Simplified Staging for Hepatocellular Carcinoma

Vauthey, Jean‐Nicolas; Lauwers, Gregory Y.; Esnaola, Nestor F.; Do, Kim‐Anh; Belghiti, Jacques; Mirza, Nadeem Q.; Curley, Steven A.; Ellis, Lee M.; Régimbeau, Jean‐Marc; Rashid, Asif; Cleary, Karen R.; Nagorney, David M.

doi:10.1200/jco.2002.20.6.1527

Cited by 462 publications

(251 citation statements)

References 34 publications

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“…Examples of common genetic alteration observed in hepatocellular carcinoma are shown in Figure 1. Since similar 5-year survivals had been suggested in hepatocellular carcinoma patients with stage I and II tumors, and that the survival of patients with multiple tumors from stage III matched that of stage IV patients, 16 we have hence examined the genomic alterations in the 100 cirrhotic hepatocellular carcinoma by grouping cases of stage I and II as early stage tumors (totaling 73 cases) and compared findings to those derived from stage III and IV as advanced stage tumors (totaling 27 cases). No difference in clinical factors such as age, gender and pathologic factors, including serum alphafetoprotein (AFP) level, and tumor encapsulation was observed with the above stratification ( Table 1).…”

Section: Resultsmentioning

confidence: 86%

Regional over-representations on chromosomes 1q, 3q and 7q in the progression of hepatitis B virus-related hepatocellular carcinoma

Wong

Lai

et al. 2005

Modern Pathology

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Hepatocellular carcinoma is a highly malignant tumor that is prevalent in Southeast Asia and China, where hepatitis B viral infection is the main etiologic factor. Despite a high incidence of hepatocellular carcinoma developing in patients with viral hepatitis B-induced liver cirrhosis, the molecular events underlying the malignant liver progression remain largely unclear. In an effort to characterize the genetic abnormalities involved in the hepatitis B-related liver carcinogenesis, we performed genome-wide explorations by the technique of comparative genomic hybridization (CGH) on 100 hepatocellular carcinoma tumors that arose from hepatitis B-induced liver cirrhosis. According to the American Joint Committee on Cancer staging, four cases were classified as stage I, 69 as stage II, 23 as stage III and four as stage IV. CGH analysis indicated chromosomal instability in both early (stages I/II) and advanced (stages III/IV) stage tumors, with common gains on 1q, 8q and 17q23-q25, and losses on 4q22-q35, 8p21-p22, 13q14-q21, 16q and 17p identified in both groups (P40.05). Nevertheless, preferential sites of chromosomal defects in relation to hepatocellular carcinoma progression were also identified. Statistical correlations suggested a higher incidence of regional 1q21-q22, 3q22-q28, 7q21-q22 and 7q34-q36 over-representations in association with the advanced stage tumors (Po0.05). In this study, our novel identification of specific chromosomal aberrations in relation to the advanced stage tumors may represent a first step towards mapping genes linked to the progression of hepatocellular carcinoma. Modern Pathology (2005) 18, 686-692, advance online publication, 17 December 2004; doi:10.1038/modpathol.3800345 Keywords: hepatocellular carcinoma; hepatitis B virus; liver cirrhosis; progression Hepatocellular carcinoma is a primary liver malignancy that is highly malignant and rapidly fatal. The dismal clinical outcome is largely due to the majority of hepatocellular carcinoma tumors being asymptomatic during the natural course of the disease, consequently rendering most patients not being diagnosed in time for curative surgery. 1 By the time of clinical presentation, intra-and extrahepatic metastases are also common, which in turn has limited the scope of curative surgery. 2 In addition, the relatively high incidences of hepatocellular carcinoma recurrence, possibly from micrometastasis prior to surgical treatment, has further lowered the 5-year survival rate for individuals diagnosed with hepatocellular carcinoma. 3 The understanding of molecular events involved in the malignant liver progression thus would hold much value in the prognosis for patients with hepatocellular carcinoma.Studies on the molecular pathogenesis have guided the development of gene-based biomarkers in a number of human cancers including breast, colon, prostate and lung. 4 In hepatocellular carcinoma, although genetic characterizations have indicated frequent chromosomal over-representations on 1q, 6p, 8q, 17q and 20q, and deletions on 1p, 4q, ...

