IP 381_2
NATIONAL INSTITUTE FOR HEALTH AND
CLINICAL EXCELLENCE
INTERVENTIONAL PROCEDURES PROGRAMME
Interventional procedure overview of microwave
ablation for the treatment of liver metastases
Treating liver metastases with microwave ablation
Microwave ablation is a procedure that uses heat from microwave energy to
destroy cancer cells. It can be used to treat cancer that has spread
(metastasised) to the liver from other parts of the body, usually from the colon
or rectum
The procedure can be performed during open abdominal surgery, by using
‘keyhole’ surgery (where specialised instruments are inserted through small
cuts in the abdomen) or by needle puncture through the skin. Whichever
method is used, special needles are inserted into the tumour(s) and
microwave energy is used to heat the tumour and destroy the cancer cells.
Introduction
The National Institute for Health and Clinical Excellence (NICE) has prepared
this overview to help members of the Interventional Procedures Advisory
Committee (IPAC) make recommendations about the safety and efficacy of an
interventional procedure. It is based on a rapid review of the medical literature
and specialist opinion. It should not be regarded as a definitive assessment of
the procedure.
Date prepared
This overview was prepared in February 2011.
Procedure name
Microwave ablation for the treatment of liver metastases
Specialty societies
British Society of Interventional Radiology
British Society of Gastrointestinal and Abdominal Radiology
Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland
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Description
Indications and current treatment
Liver metastases are a common manifestation of many primary cancers but
the liver is usually the dominant site for metastases originating from colorectal
or other gastrointestinal tract cancers.
The number, location and size of the metastases are the key determinants of
treatment intent as well as of treatment choice. For a minority of patients,
surgical resection with curative intent may be possible. For most patients,
however, treatment intent is palliative. Options for palliative treatment include
systemic chemotherapy, external beam radiotherapy, thermal ablation
techniques (such as radiofrequency or cryotherapy), arterial embolisation
techniques, and selective internal radiation therapy. Multiple treatment
modalities may be used for individual patients.
Thermal ablation techniques are usually used in patients not considered
suitable for surgery or for treating post-resection recurrence. They may also
be used as an adjunct to hepatic resection to ablate small-volume disease in
the remnant post-resection liver.
What the procedure involves
Microwave ablation is a technique that aims to destroy tumours by heating
cells, resulting in localised areas of necrosis and tissue destruction, with
minimal morbidity.
The procedure can be performed under local or general anaesthesia and
either percutaneously or surgically (either with open surgery or laparoscopy).
Needle electrodes are advanced into the liver tumour(s) under image
guidance and the targeted tumour(s) are ablated. Multiple pulses of energy
may be delivered during one session and multiple needle electrodes can be
used to treat larger tumours.
A number of devices are available for this procedure.
Literature review
Rapid review of literature
The medical literature was searched to identify studies and reviews relevant to
microwave ablation for the treatment of metastases in the liver. Searches
were conducted of the following databases, covering the period from their
commencement to 28 October 2010 and updated to 19 April 2011: MEDLINE,
PREMEDLINE, EMBASE, Cochrane Library and other databases. Trial
registries and the Internet were also searched. No language restriction was
applied to the searches (see appendix C for details of search strategy).
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Relevant published studies identified during consultation or resolution that are
published after this date may also be considered for inclusion.
The following selection criteria (table 1) were applied to the abstracts
identified by the literature search. Where selection criteria could not be
determined from the abstracts the full paper was retrieved.
Table 1 Inclusion criteria for identification of relevant studies
Characteristic
Publication type
Patient
Intervention/test
Outcome
Language
Criteria
Clinical studies were included. Emphasis was placed on
identifying good quality studies.
Abstracts were excluded where no clinical outcomes were
reported, or where the paper was a review, editorial, or a
laboratory or animal study.
Conference abstracts were also excluded because of the
difficulty of appraising study methodology, unless they reported
specific adverse events that were not available in the published
literature.
Patients with liver metastases– studies with mixed populations
including hepatocellular carcinoma where outcomes were not
reported separately are not included.
Microwave ablation (all modes of delivery)
Articles were retrieved if the abstract contained information
relevant to the safety and/or efficacy.
Non-English-language articles were excluded unless they were
thought to add substantively to the English-language evidence
base.
List of studies included in the overview
This overview is based on approximately 1659 patients from 1 randomised
controlled trial (RCT)1, 2 non-randomised controlled studies2,3, and 5 case
series4,5,6,7,8.
Other studies that were considered to be relevant to the procedure but were
not included in the main extraction table (table 2) have been listed in
appendix A.
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Table 2 Summary of key efficacy and safety findings on microwave ablation for the treatment of metastases in
the liver
Abbreviations used: CT, computed tomography; HCC, hepatocellular carcinoma; HR, hazard ratio; MW, microwave; RF, radiofrequency; US, ultrasound; W, Watts
Study details
Shibata T (2000)
1
Key efficacy findings
Key safety findings
Comments
Number of patients analysed: n = 30 (14 MW coagulation,
16 liver resection)
Operative complications
Study was included in original
overview
Follow-up issues:
Randomised controlled trial
Japan
Recruitment period: 1990–1997
Study population: patients with
primary colorectal carcinoma and
liver metastases. mean number of
tumours = 5.3, mean tumour size
30 mm
n = 30 (14 MW coagulation, 16 liver
resection)
Age: 61 years (mean)
Sex: 53% male
Survival
The mean survival time was 27 months in the MW group
and 25 months in the hepatectomy group (p = 0.83). The
mean disease-free interval was 11.3 and 13.3 months
respectively (p = 0.47).
During the follow up period there were 9 deaths among the
14 patients treated with microwave ablation, 6 of whom
died due to hepatic failure. In the hepatic resection group
there were 12 deaths among 16 patients with 7 dying from
hepatic failure.
