Assessment of prognosis in hepatocellular carcinoma (HCC) using biomarkers and serum measurements.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15093-e15093
Author(s):  
Mabel Joey Teng ◽  
Ravindhi Lakmalee Nathavitharana ◽  
Richard Fox ◽  
Sarah Berhane ◽  
Anna Skowronska ◽  
...  

e15093 Background: Factors that influence prognosis in HCC are well-recognised. They include tumour size and number, the severity of liver dysfunction and the symptomology. Several staging systems combining a number of these factors offer an estimate of prognosis. Some concerned that these staging systems encompass factors that are inherently subjective, e.g. the extent of HCC in CLIP or the use of performance status in BCLC. This have led to the development BALAD score by Toyoda et al, using serum Bilirubin and Albumin and three biomarkers: alpha-fetoprotein-L3 (L3), Alpha-fetoprotein (AFP) and Des-gamma-carboxy prothrombin (DCP). This system was developed in a Japanese population which has mainly HCV-related HCC. Our aim was to develop an objective staging system using the three biomarkers for a western population and compared it to BALAD to assess its performance. Methods: 317 subjects with HCC were recruited from Birmingham, UK between 2007 and 2011. Blood samples were collected at the time of diagnosis. Liver, renal functions plus AFP, L3 and DCP were measured. L3 and DCP were measured by microchip capillary electrophoresis and liquid-phase binding assay on a uTASWako i30 auto analyzer (Wako Pure Chemical Industries Ltd, Japan). Results: Univariable and multivariable regression analyses were performed. Our scoring system (CRCTU score) was developed based on a flexible baseline hazard functions fitted using restricted cubic splines. Suitable fractional polynomials (FP) were used to explain relationship between the outcome and covariates. The level of discrimination achieved using the risk groups was assess by Harrell’s–C statistic. The CRCTU score permitted identification of 4 clearly distinct subgroups as indicated both graphically and by Harrell’s-C values. Both the CRCTU and BALAD scores return Harrell’s-C values of 0.7. Conclusions: We have shown that it is possible to use entirely objective markers to predict prognosis of HCC in a western population. Our model is comparable to the BALAD with the same variables included. However, our treatment of variables with FP is much more robust statistical technique for continuous variable as compared to having artificial categories that were seen in the BALAD system.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4129-4129
Author(s):  
Dario Ribero ◽  
Stefano Rosso ◽  
Antonio Daniele Pinna ◽  
Gennaro Nuzzo ◽  
Alfredo Guglielmi ◽  
...  

4129 Background: Conventional staging systems have limited value for survival estimation in individual patients because of the multiple predictors of outcome. Nomograms may overcome these limitations. Thus we developed and internally validated a postoperative nomogram to predict survival after resection of intrahepatic cholangiocarcinoma (IHC) and compared its predictions to those obtained using the 7th Ed. AJCC/UICC stage groupings. Methods: Prospective clinicopathologic data from 574 patients who underwent hepatic resection at 12 tertiary hepatobiliary centres (1995-2011) were used. After inputting missing values with regression imputation, the nomogram was developed from a Cox regression model with overall survival (OS) as the primary end-point. Calibration and internal validation were performed calculating the agreement between observed and predicted outcomes in terms of percentage of predicted errors (PE). Discrimination was quantified with the concordance index (CI). Both CI and PE were then corrected for over-optimism using bootstrapping with 100-fold cross-validation sampling. Credibility intervals around 3- and 5-year predicted survival were estimated from an empirical Bayesian model. Results: At last follow-up (median duration 27.6 months) 243 patients had died. Three and five-years OS were 52% and 39%. The predictive accuracy of the nomogram (CI: 66.5), which includes 7 variables (tumour size and number, lymph-node metastases, vascular invasion, perineural invasion, CA19.9 level, and radicality of resection), was good and superior to that of the current AJCC/UICC staging system (CI: 58.4). Percentage of PE for the AJCC/UICC staging system were 24%, while the studied model offered a PE slightly under 20%. Heterogeneity was observed in the distribution of nomogram-predicted survival probabilities within stage groups. Conclusions: The nomogram developed in this study overcomes some of the prognostic limitations associated with simple models by including all prognostic variables excluded from the AJCC/UICC staging system and may serve as an instrument for future refinements in determining individual patient prognosis necessary for accurate patients stratification.


2019 ◽  
Author(s):  
Haihong Wang ◽  
Zhenyu Lin ◽  
Guiling Li ◽  
Dejun Zhang ◽  
Dandan Yu ◽  
...  

