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.