced hepatocellular carcinoma with transarterial chemoembolisation: a derivation and validation study

BackgroundTransarterial chemoembolisation (TACE) is still widely used to treat patients with advanced hepatocellular carcinoma who have no access to sorafenib in Asia. However, the indication of TACE for these patients has yet to be established. We established an objective point score to guide this decision in patients with advanced-stage hepatocellular carcinoma. MethodsWe developed a scoring system (MCCT score) based on preoperative data from a cohort of 422 patients receiving TACE as the first treatment for advanced hepatocellular carcinoma from 2006 to 2013 at Sun Yat-sen University Cancer Center, Guangzhou, China. Factors determining survival were analysed by univariate and multivariate analysis and Cox proportional hazard regression models. The scoring system was retrospectively validated in an external cohort from other two institutions (Dongguan People's Hospital and the Kaiping Central Hospital; n=237). The prognostic predictive power was compared with six different staging systems: tumour node metastasis (TNM), 7th edition; Cancer of the Liver Italian Program (CLIP); Chinese University Prognostic Index (CUPI); Okuda, Japan Integrated Staging (JIS); and Groupe d'Etude et de Traitement du Carcinome Hépatocellulaire (GRETCH). The retrospective study was approved by the institutional review board; written informed consent was obtained from each patient. FindingsThe presence of macroscopic vascular invasion (M), Child-Pugh class B (C), C-reactive protein values (C) higher than 10 mg/L, and tumour size (T) larger than 7 cm were independent negative prognostic factors for survival and were used to create the MCCT score. The patients were divided into risk groups on the basis of their MCCT scores (low risk for ≤2 points, intermediate risk for 3–4 points, and high risk for five points). The median overall survival times were 14·4 months (95% CI 10·7–18·1) for the low-risk group, 6·8 months (6·0–7·6) of the intermediate-risk group, and 3·2 months (1·7–4·7) for the high-risk group (p<0·0001). The discriminative ability, as determined by the area under the curve (AUC) at 6 and 12 months (AUCs 0·692 at 6 months and 0·702 at 12 months) seemed to be greater than the ability of the six other hepatocellular carcinoma staging systems (AUCs range 0·501 to 0·633). The findings were supported by the external validation cohort. InterpretationThe MCCT scoring system is more accurate than the six other scoring systems in selecting patients with advanced hepatocellular carcinoma for TACE. For patients with advanced hepatocellular carcinoma with no access to sorafenib, TACE may be a valuable alternative in selecting patients (MCCT score ≤2). FundingThis study was supported by grants from the National Natural Science Foundation of China (81172037/H1606, 81272639, and 81572385), Guangdong province science and technology project of China (2013B021800159), and the Fundamental Research Funds for the Central Universities of China (13ykzd24).

Comparison of the Predictive Values of Eight Staging Systems for Primary Liver Cancer in Prognosis of Combined Hepatocellular-cholangiocellular Carcinoma Patients after Surgery

To compare the predictive values of eight staging systems for primary liver cancer in the prognosis of combined hepatocellular-cholangiocellular carcinoma (cHCC-CC) patients after surgery. The clinical data of 54 cHCC-CC patients who underwent hepatectomy or liver transplantation from May 2005 to Augest 2013 in Chinese PLA General Hospital were collected. We evaluated the prognostic value of the Okuda staging system, Cancer of the Liver Italian Program (CLIP) score, French staging system, Barcelona Clinic Liver Cancer (BCLC) staging system, 7th edition of tumour-node-metastasis (TNM) staging system for hepatocellular carcinoma and intrahepatic cholangiocarcinoma (ICC), Japan Integrated Staging (JIS) score, and Chinese University Prognostic Index. The distribution, Kaplan-Meier method, Log-rank test, and area under a receiver operating characteristic curve were used to compare the prognosis-predicting ability of these different staging systems in 54 cHCC-CC patients after surgery. The TNM staging system for ICC and JIS score had a better distribution of cases. The 12-and 24-month survivals of the entire cohort were 65.5% and 56.3%, respectively. A Log-rank test showed that there was a significant difference existing in the cumulative survival rates of different stage patients when using TNM staging system for ICC (stage 1 vs. stage 2, P=0.012; stage 2 vs. stage 3-4, P=0.002), Okuda staging system (stage 1 vs. stage 2, P=0.025), and French staging system (stage A and stage B, P=0.045). The 12-and 24-month area under curve of TNM staging system for ICC, BCLC staging system, JIS score, and CLIP score were 0.836 and 0.847, 0.744 and 0.780, 0.723 and 0.764, and 0.710 and 0.786, respectively. The 7th edition of TNM staging system for ICC has superior prognostic value to other seven staging systems in cHCC-CC patients undergoing surgical treatment.

