Advancements in transarterial chemoembolization (TACE) are improving the odds for patients with a common type of liver cancer, according to researchers who have been studying the procedure for more than a decade.
In the interventional procedure, a catheter
is threaded under imaging guidance to the
artery or arteries in the liver that supply a
tumor with blood.
After having ensured that the catheter is
in good position, chemoembolytic agents
are released to destroy the tumor and
partially cut off its blood supply.
Developed in Japan in the 1980s, TACE
quickly produced benefits for patients
with intermediate-stage hepatocellular
carcinoma (HCC) that was too advanced
for surgery. Despite its promise, TACE
had a limited impact on medicine
through its first decade of use, said Jean-
François H. Geschwind, M.D., chair
of the Department of Radiology and
Biomedical Imaging, professor of radiology
and oncology, Yale University School of
Medicine, and chief of the Department
of Radiology, Yale-New Haven Hospital,
Conn., who presented a session on
TACE techniques at RSNA 2015 and
co-authored a January 2016 Radiology
study on TACE.
That changed in 2002 when two major
studies showed unequivocal survival
benefits for HCC patients who underwent
the procedure. HCC, the most common
type of liver cancer, predominantly occurs
in patients with cirrhosis. Five-year
survival rates are low partly because the
disease is often not discovered until its
later stages, Dr. Geschwind said.
“The disease grows insidiously, often
without symptoms, which makes it very
difficult to diagnose,” said Dr. Geschwind,
who received a 2000 RSNA Research Seed
Grant to study chemoembolization in the
treatment of liver cancer.
The effectiveness of TACE in battling
HCC is due to the unique vasculature of
the liver, which has a dual blood supply
courtesy of the hepatic artery and the portal
vein. Healthy liver tissue receives blood flow
mostly from the portal vein; however, most
of HCC is nourished by the hepatic artery,
making it possible to block the tumorbearing
parts of the blood supply without
harming healthy liver tissue.
“We can exploit this to our advantage
by delivering toxic chemicals and radiation
beads through the artery for natural
anatomic targeting of tumors,” Dr.
The targeted approach helps spare
patients from the side effects of systemic
chemotherapy, as evidenced in an
October 2008 study in Radiology by Dr.
Geschwind and colleagues. The researchers
examined 190 patients with HCC and
found that toxicity rates associated with
TACE were considerably lower than those
reported after treatment with systemic
Since the landmark TACE studies of 2002,
improvements in everything from catheters
to imaging technology have helped make
the technique even more effective. MRI
is typically used to plan TACE while the
actual embolization is performed under
X-ray guidance in the angiography suite.
The X-ray tube rotates around the patient,
obtaining CT-like images in two phases,
while the software automatically segments
the tumor and correlates it with blood
This technology creates something like a
Google map of the roads you have to take
to get to the tumor,” Dr. Geschwind said.
Imaging advances also allow for
more precise delivery of drugs to the
tumors. The most commonly used drug
is Lipiodol, a drug-bearing emulsion
that sticks to the tumor cells. Imaging
helps clinicians get as close to the
tumor as possible and saturate it and
the surrounding area to make sure the
entire tumor is treated, according to Dr.
“This is where imaging tools really help
you,” he said. “Many times there is more
than one vessel providing blood flow to
the tumor, and the software allows you to
see all the arteries involved.”
Riccardo A. Lencioni, M.D., professor
of radiology at the University of Miami
Miller School of Medicine and directorof interventional oncology research at the
Sylvester Comprehensive Cancer Center in
Miami, recently published a major review of
existing research on TACE using Lipiodol-based
regimens in the treatment of HCC. The review
study, which was co-authored by Dr. Geschwind
and appeared in the January 13 online edition
of Hepatology, concluded that in HCC, survival
figures for patients treated with Lipiodol
TACE were in line with those reported in the
previous key clinical trials, and that no new or
unexpected safety concerns were identified.
“This systematic review suggests that
with refinements in techniques and more
sophisticated approaches with imaging and
catheters, treatment can be offered to a broader
patient population than what was reported in
2002,” Dr. Lencioni said.
Current challenges include the adoption of
more accurate parameters for measuring the
treatment’s success. Relying on tumor size is
problematic, Dr. Geschwind said, because liver
tumors often do not shrink in response to
TACE, even when the cancer cells are killed.
“The U.S. Food and Drug Administration
(FDA) does not accept anything else but tumor
size as a measure of success,” Dr. Geschwind
said. “Clinically we have to come up with new
ways to assess response to therapy.”
In 2000, a position paper of the European
Association for Study of the Liver, co-authored
by Dr. Lencioni, developed new guidelines
based on contrast enhancement, with a lack
of enhancement indicating cell death. Dr.
Geschwind and colleagues affirmed the value
of this approach in a 2009 study published in
Radiology demonstrating a significant reduction
in tumor enhancement within 24 hours after
TACE that persisted for up to four weeks.
“The imaging technology has improved so
much that we are now already using threedimensional
contrast enhancement as measure
of the success of therapy,” Dr. Geschwind said.
“This is how far we have come.”
Along with Lipiodol, other new and improved
drugs are also being developed, including smaller
drug-eluting beads with an improved elution
profile. Researchers are working to make the
beads radio-opaque so that they can be seen at
the time of the procedure.
“The drugs currently used for TACE are
cytotoxic agents,” Dr. Lencioni said. “Several
new anticancer agents, including moleculartargeted
and immuno-oncology drugs, are
currently available and will require proper
investigation in the setting of TACE regiments.”
The January 2016 Radiology study by
Drs. Geschwind and Lencioni examined
TACE in combination with Sorafenib, a
molecular targeted agent that is taken orally
as a pill. Though no benefit to the addition of
Sorafenib was shown, the approach was well
tolerated by the patients and more studies are
on the horizon.
“We still need to understand what is the best
drug or combination of regimens that will result
in the best outcome,” Dr. Lencioni said.
The refinement to TACE points to a broader
future role in HCC treatment. TACE could
be an alternative for patients with early-stage
HCC who are not eligible for radiofrequency
ablation (RFA) or surgery, and it could be added
to RFA in patients with early stage HCC for
better local tumor control than RFA alone.
TACE has advantages over RFA, according to
Dr. Geschwind, since ablation is limited by the
size and location of the tumor. TACE could also
serve as bridge therapy for patients awaiting
“Chemoembolization is continuously
improving,” Dr. Geschwind said. “Some studies
show it could be equivalent to ablation in
early stage liver cancer, and as the technology
improves we are using it more frequently even in
The continued evolution of TACE will be
critical as there has been a doubling of the HCC
age-adjusted incidence rates in the U.S., over the
past three decades, possibly due to the increasing
rate of hepatitis C. Mortality rates have increased
faster for HCC than for those of other leading
cancers, according to Dr. Geschwind.
• The Radiology studies
authored by Drs. Geschwind,
Lencioni and colleagues are
available at RSNA.org/Radiology.
• The Hepatology study authored
by by Drs. Lencioni, Geschwind
and colleagues is available
Join a global community of leaders in the radiologic sciences.
Continue your education with top-quality learning resources.
With grant applications increasing, the R&E Foundation needs you.