Chemoembolization in the Management of Liver Tumors

Stuart, Keith

doi:10.1634/theoncologist.8-5-425

Cited by 89 publications

(47 citation statements)

References 101 publications

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“…5,6,22,23 Surgical hepatic resection of the tumor is the best therapeutic method, and the only generally accepted and potentially curative treatment for patients with CCC in the absence of primary sclerosing cholangitis, however only a small percentage of patients are candidates for curative surgery because of the advanced clinical stage at the time of diagnosis. 14,24,25 Surgical resection showed a median survival time of 13-44 months (26)(27)(28), and a 5-year survival rate of about 4.1-43%. [26][27][28][29][30] For most of the patients, palliative therapeutic options exist and are based on multimodal promising combinations including systemic chemotherapy, endoscopic biliary stenting, radiation therapy and photodynamic treatment.…”

Section: Discussionmentioning

confidence: 99%

“…The concept of TACE has been used in the management of patients with liver metastases from colorectal cancer, breast carcinoma as well as patients with unresectable hepatocellular carcinoma (HCC). [12][13][14][15][16][17] Regarding unresectable CCC there are few studies addressing this issue, and the number of patients on the existing studies is relatively small. Another problem is that there are no studies about patients who were treated with Mitomycin C, Gemcitabine, Cisplatin or with a combination of them.…”

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confidence: 99%

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Transarterial chemoembolization in the treatment of patients with unresectable cholangiocarcinoma: Results and prognostic factors governing treatment success

Vogl

Naguib

Nour-Eldin

et al. 2011

Intl Journal of Cancer

126

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The aim of the study was to evaluate the effectiveness of transarterial chemoembolization (TACE) with four chemotherapeutic protocols in terms of local tumor control and survival of patients with unresectable cholangiocarcinoma (CCC) and to identify the prognostic factors governing treatment success. In the single-centre study, 115 patients (mean ages 5 60.4 years) with unresectable CCC were repeatedly treated with TACE. In total, 819 chemoembolization sessions were performed in 4 week intervals with a mean of 7.1 (range, 3-30) sessions per patient. The chemotherapeutic used was Mitomycin C only in 20.9% of patients, Gemcitabine only in 7%, Mitomycin C with Gemcitabine in 47% and combination of Gemcitabine, Mitomycin C and Cisplatin in 25.1%. Local tumor response was evaluated by MRI according to RECIST. Survival data were calculated according to the Kaplan-Meier method. Prognostic factors for patient's survival were evaluated using log-rank-test. The local tumor controls were: partial response 8.7%, stable disease 57.4% and progressive disease 33.9% of patients. The median and mean survival times from the start of TACE were 13 and 20.8 months. Survival rate from the start of TACE was 52% after 1-year, 29% after 2-years and 10% after 3-years. Initial tumor response, high tumor vascularity and Child-Pugh class A were statistically significant factors for patient's survival. No statistically significant difference between patients treated with different chemotherapy protocols was noted. In conclusion, TACE is a palliative and safe treatment option for patients with unresectable CCC. Child Pugh class B, tumor hypovascularity and initially progressive disease were poor prognostic factors for patient survival.Cholangiocarcinoma (CCC) is the second most common primary hepatic malignancy following hepatocellular carcinoma. 1 The tumor represents less than 2-3% of all cancers and up to 19% of primary liver cancers worldwide. [1][2][3][4] In Europe and North America, the average incidence of CCC is 1-2/100,000 per year. 5,6 The incidence during the last years is increasing, and this increasing incidence is associated with an increase in mortality. 2,7-10 Because of an advanced nature of the tumor on the time of first diagnosis, the therapeutic options for patients with unresectable CCC are limited.Transarterial chemoembolization (TACE) is a local, catheter-based, minimally invasive therapeutic option for unresectable liver tumors, and is defined as a selective administration of chemotherapy usually combined with embolization of the vascular supply of the tumor. 11 For patients with liver tumors, TACE, as a combination of local-arterial application of chemotherapeutic drugs with additional usage of embolization particles, is an effective and recommended treatment. The concept of TACE has been used in the management of patients with liver metastases from colorectal cancer, breast carcinoma as well as patients with unresectable hepatocellular carcinoma (HCC). [12][13][14][15][16][17] Regarding unresectable CCC there are few...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Transarterial chemoembolization in the treatment of patients with unresectable cholangiocarcinoma: Results and prognostic factors governing treatment success

Vogl

Naguib

Nour-Eldin

et al. 2011

Intl Journal of Cancer

126

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“…22 The method presented here offers real promise to strengthen the application of TAE for unresectable liver cancers by combining it with antiangiogenic therapy when it is under pressure and suspicion due to some disappointing clinical results. [22][23][24][25] Although the effects of TAE on tumor shrinkage is certain, its efficacy in prolonging survival in HCC patients is controversial, as some studies have shown TAE improves survival of patients, [26][27][28] while a few randomized trials failed to do so. [29][30][31] The present study has demonstrated that TAE led to necrosis of liver tumors and reduced their sizes.…”

Section: Discussionmentioning

confidence: 99%

Antiangiogenic therapy enhances the efficacy of transcatheter arterial embolization for hepatocellular carcinomas