Prognosis of unresectable hepatocellular carcinoma: Comparison of seven staging systems (TNM, Okuda, BCLC, CLIP, CUPI, JIS, CIS) in a Chinese cohort.

305 Background: Many liver staging systems that include the tumor stage and the extent of liver function have been developed. However, Prognosis assessment for hepatocellular carcinoma (HCC) remains controversial. In this study, the performances of 7 staging systems were compared in a cohort of patients with HCC who underwent non-surgical treatment. Methods: A total of 196 consecutive patients with HCC who underwent non-surgical treatment seen between January 1, 2004, and December 31, 2007, were included. Performances of TNM sixth edition, Okuda, Barcelona Clinic Liver Cancer (BCLC), Cancer of the Liver Italian Program (CLIP), Chinese University Prognostic Index (CUPI), Japan Integrated Staging (JIS), and China integrated score (CIS) have been compared and ranked using concordance index (c-index). Predictors of survival were identified using univariate and multivariate Cox model analyses. Results: The median survival time for the cohort was 7.6 months (95% CI 5.6-9.7). The independent predictors of survival were performance status (P &lt;.001), serum sodium (P &lt;.001), alkaline phosphatase (P &lt;.001), tumor diameter greater than 5 cm (P =.001), portal vein invasion (P &lt;.001), lymph node metastasis (P =.025), distant metastasis (P =.004). CUPI staging system had the best independent predictive power for survival when compared with the other six prognostic systems. Performance status and serum sodium improved the discriminatory ability of CUPI. Conclusions: In our selected patient population whose main etiology is hepatitis B, CUPI was the most suitable staging systems in predicting survival in patients with unresectable HCC. BCLC was the second top-ranking staging system. CLIP, JIS, CIS, and TNM sixth edition were not helpful in predicting survival outcome, and their use is not supported by our data. Clinical trial information: 1103-10.

Comparison of five staging systems in hepatocellular carcinoma treated with sorafenib: A single-center experience.

To the best of our knowledge, none of the prognostic staging systems for hepatocellular carcinoma (HCC) patients who underwent sorafenib therapy is universally adopted or preferred. In the present study, we aimed to compare prognostic ability among five prognostic systems, including the Japan Integrated Staging (JIS) system, the Barcelona Clinic Liver Cancer classification system, the tumor-node-metastasis classification system, the Cancer of the Liver Italian Program scoring system and the Chinese University Prognostic Index (CUPI) scoring system for HCC patients who received sorafenib therapy. A total of 143 HCC patients treated with sorafenib were analysed. We compared prognostic ability among the five prognostic systems using the likelihood ratio (LR) χ2 test, linear trend χ2 test and concordance index (c-index). Our cohort included 114 men and 29 women. The median patient age was 71 years (range, 45-89 years). A total of 102 patients were classified as Child-Pugh A and 41 as Child-Pugh B, whereas 31 patients (21.7%) had portal vein invasion and 63 (44.1%) extrahepatic metastases. The median survival time was 6.9 months. In the LR χ2 test, the CUPI scoring system had the highest value (35.804), followed by the JIS system (17.469). In the linear trend χ2 test, the CUPI scoring system had the highest value (17.523), followed by the JIS system (15.819). In addition, the JIS system had the highest value in the 6-month c-index (0.659) as well as in the 1-year c-index (0.674). However, the CUPI classification system had the lowest value in the 1-year c-index (0.590). In conclusion, the JIS system may be an appropriate staging system for HCC patients undergoing sorafenib therapy.