Abstract Background The American Joint Committee on Cancer (AJCC) staging classifications and the European Neuroendocrine Tumor Society (ENETS) are two broadly used systems for pancreatic neuroendocrine tumors. This study aims to identify the most accurate and useful TNM staging system for poorly differentiated pancreatic neuroendocrine carcinomas(pNECs). Methods An analysis was performed to evaluate the application of the ENETS, 7th edition (7th) AJCC and 8th edition (8th) AJCC staging classifications using the Surveillance, Epidemiology, and End Results (SEER) registry (N = 568 patients). A modified system was proposed based on analysis of the 7th AJCC classification. Results In multivariable analyses, only the 7th AJCC staging system allocated patients into four different risk groups, compared with the 8th AJCC staging system and ENETS staging system, although there was no significant difference. We modified the staging classification by maintaining the T and M definitions of the 7th AJCC staging and adopting new staging definitions. An increased hazard ratio (HR) of death was also observed from class I to class IV for the modified 7th (m7th) staging system (compared with stage I disease; HR for stage II =1.23, 95% confidence interval (CI)= 0.73-2.06, P =0.44; HR for stage III =2.20, 95% CI =1.06-4.56, P=0.03; HR for stage IV =4.95, 95% CI =3.20-7.65, P < 0.001).The concordance index (C-index) was higher for local disease with the m7th AJCC staging system than with the 7th AJCC staging system. Conclusions The m7th AJCC staging system for pNECs proposed in this study provides improvements and may be assessed for potential adoption in the next edition.


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 305-305
Author(s):  
Feng JIN Zhang ◽  
JUN ZHI Shu ◽  
YI CHUN Xie ◽  
QI LI ◽  
Hong XI Jin ◽  
...  

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 <.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), 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.


2020 ◽  
Author(s):  
Haihong Wang ◽  
Zhenyu Lin ◽  
Guiling Li ◽  
Dejun Zhang ◽  
Dandan Yu ◽  
...  

Abstract Background: The American Joint Committee on Cancer (AJCC) and the European Neuroendocrine Tumor Society (ENETS) staging classifications are two broadly used systems for pancreatic neuroendocrine tumors. This study aims to identify the most accurate and useful tumor–node–metastasis (TNM) staging system for poorly differentiated pancreatic neuroendocrine carcinomas(pNECs).Methods: An analysis was performed to evaluate the application of the ENETS, 7th edition (7th) AJCC and 8th edition (8th) AJCC staging classifications using the Surveillance, Epidemiology, and End Results (SEER) registry (N = 568 patients), and a modified system based on the analysis of the 7th AJCC classification was proposed Results: In multivariable analyses, only the 7th AJCC staging system allocated patients into four different risk groups, although there was no significant difference. We modified the staging classification by maintaining the T and M definitions of the 7th AJCC staging and adopting new staging definitions. An increased hazard ratio (HR) of death was also observed from class I to class IV for the modified 7th (m7th) staging system (compared with stage I disease; HR for stage II =1.23, 95% confidence interval (CI)= 0.73-2.06, P =0.44; HR for stage III =2.20, 95% CI =1.06-4.56, P=0.03; HR for stage IV =4.95, 95% CI =3.20-7.65, P < 0.001).The concordance index (C-index) was higher for local disease with the m7th AJCC staging system than with the 7th AJCC staging system. Conclusions: The m7th AJCC staging system for pNECs proposed in this study provides improvements and may be assessed for potential adoption in the next edition.


2013 ◽  
Vol 79 (7) ◽  
pp. 716-722 ◽  
Author(s):  
Nicolas P. Burnett ◽  
Erik M. Dunki-Jacobs ◽  
Glenda G. Callender ◽  
Ryan J. Anderson ◽  
Charles R. Scoggins ◽  
...  

The Barcelona Clinic Liver Cancer (BCLC) staging classification is commonly used for staging hepatocellular carcinoma (HCC). This system assumes the coexistence of cirrhosis; however, a significant proportion of patients with HCC present without cirrhosis. Recently, an alternative system was proposed that stratifies patients according to alpha-fetoprotein (AFP) level. The aim of this study was to apply the AFP staging system to noncirrhotic patients with HCC and evaluate its ability to predict overall survival (OS). A prospective hepatopancreatobiliary database was reviewed for all patients with a diagnosis of HCC. Patients were staged based on BCLC classification as well as by AFP stage according to four levels: less than 10 ng/mL, 10 to 150 ng/mL, 150 to 500 ng/mL, and greater than 500 ng/mL. Cirrhotic patients were compared with noncirrhotic patients in terms of patient demographics and HCC stage. Kaplan-Meier (KM) analysis of OS was performed for noncirrhotic patients according to BCLC and AFP staging systems. Cirrhotic and noncirrhotic patients differed significantly in terms of median age at presentation (64 vs 70 years, P < 0.001) and gender (76 vs 65% male, P = 0.006). BCLS staging classification did not distinguish between cirrhotics and noncirrhotics ( P = 0.733), whereas AFP staging demonstrated a significant difference between the two groups ( P < 0.0001). KM analysis of OS for noncirrhotic patients with HCC was significant for both the BCLC and the AFP staging systems ( P = 0.003 vs P < 0.0001, respectively). Patients presenting with HCC in the absence of cirrhosis appear to have different characteristics than patients with cirrhosis. Staging according to AFP level is an appropriate predictor of prognosis in noncirrhotic patients with HCC.