Jiang

Meng

Tan

et al. 2007

Intl Journal of Cancer

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Transcatheter arterial embolization (TAE) is a well-established technique for unresectable hepatic malignancies. However, TAE can temporally halt the growth of hepatic tumors by blocking their arterial supply, but often tumors rapidly develop collateral blood vessels via angiogenesis. We have previously demonstrated that intraportal delivery of adeno-associated viral particles expressing angiostatin leads to long-term expression of angiostatin capable of inhibiting angiogenesis and suppressing the outgrowth of tumors in the liver. Thus, we hypothesize that adeno-associated virus (AAV)-mediated antiangiogenic therapy could enhance the efficacy of TAE to combat liver cancers. To achieve this objective, we engineered a recombinant AAV vector encoding rat angiostatin. Intraportal delivery of this vector led to long term and stable transgenic expression of angiostatin locally in rat hepatocytes and suppressed the growth of CBRH7919 hepatocellular carcinomas established in rat livers by inhibiting formation of neovessels. Although TAE therapy led to necrosis of liver tumors and suppressed their growth, the neovessels of tumors were rapidly reformed 3 weeks after TAE. However, intraportal injection of AAV-angiostatin inhibited the angiogenesis stimulated by TAE, synergized with TAE in suppressing growth of tumors established in livers and prolonged the survival of rats. In conclusion, these encouraging results warrant future investigation of the use of antiangiogenic therapy for enhancing the therapeutic efficacy of TAE to treat unresectable liver cancers. ' 2007 Wiley-Liss, Inc.Key words: hepatocellular carcinoma; transcatheter arterial embolization; angiogenesis; adeno-associated virus; angiostatin; gene therapy Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world with an estimated incidence of more than one million new cases per year.1,2 HCC has a very poor prognosis with less than a 6% 5-year survival rate. Only surgery offers a cure, but liver resection is feasible for less than 15% of patients, and recurrence rates remain high after tumor resection.3 Chemotherapy and radiotherapy offer unsatisfactory response rates. Therefore, new strategies to combat HCC are urgently needed.The application of transcatheter arterial embolization (TAE) to treat liver cancers has developed conceptually based on the observation that both primary and secondary liver tumors derive their blood supply mainly from the hepatic artery, 4 while blood supply to normal liver mainly depends on the portal system. 5,6 Thus, artery obstruction by embolization can cause extensive ischemic tumor necrosis, which provides the rational for its wide use as a standard treatment for unresectable HCC. 7,8 However, the effectiveness of TAE in treating HCC is debatable as any beneficial results are short-lived because collateral arterial circulations rapidly develop. It has been reported that TAE enhances the rate of intrahepatic and extrahepatic metastases, and even results in a shorter survival.9-11 Recanalization of the embo...

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“…Selective catheter-directed IAC is a standard treatment for HCC confined to the liver but that is not amenable to surgery, which is the situation in up to 75% of new cases worldwide [2,3]. IAC-like approaches such as chemoembolization have demonstrated survival benefits in randomized controlled clinical trials [4] potentially due to improved tumor dose profile.…”

Section: Introductionmentioning

confidence: 99%

Development and Validation of Endovascular Chemotherapy Filter Device for Removing High-Dose Doxorubicin: Preclinical Study

Patel

Saeed

Yee

et al. 2014

Journal of Medical Devices

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Development and Validation of Endovascular Chemotherapy Filter Device for Removing High-Dose Doxorubicin: Preclinical StudyTo develop a novel endovascular chemotherapy filter (CF) able to remove excess drug from the blood during intra-arterial chemotherapy delivery (IAC), thus preventing systemic toxicities and thereby enabling higher dose IAC. A flow circuit containing 2.5 mL of ion-exchange resin was constructed. Phosphate-buffered saline (PBS) containing 50 mg doxorubicin (Dox) was placed in the flow model with the hypothesis that doxorubicin would bind rapidly to resin. To simulate IAC, 50 mg of doxorubicin was infused over 10 min into the flow model containing resin. Similar testing was repeated with porcine serum. Doxorubicin concentrations were measured over 60 min and compared to controls (without resin). Single-pass experiments were also performed. Based on these experiments, an 18F CF was constructed with resin in its tip. In a pilot porcine study, the device was deployed under fluoroscopy. A control hepatic doxorubicin IAC model (no CF placed) was developed in another animal. A second CF device was created with a resin membrane and tested in the infrarenal inferior vena cava (IVC) of a swine. In the PBS model, resin bound 76% of doxorubicin in 10 min, and 92% in 30 min (P < 0.001). During IAC simulation, 64% of doxorubicin bound in 10 min and 96% in 60 min (P < 0.001). On average, 51% of doxorubicin concentration was reduced during each pass in single pass studies. In porcine serum, 52% of doxorubicin bound in 10 min, and 80% in 30 min (P < 0.05). CF device placement and administration of IAC were successful in three animals. No clot was present on the resin within the CF following the in vivo study. The infrarenal IVC swine study demonstrated promising results with up to 85% reduction in peak concentration by the CF device. An endovascular CF device was developed and shown feasible in vitro. An in vivo model was established with promising results supporting high-capacity rapid doxorubicin filtration from the blood that can be further evaluated in future studies.

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Chemoembolization in the Management of Liver Tumors

Cited by 89 publications

References 101 publications

Transarterial chemoembolization in the treatment of patients with unresectable cholangiocarcinoma: Results and prognostic factors governing treatment success

Transarterial chemoembolization in the treatment of patients with unresectable cholangiocarcinoma: Results and prognostic factors governing treatment success

Antiangiogenic therapy enhances the efficacy of transcatheter arterial embolization for hepatocellular carcinomas

Development and Validation of Endovascular Chemotherapy Filter Device for Removing High-Dose Doxorubicin: Preclinical Study

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