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 #
5R01CA160771-04
Application #
8699164
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Baker, Houston
Project Start
2011-09-20
Project End
2016-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
Schools of Medicine
DUNS #
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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
Fleckenstein, Florian N; Schernthaner, Rüdiger E; Duran, Rafael et al. (2016) 3D Quantitative tumour burden analysis in patients with hepatocellular carcinoma before TACE: comparing single-lesion vs. multi-lesion imaging biomarkers as predictors of patient survival. Eur Radiol 26:3243-52
Duran, Rafael; Sharma, Karun; Dreher, Matthew R et al. (2016) A Novel Inherently Radiopaque Bead for Transarterial Embolization to Treat Liver Cancer - A Pre-clinical Study. Theranostics 6:28-39
Chockalingam, Arun; Duran, Rafael; Sohn, Jae Ho et al. (2016) Radiologic-pathologic analysis of quantitative 3D tumour enhancement on contrast-enhanced MR imaging: a study of ROI placement. Eur Radiol 26:103-13
Gholamrezanezhad, Ali; Mirpour, Sahar; Geschwind, Jean-Francois H et al. (2016) Evaluation of 70-150-μm doxorubicin-eluting beads for transcatheter arterial chemoembolization in the rabbit liver VX2 tumour model. Eur Radiol 26:3474-82
Savic, Lynn Jeanette; Chapiro, Julius; Duwe, Gregor et al. (2016) Targeting glucose metabolism in cancer: new class of agents for loco-regional and systemic therapy of liver cancer and beyond? Hepat Oncol 3:19-28
Geschwind, Jean-François; Kudo, Masatoshi; Marrero, Jorge A et al. (2016) TACE Treatment in Patients with Sorafenib-treated Unresectable Hepatocellular Carcinoma in Clinical Practice: Final Analysis of GIDEON. Radiology 279:630-40
Tacher, Vania; Duran, Rafael; Lin, MingDe et al. (2016) Multimodality Imaging of Ethiodized Oil-loaded Radiopaque Microspheres during Transarterial Embolization of Rabbits with VX2 Liver Tumors. Radiology 279:741-53
Tacher, Vania; Lin, MingDe; Duran, Rafael et al. (2016) Comparison of Existing Response Criteria in Patients with Hepatocellular Carcinoma Treated with Transarterial Chemoembolization Using a 3D Quantitative Approach. Radiology 278:275-84
Sahu, Sonia; Schernthaner, Ruediger; Ardon, Roberto et al. (2016) Imaging Biomarkers of Tumor Response in Neuroendocrine Liver Metastases Treated with Transarterial Chemoembolization: Can Enhancing Tumor Burden of the Whole Liver Help Predict Patient Survival? Radiology :160838

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