Surgical parameters
Patient selection criteria: patients with
multiple (fewer than 10) metastatic
liver tumours from colorectal
primaries (at least 1 confirmed
histologically), largest tumour
< 80 mm, and no signs of cirrhosis or
chronic hepatitis
Technique: open microwave
coagulation using a tissue coagulator
for a net period between 2 and 20
minutes at between 60 W and 100 W
vs hepatic resection including
lobectomy, segmentectomy,
subsegmentectomy, and/or wedge
resection as clinically indicated.
Follow-up: not reported (imaging
follow-up every 3 months)
Conflict of interest/source of funding:
not reported.
There were no intraoperative deaths in
either group
MW
Blood loss (ml)
Blood transfused
(ml)
Patients requiring
transfusion (%)
Operation time
(min)
Length of stay
(days)
Resection
360
0
230
0
490
p
0.027
540
690
0.080
38
180
20
910
20
7
0.035
200
25
50
0.20
Post-operative complications
MW
(n = 14)
Internal
obstruction
Bile duct
fistula
Hepatic
abscess
Wound
infection
p=
0
Resection
(n = 16)
1
1
1
N/S
1
0
N/S
0
1
N/S
Hepatic function (as determined by serum
bilirubin and prothrombin time) recovered
to normal preoperative level within 2 weeks
in both groups.
0.23
12
Biochemical markers
21.6 ng/ml to 5.8
Hepatectomy: 13.5
(p < 0.01)
Randomisation was by computer
generated sequence.
Patients with all liver cancer types
were randomised and only those
with colorectal metastases
reported here.
No details were provided of
blinding.
No clear reporting of follow-up
period and completeness.
Cumulative survival calculated by
Kaplan–Meier method.
No details given of concomitant
treatment.
Study population issues:
There were no significant
differences in clinical or
demographic characteristics
between the groups at baseline.
Other issues:
MW intervention characteristics
differed for treatment of superficial
and deeply seated tumours.
Carcinoembryonic antigen levels decreased significantly
4 weeks after surgery in both groups.
MW: 18.5
N/S
25% (10/40) of patients dropped
out during the surgery phase,
outcomes for these patients were
not compared.
Study design issues:
6.3 ng/ml (p < 0.05)
11.4 ng/ml to 4.1
Authors issued caution in applying
microwave coagulation to tumours
near a large branch of a bile duct.
3.9 ng/ml
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Abbreviations used: CT, computed tomography; HCC, hepatocellular carcinoma; HR, hazard ratio; MW, microwave; RF, radiofrequency; US, ultrasound; W, Watts
Study details
Tanaka K (2006)
2
Key efficacy findings
Key safety findings
Comments
Number of patients analysed: n = 53 (n = 16 MW, n= 37
ablation alone)
Complications
Follow-up issues:
There were no deaths up to 60 days in
either group.
Rates of complications for first treatment
Microwave Resection
+ resection
Infection
2.7% (1/37) 12.5% (2/16)
Biliary fistula
2.7% (1/37) 6.3% (1/16)
Bleeding
0% (0/37) 6.3% (1/16)
Hyper2.7% (1/37) 0% (0/16)
bilirubinemia
Intestinal
8.1% (3/37) 0% (0/16)
obstruction
(measurement of significance not reported)
Retrospective study.
No loss to follow-up.
Non-randomised controlled study
Survival
Study population: patients with
multiple, bilobar colorectal liver
metastases. Mean diameter = 5.1cm.
Hepatic recurrence-free survival
Microwave +
resection
1 year
56%
3 years
39%
5 years
39%
(p=0.86)
n = 53 (16 MW, 37 ablation alone)
Overall survival
Japan
Recruitment period: 1992–2004
Age: 60 years (mean)
Sex: 62% male
Patient selection criteria: Patients
with 5 or more lesions in a bilobar
distribution.
Technique: all procedures via
laparotomy. Curative hepatectomy
plus MW ablation at 70 W for 45
seconds (repeated 4 or 5 times per
lesion) with US guidance vs
hepatectomy alone.
Follow-up: 20 months (median)
Conflict of interest/source of funding:
not reported
Microwave +
resection
80%
51%
17%
Resection
55%
42%
35%
Resection
1 year
87%
3 years
49%
5 years
44%
(p=0.43)
Treatment procedure (combined resection plus MW
ablation vs resection alone) did not influence overall
survival on multivariate analysis.
Microwave + Resection
resection
33%
26%
17%
11%
Some discrepancy between text
and tables in terms of length of
follow-up for survival outcomes.
Operative characteristics
Group mean ± standard deviation – first treatment
Microwave + Resection
resection
Blood loss (ml)
386 ± 515
379 ± 475
IP overview: microwave ablation for the treatment of liver metastases
Patients were selected for
combined MW plus resection
where resection alone could not
retain sufficient vascularised
hepatic parenchyma to support
hepatic function.
Thirty patients received
neoadjuvant chemotherapy.
Some patients in each group
underwent a second planned
hepatectomy ± MW ablation
procedure, making evaluation of
outcomes difficult.
Study population issues:
Groups were matched at baseline
in terms of demographics and
most clinical characteristics,
however those receiving
combined ablation and resection
had significantly more
metastases, were more likely to
have had neoadjuvant
chemotherapy, but less likely to
have had a major hepatectomy.
Other issues:
Disease-free survival
1 year
3 years
(p=0.54) overall.
Study design issues:
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Abbreviations used: CT, computed tomography; HCC, hepatocellular carcinoma; HR, hazard ratio; MW, microwave; RF, radiofrequency; US, ultrasound; W, Watts
Study details
Key efficacy findings
Key safety findings
Length of stay (days) 23 ± 14
22 ±10
Measurement of significance not reported.
