Efficacy of combining temperature- and power-controlled radiofrequency ablation for malignant liver tumors.

Abstract

Single mode of radiofrequency ablation (RFA) often leads to limited ablation in the zone of necrosis. This study clarifies the efficacy of combining temperature- and power-controlled RFA for malignant liver tumors.
Between April 2008 and August 2008, 58 patients with malignant liver tumors received RFA at Sun Yat-sen University Cancer Center. The patients were divided into 2 groups using a random number table: one group received combined temperature- and power-controlled RFA (the combination group), and the other group received power-controlled RFA alone (the control group).
Three patients were lost to follow-up and 55 patients were included for evaluation. Twenty-five patients with 29 tumors were treated by the combination RFA, and 27 tumors (93.1%) achieved either complete response (CR) or partial response (PR). One patient had a seriously decreased heart rate. In the control group, 30 patients with 32 tumors received power-controlled RFA, and 29 tumors (90.6%) achieved CR or PR. There were no serious complications. There was no difference between the combination and control groups in treatment time ((13.3 +/- 1.3) min vs. (10.2 +/- 2.3) min, P = 0.459). The number of sessions of RFA for the combination group was less than that of control group (1.3 sessions vs. 2.4 sessions), but the difference was not significant (P = 0.579).
RFA controlling both temperature and power is effective and safe for patients with malignant liver tumors, and the number of sessions of RFA for the combination group was less than that of the control group.

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2010; Vol. 29 Issue 4 
Chinese Journal of Cancer
窑 Clinical Research 窑
Efficacy of combining temperature­ and power­controlled
radiofrequency ablation for malignant liver tumors 
Hui­Hong Liang 1,2 , Zhen­Wei Peng 1,2 , Min­Shan Chen 1,2 , He­Ping Peng 3 , Ping Xue 3 , Yao­Jun Zhang 1,2 , 
Ya­Qi Zhang 1,2 , Jin­Qing Li 1,2 
1 State Key Laboratory of Oncology in South China, Guangzhou, Guangdong 510060, P. R. China; 2 Department of Hepatobiliary Oncology, Sun 
Yat­sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China; 3 Department of Hepatobiliary Surgery, The Second Affiliated 
Hospital of Guangzhou Medical College, Guangzhou, Guangdong 510260, P. R. China
揖Abstract铱 Background and Objective:
Methods:
Results:
Conclusion:
Key words: 
Correspondence to: Min­Shan Chen; Tel: +86­20­87343117; 
Email: Chminsh@mail.sysu.edu.cn 
This paper was translated from Chinese into English  by 
and edited by  Hope J. Lafferty on 2010­01­29. 
Medical Translation 
The Chinese version of this paper is avaiable at  http://www.cjcsysu.cn/cn/article 
.asp?id=16343. 
Received: 2009­06­08; Accepted: 2009­11­23 
Local therapy with radiofrequency ablation
important modality in the comprehensive treatment of patients 
with liver cancer. Studies have shown that the efficacy of 
percutaneous local ablation of liver cancer with diameters less 
than 5 cm is comparable to that of conventional open abdominal 
surgery, and has merits including minimal invasiveness, rapid 
recovery after procedure, and low cost [1­3] . However, local ablation 
has the disadvantage of high local recurrence rates [4,5] , resulting 
from residual tumors caused by incomplete ablation of the target 
tumor [5,6] . Thus, how to extend the scope of RFA has become a 
global research focus in the field of local ablation. 
Power­controlled RFA is the traditional method used for 
judging the completeness of RFA by the operator. It is well 
(RFA) is an 
known that the mechanism of RFA is heat production around the 
electrode by ion oscillation triggered by the electric filed produced 
by a high­frequency alternating current, which thereby causes 
heat coagulative necrosis of tumor tissue. The necrotic tissue is 
dehydratedandcarbonized,
conductivity (that is, increases impedance), and the RFA system 
can detect the alterations in impedance , then stop the power 
output to finish the RFA automatically [7,8] . The major problem with 
the power­controlled mode is that when the power output grows 
too fast, the tissue is dehydrated and carbonized too rapidly, and 
therefore the power output is limited. Although the electrical 
impedance increased, the necrotic lesion is very small, so the 
anticipated curative effect cannot be achieved [8,9] . 
