Liver cancer (hepatocellular carcinoma, HCC) continues to be a major contributor to worldwide morbidity and mortality, as the sixth most common cancer and the third most frequent cause of cancer death. The prognosis of HCC is poor, with a 1-year survival of only 54% when untreated. Systemic treatment options are extremely limited, and only approximately 5-10% of patients with HCC are candidates for surgical resection. Radiofrequency ablation (RFA) has been proven to be an effective treatment for selected hepatic tumors with similar efficacy as surgical resection but with less morbidity. However, RFA is effective only for small tumors, generally less than 3cm. We propose a novel, minimally invasive and maximally targeted strategy for treatment of hypervascular liver tumors that has the potential to dramatically improve the cure rate of tumors such as HCC, by performing infusing electrically conductive (EC) particles directly into the arteries supplying the tumor (embolization), followed by percutaneous RFA. We hypothesize that the high concentration of EC particles deposited in the tumor will modulate energy deposition resulting in an RF ablation zone that is markedly enlarged and optimally configured to the size and shape of the tumor, thus enabling complete ablation of tumors previously not treatable with minimally invasive methods. While other strategies to enhance the electrical conductance of tumors have failed to result in clinically translatable practice, we designed our approach to overcome these limitations. To prove our hypothesis, we have developed a 3-part project: 1) to demonstrate the ability of EC particles to increase the size and to modulate the shape of the radiofrequency ablation zone in a gel phantom model that simulates liver tumors; 2) to confirm in a rabbit model that infusion of EC particles into the liver results in enlarged RF ablation zones volumes; 3) to demonstrate, in a hypervascular liver tumor model in rabbits, that infusion of EC particles into the arteries feeding the tumor results in RF ablation zones that are enlarged and optimally configured to the tumor geometry regardless of probe position. The long-term goal of this project is to develop a new minimally invasive combined treatment modality with a dramatically improved ability to cure tumors that exceed conventional size thresholds for minimally invasive techniques.

Public Health Relevance

Percutaneous radiofrequency ablation for treatment of liver cancer is curative only for tumors of small size in optimal locations. Using in vitro and animal models, we will demonstrate that selective infusion of electrically conductive particles into the tumor will markedly increase the treatment zone in a shape that is optimized for complete tumor destruction. This unique approach for treatment of liver cancer has the potential to dramatically increase the cure rate using minimally invasive techniques.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Research Grants (R03)
Project #
5R03CA191978-02
Application #
9127167
Study Section
Special Emphasis Panel (ZCA1-SRB-J (O1))
Program Officer
Farahani, Keyvan
Project Start
2015-08-14
Project End
2018-01-31
Budget Start
2017-02-01
Budget End
2018-01-31
Support Year
2
Fiscal Year
2017
Total Cost
$71,550
Indirect Cost
$26,550
Name
Duke University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705