Prognostic nomogram for patients with unresectable hepatocellular carcinoma after transcatheter arterial chemoembolization

To establish an effective prognostic nomogram for patients with unresectable hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE). The nomogram was constructed based on data obtained from a retrospective study on 2938 patients who received TACE as an initial therapy from 2000 to 2008. The predictive accuracy and discriminative ability of the nomogram were compared with seven current commonly used staging systems on HCC by using data obtained from a prospective study on a cohort of 647 patients treated from January 2011 to December 2011 at the same institution. Additional external validation was performed using a data set (n=221) from another institution. Portal vein invasion, tumor number, tumor capsule, alpha fetoprotein, aspartate aminotransferase, and indocyanine green retention at 15 min formed the basis of the nomogram. The concordance index (C-index) of the nomogram was 0.755, which was significantly better than the American Joint Committee on Cancer seventh edition (0.612), the Barcelona Clinic Liver Cancer system (0.692), the Okuda system (0.579), the Japan Integrated Staging system (0.637), Cancer of the Liver Italian Program system (0.683), the Chinese University Prognostic Index (0.637) and the Groupe d'Etude et de Traitement du Carcinome Hepatocellulaire (0.577) (p<0.001 for all). The calibration curve for predicting probability of survival showed a good agreement between the nomogram and actual observation. The findings were supported by the external validation cohort. The nomogram gave better discrimination than the seven staging systems. The proposed nomogram gave accurate prognostic prediction in patients with unresectable HCC after treatment with TACE.

Evaluation of eight different clinical staging systems associated with overall survival of chinese patients with hepatocellular carcinoma.

Background:Hepatocellular carcinoma (HCC) is a common cancer in China, an area of high hepatitis B virus (HBV) infection. Although several staging systems are available, there is no consensus on the best classification to use because multiple factors, such as etiology, clinical treatment and populations could affect the survival of HCC patients.Methods:This study analyzed 743 HBV-related Chinese HCC patients who received surgery first and evaluated the predictive values of eight different commonly used staging systems in the clinic.Results:The overall 1-, 3-, 5-year survival rates and a median survival were 91.5%, 70.3%, 55.3% and 72 months respectively. Barcelona Clinic Liver Cancer (BCLC) staging systems had the best stratification ability and showed the lowest Akaike information criterion (AIC) values (2896.577), followed by tumor-node-metastasis 7th (TNM 7th) (AIC = 2899.980), TNM 6th (AIC = 2902.17), Japan integrated staging score (AIC = 2918.085), Tokyo (AIC = 2938.822), Cancer of the Liver Italian Program score (AIC = 2941.950), Chinese University Prognostic Index grade (AIC = 2962.027), and Okuda (AIC = 2979.389).Conclusions:BCLC staging system is a better staging model for HBV infection patients with HCC in Chinese population among the eight currently used staging systems. These identifications afford a large group of Chinese HCC patients with HBV infection and could be helpful to design a new staging system for a certain population.

International validation of the Chinese university prognostic index for staging of hepatocellular carcinoma: a joint United Kingdom and Hong Kong study.

The outcome of hepatocellular carcinoma (HCC) patients significantly differs between western and eastern population centers. Our group previously developed and validated the Chinese University Prognostic Index (CUPI) for the prognostication of HCC among the Asian HCC patient population. In the current study, we aimed to validate the CUPI using an international cohort of patients with HCC and to compare the CUPI to two widely used staging systems, the Barcelona Clinic Liver Cancer (BCLC) classification and the Cancer of the Liver Italian Program (CLIP). To accomplish this goal, two cohorts of patients were enrolled in the United Kingdom (UK; n = 567; 2006-2011) and Hong Kong (HK; n = 517; 2007-2012). The baseline clinical data were recorded. The performances of the CUPI, BCLC, and CLIP were compared in terms of a concordance index (C-index) and were evaluated in subgroups of patients according to treatment intent. The results revealed that the median follow-up durations of the UK and HK cohorts were 27.9 and 29.8 months, respectively. The median overall survival of the UK and HK cohorts were 22.9 and 8.6 months, respectively. The CUPI stratified the patients in both cohorts into three risk subgroups corresponding to distinct outcomes. The median overall survival of the CUPI low-, intermediate-, and high-risk subgroups were 3.15, 1.24, and 0.29 years, respectively, in the UK cohort and were 2.07, 0.32, and 0.10 years, respectively, in the HK cohort. For the patients who underwent curative treatment, the prognostic performance did not differ between the three staging systems, and all were suboptimal. For those who underwent palliative treatment, the CUPI displayed the highest C-index, indicating that this staging system was the most informative for both cohorts. In conclusion, the CUPI is applicable to both western and eastern HCC patient populations. The performances of the three staging systems differed according to treatment intent, and the CUPI was demonstrated to be optimal for those undergoing palliative treatment. A more precise staging system for early-stage disease patients is required.