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Comments
IP 381_2
Abbreviations used: CT, computed tomography; HCC, hepatocellular carcinoma; HR, hazard ratio; MW, microwave; RF, radiofrequency; US, ultrasound; W, Watts
Study details
Hompes R (2010)
3
Non-randomised controlled study
Belgium
Recruitment period: 2008
Study population: patients with liver
metastases without underlying liver
disease.
n = 19 (6 MW, 13 RF)
Age: 61 years (median)
Sex: 47% male
Patient selection criteria: tumours
smaller than 3 cm
Technique: US guidance MW ablation
either laparoscopically or
percutaneously with 40W energy
delivered for 10 minutes (combined
with hepatectomy in 1 patient) vs RF
ablation
Follow-up: 6 months (median)
Conflict of interest/source of funding:
none
Key efficacy findings
Key safety findings
Comments
Number of patients analysed: n = 19 (6 MW, 13 RF)
Recurrence
Complications
Follow-up issues:
No perioperative mortality was reported.
Haemobilia (resolved with conservative
treatment) was reported in 1 of 6 patients
in the microwave ablation group.
Patient accrual method not
reported
No loss to follow-up in the
microwave group.
Biopsy-proven local recurrence occurred in 1 out of 6
patients in the microwave ablation group at 6-month followup. There was no local recurrence in the RF treated group.
Tumour response
Study design issues:
CT scan demonstrated that tumour destruction was
complete in all patients undergoing microwave ablation at
1-week follow-up.
CT scan transverse tumour/ margin diameter: median
(range) (length of follow up not reported).
Microwave
RF
p=
Baseline 12 mm (6 to 18)
12 mm (7 to 24)
> 0.792
Post18.5 mm (12 to
34 mm (16 to 41) 0.003
operative 64)
(measurement of significance between groups at each time
point)
CT scan antero-posterior diameter: median (range)
Microwave
RF
p=
Baseline 12mm (6 to 24)
12mm (7 to 17)
> 0.792
Post26mm (14 to 60) 35mm (28 to 40) 0.046
operative
(measurement of significance between groups at each time
point)
Tumours matched for size and
location, no other characteristics
are considered.
Concomitant treatment not
standardised between groups.
Study population issues:
No comparison of groups at
baseline.
Other issues:
A larger ablation diameter
represents better outcome.
Period of follow up for CT scan
evaluation was not reported
although measurements were
taken at 1 week and 3 months.
Few clinical outcomes are
reported.
CT scan cranio-caudal diameter: median (range)
Microwave
RF
p=
Baseline 10.5 mm (6 to 20) 11 mm (8 to 20)
> 0.792
Post20 mm (10 to 73) 32 mm (20 to 45) 0.025
operative
(measurement of significance between groups at each time
point)
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Abbreviations used: CT, computed tomography; HCC, hepatocellular carcinoma; HR, hazard ratio; MW, microwave; RF, radiofrequency; US, ultrasound; W, Watts
Study details
Liang P (2009)
4
Key efficacy findings
Key safety findings
Comments
Number of patients analysed: n = 257 with metastases
(516 tumours)
Complications
Follow-up issues:
Major complications were classified as
those leading to substantial morbidity and
disability, increasing the level of care
required, or that resulted in admission or
prolonged hospital stay.
Major complications
Outcome
Rate
Skin burn requiring
< 1% (1/257)
resection
Pleural effusion
1.6% (4/257)
Liver abscess
< 1% (2/257)
Biloma
1.6% (4/257)
Patients selected for treatment
with MW ablation rather than other
treatment option by an MDT
panel.
Case series
Efficacy outcomes were not reported.
China
Recruitment period: 1994–2007
Study population: Patients with
primary or metastatic liver tumours.
Of patients with metastases primary
locations were colorectal = 86, breast
= 49, gastrointestinal = 47, lung = 30,
other = 45.
21 of 1157 patients lost to follow
up.
Prospective follow up at 1 and 3
months and then 3–6 monthly.
Study design issues:
n = 1136 (257 with metastases)
Two different MW ablation
systems were used during the
data collection period; a cooled
shaft version was introduced in
2005.
Age: 54 years
Sex: 79% male
Study population issues:
Patient demographics and clinical
characteristics relate to the study
population as a whole and not
specifically patients with
metastases.
Other issues:
Patient selection criteria: patients with
tumours <8 cm, and 7 or fewer
lesions in total.
Technique: General anaesthetic and
ultrasound guidance. Percutaneous
MW ablation with single probe used
for lesions < 1.7cm. Ablation at 60 W
for 300 seconds.
Only outcomes relating to patients
with liver metastases (not
hepatocellular or other primary
liver tumours) are extracted here.
Follow-up: Not reported
Conflict of interest/source of funding:
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Abbreviations used: CT, computed tomography; HCC, hepatocellular carcinoma; HR, hazard ratio; MW, microwave; RF, radiofrequency; US, ultrasound; W, Watts
Study details
Liang (2003)
5
Key efficacy findings
Key safety findings
Comments
Number of patients analysed: n = 74
Complications
No severe complications were reported.
Study was included in original
overview
Follow-up issues:
Case series
Survival
China
The mean survival time was 22.1 months ( 13.8 months).
The disease-free survival throughout the follow up period
was achieved in 35.1% (26/74) of patients.
Recruitment period: 1995–2002
Study population: patients with liver
metastases. Mean largest tumour size
31 mm. Primary cancer colorectal =
28, gastric/cardiac = 12, lung = 11,
breast = 11, other = 11. All patients
had undergone resection of primary
tumours 5 to 74 months prior to MW
ablation. Well differentiated = 9,
moderately differentiated = 33, poorly
differentiated = 32.
n = 74
Age: 27–81 (range)
Sex: 59% male
Patient selection criteria: patients with
liver metastases confirmed
histologically. Patients were not treated
surgically due to multiple lesions in
multiple segments or refused surgery.
Cumulative survival was 91% at 1 year falling to 29% at 5
years (absolute figures not stated).