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Section: Resultsmentioning

confidence: 86%

Regional over-representations on chromosomes 1q, 3q and 7q in the progression of hepatitis B virus-related hepatocellular carcinoma

Wong

Lai

et al. 2005

Modern Pathology

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“…31 In the same context, HCC with a high uptake of 18 F-FDG exhibited microvascular invasion more frequently, which proved to be an important histopathological parameter, resulting in treatment failures like intrahepatic/extrahepatic dissemination. 32,33 Thus, it is of note that patients with the higher baseline maximal tumor SUV were more likely to have extrahepatic metastasis within 6 months of treatment initiation (more than 2-fold increase of risk) compared with those with low maximal tumor SUV. In particular, patients with high maximal tumor SUV had an approximately 4-fold increase in the incidence of extrahepatic metastasis after completion of localized CCRT.…”

Section: Discussionmentioning

confidence: 99%

¹⁸F‐fluorodeoxyglucose uptake on positron emission tomography as a prognostic predictor in locally advanced hepatocellular carcinoma

Kim

Kang

Kim

et al. 2011

Cancer

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BACKGROUND: Metabolic activity assessed by 18 F-fluorodeoxyglocuse-positron emission tomography ( 18 F-FDG-PET) reflects biological aggressiveness and prognoses in various tumors. The authors present a correlation between tumor metabolic activity and clinical outcomes in patients with hepatocellular carcinoma (HCC). METHODS: Over a 3-year period (2005)(2006)(2007)(2008), 135 locally advanced HCC patients were treated with localized concurrent chemoradiotherapy (CCRT; external beam radiotherapy at 45 grays for 5 weeks plus concurrent hepatic arterial infusion of 5-fluorouracil during the first and fifth week) followed by repetitive hepatic arterial infusional chemotherapy with 5-fluorouracil and cisplatin. Among them, the authors studied 107 who received 18 F-FDG-PET before CCRT. Maximal standardized uptake values (SUVs) of tumors were calculated. RESULTS: The median maximal tumor SUV was 6.1 (range, 2.4-$19.2). Patients with low maximal tumor SUVs (<6.1) had a higher disease control rate than those with high maximal tumor SUVs (!6.1) (86.8% vs 68.5%, respectively, P ¼ .023). Both median progression-free survival (PFS; 8.4 vs 5.2 months; P ¼ .003) and overall survival (OS; 17.9 vs 11.3 months; P ¼ .013) were significantly longer in the low maximal tumor SUV group than in the high maximal tumor SUV group, respectively. In multivariate analysis, low maximal tumor SUV and objective responses to CCRT remained significant for PFS and OS. The high maximal tumor SUV group was more likely to have extrahepatic metastasis within 6 months than the low maximal tumor SUV group (58.1% vs 26.8%, respectively; P < .001). Similar results were obtained for the maximal tumor SUV/normal liver maximal SUV ratio (<2 vs !2) concerning progression, death, and extrahepatic metastasis. CONCLUSIONS: Metabolic activity may be useful not only in predicting prognosis and treatment responses, but also in establishing optimal treatment plans in locally advanced HCC. Cancer 2011;117:4779-

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“…[1][2][3][4][5][6]12,13,17 All staging systems that are known as effective for the prediction of prognosis in patients with HCC who are undergoing locoregional therapy were included in this study. However, prognostic scoring systems in which the number of stratifications is >7, like the Tokyo scoring system or the Chinese University Prognostic Index, were not included.…”