TNM/Okuda/Barcelona/UNOS/CLIP International Multidisciplinary Classification of Hepatocellular Carcinoma: concepts, perspectives, and radiologic implications

Hepatocellular carcinoma (HCC) is a major health problem worldwide. Moreover, the liver cancer field is evolving rapidly, with early diagnosis, new therapies, and a better understanding of HCC's biology and development. Accurate staging is important for determining prognosis and selecting the most appropriate treatment for each patient. Surgical intervention remains the most effective treatment for HCC and is the only potentially curative modality. However, in HCC patients, overall survival is also independently affected by underlying liver disease and cirrhosis, which in turn affect the applicability and efficacy of treatment. Although several staging classification and prognostic scoring systems have been proposed for determining the stage and prognosis of HCC, no consensus exists on the best classification method. The most common staging classification systems include tumor-node-metastasis stage, Okuda staging, Cancer of the Liver Italian Program score, Barcelona Clinic Liver Cancer staging classification, the French, the Chinese University Prognostic Index, Japanese Integrated Scoring, and the Tokyo score. Radiologists should be aware of the different staging classification systems for HCC and familiar with the system relevant to their respective referring clinicians, as it will provide pertinent radiological evaluation for multidisciplinary management.

Prognosis of Unresectable Hepatocellular Carcinoma: Comparison of Seven Staging Systems (TNM, Okuda, BCLC, CLIP, CUPI, JIS, CIS) in a Chinese Cohort

BackgroundMany liver staging systems that include the tumor stage and the extent of liver function have been developed. However, prognosis assessment for hepatocellular carcinoma (HCC) remains controversial. In this study, the performances of 7 staging systems were compared in a cohort of patients with HCC who underwent non-surgical treatment.MethodsA total of 196 consecutive patients with HCC who underwent non-surgical treatment seen between January 1, 2004, and December 31, 2007, were included. Performances of TNM sixth edition, Okuda, Barcelona Clinic Liver Cancer (BCLC), Cancer of the Liver Italian Program (CLIP), Chinese University Prognostic Index (CUPI), Japan Integrated Staging (JIS), and China integrated score (CIS) have been compared and ranked using concordance index (c-index). Predictors of survival were identified using univariate and multivariate Cox model analyses.ResultsThe median survival time for the cohort was 7.6 months (95% CI 5.6–9.7). The independent predictors of survival were performance status (P<.001), serum sodium (P<.001), alkaline phosphatase (P<.001), tumor diameter greater than 5 cm (P = .001), portal vein invasion (P<.001), lymph node metastasis (P = .025), and distant metastasis (P = .004). CUPI staging system had the best independent predictive power for survival when compared with the other six prognostic systems. Performance status and serum sodium improved the discriminatory ability of CUPI.ConclusionIn our selected patient population whose main etiology is hepatitis B, CUPI was the most suitable staging system in predicting survival in patients with unresectable HCC. BCLC was the second top-ranking staging system. CLIP, JIS, CIS, and TNM sixth edition were not helpful in predicting survival outcome, and their use is not supported by our data.

