Around the world, primary
liver cancer, known as hepatocellular carcinoma
(HCC), is one of the five most common cancers.
The cancer begins in the main cells of the
liver (hepatocytes) and most frequently occurs
in those persons who have liver disease and
scarring called cirrhosis. Cirrhosis typically
occurs in patients who have chronic infection
with hepatitis B or C, or in patients who
have a long history of alcohol abuse. While
HCC is not quite as common in the United States
as it is in other parts of the world, particularly
in Asia and Africa, where it is the most common
type of cancer, its incidence continues to
rise in the U.S., presumably coinciding with
the ever-increasing number of cases of hepatitis
B and C infections.
The liver is also a common site of spread
of many cancers from other parts of the body
(metastases). The most common cancer to spread
to the liver is colon cancer, although virtually
any cancer can spread to the liver. Some liver
metastases are detected at the time the original
cancer is diagnosed, while others may not
be found for many years as the cancer cells
may spread but may grow so slowly as to only
be seen on x-ray studies many years later.
Liver metastases are many times more common
in the United States than hepatocellular carcinoma.
In cases of HCC, the treatment of choice is
liver transplantation. Because cirrhosis typically
causes scarring of the entire liver, simple
surgical removal of the liver tumor leaves
the patient at high risk of developing a new
tumor in the liver. Unfortunately most patients
are not candidates for transplantation due
to tumor size (over 5-6 cm), location in the
liver, or poor health making the patient unable
to tolerate major open surgery. Only about
20% of patients are offered a transplant option.
Unfortunately treatment options for HCC with
traditional chemotherapy or radiation therapy
are very limited and not very successful.
Without treatment, average survival in patients
with HCC is about 6-9 months.
Patients with metastatic tumor to the liver
are generally not felt to be transplant candidates
due to the spread of tumor from other parts
of the body. However, surgical removal of
metastatic tumor has been considered the standard
of care for these patients when possible,
as about 1 in 10 patients with metastatic
tumor that are surgical candidates may be
cured with surgery. Again, however, only about
10-20% of patients with liver metastases are
felt to be surgical candidates because of
an excessively large number of tumors within
the liver, large size or poor location of
the tumors, or poor general health of the
patient. While traditional radiation therapy
is not useful in the liver, some metastatic
cancers do respond favorably to chemotherapy,
particularly some of the most recently developed
chemotherapy regimens.
Interventional radiologic treatments have
developed to offer options to patients who
may not be surgical candidates or do not desire
surgical care, and also to those patients
who do not respond favorably to chemotherapy,
or respond incompletely. The mainstays of
interventional treatment include radiofrequency
ablation and chemoembolization.
Chemoemboliztion
Chemoembolization, formally
known as transhepatic arterial chemoembolization
or TACE, is typically used for the treatment
of hepatocellular carcinoma but can also be
useful in the treatment of metastatic tumor
to liver. It can be used alone if the tumor
is too large in size or in a poor location
to allow other treatment options. It can also
be used in conjunction with surgery to shrink
tumor prior to surgical removal, or with radiofrequency
ablation to affect better cell death in the
treated tumor.
TACE takes advantage of the fact that the
liver has a dual blood supply, getting blood
from both the hepatic artery and the portal
vein that carries blood from the stomach and
bowel to the liver. Normal liver gets the
greatest amount of its blood and nutrients
from the portal vein, while tumor, on the
other hand, gets nearly all of its blood supply
from the hepatic artery. As such, TACE can
be performed with significant effect on tumor
tissue after closure of tumor branches from
the hepatic artery, with little effect, in
most cases, upon normal liver tissue.
Figure
1
In the TACE procedure, a tiny catheter is
guided, under x-ray visualization, from the
femoral artery at the top of the leg into
the blood vessels that supply the liver tumor
(figure 1). A mixture of chemotherapy drugs
and small particles is then injected into
the tumor. The particles act to keep the chemotherapy
drugs in the tumor and allow much higher doses
of drugs to be delivered to than could typically
achieved with standard chemotherapy (figure2)
given through an IV line – as much as
200-400 times higher doses. Even with the
higher chemotherapy dose to the liver, the
associated side effects of the chemotherapy
are decreased as less chemotherapy drug is
circulating in the bloodstream. TACE is typically
performed as a short-stay procedure with patients
admitted to the hospital the morning of the
procedure and discharged the following morning.
Most patients typically experience some fatigue
as the most common side effect, usually lasting
for 1-2 weeks.
Figure 2 –
Hepatocellular carcinoma in liver
before and after embolization
with chemotherapy mixture.
Chemoembolization by itself is felt to be
a palliative procedure, as permanent cure
is only rarely achieved. However, it can be
extremely effective in controlling liver cancer
and may be even more effective when combined
with other treatment options such as ablation.
Radiofrequency
Ablation
Radiofrequency ablation
(RFA) offers patients an option for treatment
when a traditional surgical option may not
exist. Under CAT scan or ultrasound guidance,
the ablation needle is advanced through
the skin, into the liver, with the tip of
the needle probe positioned in tumor. An
electric current is then administered through
the needle to cause heating and death of
the tumor cells (figure 3)
Figure 3 –
Hepatocellular carcinoma in liver
(arrow). CAT scan shows ablation
probe in place.
The procedure is generally
very well tolerated by the patient and most
are discharged the following morning with
little residual discomfort. Because the
ablation effect is localized to the area
of tumor, the procedure can usually be repeated
as needed, particularly if new areas of
tumor arise. Complication rates are low,
typically in the range if 2-3%.
While transplantation will always offer
the best chance of cure with any liver tumor,
RFA may provide an option with equal effectiveness
to surgical removal of tumor. As the procedure
is relatively new, surgical removal of tumor
remains the treatment of choice. However,
early studies of RFA are quite promising.
Some studies have shown RFA in the treatment
of some hepatocellular carcinomas to have
a five-year survival rate in the range of
40-50% while studies on treatment of metastatic
disease have shown 3-year survival rates
in the range of 45-50%. These outcomes compare
very favorably to surgical removal of tumor
as a treatment option, possibly with less
associated complications and shorter post-procedure
recovery time.
Of course, as with all cancer treatments,
close follow-up examination is required.
Typically with TACE and RFA, follow-up CAT
scans and/or MRI are performed every 3 months
for at least one or two years. Any regrowth
of tumor or new tumors are best treated
at the smallest size possible.
Micro-Sphere Therapy
Treatment with radioactive micro-spheres is, in some ways, similar to chemoembolization or TACE described above. The procedure again takes advantage of the fact that the liver has dual blood supply, getting blood from both the hepatic artery and the portal vein that carries blood from the stomach and bowel to the liver. Normal liver gets the greatest amount of its blood and nutrients from the portal vein, while tumor, on the other hand, will get nearly all of its blood supply from the hepatic artery. A tiny catheter is again directed into the tumor blood vessels that arise from the hepatic artery. The micro-sphere particles are then injected and directed preferentially to the tumor tissue.
SIR-sphere micro-sphere particles developed by Sirtex Medical (see Links page) are tiny plastic beads that are not much than the size of a few blood cells and are combined yttrium-90 radioisotope. Each particle that is trapped in the vascular bed of the liver tumor delivers radiation that penetrates only about 2.5mm of tissue, minimizing effects upon normal healthy tissue. This targeted radiation has its effects over a period of about two weeks.
Patients treated with micro-spheres can often go home and resume normal activities the same day. As with all treatments for cancer, close follow-up care is utilized to determine tumor response and any possible recurrence. Micro-sphere therapy may be an option in cases of recurrence of regrowth of tumor, or many be used in conjunction with other types of treatments to control tumor growth.