2020 ◽  
Author(s):  
Haihong Wang ◽  
Zhenyu Lin ◽  
Guiling Li ◽  
Dejun Zhang ◽  
Dandan Yu ◽  
...  

Abstract Background: The American Joint Committee on Cancer (AJCC) and the European Neuroendocrine Tumor Society (ENETS) staging classifications are two broadly used systems for pancreatic neuroendocrine tumors. This study aims to identify the most accurate and useful TNM staging system for poorly differentiated pancreatic neuroendocrine carcinomas(pNECs).Methods: An analysis was performed to evaluate the application of the ENETS, 7th edition (7th) AJCC and 8th edition (8th) AJCC staging classifications using the Surveillance, Epidemiology, and End Results (SEER) registry (N = 568 patients). A modified system was proposed based on analysis of the 7th AJCC classification. Results: In multivariable analyses, only the 7th AJCC staging system allocated patients into four different risk groups, compared with the 8th AJCC staging system and ENETS staging system, although there was no significant difference. We modified the staging classification by maintaining the T and M definitions of the 7th AJCC staging and adopting new staging definitions. An increased hazard ratio (HR) of death was also observed from class I to class IV for the modified 7th (m7th) staging system (compared with stage I disease; HR for stage II =1.23, 95% confidence interval (CI)= 0.73-2.06, P =0.44; HR for stage III =2.20, 95% CI =1.06-4.56, P=0.03; HR for stage IV =4.95, 95% CI =3.20-7.65, P < 0.001).The concordance index (C-index) was higher for local disease with the m7th AJCC staging system than with the 7th AJCC staging system. Conclusions: The m7th AJCC staging system for pNECs proposed in this study provides improvements and may be assessed for potential adoption in the next edition.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3618-3618
Author(s):  
Lindsay A. Renfro ◽  
Axel Grothey ◽  
Leonard Saltz ◽  
Thierry André ◽  
Roberto Labianca ◽  
...  

3618 Background: Current prognostic tools and staging systems in CC use relatively few patient (pt) characteristics; including additional covariates may improve prediction. Using the large ACCENT database, we constructed clinically based NGs for OS and TTR in stage III CC that better separate pts into risk groups compared to AJCC v7 staging. Methods: 15,936 stage III pts accrued to phase III clinical trials since 1989 were used to construct Cox models for TTR and OS. Variables included age, sex, race, BMI, performance status, tumor grade, tumor stage, ratio of positive lymph nodes to nodes examined, number/location of primary tumors (any multiple versus single left, right, or transverse), and treatment (5FU variations vs. 5FU with oxaliplatin or irinotecan). Missing data (<18%) were imputed, continuous variables modeled with splines, and clinically relevant pairwise interactions included if p < 0.001. Final models were internally validated via bootstrapping for corrected calibration and C-indices for survival data. NG-defined risk tertiles were compared to AJCC v7 stage III for observed 3-year (yr) TTR and 5-yr OS for a subset of 7400 pts with complete data. Results: All variables were statistically and clinically significant for OS; age and race did not predict TTR. No meaningful interactions existed. NGs for OS and TTR were well calibrated and associated with C-indices of 0.66 and 0.65, respectively, vs. 0.58 and 0.59 for AJCC. NG risk tertiles were better separated than AJCC groups, (3-yr TTR, 5-yr OS below), with fewer mid-risk NG pts. Removing treatment from NGs did not affect performance (C=0.66 for OS and 0.65 for TTR). Conclusions: The proposed ACCENT NGs are internally valid and have the potential to aid prognostication, decision-making, and patient/physician communication in pts with stage III CC. [Table: see text]


2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 347-347
Author(s):  
Ying-Fen Hong ◽  
Zhan-Hong Chen ◽  
Qu Lin ◽  
Min Dong ◽  
Xing Li ◽  
...  