Another monitoring method is temperature controlled, with 
which the ablation procedure is controlled by maintaining a 
certain temperature level for a predefined duration. Although 
temperature control can prevent the rapid upsurge of temperature 
around the needle and the subsequent rapid dehydration and 
carbonization, which compromises power output, because of 
power loss(the heat may be carried away by blood flow when 
the tumor is near  major vessels), the ablation scope may be 
which reducestheelectrical 
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Chinese Journal of Cancer 
suboptimal [10] . 
Considering
approaches, both single modes of RFA share the disadvantage 
of a limited scope of ablation. The present study aimed to treat 
patients with malignant liver tumors by using the combination of 
temperature­ and power­controlled RFA. We presumed that these 
two methods were complementary and the combination could 
expand the scope of ablation, so the operator could better judge 
the completeness of the treatment. And we aimed to clarify the 
efficacy and safety of the combination of temperature­ and 
power­controlled RFA compared
method alone. 
theseintrinsicshortcomings ofthe two 
withthe power­controlled 
Between April 2008 and August 2008, 58 patients with 
malignant tumors in the liver received RFA at the Department of 
Hepatobiliary Surgery, Sun Yat­sen University Cancer Center. 
The inclusion criteria were as follows: (1) the diameter was 
less than 5 cm for solitary tumor, and the largest tumor less than 
3 cm in diameter for multiple tumors
less than 3); (2) liver function was Child­Pugh Grade A or B; (3) 
there was a safe puncture path from the skin to the tumor mass 
as determined by ultrasonography;
(the number of tumors is 
(4) there was no distal 
metastasis or tumor thrombus in the portal vein and its branches; 
(v) the patient had no hepatoencephalopathy, refractory ascites, 
or upper gastrointestinal tract bleeding in the past; (vi) no severe 
coagulopathy; and(vii) indocyanine green retention rate at 15 
minutes (ICGR15) < 30%. 
Primary liver cancer was diagnosed according to guidelines 
of the American Association for the Study of Liver Diseases 
(AASLD) or confirmed by pathology. Metastatic tumors were 
confirmed by the pathology of the primary tumor. 
The included patients were randomly assigned to two groups 
using a random numbers table: a group receiving the combined 
methods (the combination group) and a control group. The 
combination group received RFA with combined temperature­ 
and power­controlled methods, and the control group received 
power­controlledRFAalone.
instrument(including the radiofrequency generator and surgical 
electrodes, there were 10 electrodes at most, the extending 
diameter was 5 cm at most, and the electrode rod had a 
maximum length of 15 cm) was used in the combination group, 
which had both temperature­ and power­controlled mode. The 
RF2000 radiofrequency system
system; Radiotherapeutics) was used in the control group, which 
had single power­controlled mode. Baseline characteristics of 
patients in both groups are shown in Table 1.
AnS­1500radiofrequency 
(a multiple warhead therapeutic 
Item
Sex
Men
Women
Age (years)
Tumor size (cm)
Number of tumors
Gamma-glutamyltranspeptidase (U/L)
Alanine aminotransferase (U/L)
Albumin (g/L)
Total bilirubin (滋 mol/L)
Tumor type
Primary liver cancer
Liver metastasis
Alpha鄄 fetoprotein (ng/mL)
臆 400
> 400
Indocyanine green retention rate in 15 minutes
约 10%
10%-15%
Combination group
20
5
53.7 依 13.1
2.78 依 1.27
1.20 依 0.40
90.32 依 103.2
30.78 依 12.33
38.43 依 5.02
16.00 依 5.31
18
7
14
11
22
3
Control group
24
6
54.3 依 10.2
2.45 依 1.47
1.15 依 0.25
103.45 依 95.36
36 依 12.25
39.85 依 4.34
17.81 依 10.25
24
6
14
16
28
2
P
0.999
0.622
0.657
0.999
0.999
0.999
0.728
0.999
0.487
0.491
0.493
Puncture was performed for all patients under the guidance 
of Hitachi EUB­2000 ultrasound instrument. Local anesthesia 
combined with intravenous injection of Diprivan were performed. 
