Debulking surgery followed by intraarterial 5-fluorouracil chemotherapy plus subcutaneous interferon alfa for massive hepatocellular carcinoma with multiple intrahepatic metastases: A pilot study

Tanaka, Kuniya; Yabushita, Yasuhiro; Nakagawa, Kazuhiko; Kumamoto, Takafumi; Matsuo, Keitaro; Taguri, Masataka; Endo, Itaru

doi:10.1016/j.ejso.2013.10.007

Cited by 14 publications

(13 citation statements)

References 30 publications

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“…In patients with interval of recurrence from initial treatment of more than 1 year, the median survival time was 18.0 months (95% CI: 14.3, 21.7) in the combination group The previously mentioned evidence implies that intrahepatic tumor burden seemed to play a more important role in survival outcomes in selected patients with advanced rHCC. Results from other studies indicate that debulking tumor burden in the liver can prolong survival time in patients with advanced HCC (11,12), which further proves the rationale for concurrent use of TACE-RFA with sorafenib to effectively control intrahepatic tumors. Second, sorafenib might improve local tumor control by inhibiting hypoxiainduced angiogenesis after TACE-RFA.…”

Section: Discussionmentioning

confidence: 72%

“…One study showed that extrahepatic metastasis (19,31). Second, in a previous study of patients with advanced HCC, those with fewer than five tumors had better survival than did those with five or more tumors (11). Furthermore, the possibility of incomplete removal of tumors increases as the number of tumors increases.…”

Section: Discussionmentioning

confidence: 98%

“…Sorafenib is typically used as the first-option therapy in patients with primary advanced HCC; however, its efficacy as a monotherapy is relatively limited (4)(5)(6). Given that most patients with advanced HCC die of intrahepatic tumor progression rather than extrahepatic metastatic disease (7-10), debulking the intrahepatic tumor burden is thought to prolong survival time of patients with advanced HCC (11,12).…”

Section: Implication For Patient Carementioning

confidence: 99%

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Advanced Recurrent Hepatocellular Carcinoma: Treatment with Sorafenib Alone or in Combination with Transarterial Chemoembolization and Radiofrequency Ablation

Peng¹,

Chen²,

Wei³

et al. 2018

Radiology

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Purpose To retrospectively investigate the safety and efficacy of sorafenib combined with transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) (hereafter, TACE-RFA) in the treatment of recurrent hepatocellular carcinoma (rHCC) with portal vein tumor thrombosis, extrahepatic metastases (advanced hepatocellular carcinoma), or both after initial hepatectomy. Materials and Methods The study was centrally approved by the ethics committee of three tertiary medical centers in China. From January 2010 to January 2015, 207 consecutive patients with advanced rHCC after initial hepatectomy received sorafenib combined with TACE-RFA (combination group, n = 106) or sorafenib alone (sorafenib group, n = 101) at the three medical centers. Overall survival (OS) and time to progression (TTP) were compared between the two groups. Complications were assessed. Survival curves were constructed with the Kaplan-Meier method and were compared with the log-rank test. Results Baseline characteristics were balanced between the two groups. No treatment-related death occurred in either group. The toxicity profile in the combination group was similar to that in the sorafenib group. After treatment, median OS (14.0 vs 9.0 months, respectively; P < .001) and TTP (7.0 vs 4.0 months, respectively; P < .001) were significantly longer in the combination group than in the sorafenib group. Multivariate analysis showed that treatment allocation was a significant predictor of OS and TTP, while the number of intrahepatic tumors was another prognostic factor of OS. Conclusion Sorafenib combined with TACE-RFA was well tolerated and safe and was superior to sorafenib alone in improving survival outcomes in patients with advanced rHCC after initial hepatectomy. RSNA, 2018 Online supplemental material is available for this article.

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Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 98%

Section: Implication For Patient Carementioning

confidence: 99%

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Advanced Recurrent Hepatocellular Carcinoma: Treatment with Sorafenib Alone or in Combination with Transarterial Chemoembolization and Radiofrequency Ablation

Peng¹,

Chen²,

Wei³

et al. 2018

Radiology

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“…Accumulating evidences have demonstrated that IFNα possessed chemo-sensitizing characteristics under different drugs. Radical surgery followed by IFNα and 5-FU combination chemotherapy offers possibility of long-term survival despite massive hepatocellular carcinoma with multiple intrahepatic metastases 29 , 30 . IFNα pre-treatment followed by a combination of IFNα plus Erlotinib significantly enhanced the sensitivity of colon cancer cell lines 31 .…”

Section: Discussionmentioning

confidence: 99%

Interferon-α Promotes the Expression of Cancer Stem Cell Markers in Oral Squamous Cell Carcinoma