347 Background: HBV infection is one of the main reasons for hepatocellular carcinoma(HCC). Patients with advanced HBV-associated HCC have poor prognosis. Life expectancy more than 3 months is one inclusion criteria for molecular targeted drugs in clinical trials. Prediction of 3-month OS and OS survival rate of advanced HCC patients is very important. A new prognostic system called PS-JIS system (proposed Performance Status combined Japan Integrated Staging system, variables and risk classification criteria are listed below) was established in 2015 and now we want to compare this new prognostic system and other three current staging systems in predicting the survival rate of patients with advanced HBV-associated HCC. Methods: From September 2008 to June 2010, 220 patients with advanced HCC who didn’t receive anti-cancer therapy recommended by NCCN guidelines were analyzed. Data were collected to classify patients according to CLIP (Cancer of the Liver Italian Program), PS-JIS, GETCH(Groupe d’étude et de Traitement du Carcinome Hepatocellulaire) and TNM staging system 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 CLIP, PS-JIS, GETCH and TNM is 0.806, 0.761, 0.654 and 0.643. AUC of CLIP and PS-JIS is similar (P=0.1174), both significantly higher than the other two staging system (P<0.01). When predicting overall survival, likelihood ratio test show χ2 of CLIP, PS-JIS, GETCH and TNM is 74.00, 39.71, 23.09, 21.40. AIC of CLIP, PS-JIS, GETCH and TNM is 1601.46, 1635.80, 1655.06, 1654.77. The CLIP system has best performance in terms of discriminatory ability, homogeneity and monotonicity. Conclusions: The PS-JIS and CLIP systems were both the best score system in prediction of 3-month OS among the 4 systems and CLIP was still the best to predict OS analyzed for Chinese advanced HBV-associated HCC patients. [Table: see text]


2020 ◽  
Vol 18 (Sup10) ◽  
pp. S18-S26
Author(s):  
Sofi Dhanaraj ◽  
Tahir Shah ◽  
Joanne O'Rourke ◽  
Shishir Shetty

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, with increasing prevalence and mortality worldwide. The greatest risk factor for HCC is liver cirrhosis; however, these patients are often asymptomatic, making them difficult to identify for surveillance. Diagnosis is made with contrast-enhanced imaging and/or liver biopsy. HCC is assessed with the validated Barcelona Clinic Liver Cancer staging system, which encompasses tumour size, liver function and patient performance status. HCC without extrahepatic manifestations or vascular invasion may be cured with surgical intervention, involving either partial resection or full resection and liver transplantation. Locoregional therapies include tumour ablation, used for minimally invasive cure of early disease, and transarterial chemo-embolisation (TACE), used for control of intermediate disease. Both ablation and TACE are also used for downstaging as a bridge to transplantation. More advanced HCC can be controlled with drug-based systemic therapies involving either an oral kinase inhibitor (e.g. sorafenib, lenvatinib or regorafenib) or intravenous immunotherapy with one or more monoclonal antibodies (e.g. atezolizumab and bevacizumab). Best outcomes in HCC management require a multidisciplinary approach, including nutritional support and palliative care. The clinical nurse specialist plays an integral role by co-ordinating the treatment care pathway and responding to patient needs.


2017 ◽  
Vol 83 (1) ◽  
pp. 82-89 ◽  
Author(s):  
Folashade A. Adeshuko ◽  
Malcolm H. Squires ◽  
George Poultsides ◽  
Timothy M. Pawlik ◽  
Sharon M. Weber ◽  
...  

Controversy exists over the staging of gastroesophageal junction (GEJ) adenocarcinomas. The aim of our study was to assess the adequacy of the American Joint Committee on Cancer 7th edition esophageal (E7) and gastric (G7) staging systems for GEJ tumors in a western population. All patients with GEJ adenocarcinoma who underwent curative resection from 2000 to 2012 were identified from the United States Gastric Cancer Collaborative database and assessed according to the E7 and G7 systems. Fifty-one patients were identified. Neither the E7 nor G7 system adequately stratified patients by Tor N stage with a loss of distinctiveness between T1 to 4 and N0 to 3 tumors. On final stage analysis, the outcomes were similar between both systems; however, neither system, with the exception of the G7 stage I versus II, adequately stratified patients by stage (E7: I vs II, P = 0.07; II vs III, P = 0.23; G7: I vs II, P = 0.02; II vs III, P = 0.13). Histologic grade was not associated with survival (P = 0.27) and did not improve the ability to stratify patients in the E7 system. Our study identifies limitations in the proper stratification of patients with GEJ adenocarcinoma using either the American Joint Committee on Cancer 7th esophageal or gastric systems. The classification of GEJ adenocarcinoma within either system needs to be further studied in a larger patient population.


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