After inducing the anesthesia, under the guidance of ultrasound, 
the electrode needle was inserted into the liver tumor and the 
inner hook­shape expandable electrode tines were deployed. For 
the combination mode, the temperature control was set for 15 
min followed by the power control. In the temperature­controlled 
mode, the temperature was set at 90­95益  and the ablation 
duration was 15 min for each time. The power control mode 
began at 10 W, followed by stepwise increments of 10 W each 
minute until electrical impedance increased abruptly. The needle
a, Continuous variables are presented as mean 依 SD, and compared by Student t test; otherwise, values represented number of patients are compared using 字
2 test.
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2010; Vol. 29 Issue 4 
Chinese Journal of Cancer 
was extracted 1 cm  and rotated 180毅   , and another period of 
ablation was  performed. Single­mode ablation was based on 
power­controlled mode. For patients with large tumors, the 
needles were deployed in a multidirectional pattern and ablation 
was conducted multiple times from multiple angles to ensure 
complete tumor ablation and ablation to potential malignant 
tissue in the 5­10 mm zone surrounding the tumor. Of the 58 
patients, 56 received single ablation and 2 patients
single­mode [control] group) received ablations twice. 
(in the 
General conditions, routine blood tests, and liver function of 
these patients were examined 1 week
procedure.Imagingstudies
tomography (CT), magnetic resonance imaging
ultrasonography),liver function,
carcinoembryonic antigen (CEA) (for patients whose preoperative 
levels were abnormal), and routine laboratory examinations were 
performed 1 month(依 7 days) and 3 months
the procedure. 
(依  3 days) after the 
(contrast­enhanced computed 
(MRI), or 
(AFP)alpha­fetoprotein or 
(依 21 days) after 
Clinical response was assessed according to the WHO 
response criteria for solid tumors [12] . Complete remission (CR) 
was defined as the complete disappearance of the lesion for 
more than 1 month. Partial response
tumor size by 50% for more than 4 weeks. No change (NC) was 
a less than 50% reduction in tumor size or tumor enlargement 
less than 25%. Progressive disease
of the tumor by more than 25% or the occurrence of new 
lesions. The rate of effectiveness was calculated by CR + PR 
(lesions that could not be ablated at one time should receive 
another ablation, and the later result was used as evaluating 
index). 
Adverse reactions were described using the number of 
adverse events and the incidence. The severity of the adverse 
events and their association with the treatment are described in 
the results section. 
(PR) was the reduction of 
(PD) was the enlargement 
Of the 58 patients in our study, 3 patients failed to follow up 
in 1 month after the procedure
and1 from thecontrol group),
examination at 3 months after the procedure and were thus 
included in the analysis. Another 3 patients were lost to follow­up 
at 3 months after the procedure
examination) with 2 in the combination group and 1 in the control 
group. The missing rate was 5.2%. 
(2 from the combination group 
buttheycompleted the 
(noncompliance with the 
Twenty­seven patients were included in the combination 
group, of whom 2 were lost to follow­up, and thus 25 were 
involved in the final analysis(29 tumor masses). There were 20 
men and 5 women with a median age of 51 years (range, 39­69 
years). There were 18 patients with primary liver cancer and 7 
with metastatic tumors(4 patients with colon cancer, 1 with 
gastric cancer, 1 with nasopharyngeal carcinoma, and 1 with 
cancer of the pancreatic head). A total of 21 patients had single 
tumors and 4 patients had two tumors. In total, there were 29 
tumors in the 25 patients, of which, there were 18 tumors with 
diameters 约 3 cm, 11 tumors 3­5 cm, and the mean diameter of 
the tumors was (2.78 依 1.27) cm. After ablation, the rate of CR 
was 82.8%(24/29), PR was 10.3%
(2/29). 
