Open Journal of Radiology, 2013, 3, 159-164
http://dx.doi.org/10.4236/ojrad.2013.33026 Published Online September 2013 (http://www.scirp.org/journal/ojrad)
Effectiveness and Safety of CT-Guided 125I Brachytherapy
for Lung Metastasis from Hepatocellular Carcinoma
Yongxin Chen1,2, Fei Gao1,2*, Lin Chen1,2, Sheng Peng1,2, Yingjie Huang1,2, Yao Wang 1,2
1Department of Interventional Radiology, Sun Yat-sen University Cancer, Guangzhou, China
2State Key Laboratory of Oncology in South China, Guangzhou, China
Received July 20, 2013; revised August 20, 2013; accepted August 27, 2013
Copyright © 2013 Yongxin Chen et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
To retrospectively evaluate effectiveness and safety of CT-guided 125I brachytherapy in patients with lung metastasis
from hepatocellular carcinoma, sixty lung metastatic lesions in 29 patients were percutaneously treated in 34 125I
brachytherapy sessions. Each metastatic lesion was treated with computed tomographic (CT) guidance. Follow-up con-
trast material-enhanced CT scans were reviewed and the efficacy of treatment was evaluated. Months are counted from
the first time of 125I brachytherapy and the median duration of follow-up was 11 months (ranging from 6 - 17 months).
The local control rates after 3, 6, 10 and 15 months were 86.2, 71.4, 60.9 and 50.0% respectively. At the time of writing,
ten patients are alive without evidence of recurrence at 11 - 15 months. The 10 patients presented good control of local
tumor and no systemic recurrence, and survived throughout the follow-up period. Other 11 patients died of multiple
hematogenous metastases 5 - 15 months after brachytherapy. A small amount of local hematoma occurred in 5 patients
that involved applicator insertion through the lung. Four patients presented pneumothorax with pulmonary compression
of 30% - 40% after the procedure and recovered after drainage. Two patients had minor displacement of radioactive
seeds. Severe complications such as massive bleeding and radiation pneumonitis did not occur. So CT-guided 125I
brachytherapy is effective and may be safely applied to lung metastasis from hepatocellular carcinoma.
Keywords: 125Iodine; Brachytherapy; Lung Metastasis; Hepatocellular Carcinoma
1. Introduction
Hepatocellular carcinoma (HCC) is a very highly inva-
sive tumor that metastasizes hematogenously and lym-
phogenously to distant sites. Most frequently affected
sites are the lungs, regional lymph nodes, bones, and
adrenal glands [1,2]. Since lung is the most common
metastatic organ for hepatocellular carcinoma, lung me-
tastasis is thus considered as a major prognostic factor
for these metastatic patients. However, treatment of lung
metastasis from hepatocellular carcinoma is usually chal-
lenging because the previous therapies (including surgery,
chemoembolization, radiofrequency ablation, and various
combinations of these treatments) limit the options avail-
able for subsequent treatment. 125I brachytherapy has
been widely applied for tumor treatment in clinic with
significant efficacy providing promising results for local
control of solid tumors such as prostate carcinoma, lung
cancer, HCC, liver metastasis and pancreatic cancer
[3-10]. When permanently implanted into the tumor, 125I
seeds send out continuous low-dose X-ray and γ-ray,
leading to a dose of 160 - 180 Gy within the local tissue
during the half-life of 125I. The killing radius of 125I seeds
is 1.7 cm, with minimal effects on normal tissues since
the radioactive energy is inversely correlated with the
square of the radius [4]. The specific effect of 125I radia-
tion on tumor cells can efficiently inhibit the prolifera-
tion and repair of tumor cells, while the surrounding
normal tissue only receives less than 25% of the doses
received by the tumor cells [8]. The slow emission of
radiation from the 125I seeds also allows the surrounding
normal tissue that receives sub-lethal or potentially lethal
dose of radiation to have sufficient time for repair and
recover [10].
However, there are few reports about the effects of
lung metastasis with the methods of 125I brachytherapy.
We considered the possibility that it might be an alterna-
tive treatment for lung metastasis. Especially for patients
whose condition is unsuitable for surgical resection, 125I
brachytherapy may provide an opportunity to achieve re-
mission. This research retrospectively evaluated the cli-
*Corresponding author.
C
opyright © 2013 SciRes. OJRad

Y. X. CHEN ET AL. 160
nical value of 125I brachytherapy for lung metastasis from
hepatocellular carcinoma.
2. Materials and Methods
2.1. Ethics
This work has been carried out in accordance with the
Declaration of Helsinki (2000) of the World Medical
Association. This study was approved ethically by Sun
Yat-sen University Cancer Center. All patients provided
informed written consent.
