Predictive factors for intrahepatic recurrence after percutaneous ethanol injection therapy for small hepatocellular carcinoma

Koda, Masahiko; Murawaki, Yoshikazu; Mitsuda, Akeri; Ohyama, Kenji; Horie, Yutaka; Suou, Takeaki; KAWASAKI, Hironaka; Ikawa, Shiro

doi:10.1002/(sici)1097-0142(20000201)88:3<529::aid-cncr6>3.3.co;2-d

Cited by 48 publications

(58 citation statements)

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“…9 Despite the many options available for treatment, the prognosis of hepatocellular carcinoma remains poor, as the incidence of intrahepatic disease recurrence is high even if curative treatment is successfully performed. 10,11 We began our investigation of the potential benefit of proton beam therapy for patients with hepatocellular carcinoma at a local physics institution in 1983. Despite technical limitations imposed by fixed gantries, an analysis of patients treated at this facility showed excellent local control rates with minimal adverse effects.…”

Section: -5mentioning

confidence: 99%

Proton beam therapy for hepatocellular carcinoma

Nakayama

Sugahara

Tokita

et al. 2009

Cancer

118

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BACKGROUND:The authors have published a series of studies evaluating the safety and efficacy of proton beam therapy for the treatment of hepatocellular carcinoma in a variety of clinical settings. In the current study, they retrospectively reviewed their entire experience treating hepatocellular carcinoma patients with proton beam therapy at their hospital-based facility at the University of Tsukuba. METHODS: From November 2001 to December 2007, 333 patients with hepatocellular carcinoma were treated with proton beam therapy at the University of Tsukuba. A total of 318 patients were included in this study. Total dose delivered and fractionation scheme were determined by protocols that varied based on location of tumor. Survival rates and prognostic factors were assessed. RESULTS: Overall actuarial survival rates at 1-year, 3-years, and 5-years were 89.5% (95% confidence interval [95% CI], 85.7-93.1%), 64.7% (95% CI, 56.6-72.9%), and 44.6% (95% CI, 29.7-59.5%), respectively. Child-Pugh liver function (hazards ratio [HR], 2.84; P < .01), T stage (HR, 1.94; P < .05), performance status (HR, 2.12; P < .01), and planning target volume (HR, 2.12; P < .05) significantly impacted survival. The 3-year and 5-year survival rates were 69.1% (95% CI, 59.9-78.3%) and 55.9% (95% CI, 41.5-70.3%), respectively, for patients with Child-Pugh A disease and 51.9% (95% CI, 32.3-71.5%) and 44.5% (95% CI, 23.1-65.8%), respectively, for patients with Child-Pugh B disease. The actuarial survival rates of patients with Child-Pugh class A were statistically different between groups of planned target volume 125 mL and >125 mL (P < .05). CONCLUSIONS: The authors have shown proton beam therapy to be both safe and effective for the treatment of patients with hepatocellular carcinoma. They strongly recommend the consideration of proton beam therapy in patients for whom other treatment options are risky or contraindicated.

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Section: -5mentioning

confidence: 99%

Proton beam therapy for hepatocellular carcinoma

Nakayama

Sugahara

Tokita

et al. 2009

Cancer

118

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“…The prognosis for patients with hepatoma is poor because there is no effective treatment of metastatic disease. Furthermore, even in early stage cases where surgical treatment might be expected to be curative, the incidence of recurrence in patients with underlying cirrhosis is ϳ20 to 25% a year (2,3). In addition, at present there are no effective chemopreventive agents for hepatoma.…”

Section: Introductionmentioning

confidence: 99%

Synergistic Effects of Acyclic Retinoid and OSI-461 on Growth Inhibition and Gene Expression in Human Hepatoma Cells