Prognostic factors for survival
Outcome
Local pain
Minor to moderate pleural
effusion
Slight subcapsular bleeding
(assessed by ultrasound)
resolved without transfusion
Skin burns, where lesion
protruded beyond liver
capsule
Multivariate analysis (encompassing sex age, location of
primary, tumour differentiation grade, number of tumours,
size of tumours, change in tumour size at 3 months follow
up, and local recurrence or new metastases occurring)
showed that three of these factors were independent
predictors of survival: the number of tumours (p = 0.03) HR
1.94 (95% CI 1.06 to 3.53), tumour differentiation grade (p
= 0.02) HR 0.46 (95%CI 0.23 to 0.91), and recurrence or
new tumour development (p = 0.04) HR 3.58 (95% CI 1.02
to 12.64).
2.7% (2/74)
Consecutive patients treated at
one institution
Good description of the proportion
of patients available at each follow
up point.
4.1% (3/74)
Study design issues:
Cox multivariate analysis used to
determine factors predictive of
survival. No details provided of
sequence of adding univariate
factors into the model.
Study population issues:
None
Other issues:
Difficult to assess the specific
efficacy of MW ablation when
combined with chemotherapy
management.
Authors advocate the use of a 10
mm margin around the tumour
during ablation.
Technique: Percutaneous microwave
coagulation using an electrode though
a 14-gauge needle under sonographic
guidance. Power range 10–80 W. 77%
(57/74) of patients had concomitant
chemotherapy.
Follow-up: 25 months (mean)
Conflict of interest/source of funding:
supported by a grant from a national
foundation
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Rate (n=74)
90.5%
(67/74)
9.5% (7/74)
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Abbreviations used: CT, computed tomography; HCC, hepatocellular carcinoma; HR, hazard ratio; MW, microwave; RF, radiofrequency; US, ultrasound; W, Watts
Study details
Zhang X (2008)
6
Key efficacy findings
Key safety findings
Comments
Number of patients analysed: n = 88 patients followed up
for a minimum of 1 year
Complications
Follow-up issues:
There were no operative deaths, and
complications were easily treated
Outcome
rate
Fever up to 7 days
76.3% (122/160)
Pleural effusions (one
8.8% (14/160)
required drainage)
Jaundice secondary to 1.3% (2/160)
infection
Retrospective study
No efficacy outcomes reported for
patients with less than 1-year
follow-up.
Case series
Survival
China
Recruitment period: not reported
Over all 1-year survival (in 88 patients with a minimum of 1
year follow up) was significantly higher in patients with
primary liver cancer (96.6% [56/58]), than in patients with
liver metastases (82.1% [23/28]) (p=0.022).
Study population: patients with
unresectable hepatic primary or
metastatic tumours. Mean tumour
length 5.3 cm.
Safety outcomes were not
reported separately for patients
with liver metastases.
Study population issues:
Not clear how patients were
selected as having unresectable
tumours.
Patients with metastases also
received systemic chemotherapy
Other issues:
n = 160 (63 with metastases)
Age: 62 years (mean)
Sex: 78% male
Patient selection criteria: not reported
Ten patients received repeat MW
ablation treatment.
Technique: with direct observation or
real-time ultrasound guidance,
microwave ablation at 50–70 W for 20
to 30 minutes. For tumours with
abundant blood supply transarterial
chemoembolisation was performed,
and for those with tumours close to
bile ducts, stomach, intestine or large
vessels, percutaneous ethanol
injection was undertaken prior to
treatment.
Follow-up: not reported
Conflict of interest/source of funding:
not reported.
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Study design issues:
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Abbreviations used: CT, computed tomography; HCC, hepatocellular carcinoma; HR, hazard ratio; MW, microwave; RF, radiofrequency; US, ultrasound; W, Watts
Study details
Martin R C G (2010)
7
Key efficacy findings
Key safety findings
Comments
Number of patients analysed: n = 100 (83 with
metastases)
Complications
Probably some of the same
patients as reported in Iannitti
(2007)
Follow-up issues:
Case series
Tumour response
USA
Recruitment period: 2004–2009
Study population: patients with liver
metastases or primary disease
amenable to complete ablation or
resection plus ablation. Tumour size
= 3cm, median number of tumours =
2.
n = 100 (83 with metastases)
Age: 60 years (median)
Sex: 55% male
Patient selection criteria: patients with
metastases amenable to resection
alone were excluded. No metastases
> 5cm (although primary tumours
> 6cm were allowed).
Technique: MW ablation with US
guidance with up to 3 probes
(depending on tumour size) either
laparascopically or open following
segmental or wedge resection.
Follow-up: 3 years (median)
Conflict of interest/source of funding:
not reported.
Complete ablation was defined as CT scan in which all
viable tumour was ablated and without vascular perfusion.
Cancer type
Ablation success
Colorectal mets 98%
Hepatocellular
100%
cancer
Carcinoid mets 90%
Other mets
100%
(absolute numbers not reported)
There were no perioperative deaths.
Patients with 1 or more complication
Cancer type
Rate
Highest
grade
Colorectal
30.0% (15/50) 3
mets
Hepatocellular 23.5% (4/17) 2
cancer
Carcinoid
2.7% (3/11)
1
mets
Other mets
31.8% (7/22) 2
Compilation grade based on a 5 point scale
(no further details reported)
Group rate of recurrence at site of ablation
Colorectal
HCC
Carcinoid Other
p=
6.0% (3/50) 5.9% (1/17) 0% (0/11) 9.1% (2/22) 0.6
p=
0.04
Group median overall survival (months)
Colorectal
HCC
Carcinoid Other
36
41
18
12
p=
0.01
Not all outcomes reported
separately for patients with liver
metastases – particularly safety
outcomes.
It is not clear for what comparison
the p values presented represent.
Study population issues:
Other issues:
Additional analysis on resource
use of MW compared to RF is
reported but not extracted here.
