Liver cancer is one of the most common cancers worldwide with >500,000 new cases/yr of hepatocellular carcinoma (HCC, primary liver cancer) and >200,000 new cases/yr of liver dominant colorectal cancer metastases (secondary liver cancer). Treatment options are limited and clinical outcomes are generally poor with a median survival rate of less than one year. Given the fact that liver cancer (primary and metastatic) is primarily supplied by the hepatic artery and is generally confined to the liver, drug delivery directly into the hepatic artery has been shown to be effective in the management of these patients. Transcatheter arterial chemoembolization (TACE) is an x-ray imaged guided, interventional oncology procedure in which chemotherapeutic drug is delivered from a catheter in the hepatic artery. Level I evidence has demonstrated that patients have better symptom control and prolonged survival after TACE as compared to those receiving supportive care only (5-year survival rate increases from 3% to 26%);this has resulted in TACE being the mainstay of intermediate stage HCC therapy. Recently, there has been a shift in the chemotherapeutic drug delivery system from the conventional lipiodol-doxorubicin cocktail (c-TACE) to drug-eluting microsphere beads (DEB-TACE). Despite these successes, TACE (with or without using DEBs) relies heavily on clinician experience and subjective decision making during the procedure, which can result in non-target drug delivery and a high recurrence rate (either due to incomplete tumor kill or partial treatment). The goals of this grant are to see, reach, and treat the tumor by 1) removing the subjectivity in catheter placement, 2) optimizing the drug delivery protocol, and 3) quantifying treatment success. The main tool that we will use to realize these goals is the x-ray C-arm cone-beam CT (CBCT). We will greatly expand the limited role CBCT currently plays in the TACE procedure.
Specific aims i nclude: (1) Develop new image guidance software to improve tumor imaging and targeting, (2) Optimize the drug delivery protocol and validate it in a clinical pilot study, and (3) Develop quantifiable measures of treatment success and compare these with post-procedure MRI. The academia-industry partnership will help translate results from animal and retrospective human studies into improved commercial products which will then be tested prospectively in humans.

Public Health Relevance

Liver cancer is one of the most common cancers worldwide and its incidence continues to rise. Although loco-regional intra-arterial drug delivery has been shown to increase survival, it remains plagued by unresolved issues such as incomplete tumor kill, absence of a standard protocol, and systemic toxicities. Our goals with this research are to improve tumor targeting, optimize the drug delivery protocol, and quantify treatment success.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA160771-01
Application #
8161721
Study Section
Special Emphasis Panel (ZRG1-SBIB-U (55))
Program Officer
Baker, Houston
Project Start
2011-09-20
Project End
2016-07-31
Budget Start
2011-09-20
Budget End
2012-07-31
Support Year
1
Fiscal Year
2011
Total Cost
$565,961
Indirect Cost
Name
Johns Hopkins University
Department
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Do Minh, Duc; Chapiro, Julius; Gorodetski, Boris et al. (2017) Intra-arterial therapy of neuroendocrine tumour liver metastases: comparing conventional TACE, drug-eluting beads TACE and yttrium-90 radioembolisation as treatment options using a propensity score analysis model. Eur Radiol 27:4995-5005
Duran, Rafael; Mirpour, Sahar; Pekurovsky, Vasily et al. (2017) Preclinical Benefit of Hypoxia-Activated Intra-arterial Therapy with Evofosfamide in Liver Cancer. Clin Cancer Res 23:536-548
Smolka, Susanne; Chapiro, Julius; Manzano, Wilfred et al. (2017) The impact of antiangiogenic therapy combined with Transarterial Chemoembolization on enhancement based quantitative tumor response assessment in patients with hepatocellular carcinoma. Clin Imaging 46:1-7
Sohn, Jae Ho; Duran, Rafael; Zhao, Yan et al. (2017) Validation of the Hong Kong Liver Cancer Staging System in Determining Prognosis of the North American Patients Following Intra-arterial Therapy. Clin Gastroenterol Hepatol 15:746-755.e4
Daddacha, Waaqo; Koyen, Allyson E; Bastien, Amanda J et al. (2017) SAMHD1 Promotes DNA End Resection to Facilitate DNA Repair by Homologous Recombination. Cell Rep 20:1921-1935
Gorodetski, Boris; Chapiro, Julius; Schernthaner, Ruediger et al. (2017) Advanced-stage hepatocellular carcinoma with portal vein thrombosis: conventional versus drug-eluting beads transcatheter arterial chemoembolization. Eur Radiol 27:526-535
Zhao, Yan; Duran, Rafael; Chapiro, Julius et al. (2016) Transarterial Chemoembolization for the Treatment of Advanced-Stage Hepatocellular Carcinoma. J Gastrointest Surg 20:2002-2009
Schernthaner, Ruediger E; Haroun, Reham R; Duran, Rafael et al. (2016) Improved Visibility of Metastatic Disease in the Liver During Intra-Arterial Therapy Using Delayed Arterial Phase Cone-Beam CT. Cardiovasc Intervent Radiol 39:1429-37
Gholamrezanezhad, Ali; Mirpour, Sahar; Geschwind, Jean-Francois H et al. (2016) Evaluation of 70-150-?m doxorubicin-eluting beads for transcatheter arterial chemoembolization in the rabbit liver VX2 tumour model. Eur Radiol 26:3474-82
Wang, Zhijun; Hansis, Eberhard; Chen, Rongxin et al. (2016) Automatic bone removal for 3D TACE planning with C-arm CBCT: Evaluation of technical feasibility. Minim Invasive Ther Allied Technol 25:162-70

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