Shimizu

Suzui²,

Deguchi³

et al. 2004

Clinical Cancer Research

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Hepatoma is one of the most frequently occurring cancers worldwide. However, effective chemotherapeutic agents for this disease have not been developed. Acyclic retinoid, a novel synthetic retinoid, can reduce the incidence of postsurgical recurrence of hepatoma and improve the survival rate. OSI-461, a potent derivative of exisulind, can increase intracellular levels of cyclic GMP, which leads to activation of protein kinase G and induction of apoptosis in cancer cells. In the present study, we examined the combined effects of acyclic retinoid plus OSI-461 in the HepG2 human hepatoma cell line. We found that the combination of as little as 1.0 mol/L acyclic retinoid and 0.01 mol/L OSI-461 exerted synergistic inhibition of the growth of HepG2 cells. Combined treatment with low concentrations of these two agents also acted synergistically to induce apoptosis in HepG2 cells through induction of Bax and Apaf-1, reduction of Bcl-2 and Bcl-x L , and activation of caspase-3, -8, and -9. OSI-461 enhanced the G 0 -G 1 arrest caused by acyclic retinoid, and the combination of these agents caused a synergistic decrease in the levels of expression of cyclin D1 protein and mRNA, inhibited cyclin D1 promoter activity, decreased the level of hyperphosphorylated forms of the Rb protein, induced increased cellular levels of the p21 CIP1 protein and mRNA, and stimulated p21 CIP1 promoter activity. Moreover, OSI-461 enhanced the ability of acyclic retinoid to induce increased cellular levels of retinoic acid receptor ␤ and to stimulate retinoic acid response element-chloramphenicol acetyltransferase activity. A hypothetical model involving concerted effects on p21 CIP1 and retinoic acid receptor ␤ expression is proposed to explain these synergistic effects. Our results suggest that the combination of acyclic retinoid plus OSI-461 might be an effective regimen for the chemoprevention and chemotherapy of human hepatoma and possibly other malignancies.

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“…1,2 Moreover, the incidence of posttherapeutic recurrence is approximately 20% to 25% a year in cirrhotic patients who have already undergone curative treatment of the primary HCC. 3,4 Importantly, at least one third of the second tumors are primary de novo cancers because of multicentric carcinogenesis and not intrahepatic recurrence or metastatic tumor. 5 Therefore, strategies to prevent a second primary HCC are required to improve the prognosis.…”

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confidence: 99%

Synergistic induction of apoptosis by acyclic retinoid and interferon-β in human hepatocellular carcinoma cells

et al. 2002

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H epatocellular carcinoma (HCC) is characterized by its high incidence in hepatitis virus-associated liver diseases, reaching approximately 3% in hepatitis B virus (HBV)-infected cirrhotic patients and 7% in hepatitis C virus (HCV)-infected cirrhotic patients. 1,2 Moreover, the incidence of posttherapeutic recurrence is approximately 20% to 25% a year in cirrhotic patients who have already undergone curative treatment of the primary HCC. 3,4 Importantly, at least one third of the second tumors are primary de novo cancers because of multicentric carcinogenesis and not intrahepatic recurrence or metastatic tumor. 5 Therefore, strategies to prevent a second primary HCC are required to improve the prognosis. 6 Clinical trials have succeeded in inhibiting the development of HCC with the compounds, including a retinoid analog (vitamin A and its derivatives), acyclic retinoid, 7,8 and interferon alfa and beta (IFN-␣ and -␤). 9-12 Acyclic retinoid is a member of the family of chemopreventive agents, whereas IFNs belong to a category of biopreventive agents, functioning as biologic response modifiers.Acyclic retinoid is a synthetic retinoid 13 and transactivates the 2 retinoid receptors, retinoic acid receptor (RAR), and retinoid X receptor (RXR). 14 Oral administration of the retinoid induces apoptosis in human HCC cell lines 15 and a clinical study we previously reported demonstrated a reduced incidence of posttherapeutic recurrence of HCC and, thereby, a significant improvement of survival rate. 7,8 In that clinical study, we

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Predictive factors for intrahepatic recurrence after percutaneous ethanol injection therapy for small hepatocellular carcinoma

Cited by 48 publications

References 0 publications

Proton beam therapy for hepatocellular carcinoma

Proton beam therapy for hepatocellular carcinoma

Synergistic Effects of Acyclic Retinoid and OSI-461 on Growth Inhibition and Gene Expression in Human Hepatoma Cells

Synergistic induction of apoptosis by acyclic retinoid and interferon-β in human hepatocellular carcinoma cells

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