Operative characteristics
Authors note that it is the bias at
the participating centre to use
ablation as an adjunct to resection
and not to replace resection as
the optimal technique.
Overall for all patients treated, the mean MW ablation time
was 13 minutes, and median operating room time 131
minutes. Mean estimated blood loss was 200ml.
Median length of stay was 5 days.
IP overview: microwave ablation for the treatment of liver metastases
Study design issues:
Origin of primary in patients with
carcinoid metastases is not
reported.
Patients with hepatocellular
cancer had significantly larger
tumours (p < 0.001) bur fewer
tumours (p = 0.003).
Survival
Group median disease-free survival (months)
Colorectal
HCC
Carcinoid Other
12
18
8
6
Prospective follow-up.
Single centre study.
No loss to follow-up.
CT scans at 2-week follow-up and
then 3 to 6 monthly thereafter.
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Abbreviations used: CT, computed tomography; HCC, hepatocellular carcinoma; HR, hazard ratio; MW, microwave; RF, radiofrequency; US, ultrasound; W, Watts
Study details
Key efficacy findings
8
Key safety findings
Number of patients analysed: n = 87 (64 with metastases)
Complications
Case series
Tumour response
There were no procedure-related
deaths.
USA
Local recurrence at ablation sites occurred in 2.7% (6/224) of
tumours treated, and regional recurrence was reported in 42.5%
(37/87) of patients.
Iannitti D A (2007)
Recruitment period: 2004–2006
Study population: Patients with
unresectable primary or metastatic
liver cancer. Colorectal metastases =
33, HCC = 23, Breast metastases =
11, carcinoid metastases = 8. Mean
tumour diameter = 2.6 cm.
n = 87 (64 with metastases) 224
tumours
Age: 67 years (mean)
Sex: 47% male
Patient selection criteria: not reported
Technique: MW ablation via
percutaneous, laparascopic or open
approach. 45 W delivered for 10
minutes.
Survial
Overall 47.1% (41/87) of patients were alive with no evidence of
disease at 16-month follow-up.
Outcome by cancer type at 19-month follow-up.
Cancer type
Alive with no Alive with
Died of
disease
disease
disease
HCC
60.8% (14/23) 13.0% (3/23) 26.1% (6/23)
Colorectal mets.
57.6% (19/33) 24.2% (8/33) 18.2% (6/33)
Breast mets.
36.4% (4/11) 9.1% (1/11)
54.5% (6/11)
Carcinoid mets.
25.0% (2/8)
75.0% (6/8)
0% (0/8)
Renal mets.
0% (0/3)
0% (0/3)
100% (3/3)
Lung mets.
0% (0/3)
33.3% (1/3)
66.7% (2/3)
Adrenal mets.
100% (1/1)
0% (0/1)
0% (0/1)
Oesophageal mets 0% (0/1)
0% (0/1)
100% (1/1)
Gallbladder mets. 0% (0/1)
0% (0/1)
100% (1/1)
Gastric mets.
0% (0/1)
0% (0/1)
100% (1/1)
Melanoma mets. 100% (1/1)
0% (0/1)
0% (0/1)
Ovarian mets.
0% (0/1)
100% (1/1)
0% (0/1)
Procedure-related complications (for
all cancer types) per person
Outcome
Rate
Skin wound
3.4% (3/87)
‘Wound breakdown’
2.3% (2/87)
Readmission (nausea 1.1% (1/87)
/ sedation)
Pain – requiring
1.1% (1/87)
termination of
procedure
Fluid collection
2.3% (2/87)
‘Persistent post2.3% (2/87)
operative ileus’ (not
otherwise described)
Haematoma
1.1% (1/87)
Fever/infection
1.1% (1/87)
(time of events not reported).
Probably some of the same
patients as reported in Martin
(2010)
Follow-up issues:
Loss to follow-up not reported.
Patients underwent imaging at 1
month, then every 4 months for 2
years.
Study design issues:
A variety of approaches for MW
ablation delivery were used,
outcomes for each were not
reported separately.
Study population issues:
A mixed study population with
both primary liver cancer and liver
metastases. Not all outcomes are
reported separately for each.
Origin of primary in patients with
carcinoid metastases is not
reported
Other issues:
None.
Follow-up: 19 months (mean)
Conflict of interest/source of funding:
not reported
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Efficacy
Survival
An RCT of 30 patients with multiple colorectal liver metastases reported that the
mean overall survival was 27 months in patients treated by MW ablation alone,
and 25 months in patients treated by hepatectomy (p = 0.83)1. In the same study,
the mean disease-free survival period was 11.3 and 13.3 months respectively (p
= 0.47).
A non-randomised controlled study of 53 patients with liver metastases reported
that there was no statistically significant difference in overall survival between
patients treated by resection plus MW ablation (17%) or by resection alone (44%)
at 5-year follow-up (p = 0.43)2. Similarly, there was no statistically significant
difference in hepatic recurrence-free survival (39% and 35% respectively) at 5year follow-up (p = 0.86). Disease-free survival at 3 years was 17% and 11%
among patients treated by resection plus MW ablation and resection alone,
respectively (p=0.54).A case series of 74 patients with liver metastases reported
that mean overall survival time was 22.1 months following MW ablation and that
disease-free survival was achieved in 35% (26/74) of patients at 25-month followup5.
Tumour response
A non-randomised controlled study of 19 patients with liver metastases reported
that the mean ablation diameter on post-operative computed tomography (CT)
scan (transverse) was significantly smaller following MW ablation (18.5 mm) than
following radiofrequency ablation (RFA) (18.5 mm vs 34 mm, p = 0.003)3.
A case series of 100 patients (83 with liver metastases) reported that complete
ablation on post-operative CT scan was achieved in 98% of patients with
colorectal liver metastases, 90% of patients with carcinoid metastases (origin of
primary not reported), and 100% of patients with other metastases (absolute
figures not reported)7.
