Society adopts new name

More than 5,000 people attended the 27th Annual Scientific Meeting of the Society of Cardiovascular & Interventional Radiology (SCVIR), April 6 to 11, 2002 in Baltimore. Highlights from the meeting included new data on the effectiveness of uterine artery embolization, the use of remotely controlled robots for percutaneous needle biopsy, and the use of a genetically engineered adenovirus to kill cancer cells.

In addition, the 29-year-old society voted to change its name to the Society of Interventional Radiology (SIR) to more accurately reflect its role in today's medical practice. "The issues of our name and creating a stronger identity for interventional radiology have been raised consistently by members for a number of years," said society president, Michael Darcy, MD. "The society has spent the past year formulating a strategic plan, and there was consensus that a name change and stronger identity was important if we are to continue making progress in educating other physicians and the public about the scope and breadth of interventional radiology."

The society also changed its logo and its motto. The new motto is "Enhanced care through advanced technology."

Uterine artery embolization

Uterine artery embolization (UAE) is a safe and effective treatment option for leiomyomata, according to the results of a study presented by James B. Spies, MD, associate professor of radiology and vice chairman of the department of radiology, Georgetown University Medical Center, Washington, DC.

In this multicenter, prospective, parallel cohort study, patients underwent either UAE or hysterectomy for the treatment of menorrhagia. All patients completed a baseline symptom severity questionnaire, a menorrhagia questionnaire, and a SF-12 health survey. Patients in the UAE group also underwent baseline imaging. Bilateral uterine embolization was performed in the standard fashion using Embosphere Microspheres (BioSphere Medical, Inc., Rockland, MA). Hysterectomy was performed using standard surgical techniques. Patients were followed up clinically at 1, 3, 6, and 12 months and underwent imaging at 3 and 6 months.

To date, 67 patients have undergone UAE and 20 have been treated with hysterectomy. Of the 27 UAE patients available for 3-month follow-up imaging, a 29% reduction was seen in uterine volume and 42% reduction in the dominant leiomyoma. Clinically, 83% of the UAE patients reported improved menstrual bleeding at 3 months, with only 7% rating bleeding as extremely heavy, compared with 61% at baseline. Also for UAE patients, the SF-12 physical score increased from 42 to 52 and the mental score increased from 45 to 53. Minor complications occurred in 12 (17%) of the UAE patients. One UAE patient did go on to hysterectomy due to the development of pelvic inflammatory disease 9 weeks after UAE. This was not directly related to the UAE.

Of the 20 hysterectomy patients, only 7 were available for follow-up. In this group, the SF-12 physical scores increased from 35 to 52. The mental scores, however, did not change. Complications occurred in 4 (25%) of the hysterectomy patients.

The researchers concluded that "initial results suggest that UAE using Embospheres is safe and effective when compared with hysterectomy."

Co-authors on this paper were J.M. Cooper, R.L. Worthington-Kirsch, J.C. Lipman, J.F. Benenati, and B. McLucas.

Robotically driven CT biopsies

Stephen B. Solomon, MD, assistant professor of radiology and urology at Johns Hopkins Medical Institutions, Baltimore, MD, presented the results of a study that used a remotely controlled robot to perform computed tomography (CT)-guided needle biopsies.

In the study procedure, a robot arm, attached to the gantry and registered in space, held a core biopsy needle in the CT scanner. The needle tip was placed in a small nick in the skin and a first image, indicating needle location, was acquired. Then a second image was obtained showing the target lesion. The locations of the needle tip and the lesion were then indicated on the robot's computer via mouse clicks. The robot arm then rotated, either through computer control or joystick control, and drove the needle to the target. CT fluoroscopic imaging was used to visualize the placement of the needle.

Ten patients with lesions ranging in size from 1.0 to 3.0 cm in the lung, liver, or kidney participated in this study. All biopsies were completed successfully using this system.

Solomon concluded that "robotically driven CT-guided percutaneous biopsies are feasible. The ability to correctly choose the appropriate trajectory for lesions in different slice planes and the potential to limit radiation exposure to hands in the CT fluoroscopic unit may make this a helpful adjunct to CT-guided interventional procedures."

Currently, the robot system must be set up for each procedure, but Solomon believes that one day robots will be attached permanently to CT units and other equipment. "Robots could really help make procedures more accurate and streamlined," said Dr. Solomon.

