"These rods serve as magic bullets, which will be inserted into a tumor in the liver using an image-guided minimally invasive procedure. Each rod is smaller than the tip of a sharpened pencil and provides dual release kinetics of an anti-tumor agent -- an initial burst of drug therapy followed by sustained release," said Jinming Gao, the lead researcher and assistant professor in the department of biomedical engineering at CWRU. "The design of dual-release kinetics is novel and can potentially allow the most effective and safest means of local drug therapy."
Gao developed the device with the help of a $1.2 million grant from the National Cancer Institute, an arm of the National Institutes of Health. He has collaborated closely with John Haaga, M.D., chair of radiology at University Hospitals of Cleveland. Haaga originally conceived the concept of combining radiofrequency ablation with polymer/chemical implantation.
The researchers plan to evaluate the new device and treatment approach in a rabbit liver tumor model. The combined procedure is not currently being used in patients. The research team plans to compare this new method to single treatment by radiofrequency ablation, a minimally invasive procedure in which a needle electrode is inserted through the skin and guided into a tumor by an imaging method such as computed tomography (CT) or magnetic resonance imaging (MRI). An electric current is then introduced through the electrode to elevate the tissue temperature to 80-90 °C to destroy the tumors. Radiofrequency ablation research is under Phase II clinical trials at University Hospitals of Cleveland under the leadership of Haaga and Jonathan Lewin, professor of radiology at CWRU.
"Because not all cancer cells can be killed by thermal ablation without significant damage to normal cells, we believe the follow up procedure with local drug therapy is essential to prevent regrowth of the tumor," said Haaga. "Compared to conventional systemic chemotherapy, this intratumoral drug delivery strategy has the potential to reduce the exposure of normal tissues to the drug while increasing the drug dosage to the tumor site. Patients can receive much higher local doses of anti-tumor agents without being at risk for side effects that can significantly decrease their quality of life."
Each year in the United States an estimated 14,500 new cases of liver and intrahepatic bile duct carcinomas are diagnosed; the five-year survival rate for these patients is less than 10 percent. In another 20 to 30 percent of the 160,000 patients diagnosed with colorectal carcinoma, tumors move through the lymph or blood system. These patients develop liver metastases, the progressive involvement of which becomes the major or sole determination of survival.
"The current standard for liver cancer treatment is tumor resection where the tumor is removed followed by chemotherapy. But the majority of patients afflicted with primary or secondary hepatic cancers can't undergo tumor resection due to factors like age, poor general health and liver function and advanced cirrhosis where the liver is filed with fibrous tissue," Haaga said. "In the last 10 years, image-guided thermal ablation has emerged as a minimally invasive alternative to tumor resection for cancers in the liver, pancreas and prostate. Our new device is designed to work in synergy with image-guided thermal ablation and looks to offer a bright new combination therapy."
Gao, Haaga and their research team are establishing a rational approach for the design of the dual-release millirods, looking into the drug transport and pharmacological issues involved in controlling the device so it dispenses the proper concentrations of anti-tumor agents during drug therapy. "We need to be able to maintain the drug concentration within the therapeutic window for a prolonged period of time at the boundary of the tumor tissue," said Gao. "Our current funding from the National Cancer Institute provides the necessary support and brings us closer to a viable treatment option."
The researchers are confident that their polymer device will be of interest to clinical oncologists, radiologists and others in the medical field that strive to improve the therapeutic outcome for cancer patients. "Dr. Haaga will lead the clinical trials at the University Hospitals of Cleveland when we advance to that stage," Gao said.
In addition to the $1.2 million funding from the National Cancer Institute, the research also received a Presidential Technology Development Fund from CWRU to facilitate the technology transfer from the laboratory to commercialization.