Safety
Mortality
There were no procedure-related deaths following MW ablation in the RCT of 30
patients1, two non-randomised controlled studies of 532 and 193 patients, or three
case series of 1606, 1007 and 878 patients.
Fistulae
The non-randomised controlled study of 53 patients reported that biliary fistula
(not otherwise described) occurred in 1 out of 37 patients undergoing combined
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resection and MW ablation, and in 1 out of 16 patients undergoing resection
alone (measurement of significance and length of follow-up not reported)2.
Pleural effusion
A case series of 1136 patients (257 with metastases) reported that pleural
effusion occurred in 2% (4/257) of those with liver metastases treated by MW
ablation (length of follow-up not reported)4. The case series of 74 patients
reported minor to moderate pleural effusion in 9% (7/74) of patients (length of
follow up not reported)5. The case series of 160 patients (63 with liver
metastases) reported pleural effusions (1 requiring drainage) in 9% (14/160) of
patients (length of follow-up not reported)6.
Ileus
The case series of 87 patients (64 with metastases) reported ‘persistent postoperative ileus’ (not otherwise described) in 2% (2/87) of patients treated by MW
ablation 8.
Pain
The case series of 87 patients (64 with metastases) reported pain requiring
termination of the MW ablation procedure in 1 out of 87 patients8.
Validity and generalisability of the studies
Very little randomised controlled data or data comparing the procedure with
other ablative treatment modalities.
Limited long-term data with only 1 study to 5-year follow-up.
Most studies also included patients with primary liver cancer and metastases,
and results not always reported separately for these groups.
Some studies report outcomes per patient and some per tumour, making
comparison between studies difficult.
Patient selection not always clearly defined in studies, particularly with regard
to whether patients had tumours that were resectable or not.
Existing assessments of this procedure
There were no published assessments from other organisations identified at the
time of the literature search.
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Related NICE guidance
Below is a list of NICE guidance related to this procedure. Appendix B gives
details of the recommendations made in each piece of guidance listed.
Interventional procedures
Selective internal radiation therapy for non-resectable colorectal metastases in
the liver. NICE interventional procedures guidance 93 (2004). Available from
www.nice.org.uk/guidance/IPG093. This guidance is currently under review
and is expected to be updated in 2011.
Laparoscopic liver resection. NICE interventional procedures guidance 135
(2005). Available from www.nice.org.uk/guidance/IPG135
Radiofrequency ablation for colorectal liver metastases. NICE interventional
procedures guidance 327 (2009). Available from
www.nice.org.uk/guidance/IPG327
Cryotherapy for the treatment of liver metastases. NICE interventional
procedures guidance 369 (2010). Available from
www.nice.org.uk/guidance/IPG369
Specialist Advisers’ opinions
Specialist advice was sought from consultants who have been nominated or
ratified by their Specialist Society or Royal College. The advice received is their
individual opinion and does not represent the view of the society.
Dr F Miller (British Society of Interventional Radiology), Mr G Poston (British
Association of Surgical Oncology), Mr G Toogood (Great Britain and Ireland
Hepato-Pancreato-Biliary Association), Dr R Uberoi (British Society of
Interventional Radiology).
Two Specialist Advisers classified the procedure as a minor variation on an
existing procedure that is unlikely to alter that procedure’s safety and efficacy.
One Adviser said that it is novel and of uncertain safety and efficacy, and one
considered it to be the first in a new class of procedures.
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The main comparator for this procedure is RFA. Other interventions used
include trans-arterial chemoembolisation, percutaneous ethanol injection, and
other forms of percutaneous tumour ablation.
Adverse events reported or known from experience include abscess, bleeding,
infection, pneumothorax, colonic perforation, fever, pain, tumour seeding,
pleural effusion, and (rarely) bile duct injury.
Additional, theoretical complications might include deterioration in liver
function, and adjacent organ damage to kidney, lung or heart.
The key efficacy outcomes for this procedure are disease-free and long-term
survival.
One Specialist Adviser noted that there are relatively poor data on survival
rates and minimal data comparing the procedure with radiofrequency ablation
The procedure is essentially the same as RFA. Additional training may be
required for medical device training to operate the microwave generator.
The procedure is being taken up by most units in the UK, and with the
availability of the percutaneous probe, it is likely to find increasing applications.
It is currently overtaking RFA.
Patient Commentators’ opinions
NICE’s Patient and Public Involvement Programme was unable to gather patient
commentary for this procedure.
Issues for consideration by IPAC
Non-English language studies were not selected for inclusion in this overview.
Data have been included for metastases from all primary sites, as in most
studies the results for patients with metastases from colorectal primaries were
not reported separately.
Studies including microwave ablation by any approach (laparoscopic / open /
percutaneous) have been included on the advice of clinical opinion, and many
studies include a mixture of these approaches.
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IP 381_2
This is the third ablation procedure for liver metastases that IPAC has been
asked to consider. Previous guidance has been produced on radiofrequency
and cryotherapy ablation. Please see Appendix B.
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References
1
Shibata T, Niinobu T, Ogata N et al. (2000) Microwave coagulation therapy
for multiple hepatic metastases from colorectal carcinoma. Cancer 89:276284.
2
Tanaka K, Shimada H, Nagano Y et al. (2006) Outcome after hepatic
resection versus combined resection and microwave ablation for multiple
bilobar colorectal metastases to the liver. Surgery 139:263-273.
3
Hompes R, Fieuws S, Aerts R et al. (2010) Results of single-probe
microwave ablation of metastatic liver cancer. European journal of surgical
oncology : the journal of the European Society of Surgical Oncology and the
British Association of Surgical Oncology 36:725-730.
4
Liang P, Wang Y, Yu X et al. (2009) Malignant liver tumors: treatment with
percutaneous microwave ablation–complications among cohort of 1136
patients. Radiology 251:933-940.
