Natural history of small untreated hepatocellular carcinoma in cirrhosis: A multivariate analysis of prognostic factors of tumor growth rate and patient survival

Barbara, L; Benzi, G; Gaiani, Stefano; Fusconi, Fabio; Zironi, Gianni; Siringo, S.; Rigamonti, Alessandra; Barbara, C.; Grigioni, Francesco; Mazziotti, Alighieri; Bolondi, Luigi

doi:10.1002/hep.1840160122

Cited by 393 publications

(230 citation statements)

References 26 publications

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“…This parameter is scarcely reported, but it is known that there is a shortage of donors and that the length of the waiting period is increasing all over the world. In our series the mean waiting time was 2 months, whereas in other programs it may exceed 1 year, a period of time during which HCC may progress 35,36 and contraindicate the procedure. Up to now, we have not experienced such an event, but this possibility emphasizes the need of providing an intention to treat analysis when reporting the results of OLT, an aspect that is usually neglected.…”

Section: Discussionmentioning

confidence: 59%

Liver transplantation for small hepatocellular carcinoma: The tumor-node-metastasis classification does not have prognostic power

et al. 1998

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From a theoretical point of view, orthotopic liver transplantation (OLT) should be considered the ideal therapeutic option for patients with hepatocellular carcinoma (HCC).This neoplasm usually appears in the setting of liver cirrhosis, 1,2 and thus, OLT would eliminate the tumor and the oncogenic underlying liver. However, the first series of OLT for HCC showed disappointing results. [3][4][5][6] The inclusion of patients with advanced HCC prompted a high recurrence rate (higher than 50% at 3 years) whereas the survival rate (20%-50% at 5 years) was clearly less than that of non-HCC patients. Subsequent reports showed that HCC stage is a key point in determining the success of OLT in these patients and suggested that patients with early HCC could benefit from OLT both in terms of recurrence and survival. 5,7-10 Thereby, the recurrence rate of patients with incidental tumors which were discovered at the time of the pathological examination of the explanted liver is negligible. 3,7 Finally, two recent studies have shown that if OLT is restricted only to patients with early HCC (some years ago these tumors would have been identified only in the explanted livers), the risk of recurrence is minimal and the survival is identical to that of patients without HCC. 11,12 These encouraging data would favor OLT as the first therapeutic option to be considered in patients with HCC 13 as surgical resection is hampered by a higher recurrence rate during follow up [14][15][16][17] ; however, OLT is a highly invasive procedure with potentially severe complications in the early, medium, and long-term follow up. In addition, it must be stressed that HCC in most of the patients arises on liver cirrhosis caused by infection with HBV or HCV, 2,18 which frequently infects the graft, 19,20 and that the progression of the liver disease may be faster than in immunologically competent individuals. 21 As previously reported, 22-25 the treatment schedule applied in our Liver Unit in patients with HCC considered OLT only for those patients with solitary tumors smaller than 5 cm in whom resection was contraindicated, whereas the stage according to the TNM staging system was not taken into account. The present study analyzes the outcome of the cohort of the first 58 HCC patients submitted to OLT following this pre-established treatment algorithm, describing the accuracy of the preoperative staging, the recurrence and survival data, and also the rate of viral infection of the new liver. PATIENTS AND METHODS PatientsBetween January 1989 and December 1995, 877 patients with HCC were diagnosed, staged, and treated in our Liver Unit according to a previously published schedule. [22][23][24][25] Patients with HCC were Abbreviations: HCC, hepatocellular carcinoma; OLT, orthotopic liver transplantation; TNM, tumor-node-metastasis classification system; pTNM, pathological tumor-nodemetastasis classification.From the

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Section: Discussionmentioning

confidence: 59%

Liver transplantation for small hepatocellular carcinoma: The tumor-node-metastasis classification does not have prognostic power

et al. 1998

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“…Extensive searching revealed a total of nine papers 324,327,328,[349][350][351][352][353][354] (Table 20). We were unable to locate studies based on UK populations or studies in which the tumour growth rates in patients with different cirrhosis aetiologies were reported.…”

Section: Tumour Growth Ratementioning

confidence: 99%

Surveillance of cirrhosis for hepatocellular carcinoma: systematic review and economic analysis