Of the 25 patients, 18 had primary liver cancer, and 11 had 
positive AFP preoperatively. Three months after ablation, the 
AFP returned to within normal level in 3 patients
patients (27.3% ) showed significantly reduced AFP, and 5 
patients(45.4% ) showed an unremarkable decrease or an 
increase. 
In the 27 patients that underwent RFA (including the missing 
patients), 1 patient showed a reduced heart rate during the 
procedure. The lowest rate was 40 bpm and sustained for 10 s, 
and the heart rate returned to normal after discontinuing the 
ablation. No severe adverse events or complications, such as 
needle path burn, burn at the site of the circuit electrode plate, 
needle path metastasis, tumor rupture after the procedure, 
gastrointestinal (or peritoneal) hemorrhage, liver abscesses or 
death, were reported. 
(3/29), and PD was 6.9% 
(27.3% ), 3 
Of the 31 enrolled patients, 1 was lost to follow up, and 30 
patients were included in the analysis
24 men and 6 women with a median age of 53 years (42­66 
years). A total of 24 patients had primary carcinoma and 6? 
patients had metastatic liver tumors
cancer; 1 with gastric cancer, 1 with nasopharyngeal carcinoma, 
and 1 with breast cancer). There were 28 patients with single 
tumors and 2 patients with 2 tumors. There were 32 lesions in 
the 30 patients, including 22 with diameters 约 3 cm, 10 with 
diameter 3­5 cm, and the mean diameter of the tumors was 
(2.45 依 1.47) cm. Of the 32 lesions, there were 28 CR (87.5%), 
1 PR (3.1%), and 3 PD (9.4%). 
Of the 30 patients, 24 had primary liver cancer, and 16 of 
them had positive AFP preoperatively. At 3 months after ablation, 
the AFP returned normal in 4 patients (25%), 8 patients (50%) 
showed significantly reduced AFP, and 4 patients (25%) showed 
an unremarkable decrease or an increase. No severe adverse 
events or complications were reported. 
(32 tumors). There were 
(3 patients with colon 
The effectiveness rates of the combination and control groups 
were 93.1% and 90.6%, respectively. There was no significant 
difference between the two groups in the effectiveness of tumor 
control (  = 0.999). The incidence rates of severe complications 
for the combination and control groups were 4%  (1/25) and 0% 
(0/30), respectively, which was not statistically significant
0.464). The mean lengths of treatment of the combination and 
control groups were similar ((13.3 依 1.3) min vs.
min; = 0.459). The number of needle insertion events in the 
combination group was slightly less than in the control group (1.3 
vs. 2.4, = 0.579). 
( = 
(10.2 依 2.3) 
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Ourstudy demonstratedthatthecombinationof 
temperature­ and power­controlled modes of RFA for malignant 
tumors in the liver was effective. Besides its high efficacy, its 
length of treatment was similar to that of the single­mode group. 
However, in terms of the number of needle insertion events, the 
combination mode required fewer insertions. Although it is not 
statistically significant, the trend also informed us that the 
combination mode might reduce the potential complications of 
hemorrhage and needle path seeding brought by repeated 
needle insertions. Because the present study is in nature clinical 
validation and the sample size is small, it does not have enough 
statistical powertodetect
conventional mode and the combination mode. Theoretically, the 
single power­controlled or temperature­controlled modes have 
their own instinct shortcomings, and the combination is expected 
toexpand theablationscope,
effectiveness. 