5
Liang P, Dong B, Yu X et al. (2003) Prognostic factors for percutaneous
microwave coagulation therapy of hepatic metastases. AJR Am J
Roentgenol. 181:1319-1325.
6
Zhang X, Chen B, Hu S et al. (2008) Microwave ablation with cooled-tip
electrode for liver cancer: an analysis of 160 cases. Hepato-Gastroenterology
55:2184-2187.
7
Martin RC, Scoggins CR, and McMasters KM. (2010) Safety and efficacy of
microwave ablation of hepatic tumors: a prospective review of a 5-year
experience. Annals of Surgical Oncology 17:171-178.
8
Iannitti DA, Martin RC, Simon CJ et al. (2007) Hepatic tumor ablation with
clustered microwave antennae: the US Phase II trial. HPB 9:120-124.
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Appendix A: Additional papers on microwave ablation
for the treatment of liver metastases
The following table outlines the studies that are considered potentially relevant to
the overview but were not included in the main data extraction table (table 2). It is
by no means an exhaustive list of potentially relevant studies.
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IP 381_2
Article
Number of
patients/follow-up
Direction of conclusions
Reasons for noninclusion in table 2
Abe H, Kurumi Y, Naka S et
al. (2005) Openconfiguration MR-guided
microwave
thermocoagulation therapy
for metastatic liver tumors
from breast cancer. Breast
Cancer 12: 26–31
n=8
Follow-up = 26
months
No major complications; 5
patients alive with new
metastatic foci
Larger series included
in table 2.
Ahmad F, Strickland AD,
Wright GM et al. (2005)
Laparoscopic microwave
tissue ablation of hepatic
metastasis from a
parathyroid carcinoma.
European Journal of
Surgical Oncology 31: 321–
2
n=1
Follow-up = 15
months
No local or distal
recurrence at final followup
Larger series included
in table 2.
Idani H, Narusue M, Kin H et
al. (2001) Hepatic resection
for liver metastasis of
sigmoid colon cancer after
incomplete percutaneous
microwave coagulation
therapy. HepatoGastroenterology 48: 244–6
n=1
Follow-up = 22
months
Incomplete necrosis
required surgical resection
Larger series included
in table 2.
Follow up treatment of
resection in case of
failed microwave
coagulation
Jagad RB, Koshariya M,
Kawamoto J et al (2008)
Laparoscopic microwave
ablation of liver tumors: our
experience.
Hepato-Gastroenterology 55
(81) 27-32
n = 57 (46 with
metastases)
Follow-up = 21
months
Laparoscopic microwave
ablation is a feasible and
safe alternative to open
microwave ablation of the
liver tumors. It carries all
the advantage of minimal
invasive surgery. In
experienced hands,
microwave ablation using
laparoscopic technique can
be done safely and
effectively
Larger series included
in table 2.
Jiao D, Qian L, Zhang Y et
al (2010) Microwave ablation
treatment of liver cancer with
2,450-MHz cooled-shaft
antenna: an experimental
and clinical study.
Journal of Cancer Research
& Clinical Oncology 136 (10)
1507-1516
n = 60 (20 with
metastases)
Follow-up = 17
months
Effective local tumor
control was achieved
during one microwave
ablation session
Larger series included
in table 2.
Mitsuzaki K, Yamashita Y,
Nishiharu T et al. (1998) CT
appearance of hepatic
tumors after microwave
coagulation therapy. AJR
American Journal of
Roentgenology 171: 1397–
403
n = 63
Follow-up = not
reported
Complications included
abscess n = 4, haematoma
n = 2, nodular
dissemination n = 3,
ascites n = 5 and portal
vein thrombosis n = 1
Only 9 of the 63 cases
had secondary
metastases the other
53 had primary
tumours. Outcomes
were not reported
separately for each
group
Larger series included
in table 2
Ong SL, Gravante G,
n = 328 metastases
MW ablation is a minimally
Systematic review with
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IP 381_2
Metcalfe MS et al (2009)
Efficacy and safety of
microwave ablation for
primary and secondary liver
malignancies: A systematic
review.
European Journal of
Gastroenterology and
Hepatology 21 (6) 599-605
Follow-up = not
reported
invasive technique that has
broadened the therapeutic
option for patients with
conventionally
unresectable liver tumours
with promising survival
data. Future advances in
the applicator design and
treatment monitoring may
further improve its efficacy
and widen the indications
no meta-analysis.
Mixed patient
population with HCC
and liver metastases
without outcomes
reported separately.
Sato M, Watanabe Y, Kashu
Y et al. (1998) Sequential
percutaneous microwave
coagulation therapy for liver
tumor. American Journal of
Surgery 175: 322–4
n=6
Follow-up = not
reported
3 patients undergoing
curative MW coagulation
had no recurrence
Larger series included
in table 2.
Seki T, Wakabayashi M,
Nakagawa et al (1999)
Percutaneous microwave
coagulation therapy for
solitary metastatic liver
tumours from colorectal
cancer. A pilot clinical study.
The American Journal of
Gastroenterology 94: 322327
n = 15
Follow-up = not
reported
Percutaneous microwave
coagulation therapy is a
safe and effective
treatment for metachronus
small liver tumours that
have metastasized from
colorectal cancer
Larger series included
in table 2.
Shibata T, Yamamoto Y,
Yamamoto N et al. (2003)
Cholangitis and liver
abscess after percutaneous
ablation therapy for liver
tumors: incidence and risk
factors. Journal of Vascular
and Interventional
Radiology: JVIR 14: 1535–
1542
n = 70
Follow-up = not
reported
Cholangitis or liver abscess
occurred in 10 patients
(1.5% of treatments)
Outcomes of patients
with hepatocellular
carcinoma or
secondary metastases
are not distinguished.
Tanemura H, Ohshita H,
Kanno A et al. (2002) A
patient with small-cell
carcinoma of the stomach
with long survival after
percutaneous microwave
coagulating therapy (PMCT)
for liver metastasis.