The robot was developed by engineers at Johns Hopkins, led by Dan Stoianovici, PhD. Additional co-authors were A. Patriciu, M.E. Bohlman, and L.R. Kavoussi.

Killing cancer with a virus

This year's Dr. Gary J. Becker Young Investigator Award was presented to Daniel Y. Sze, MD, PhD, assistant professor of radiology at Stanford University Medical Center, Stanford, CA, for groundbreaking research that used a genetically engineered adenovirus to treat metastatic gastrointestinal adenocarcinoma.

In this study, the researcher examined the safety, biological activity, and radiographic response patterns following intra-arterial administration of a replication-competent adenovirus selective for tumor suppressor mutation in patients with metastatic gastrointestinal adenocarcinoma.

In the first phase, 6 patients participated in a dose-escalation study to assess safety and to determine the optimal dosage. In the second phase, 27 patients were treated at the highest dose level. All patients included in the study had gastrointestinal cancer that had spread to the liver, with up to 50% hepatic volume replacement by tumor. All had a life expectancy of approximately 6 months at the time of study entry and none were candidates for surgical removal of the tumors. Nearly all had previously received chemotherapy that had been either unsuccessful or only temporarily successful.

An attenuated adenovirus, specifically engineered to selectively replicate in p53-deficient cells (Onyx-015, Onyx Pharmaceuticals, Inc., Richmond, CA) was administered by hepatic arterial infusion for two cycles. Up to six additional cycles were administered in combination with intravenous 5-FU and leucovorin. Patients were assessed with serial CT scans, tumor markers, and laboratory studies including assays of circulating cytokines, neutralizing antibodies, and viral genomes.

Nearly all patients developed flu-like symptoms with mild to moderate fever, rigors, and fatigue for up to a week following administration; however, no dose-limiting toxicity or treatment-emergent hepatotoxicity was found. Marked increases in expression of IL-1, IL-6, IL-10, tumor necrosis factor (TNF), and interferon were seen. Objective tumor responses were demonstrated in combination with chemotherapy. Typically, the response seen on CT examination involved acute tumor enlargement, thought to be an inflammatory response, followed by regression.

"The tumors shrank somewhat, but more impressive was that blood tests showed that abnormal proteins being secreted by the tumors either decreased significantly, or became completely undetectable," reported Sze. "That suggests the tumors, although still visible on the CT scan, are dying or dead."

Median survival for those patients treated at the highest dose was 342 days, compared with 155 days for those patients who participated in the dose-escalation phase.

The researchers concluded that "hepatic arterial infusion of the replication-selective adenovirus Onyx-015 was well-tolerated at the prescribed dosages, and did not result in clinical hepatotoxicity. At the higher doses, viral replication and oncolytic activity were demonstrated. A biphasic radiographic response pattern was demonstrated."

"Normally with gene therapy, a specific gene is spliced into a deactivated virus, and the virus acts as a 'vector,' a vehicle to get the gene inside the body's cells," said Sze. "In this case, we're using the live virus itself, without any extra gene, as the treatment. Rather than inject it directly into the tumor using a syringe and needle, where it might not get distributed evenly, we inject it into the artery, so that the flow of blood carries it throughout the liver, treating the entirety of each tumor."

"You could think of this virus as a new generation of chemotherapy that is much more selective about what it attacks," he continued. "Standard chemotherapy kills some healthy cells along with the cancer. This engineered adenovirus is designed to kill only the cancer and not to harm healthy cells."

In addition, because the adenovirus retains its ability to replicate, it is highly effective at depleting the cancer cells' resources. Once the cancerous cell dies, it breaks open, releasing the adenovirus, thereby allowing it to infect other cancer cells.

"The serendipitous finding was that although the lack of p53 makes a cell mean, aggressive, and cancerous, it also cannot recognize when it's been infected by a virus," said Sze. "That is its Achilles' heel: it makes the cell particularly susceptible to viral infection by this particular engineered virus."

Phase II trials, scheduled to begin this year, will assess the efficacy of this therapy when combined with chemotherapy.

"It could be years before this treatment is ready for prime time, but it could eventually be a frontline therapy to treat various types of primary cancer, as well as tumors that have spread from the original site," concluded Sze.

The co-authors of this study, "Intra-Arterial Adenovirus for Metastatic Colorectal Cancer: Safety, Activity, Radiographic Response, and Early Survival," were T.R. Reid, E. Galanis, J. Abbruzzese, J. Andrews, and D. Kirn.