Natural history of untreated nonsurgical hepatocellular carcinoma: Rationale for the design and evaluation of therapeutic trials

Llovet, Josep M.; Bustamante, Javier; Castells, Antoni; Vilana, R.; Ayuso, Maria Del Carmen; Sala, María; Brú, Concepció; Rodés, Joan; Bruix, Jordi

doi:10.1002/hep.510290145

Cited by 1,080 publications

(830 citation statements)

References 29 publications

(75 reference statements)

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“…Performance status had been shown to be an independent predictor of survival in a study on the natural history of untreated HCC and in other solid tumors. 24,25 Almost all our patients had underlying cirrhosis, so it is not surprising that survival was related to hepatic function. We found that MELD score was a better predictor of survival compared with CTP classification and individual laboratory tests of hepatic function.…”

Section: Discussionmentioning

confidence: 93%

Prognosis of hepatocellular carcinoma: Comparison of 7 staging systems in an American cohort

et al. 2005

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Currently there is no consensus which staging system is best in predicting the survival of patients with hepatocellular carcinoma (HCC). The aims of this study were to identify independent predictors of survival and to compare 7 available prognostic staging systems in patients with HCC. A total of 239 consecutive patients with cirrhosis and HCC seen between January 1, 2000, and December 31, 2003, were included. Demographic, laboratory, and tumor characteristics and performance status were determined at diagnosis and before therapy. Predictors of survival were identified using the Kaplan-Meir test and the Cox model. Sixty-two percent of patients had hepatitis C, 56% had more than 1 tumor nodule, 24% had portal vein thrombosis, and 29% did not receive any cancer treatment. At the time of censorship, 153 (63%) patients had died. The 1-and 3-year survival of the entire cohort was 58% and 29%, respectively. The independent predictors of survival were performance status (P < .0001), MELD score greater than 10 (P ‫؍‬ .001), portal vein thrombosis (P ‫؍‬ .0001), and tumor diameter greater than 4 cm (P ‫؍‬ .001). Treatment of HCC was related to overall survival. The Barcelona Clinic Liver Cancer (BCLC) staging system had the best independent predictive power for survival when compared with the other 6 prognostic systems. In conclusion, performance status, tumor extent, liver function, and treatment were independent predictors of survival mostly in patients with cirrhosis and HCC. The BCLC staging system includes aspects of all of these elements and provided the best prognostic stratification for our cohort of patients with HCC. ( H epatocellular carcinoma (HCC) is the fifth most common tumor worldwide. In the United States, the incidence of HCC has been rising, 1 and it is the tumor with the largest increase in incidence over the last 12 years. 2 Furthermore, the overall survival of patients with HCC has not improved over the last 20 years, with the incidence rate almost equal to the death rate. 3 It is projected that the increase in incidence of HCC will continue over the next 20 years in the United States. 4 Therefore, it is important to understand the factors that predict survival of patients with HCC.

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Section: Discussionmentioning

confidence: 93%

Prognosis of hepatocellular carcinoma: Comparison of 7 staging systems in an American cohort

et al. 2005

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“…This development presents a challenge with respect to prognostic modeling of HCC, because the natural history of early HCC is unknown. 12 In addition, intermediate and advanced HCC are quite heterogeneous, 33 even though the natural history and prognostic factors are well defined. 12 Therefore, it is necessary to establish robust methods capable of evaluating the prognosis of patients diagnosed at the early, intermediate, and late stages of HCC.…”

Section: Discussionmentioning

confidence: 99%

Classification and prediction of survival in hepatocellular carcinoma by gene expression profiling

