Neoadjuvant chemotherapy and liver transplantation for hepatocellular carcinoma: A pilot study in 20 patients

Stone, Marvin J.; Klintmalm, Göran B.; Polter, Daniel E.; Husberg, Bo S.; Mennel, Robert G.; Ramsay, Michael A. E.; Flemens, E.Eron; Goldstein, Robert M.

doi:10.1016/0016-5085(93)90852-4

Cited by 191 publications

(70 citation statements)

References 23 publications

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“…A second important parameter that has to be discussed is the lack of coadjuvant treatment while being on the waiting list. Several groups perform chemoembolization 37,38 or percutaneous ethanol injection 39 aiming to necrose almost all the tumor and prevent its dissemination. However, it has been suggested that these invasive treatments may indeed induce tumor cell dissemination.…”

Section: Discussionmentioning

confidence: 99%

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: 99%

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

et al. 1998

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“…In the worst subgroup, however, resection is precluded according to the poor results obtained, and thus other medical treatments should be assessed. In that regard, percutaneous treatments, chemoembolization or chemotherapy could be proposed to prevent tumor progression, but the benefit of this commonly applied strategy [42][43][44] has not been shown by RCTs. Accordingly well-designed clinical studies should be engaged to define the best management strategy of HCC patients on the waiting list and its cost effectiveness.…”

Section: Discussionmentioning

confidence: 99%

Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: Resection versus transplantation

1999

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Liver transplantation is proposed as the best therapy for early hepatocellular carcinoma in cirrhotic patients. However, the confrontation with the results obtained by surgical resection has never been done on an intention-to-treat basis. Between 1989 and 1997, 164 out of 1,265 patients with hepatocellular carcinoma were evaluated for surgery. Seventyseven (48 men, mean 61 years of age, 74 Child-Pugh class A, size 33 ؎ 18 mm) were resected (first line option) and 87 (65 men, mean 55 years of age, 50 Child-Pugh class B/C, size 24 ؎ 14 mm) were selected for transplantation. The 1-, 3-, and 5-year ''intention-to-treat'' survival was 85%, 62%, and 51% for resection and 84%, 69%, and 69% for transplantation (8 drop-outs on waiting list). Bilirubin and clinically relevant portal hypertension were independent survival predictors after resection. Thereby, the 5-year survival of the best candidates (absence of clinically relevant portal hypertension, n ‫؍‬ 35) was 74%, whereas it was 25% for the worst candidates (portal hypertension and bilirubin H1 mg/dL, n ‫؍‬ 27) (P F .00001). The variable ''drop-out on waiting list'' was the sole survival predictor after transplantation. The 2-year survival rate of patients evaluated for transplantation was 84% in the 1989 to 1995 period (mean waiting time, 62 days; no drop-outs) and 54% during 1996 to 1997 (mean waiting time, 162 days; 8 drop-outs)(P F .003). This outcome was significantly lower than that of the best candidates for resection (P ‫؍‬ .002). In conclusion, a proper selection of candidates for resection promotes better results than transplantation, in which the results are significantly hampered by the growing incidence of drop-outs because of the increasing waiting time. (HEPATOLOGY 1999;30:1434-1440.)There are no randomized controlled clinical trials (RCTs) comparing orthotopic liver transplantation (OLT) versus surgical resection for early hepatocellular carcinoma (HCC) in cirrhotic patients. By now, such an RCT should be considered largely unfeasible because it would require a very large sample size, thus involving several centers sharing the same selection criteria and therapeutic skills. Thus, the debate regarding which should be the preferred treatment option is based on the comparison between the outcomes of independent cohorts of patients. This approach suggests that OLT offers better life expectancy, 1-7 but this assumption is misleading. There are no intention-to-treat studies, and this is of paramount importance because a noteworthy proportion of patients will be excluded from the transplantation program because of tumor growth or development of contraindications while waiting for a donor. Spain has the highest liver donation rate throughout the world (20 liver donors/10 6 inhabitants), 8 and the proportion of drop-outs (because of death or appearance of contraindications) is nowadays around 15%. 9 Furthermore, although the encouraging survival data described for HCC patients effectively transplanted (75% at 5 years) are due both to a restrictive selection p...

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“…6 -11 Resection and liver transplantation are the treatments for HCC with the most mature outcome data. [12][13][14][15] Five-year survival after resection ranges from 31% 16 to 56%, 17 with serious morbidity and mortality rates of approximately 5%. 18 Resection often is not possible because of poor liver function or macrovascular tumor invasion.…”

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confidence: 99%

Radiation therapy for hepatocellular carcinoma

Hawkins

Dawson

2006

Cancer

221

171

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Technologic advances have provided the means to deliver tumoricidal doses of radiation therapy (RT) to patients with unresectable hepatocellular carcinoma (HCC) while avoiding critical normal tissues, providing the opportunity to use RT for curative intent treatment of HCC. For the current report, the expanded role of external beam RT in the setting of HCC from palliation to cure was reviewed. A systematic literature search was undertaken using the MEDLINE data base and secondary references to identify peer-reviewed, English-language articles that re- control response rates ranged from 40% to 90%, and the median survival ranges from 10 months to 25 months. For patients with HCC who had portal vein thrombus, the median survival after RT to treat the thrombus and/or the hepatic tumor with or without TACE ranged from 5.3 months to 9.7 months. Although outcomes after high-dose conformal RT for liver-confined HCC were excellent, the potential survival benefit of RT should be tested in randomized controlled trials that require international collaboration.

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Neoadjuvant chemotherapy and liver transplantation for hepatocellular carcinoma: A pilot study in 20 patients

Cited by 191 publications

References 23 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

Intention-to-treat analysis of surgical treatment for early hepatocellular carcinoma: Resection versus transplantation

Radiation therapy for hepatocellular carcinoma

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