Ma¹,

Jin²,

Yang³

et al. 2017

J. Cancer

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Objectives: IFNα can stimulate an antitumor immune response and has a direct inhibition on cancer cells. This study is to test whether IFNα can activate dormant cancer stem cell (CSC) in oral squamous cell carcinoma (OSCC) to facilitate their elimination by chemotherapy.Materials and methods: Nude mouse transplantation tumor model was established and administrated with IFNα and saline. The influence on CD44 and ALDH1A1 expression under IFNα treatment was detected by in vivo experiments. Flow cytometry, western blot, and immunofluorescence were used to detect the expression of CD44 and ALDH1A1 after INFa treatment in OSCC cell lines. Tumorsphere formation assay was conducted under incubation with IFNα for 2 weeks. Chromatin immunoprecipitation (ChIP) assays was used to examine the IFNα-induced transcriptional regulation of CD44 and ALDH1A1 expression. That IFNα-primed enhanced killing effect of chemotherapy was evaluated by MTT and western blot.Results: IFNα transcriptionally activated the expression of CD44 and ALDH1A1 expression both in vivo and in vitro. IFNα-primed enhanced the cytotoxic inhibition effect of CDDP, erlotinib and nimotuzumab on OSCC cells.Conclusion: These results suggest that IFNα could be administrated to patients prior to chemotherapeutic drugs, which will facilitate the killing of cancer stem cells in OSCC.

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“…For patients with large HCC tumors with multiple intrahepatic metastases, debulking surgery followed by IFN-α and 5-FU combination therapy offers the possibility of long-term survival; however, optimal debulking is essential for prolonged survival during subsequent treatment ( 94 ), for example, postoperative adjuvant TACE is typically administered to HCC patients at a high risk of recurrence ( 95 , 96 ). In 27 patients with large HCC tumors and multiple intrahepatic metastases, Tanaka et al ( 97 ) performed IFN-α and TACE combination therapy following maximal liver tumor resection, and identified that this treatment strategy offered the possibility of long-term survival despite the late stage of the disease. In a preliminary report of 33 patients, Kumamoto et al ( 98 ) proposed that combination of subcutaneous IFN-α and intra-arterial 5-FU infusion therapy may delay the development of recurrence and reduce the number of recurrent nodules in the remnant liver following curative resection.…”

Section: Synergistic Effects Of Ifn-α and Other Agents On Hbv-assomentioning

confidence: 99%

Role of antiviral therapy in reducing recurrence and improving survival in hepatitis B virus-associated hepatocellular carcinoma following curative resection (Review)

Zuo

Xia

et al. 2014

Oncology Letters

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Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related mortality worldwide, with the majority of cases associated with persistent hepatitis B virus (HBV) or hepatitis C virus infection. In particular, chronic HBV infection is a predominant risk factor for the development of HCC in Asian and African populations. Hepatic resection, liver transplantion and radiofrequency ablation are increasingly used for the curative treatment of HCC, however, the survival rate of HCC patients who have undergone curative resection remains unsatisfactory due to the high recurrence rate. HCC is a complex disease that is typically resistant to the most commonly used types of chemotherapy and radiotherapy; therefore, the development of novel treatment strategies is required to improve the survival rate of this disease. A high viral load of HBV DNA is the most important correctable risk factor for HCC recurrence, for example nucleos(t)ide analogs improve the outcome following curative resection of HBV-associated HCC, and interferon-α exhibits antitumor activity against various types of cancer via direct inhibitory effects on tumor cells, anti-angiogenesis, enhanced immunogenicity of tumors, immunomodulatory effects and liver dysfunction. In the present review, antiviral treatment for HBV-associated HCC is described as a strategy to reduce recurrence and improve survival.

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Debulking surgery followed by intraarterial 5-fluorouracil chemotherapy plus subcutaneous interferon alfa for massive hepatocellular carcinoma with multiple intrahepatic metastases: A pilot study

Cited by 14 publications

References 30 publications

Advanced Recurrent Hepatocellular Carcinoma: Treatment with Sorafenib Alone or in Combination with Transarterial Chemoembolization and Radiofrequency Ablation

Advanced Recurrent Hepatocellular Carcinoma: Treatment with Sorafenib Alone or in Combination with Transarterial Chemoembolization and Radiofrequency Ablation

Interferon-α Promotes the Expression of Cancer Stem Cell Markers in Oral Squamous Cell Carcinoma

Role of antiviral therapy in reducing recurrence and improving survival in hepatitis B virus-associated hepatocellular carcinoma following curative resection (Review)

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