Coon¹,

Rogers²,

Hewson³

et al. 2007

Health Technol Assess

150

108

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Non-UK purchasers will have to pay a small fee for post and packing. For European countries the cost is £2 per monograph and for the rest of the world £3 per monograph.You can order HTA monographs from our Despatch Agents:-fax (with credit card or official purchase order) -post (with credit card or official purchase order or cheque) -phone during office hours (credit card only).Additionally the HTA website allows you either to pay securely by credit card or to print out your order and then post or fax it. NHS libraries can subscribe free of charge. Public libraries can subscribe at a very reduced cost of £100 for each volume (normally comprising 30-40 titles). The commercial subscription rate is £300 per volume. Please see our website for details. Subscriptions can only be purchased for the current or forthcoming volume. Contact details are as follows: Payment methods Paying by chequeIf you pay by cheque, the cheque must be in pounds sterling, made payable to Direct Mail Works Ltd and drawn on a bank with a UK address. Paying by credit cardThe following cards are accepted by phone, fax, post or via the website ordering pages: Delta, Eurocard, Mastercard, Solo, Switch and Visa. We advise against sending credit card details in a plain email. Paying by official purchase orderYou can post or fax these, but they must be from public bodies (i.e. NHS or universities) within the UK. We cannot at present accept purchase orders from commercial companies or from outside the UK. How do I get a copy of HTA on CD?Please use the form on the HTA website (www.hta.ac.uk/htacd.htm). Or contact Direct Mail Works (see contact details above) by email, post, fax or phone. HTA on CD is currently free of charge worldwide.The website also provides information about the HTA Programme and lists the membership of the various committees. Declared competing interests of authors: K Stein received an unrestricted grant from Schering Plough (UK) to carry out work on the cost-effectiveness of combination therapy for hepatitis C in 2000. KS is also a member of the editorial board for Health Technology Assessment, but he was not involved in the editorial process for this report. M Cramp sits on hepatitis C advisory boards for Schering Plough, Gilead and Roche. He has received unrestricted educational grants from Roche and Schering Plough to support research and service development. He has been awarded an NHS R&D grant looking at injecting drug users who do not have hepatitis C virus infection. J Thompson Coon received a grant from the Hepatitis C Trust to conduct a systematic review of complementary and alternative therapies for the treatment of chronic hepatitis C. HTA Published September 2007This report should be referenced as follows: NIHR Health Technology Assessment ProgrammeT he Health Technology Assessment (HTA) programme, now part of the National Institute for Health Research (NIHR), was set up in 1993. It produces high-quality research information on the costs, effectiveness and broader impact of health technologies for those who use, man...

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“…4,5 However, several natural history studies have pointed out that HCC tumor growth is not always constant. [6][7][8] We previously developed a computer simulation that captured different growth rates and patterns of HCC tumor growth. 9 For this analysis, we applied this model to estimate the probability of tumor growth and survival for patients with early HCC and well-compensated cirrhosis while waiting for a transplant.…”

mentioning

confidence: 99%

Predicting the probability of progression-free survival in patients with small hepatocellular carcinoma

Cheng

2002

Liver Transplantation

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Allocation of cadaveric livers to patients based on such objective medical urgency data as the Model for End-Stage Liver Disease (MELD) score may not benefit patients with small hepatocellular carcinomas (HCCs). To ensure that these patients have a fair opportunity of receiving a cadaveric organ, the risk for death caused by HCC and tumor progression beyond 5 cm should be considered. Using a Markov model, two hypothetical cohorts of patients with small hepatomas were assumed to have either (1) Gompertzian tumor growth, in which initial exponential growth decreases as tumor size increases; or (2) rapid exponential growth. The model tracked the number of patients who either died or had tumor progression beyond 5 cm. These results were used to back-calculate an equivalent MELD score for patients with small HCCs. All probabilities in the model were varied simultaneously using a Monte Carlo simulation. The Gompertzian growth model predicted that patients with a 1-and 4-cm tumor have 1-year progression-free survival rates of 70% (HCC-specific MELD score 6) and 66% (HCC-specific MELD score 8), respectively. When assuming rapid exponential growth, patients with a 1-and 4-cm tumor have progression-free survival rates of 69% (HCC-specific MELD score 6) and 12% (HCC-specific MELD score 24), respectively. Our model predicted that the risk for death caused by HCC or tumor progression beyond 5 cm should increase with larger initial tumor size in patients with small hepatomas. To ensure that these patients have a fair opportunity to receive a cadaveric organ, HCC-specific scores predicted by our model could be added to MELD scores of patients with HCC. (Liver Transpl 2002;8:323-328.) T he mandate by the Department of Health and Human Services to allocate livers to the sickest patients based on objective medical urgency data has led to the proposal that prioritization of liver transplant candidates be based on a model developed by the Mayo Clinic, the Model for End-Stage Liver Disease (MELD). 1-3 The MELD formula uses prognostic factors and disease cause to calculate a risk score for mortality on the waiting list. Patients with a higher score have a higher priority for receiving a donor liver. Under the MELD scoring system, patients with early hepatocellular carcinoma (HCC) are unlikely to achieve a high score because many of these patients have well-maintained liver synthetic function. However, without a timely transplant for these patients, HCC may progress in size and lead to death.How could access to timely transplantation be improved for patients with HCC under the MELD system? One approach would be to incorporate into the MELD the likelihood of being removed from the waiting list because of death secondary to HCC or disease progression. In the absence of a published trial, decision analytic modeling is a method that can be used to estimate this likelihood. Previously published decision models have assessed the risk for HCC tumor progression by assuming that tumor growth is constant. 4,5 However, several natural history st...

show abstract

Natural history of small untreated hepatocellular carcinoma in cirrhosis: A multivariate analysis of prognostic factors of tumor growth rate and patient survival

Cited by 393 publications

References 26 publications

Liver transplantation for small hepatocellular carcinoma: The tumor-node-metastasis classification does not have prognostic power

Liver transplantation for small hepatocellular carcinoma: The tumor-node-metastasis classification does not have prognostic power

Surveillance of cirrhosis for hepatocellular carcinoma: systematic review and economic analysis

Predicting the probability of progression-free survival in patients with small hepatocellular carcinoma

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