Section: Analysis Of the Prognostic Factors For Overall Survival And mentioning

confidence: 99%

“…[1][2][3][4][5][6][7] However, it is neither easy nor feasible to satisfy the aspects of both treatment and prognosis simultaneously by using the available staging systems. Primary staging systems like the Barcelona Clinic Liver Cancer (BCLC) system or the Japanese Integrated Staging (JIS) system have been developed based on databases from surgically oriented centers.…”

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confidence: 99%

Comparison of 7 staging systems for patients with hepatocellular carcinoma undergoing transarterial chemoembolization

Cho

Chung

Kim

et al. 2007

Cancer

110

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BACKGROUND.Many liver staging systems have been proposed for patients with hepatocellular carcinoma after locoregional therapy; however, controversies persist regarding which system is the best. In this study, the authors compared the performance of 7 staging systems in a cohort of patients with hepatocellular carcinoma who underwent transarterial chemoembolization.METHODS.In total, 131 patients with hepatocellular carcinoma who underwent transarterial chemoembolization between August 1998 and February 2005 were included in the study. Demographic, laboratory, and tumor characteristics were determined at diagnosis and before therapy. At the time of censorship, 109 patients had died (83.2%). Predictors of survival were identified by using the Cox proportional hazards model. The likelihood‐ratio chi‐square statistic and the Akaike Information Criterion were calculated for 7 prognostic systems to evaluate their discriminatory ability. Comparisons of the survival rate between each stage were performed to evaluate the monotonicity of the gradients using Kaplan‐Meier estimation and the log‐rank test.RESULTS.The 5‐year survival rate for the entire cohort was 13.6%. The independent predictors of survival were serum albumin level (≤3.4 g/dL), the presence of ascites, serum α‐fetoprotein level (>60 ng/mL), and portal or hepatic vein tumor thrombosis (P = .001, P = .001, P = .004, and P = .000, respectively). The Cancer of the Liver Italian Program classification system was superior to the other 6 prognostic systems regarding discriminatory ability and the monotonicity of the gradients.CONCLUSIONS.In this comparison of many staging systems, the Cancer of Liver Italian Program system provided the best prognostic stratification for a cohort the patients with hepatocellular carcinoma who underwent transarterial chemoembolization. Cancer 2008. © 2007 American Cancer Society.

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Simplified Staging for Hepatocellular Carcinoma

Abstract: The current AJCC staging system for HCC is unnecessarily complex. We propose a simplified model of stratification that is based on vascular invasion, tumor number, and tumor size and incorporates the effect of fibrosis on survival.

Cited by 462 publications

References 34 publications

Regional over-representations on chromosomes 1q, 3q and 7q in the progression of hepatitis B virus-related hepatocellular carcinoma

Regional over-representations on chromosomes 1q, 3q and 7q in the progression of hepatitis B virus-related hepatocellular carcinoma

¹⁸F‐fluorodeoxyglucose uptake on positron emission tomography as a prognostic predictor in locally advanced hepatocellular carcinoma

Comparison of 7 staging systems for patients with hepatocellular carcinoma undergoing transarterial chemoembolization

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Simplified Staging for Hepatocellular Carcinoma

Abstract: The current AJCC staging system for HCC is unnecessarily complex. We propose a simplified model of stratification that is based on vascular invasion, tumor number, and tumor size and incorporates the effect of fibrosis on survival.

Cited by 462 publications

References 34 publications

Regional over-representations on chromosomes 1q, 3q and 7q in the progression of hepatitis B virus-related hepatocellular carcinoma

Regional over-representations on chromosomes 1q, 3q and 7q in the progression of hepatitis B virus-related hepatocellular carcinoma

18F‐fluorodeoxyglucose uptake on positron emission tomography as a prognostic predictor in locally advanced hepatocellular carcinoma

Comparison of 7 staging systems for patients with hepatocellular carcinoma undergoing transarterial chemoembolization

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¹⁸F‐fluorodeoxyglucose uptake on positron emission tomography as a prognostic predictor in locally advanced hepatocellular carcinoma