Ablative therapies showcase innovative potential

The swift rise of percutaneous ablative interventions represents one example of the power of innovation - crushing barriers that stand between discovery and adoption into routine medical practice.

In his 2006 Pendergrass Lecture, Dr. William Charboneau, a radiologist at the Mayo Clinic in Rochester, MN, traced the past, present, and future trajectory of percutaneous ablative interventions. As with radiology as a whole, innovation is the key to the field's continued success, he said.

"When you look at how far we've come in just 10 short years and imagine where we will be in another 10 or 20 years, it is quite exciting, and we have many reasons to be excited about what's next," he said.

Percutaneous ablation has transformed patient management on several fronts. One case cited by Charboneau involved a patient who underwent nephrectomy to treat right renal cell carcinoma. Three years later, the patient underwent radiofrequency thermal ablation for the same disease in his left kidney. Open surgery produced a scar that extended from the patient's flank to midline. He was hospitalized for five days and needed 35 days to recover. The procedure cost $33,000.

Percutaneous ablation was performed when a second renal cell carcinoma appeared in the lower pole of his left kidney. This time, intervention produced a skin puncture that was covered with a bandage. He was discharged after one day and recovered two days later. Normal renal function was restored to his surviving kidney. The procedure cost $7000.

"This is this kind of case that gives you a sense of the value for this kind of therapy in day-to-day medicine," Charboneau said.

Such experiences have fueled explosive growth of ablative cancer therapy. Utilization at the Mayo Clinic rose from nine procedures in 1997 to 245 procedures in the first 11 months of 2006, he said. In terms of scholarship, about 450 abstracts were submitted to the RSNA under the topic of tumor ablation in 2006, compared to only a handful in 1996. About 700 scholarly articles on the topic have been published in the English-language medical literature thus far in 2006.

The development and acceptance cycle for new ablative techniques has been swift. For 50 years, the only treatment for osteoid osteoma, for example, was open surgery. Now, the condition is almost always addressed with RFA. The success rate for surgical resection is just 70%, compared to a 90% for RFA. Open surgery is invasive and complex, while ablation is noninvasive and simple. The standard three-day hospital stay associated with surgery has been replaced by an outpatient procedure.

"By all accounts, percutaneous ablation is a superior method which has led to a change in management throughout the world, without a series of large, multicenter trials," he said.

Buoyed by such successes, image-guided interventional oncology is headed in three directions: more precise treatments; adoption of better treatment devices; and combined therapies that simultaneously exploit the strengths of several technologies, Charboneau said.

The inherent imprecision of accepted pretreatment planning techniques will be addressed, he said. Preprocedural CT and MRI used for planning are often performed weeks before the intervention. They are performed with the patient in a supine position, which is often inappropriate for planning purposes. He predicted that better protocols inspired by methods first developed for radiation therapy planning will be applied to ablative therapy planning. These techniques include computer software for volumetric isolated targeted tissue and computer simulations.

Better treatment devices will be adopted. Cryoablation is gaining popularity because it is more accurate for margin containment than RFA, Charboneau said. Microwave ablation will produce sharper margins and more spherical ablation volumes than RFA. Electronically steerable antennas may allow the interventionalist to ablate predefined asymmetrical volumes to improve targeting. Focused ultrasound also shows great potential, along with combined therapies, such as embolization/chemoembolization and focused ultrasound/cryoablation combinations.

None of the current options for image guidance - ultrasound, CT, or MR - provide an ideal solution for needle guidance, so researchers are developing multimodality approaches to compensate. Fusion strategies include a method for reformatting baseline axial CT imaging to conform to real-time ultrasound and CT. Developed by Dr. Luigi Solbiati, at the General Hospital of Busto Arsirzio in Busto Arizio, Italy, this technique should be ready for adoption in three years.

Robotic devices, such as the da Vinci surgical system, will help improve the precision of needle guidance in small lesions and multiple needle insertions to ablate large lesions. Targeted drugs, such as liposomal doxorubicin and other heat-activated drugs will help boost the tumor-killing effectiveness of thermal treatment around the sub-lethal zone at the edges of the ablative volume. Heat-activated drug delivery is also under development.

Researchers are also leveraging the amount of local ablation for a wider systemic effect. Heat shock protein, a stress protein released after sub-lethal damage, has attracted great interest, Charboneau said. Phase II trials are under way in immunology and oncology to test its effectiveness for melanoma and renal cell carcinoma. Complex ex vivo methods of harvesting and cultivating a patient's heat shock protein could be improved using ablation to produce it in vivo.

A preliminary human clinical trial at the Mayo Clinic has been approved for nine patients with melanoma and renal cell carcinoma to test the technique. Sub-lethal heating with a conventional RF device will be directed to renal cell carcinoma to stimulate the release of heat shock protein. The immune system will then be stimulated with granulocyte-macrophage colony-stimulating factor, leading the heat shock protein to migrate through the lymphatic system to lymph nodes. White blood cells harboring surface antigens targeted renal cell cancer cells will be released to kill cancer cells in the primary tumor and distant metastases, he said.