Controlling temperature and power are the two major 
monitoring modalities in RFA. The power­controlled method 
judgesthe completenessof
inpedance. However, due to the differences in chemical and 
physical properties, the same parameter set may result in 
premature dehydration and carbonization in some tissues, so the 
radiofrequency power cannot be output and spread adequately. 
Currently, the international standard to solve this problem is to 
improve the design of RFA needles and adjust the ablation 
parameters. The former includes the use of a cold water RFA 
needle or to combine with intratumor normal saline injection [13,14] . 
The principle is to cool the RFA needle or inject normal saline to 
delay the dehydration and carbonization of ablated tissues, 
thereby increasing the output of RFA power and expanding the 
ablation scope. The latter method is to balance the power output 
and increase the ablation scope by emitting RFA power in 
pulses [15] or using lower initial power and slower incremental 
power [9] . The temperature control mode can compensate for the 
shortcomings of power control mode. With the preset of a target 
temperature, the ablation system can adjust the output power 
automatically to maintain a certain temperature, and thereby the 
energy output can be balanced. For tumors at some particular 
sites, including those beside major vessels, the blood flow may 
take away some energy, resulting in incomplete ablation [16,17] . 
Clinicians both home and abroad prefer to temporarily interrupt 
the afferent flow of blood to the liver to expand the ablation 
scope, which has been validated in some studies [18] . Some clinical 
investigations also reported that the RFA after chemotherapy for 
vascular interventional embolisms could benefit patient survival [19] . 
Because vascular embolism agents are injected into the tumor 
vessels and the blood flow in the tumor declines, the ablation 
energy can be more effectively focused to produce a larger 
ablation scope. 
Reportsonthecombination
power­controlled RFA for malignant tumors in the liver are rare 
thedifference betweenthe 
therebyimprovingRFA 
ablationbydetectingcircuit 
of temperature­and 
both at home and abroad, so no experiences of this combination 
can be referenced. The combination mode designed in our study 
began with the first session of temperature control for 15 min and 
was followed by the power control mode to finish the ablation. 
There are two principles for this design. First, the determination 
of endpoints with altered resistance in the power control mode is 
more reliable than that determined by temperature for judging the 
completeness of the ablation. Thus, we control the temperature 
to achieve a certain ablation scope and then control the power to 
validate the completeness of the ablation. Second, the authors 
use power­controlled RFA in their daily clinical practice and have 
accumulated a large amount of experience. Thus, this clinical 
trial combines temperature­controlled RFA with the guarantee 
that patients have received effective treatment. As a matter of 
fact, the combination of the two modalities should be balanced to 
ensure that the power output can be maximized, the output 
power is focused on the target tumor tissues, and the power loss 
can be minimized. A balance between power output and effective 
temperature should be reached, which cannot only prevent 
premature carbonization and dehydration, but also reach effective 
temperatures to maximize the ablation scope. The S­1500 RFA 
instrument combined temperature and power controls and can 
combine the two modes in different proportions. As compared 
with conventional RFA instruments, the power output in the 
S­1500 RFA instrument is more flexible and the assessment of 
response is more reliable. 
However,thepresent study
statistically significant preference for the combination modality. 
The reasons may be either the small sample size or the way the 
two modes were combined. The present study only explored the 
effectiveness of the combination pattern of temperature and 
power, when in fact, the combination patterns are varied, 
including the specific means of the combination, the setting of 
temperature and time, as well as the setting of the initial and 
step­up power. In conclusion,
combination of temperature­ and power­controlled RFA was 
effective in treating malignant turnors in the liver, and the desired 
ablation scope can be achieved by fewer needle punctures. 
Consequently,thecombination
complications and improve efficacy. Nevertheless, to verify the 
relationshipbetweenthe combined
effectiveness requires larger scale, prospective, and controlled 
trials.
failed todemonstratea 
our study showed that the 
treatmentmayreduce 
methodand itsactual 
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