et al. 2004

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We analyzed global gene expression patterns of 91 human hepatocellular carcinomas (HCCs) to define the molecular characteristics of the tumors and to test the prognostic value of the expression profiles. Unsupervised classification methods revealed two distinctive subclasses of HCC that are highly associated with patient survival. This association was validated via 5 independent supervised learning methods. We also identified the genes most strongly associated with survival by using the Cox proportional hazards survival analysis. This approach identified a limited number of genes that accurately predicted the length of survival and provides new molecular insight into the pathogenesis of HCC. Tumors from the low survival subclass have strong cell proliferation and antiapoptosis gene expression signatures. In addition, the low survival subclass displayed higher expression of genes involved in ubiquitination and histone modification, suggesting an etiological involvement of these processes in accelerating the progression of HCC. In conclusion, the biological differences identified in the HCC subclasses should provide an attractive source for the development of therapeutic targets (e.g., HIF1a) for selective treatment of HCC patients. H epatocellular carcinoma (HCC) is the fifth most common cancer in the world, accounting for an estimated 500,000 deaths annually. 1 Although HCC is prevalent in Southeast Asia and sub-Sahara Africa, the incidence of HCC has doubled in the United States over the past 25 years, and incidence and mortality rates are likely to double over the next 10 -20 years. 2 Although much is known about both the cellular changes that lead to HCC and the etiological agents responsible for the majority of HCC cases (hepatitis B virus, hepatitis C virus, alcohol), the molecular pathogenesis of HCC is not well understood. 3 Considerable efforts have been devoted to establishing a prognostic model for HCC by using clinical information and pathological classification to provide information at diagnosis on both survival and treatment options. 4 -10 Although much progress has been made (reviewed by Llovet et al. 11 ), many issues still remain unresolved. For example, a staging system that reliably separates patients with early HCC as well as intermediate to advanced HCC into homogeneous groups with respect to prognosis does not exist. This is particularly important because the natural course of early HCC is unknown and the natural progression of intermediate and advanced HCC are known to be quite heterogeneous. 12 It therefore appears axiomatic that improving the classification of HCC patients into groups with homogeneous prognosis would at least improve the application of currently available treatment modalities and at best provide new treatment strategies.Recently, microarray technologies have been successfully used to predict clinical outcome and survival as well as classify different types of cancer. [13][14][15]

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“…In contrast to a series of other published studies (Chevret et al, 1999;Llovet et al, 1999; The Cancer of the Liver Italian Program, 2000; Villa et al, 2000;Rabe et al, 2001;Herold et al, 2002), this study included a high number of patients treated by TACE and PEI, which have become the most frequently used treatments in the Western World. No patient was excluded from our retrospective analysis in contrast to those studies, who investigated only the effect of surgery or local ablative therapy (Tanaka et al, 1998;Schlitt et al, 1999;O'Suilleabhain et al, 2003;Jaeck et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Survival rate in patients with hepatocellular carcinoma: a retrospective analysis of 389 patients

Greten¹,

Papendorf

Bleck³

et al. 2005

Br J Cancer

174

101

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Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. However, treatment options are limited and often inefficient. The aim of this study was to determine current survival rates for patients diagnosed with HCC and to identify prognostic factors, which will help in choosing optimal therapies for individual patients. A retrospective analysis of medical records was performed on 389 patients who were identified through the central tumour registry at our institution from 1998 to 2003. Clinical parameters, treatments received and survival curves from time of diagnosis were analysed. Overall median survival was 11 months. Liver cirrhosis was diagnosed in 80.5% of all patients. A total of 170 patients received transarterial chemoembolisation (TACE) and/or percutaneous ethanol injections (PEI) with a median survival rate of 16 months for patients receiving TACE, 11 months for patients receiving PEI and 24 months for patients receiving TACE followed by PEI. Independent negative prognostic parameters for survival were the presence of portal vein thrombosis, advanced liver cirrhosis (Child -Pugh score B or C) and a score of 42. This study will help to estimate survival rates for patients with HCC according to their clinical status at diagnosis and the treatments received.

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Natural history of untreated nonsurgical hepatocellular carcinoma: Rationale for the design and evaluation of therapeutic trials

Cited by 1,080 publications

References 29 publications

Prognosis of hepatocellular carcinoma: Comparison of 7 staging systems in an American cohort

Prognosis of hepatocellular carcinoma: Comparison of 7 staging systems in an American cohort

Classification and prediction of survival in hepatocellular carcinoma by gene expression profiling

Survival rate in patients with hepatocellular carcinoma: a retrospective analysis of 389 patients

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