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Transarterial Administration of Oncolytic Viruses for Locoregional Therapy of Orthotopic HCC in Rats.

ABSTRACT: Hepatocellular carcinoma (HCC) is a disease with limited treatment options and poor prognosis. In recent years, oncolytic virotherapies have proven themselves to be potentially powerful tools to fight malignancy. Due to the unique dual blood supply in the liver, it is possible to apply therapies locally to orthotopic liver tumors, which are predominantly fed by arterial blood flow. We have previously demonstrated that hepatic arterial delivery of oncolytic viruses results in safe and efficient transduction efficiency of multifocal HCC lesions, resulting in significant prolongation of survival in immune competent rats. This procedure closely mimics the application of transarterial embolization in patients, which is the standard palliative care provided to many HCC patients. The ability to administer tumor therapies through the hepatic artery in rats allows for a highly sophisticated preclinical model for evaluating novel viral vectors under development. Here we describe the detailed protocol for microdissection of the hepatic artery for infusion of oncolytic virus vectors to treat orthotopic HCC.

SUBMITTER: Altomonte J

PROVIDER: S-EPMC4941927 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Transarterial Administration of Oncolytic Viruses for Locoregional Therapy of Orthotopic HCC in Rats.

Altomonte Jennifer J Muñoz-Álvarez Kim A KA Shinozaki Katsunori K Baumgartner Christine C Kaissis Georgios G Braren Rickmer R Ebert Oliver O

Journal of visualized experiments : JoVE 20160415 110

Hepatocellular carcinoma (HCC) is a disease with limited treatment options and poor prognosis. In recent years, oncolytic virotherapies have proven themselves to be potentially powerful tools to fight malignancy. Due to the unique dual blood supply in the liver, it is possible to apply therapies locally to orthotopic liver tumors, which are predominantly fed by arterial blood flow. We have previously demonstrated that hepatic arterial delivery of oncolytic viruses results in safe and efficient t ...[more]

PMID: 27167921

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Project description:Response Evaluation Criteria in Solid Tumors (RECIST) (unidimensional), World Health Organization (WHO) (bidimensional), and European Association for Study of the Liver (EASL) (necrosis) guidelines are commonly used to assess response following therapy for hepatocellular carcinoma (HCC). No universally accepted standard exists.To evaluate intermethod agreement between these 3 imaging guidelines and to introduce the concept of the "primary index lesion" as a biomarker for response.Single-center comprehensive imaging analysis including 245 consecutive patients with HCC who were treated with chemoembolization or radioembolization between January 2000 and December 2008. Computed tomography and magnetic resonance imaging scans (N = 1065) were reviewed to assess response in the "primary index lesion," defined as the largest tumor targeted during first treatment.Intermethod agreement (kappa statistics) between RECIST, WHO, and EASL guidelines response; correlation of WHO and EASL response in the primary index lesion with time to progression and survival.Kappa coefficients were 0.86 (95% confidence interval [CI], 0.80-0.92) between the WHO and RECIST guidelines, 0.24 (95% CI, 0.16-0.33) between RECIST and EASL, and 0.28 (95% CI, 0.19-0.36) between WHO and EASL. Disease progressed in 96 patients; 113 died. The hazard ratio for time to progression in responders compared with nonresponders was 0.36 (95% CI, 0.23-0.57) for WHO, 0.38 (95% CI, 0.24-0.58) for RECIST, and 0.38 (95% CI, 0.22-0.64) for EASL. Hazard ratios for survival in responders compared with nonresponders in univariate and multivariate analyses were 0.46 (95% CI, 0.32-0.67) and 0.55 (95% CI, 0.35-0.84) for WHO and 0.36 (95% CI, 0.22-0.57) and 0.54 (95% CI, 0.34-0.85) for EASL. Hazard ratios for survival in responders vs nonresponders in patients with solitary and multifocal HCC were 0.39 (95% CI, 0.19-0.77) and 0.51 (95% CI, 0.32-0.82) for WHO and 0.26 (95% CI, 0.10-0.67) and 0.47 (95% CI, 0.28-0.79) for EASL.Among a group of patients with HCC, agreement for classification of therapeutic response was high between the RECIST and WHO guidelines but low between each of these and EASL. Application of these methods to measure response in a primary index lesion resulted in statistically significant correlations with disease progression and survival.

Dataset Information

Transarterial Administration of Oncolytic Viruses for Locoregional Therapy of Orthotopic HCC in Rats.

Publications

Transarterial Administration of Oncolytic Viruses for Locoregional Therapy of Orthotopic HCC in Rats.

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