Comparative Study of Staging Systems for Hepatocellular Carcinoma in 428 Patients Treated with Radioembolization

PurposeTo compare the utility of different staging systems and analyze independent predictors of survival in patients with hepatocellular carcinoma (HCC) treated with yttrium-90 (90Y) radioembolization. Materials and MethodsDuring the period 2004–2011, 428 patients with HCC were treated with 90Y radioembolization. All patients were staged prospectively by the following staging systems: Child-Turcotte-Pugh (CTP), United Network for Organ Sharing, Barcelona Clinic Liver Cancer (BCLC), Okuda classification, Cancer of the Liver Italian Program (CLIP), Groupe d’Etude et de Traitement du Carcinome Hepatocellulaire, Chinese University Prognostic Index, and Japan Integrated Staging. The ability of the staging systems to predict survival was assessed. The staging systems were compared using Cox proportional hazards regression model, linear regression, Akaike information criterion (AIC), and concordance index (C-index). Univariate and multivariate analyses were employed to assess independent predictors of survival. ResultsWhen tested independently, all staging systems exhibited significant ability to discriminate early (long survival) from advanced (worse survival) disease. CLIP provided the most accurate information in predicting survival outcomes (AIC = 2,993, C-index = 0.8503); CTP was least informative (AIC = 3,074, C-index = 0.6445). Independent predictors of survival included Eastern Cooperative Oncology Group performance status grade 0 (hazard ration [HR], 0.56; confidence interval [CI], 0.34–0.93), noninfiltrative tumors (HR, 0.62; CI, 0.44–0.89), absence of portal venous thrombosis (HR, 0.60; CI, 0.40–0.89), absence of ascites (HR, 0.56; CI, 0.40–0.76), albumin ≥ 2.8 g/dL (HR, 0.72; CI, 0.55–0.94), alkaline phosphatase ≤ 200 U/L (HR, 0.68; CI, 0.50–0.92), and α-fetoprotein ≤ 200 ng/mL (HR, 0.67; CI, 0.51–0.86). ConclusionsCLIP was most accurate in predicting survival in patients with HCC. Given that not all patients receive the recommended BCLC treatment strategy, this information is relevant for clinical trial design and predicting long-term outcomes after 90Y radioembolization.

Comparison of a new prognostic system and five current staging systems in predicting the survival rate of patients with advanced hepatocellular carcinoma.

193 Background: Prognosis of patients with advanced HCC is very poor, median overall survival varies from 3 to 6 months. Life expectancy more than 3 months is one inclusion criteria for molecular targeted drugs in clinical tirals. We have established a new prognostic system called SYSU system (variables and risk classification criteria are listed below, reported in MASCC 2013) and now we want to compare this new prognostic system and 5 current staging systems in predicting the survival rate of patients with advanced HCC. Methods: From September 2008 to June 2010, a total of 253 patients with advanced HCC who were not amendable to locoregional therapy were analyzed. The median follow-up is 38.5 months and the median survival is 7 months. Data were collected to classify patients according to our new system(SYSU system), Barcelona Clinic Liver Cancer staging for hepatocellular carcinoma (BCLC), Advanced Liver Cancer Prognostic System (ALCPS), Chinese University Prognostic Index staging system for HCC (CUPI), OKUDA score system and French scoring system(GETCH) at diagnosis. OS and 3-month OS were the end points used in the analysis. Results: When predicting 3-month survival, ROC analysis show AUC of SYSU system, ALCPS, CUPI,OKUDA, GETCH and BCLC is 0.822,0.821,0.777,0.756,0.688 and 0.621. AUC of SYSU system and ALCPS is similar and they are significantly better than the other four staging system (p&lt;0.05). When predicting overall survival, likelihood ratio test show χ2 of SYSU system, ALCPS, CUPI,OKUDA, GETCH and BCLC is 97.7,85, 50.5, 46.4,22.6 and 8.4 and AIC of SYSU system, ALCPS, CUPI,OKUDA, GETCH and BCLC is 1939,1952,1986,1990,2014 and 2028. Our SYSU system has best performance in terms of discriminatory ability, homogeneity and monotonicity. Conclusions: Our SYSU system is the best score system in prediction of OS and 3-month OS among the 6 systems analyzed for Chinese advanced HCC patients. [Table: see text]