International Journal of
Clinical Oncology 7: 128–32
n=1
Follow-up = 33
months
Complete necrosis on CT
scan and no recurrence to
final follow-up
Larger series included
in table 2.
Umeda T, Abe H, Kurumi Y
et al. (2005) Magnetic
resonance-guided
percutaneous microwave
coagulation therapy for liver
metastases of breast cancer
in a case. Breast Cancer 12:
317–21
n=1
Follow-up = 15
months
No recurrence of
metastatic tumour at final
follow-up
Larger series included
in table 2.
Yamashita Y, Sakai T,
Maekawa T et al. (1998)
Thoracoscopic
n=6
Follow-up = 4–23
months
Average length of stay was
11 days, no recurrence
during follow-up period
Larger series included
in table 2.
IP overview: microwave ablation for the treatment of liver metastases
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All studies included
with liver metastases
populations are
included elsewhere in
this overview
IP 381_2
transdiaphragmatic
microwave coagulation
therapy for a liver tumor.
Surgical Endoscopy 12:
1254–8
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Appendix B: Related NICE guidance for microwave
ablation for the treatment of liver metastases in the liver
Guidance
Interventional
procedures
Recommendations
Selective internal radiation therapy for colorectal metastases in
the liver. NICE interventional procedures guidance 093 (2004).
1.1 Current evidence on the safety of selective internal radiation
therapy (SIRT) for colorectal metastases in the liver appears adequate.
With regard to efficacy, the procedure may reduce tumour bulk, but
there is a lack of evidence of symptom relief or increased survival, and
combination with other treatments makes interpretation of the published
literature difficult
1.2 Clinicians wishing to undertake selective internal radiation therapy
for colorectal metastases in the liver should take the following actions.
• Ensure that patients understand the uncertainty about the procedure’s
safety and efficacy and provide them with clear written information. Use
of the Institute’s Information for the Public is recommended.
• Audit and review clinical outcomes of all patients having selective
internal radiation therapy for colorectal metastases in the liver.
1.3 Publication of research studies with outcome measures which
include survival will be useful in reducing the current uncertainty about
the efficacy of the procedure. The Institute may review the procedure
upon publication of further evidence.
Laparoscopic liver resection. NICE interventional procedures
guidance 135 (2005).
1.1 Current evidence on the safety and efficacy of laparoscopic liver
resection appears adequate to support the use of this procedure,
provided that the normal arrangements are in place for consent, audit
and clinical governance.
1.2 Patient selection for laparoscopic liver resection should be carried
out by a multidisciplinary team. Surgeons undertaking laparoscopic
liver resection should have specialist training and expertise both in
laparoscopic techniques and in the specific issues relating to liver
surgery.
Radiofrequency ablation for the treatment of colorectal liver
metastases. NICE interventional procedures guidance 327 (2009).
1.1 Current evidence on the safety and efficacy of radiofrequency (RF)
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ablation for colorectal liver metastases is adequate to support the use
of this procedure in patients unfit or otherwise unsuitable for hepatic
resection, or in those who have previously had hepatic resection,
provided that normal arrangements are in place for clinical governance,
consent and audit.
1.2 Patient selection should be carried out by a hepatobiliary cancer
multidisciplinary team
Cryotherapy for the treatment of liver metastases. NICE
interventional procedures guidance 369 (2010).
1.1 Current evidence on the safety of cryotherapy for the treatment of
liver metastases appears adequate in the context of treating patients
whose condition has such a poor prognosis, but the evidence on
efficacy is inadequate in quality. Therefore cryotherapy for the
treatment of liver metastases should only be used with special
arrangements for clinical governance, consent and audit or research
1.2 Clinicians wishing to undertake cryotherapy for the treatment of
liver metastases should take the following actions.
• Inform the clinical governance leads in their Trusts.
• Ensure that patients and their carers understand that other ablative
treatments are available and provide them with clear written
information. In addition, the use of NICE’s information for patients
(‘Understanding NICE guidance’) is recommended (available from
www.nice.org.uk/guidance/IPG369/publicinfo).
• Audit and review clinical outcomes of all patients having cryotherapy
for liver metastases (see section 3.1).
1.3 Patient selection and treatment should be carried out by a
hepatobiliary multidisciplinary team with expertise in the use of ablative
techniques
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Appendix C: Literature search for microwave ablation
for the treatment of liver metastases
Database
Cochrane Database of
Systematic Reviews – CDSR
(Cochrane Library)
Database of Abstracts of
Reviews of Effects – DARE
(CRD website)
HTA database (CRD website)
Cochrane Central Database of
Controlled Trials – CENTRAL
(Cochrane Library)
MEDLINE (Ovid)
MEDLINE In-Process (Ovid)
EMBASE (Ovid)
CINAHL (NLH Search 2.0)
Date searched
20/04/2011
Version/files
Issue 4 of 12, Apr 2011
20/04/2011
-
20/04/2011
20/04/2011
Issue 4 of 12, Apr 2011
20/04/2011
20/04/2011
20/04/2011
20/04/2011
1948 – April Week 12011
April 19, 2011
2011 week 15
1981-Present
The following search strategy was used to identify papers in MEDLINE. A similar
strategy was used to identify papers in other databases.
1
((microwave* or micro-wave*) adj3 (ablat* or coagulat*
or therap* or themotherap* or thermoablat*)).tw.
2 (mct or pmct or mwa or mw).tw.
3 Microwaves/tu [Therapeutic Use]
4 or/1-3
((liver or hepatic*) adj3 (secondar* or neoplasm* or
5 cancer* or carcinoma* or adenocarcinom* or tumour*
or tumor* or malignan* or metastas*)).tw.
6 Liver Neoplasms/
7 or/5-6
8 4 and 7
9 Animals/ not Humans/
10 8 not 9
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