2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

RADIOLOGY AND COLORECTAL LIVER METASTASES
can occasionally downstage the patient with inoperable liver
metastases to an operable status. As a whole, intra-arterial
therapies rely on the fact that liver cancers derive their
blood supply predominantly from hepatic arteries, whereas
normal liver parenchyma has a predominantly portal vein
source of blood supply. 10
Intra-arterial Hepatic Chemotherapy
Intra-arterial hepatic chemotherapy (IAHC) aims to increase
the drug concentration in liver metastases and
thereby improve response rates. 11 This approach can be best
applied with drugs having a high first pass effect. Floxuridine
with a first pass extraction rate of 95% can increase the
liver dose by 100 to 300 times higher than the systemic
perfusion. Historically, repeated or continuous IAHC has
been delivered by a catheter and pump system requiring
laparotomy. More recently, IAHC can be delivered through
an interventional radiology approach with a subcutaneous
port placed. 12 In one study of 36 patients with extensive
nonresectable liver metastases (i.e., � 4 metastases in 86%
and bilobar in 91%), IAHC was used with oxaliplatin (100
mg/m 2 in 2 hours) plus intravenous 5-fluorouracil (5-FU)
and leucovorin (leucovorin 400 mg/m 2 in 2 hours; 5-FU 400
mg/m 2 bolus then 2,500 mg/m 2 in 46 hours) and cetuximab
(400 mg/m 2 then 250 mg/m 2 /week or 500 mg/m 2 every 2
weeks) as first-line treatment. Overall response rate (ORR)
was 90% and disease control rate was 100%. Forty-eight
percent of patients were downstaged enough to undergo an
R0 resection and/or RFA. 13
TACE
There are several different regimens used to deliver
TACE. One group using the regimen of cisplatin, doxorubicin,
mitomycin C, ethiodol, and polyvinyl alcohol has shown
an ORR of 43%. In this study, the median survival of 33
months from initial diagnosis, 27 months from the time of
liver metastases, and 9 months from the start of chemoembolization
suggests a possible improvement over reported
survival time for systemic therapies alone. 14 Another group
using mitomycin C alone (52.5%), mitomycin C with gemcitabine
(33%), or mitomycin C and irinotecan (14.5%) has
shown an ORR of 63%. 15
KEY POINTS
● Interventional radiologists play an important role in
the multidisciplinary care of patients with colorectal
cancer with liver metastases.
● Ablation therapy can focally destroy liver metastases,
providing long-term survival in select cases.
● The “test of time” approach with ablation before
hepatic metastatectomy can help select which patients
will benefit from surgery and which patients’
biology will lead to innumerable metastases making
them ultimately not a good surgical candidate.
● Intra-arterial therapies with chemoembolization, radioembolization,
drug-eluting beads, intra-arterial
chemotherapy, and isolated hepatic perfusion can
play a role in treating unresectable liver metastases
and liver-dominant disease.
Recently, DEB have been developed that allow drug release
after the bead has been embolized into the tumor
microcirculation. The advantage of the beads is a reduced
systemic delivery of chemotherapy. One of the drugs that
has been loaded on these beads is irinotecan, which had a
75% reduced systemic plasma level compared with intraarterial
irinotecan alone. 16
In a randomized study of two courses of DEB with irinotecan
(36 patients) compared with eight courses of intravenous
irinotecan, 5-FU, and leucovorin (FOLFIRI; 36
patients) for 72 patients who failed at least two lines of
chemotherapy, the response rates were 70% for the DEB
group compared with 30% for the systemic FOLFIRI
group. 17 Similarly the 2-year overall survival (OS) was 38%
compared with 18%, and the median OS was 690 days
compared with 482 days. These both favored the DEB arm.
Improvement in quality of life was 60% for the DEB group
compared with 22% for the FOLFIRI group. Finally, overall
cost was lower for the DEB treatment arm.
In a multicenter, single-arm study of 55 patients who
underwent DEB with irinotecan after failing systemic chemotherapy,
response rates were 66% at 6 months and 75% at
12 months with an OS of 19 months and a progression-free
survival (PFS) of 11 months. 18
Radioembolization
External beam radiation therapy is challenged by the
sensitivity of normal liver to radiation. The dose to treat a
liver tumor is estimated at 70 Gy, while the liver tolerance
dose is 35 Gy. Radioembolization refers to the targeted
intra-arterial delivery of yttrium-90 (90Y) permanently
bound to microspheres. Selective intra-arterial delivery enables
doses over 120 Gy to target the tumor without reaching
the liver toxicity threshold. An Italian multicenter,
phase II study examined 50 patients with liver-only or
liver-dominant colorectal metastases who failed at least
three lines of systemic chemotherapy with at least one
oxaliplatin and one irinotecan regimen and who underwent
radioembolization. The ORR was 24%, the PFS was 3.7
months with a median OS of 12.6 months, and the 1- and
2-year survival rates were 50.4% and 19.6%, repectively. 19
In a randomized study by Van Hazel et al comparing
radioembolization plus systemic chemotherapy with chemotherapy
alone as first-line therapy for colorectal liver metastases,
the authors found an improved median survival of
29.4 months compared with 11.8 months in the
chemotherapy-alone group. 20 In a Belgian multicenter
phase III study, patients were randomly selected to receive
Y90 microspheres in addition to intravenous 5-FU infusion
compared with intravenous 5-FU alone. Median time to
tumor progression was 4.5 compared with 2.1 months,
respectively (hazard ratio � 0.51; 95% CI, 0.28 to 0.94; p �
0.03). 21 There are at least 10 prospective clinical trials of
radioembolization that are open to accrual. 9
IHP
IHP allows high-dose chemotherapy to be delivered
through the hepatic artery to the liver without reaching the
systemic circulation. The venous outflow from the liver is
circulated through extracorporeal filters to remove the drug
before the blood is returned to the patient’s circulation. This
technique opens the possibility of chemotherapy agents to
those that do not necessarily have a high liver first pass
203