2.2. Patients
From March 2005 to March 2012, twenty-nine patients
underwent 125I brachytherapy of lung metastasis from
hepatocellular carcinoma. Twenty-two men and seven
women (mean age, 59 years; range, 35 - 76 years) were
enrolled in our study. All patients were pathologically
proved as hepatocellular carcinoma. Treatment of the
primary cancer were surgical resection in 16 patients,
surgical resection combined with chemoembolization in
5 patients, radiofrequency ablation in 3 patients, and ra-
diofrequency ablation combined with chemoemboliza-
tion in 5 patients. The lung metastatic lesions was seen
on computed tomographic (CT) images 6 - 13 months
(mean, 9 months) after the first treatment of the primary
cancer.
Our diagnosis was confirmed with pathologic proof at
CT-guided needle biopsy before 125I brachytherapy in all
patients. The mean size of the lung metastatic lesions
was 1.3 cm ± 0.7 (standard deviation) (range, 0.8 - 2.9
cm) in largest diameter. Our indication criteria for 125I
brachytherapy of lung metastatic lesions were as follows:
1) the metastatic lesion was solitary in the lung and the
patient was not a candidate for surgical resection; 2) the
number of lung metastatic lesions was not more than 3;
and 3) the lung metastasis was the only evidence of re-
currence.
2.3. Methods
The 125I seed (Beijing Atom High Tech) in this study was
shaped as cylindrical titanium package body with length
of 4.5 mm, diameter of 0.8 mm and 3.0 mm × 0.5 mm
inside the silver column (adsorption of 125I, radioactivity:
0.8 mci, the average energy: 27 - 35 keV, half-life: 59.6
days, half layer: 0.025 mm of lead; anti-tumor activity:
1.7 cm, the initial dose rate: 7 cGy/h), and 0.05 mm wall
thickness of titanium in its external shell.
Before 125I brachytherapy, CT images with 5 mm sec-
tion thickness were obtained for targeting the area of
interest. A treatment plan was made for each patient us-
ing a computerized treatment planning system (TPS)
(BT-RSI model TPS, YuanBo, Beijing, China) to deter-
mine the dose of radioactive seeds implanted and the
placed site. A careful delineation of the tumor target
volume was performed in every CT slice. Based on the
three perpendicular diameters within the target tumor and
a prescribed matched peripheral dose (MPD) of 100 -
140 Gy, TPS generated a dose-volume histogram (DVH),
isodose curves of different percentages, and calculated
the position (coordinates) of brachytherapy applicator,
dose and number of implanted seeds. Planning target
volume (PTV) is defined as a 1.5 cm of expansion exter-
nal to the gross tumor volume. PTV edge was covered by
isodose curve from 70% to 90% (Figure 1). The entry
site and path of the needle were determined to avoid vital
structures such as large vessels.
With CT (Siemens, Germeny) fluoroscopic guidance, a
18G brachytherapy applicator (Beijing Atom High Tech)
was inserted into a lesion and positioned against its
deepest margin after local anesthesia. A turntable or clip
implant gun (Beijing Atom High Tech) was then attached
to the applicator for implantation. Every 125I seed was
placed at a distance of 0.5 - 1.0 cm from each other (Fig-
ures 2 and 3). Within one month, a CT scan was per-
Figure 1. Pre-planning of 125I brachytherapy. (A)
Two-dimensional image of tumor on computerized radioac-
tive treatment planning system (TPS), the PTV edge was
cov- ered by isodose curve from 70% to 90%. (B)
Three-dimen- sional graph of planar implantation and dose
distribution on TPS.

Y. X. CHEN ET AL. 161
formed to verify the position and intensity of 125I seeds
according to TPS (Figure 4). For tumors showing insuf-
ficient radioactivity, more 125I seeds were implanted.
2.4. Follow-Up
According to our follow-up protocol, chest CT images
were obtained each month before and after intravenous
administration of contrast medium for up to 6 months
and then at 2- to 3- month intervals (Figures 2, 3). The
efficacy of 125I brachytherapy was assessed according to
World Health Organization (WHO) response evaluation
criteria for solid tumor as follows. 1) Complete response
(CR) was defined as complete disappearance of tumor,
Figure 2. Case 1. (A) Lung metastasis from hepatocellular
carcinoma, as indicated by the arrowhead. (B) During
brachytherapy, an applicator accurately inserted into the
tumor to implant 125I seeds. (C) Three months after
brachytherapy, tumor disappeared, with well distributed
radioactive seeds remaining only, as indicated by the ar-
rowhead.
Figure 3. Case 2. (A) During brachytherapy, an applicator
accurately inserted into the tumor to implant 125I seeds. (C)
Three months after brachytherapy, tumor disappeared,
with well distributed radioactive seeds remaining only, as
indicated by the arrowhead.
Figure 4. Verification of post-125I brachytherapy. (A) Two-
dimensional image of tumor on TPS, the PTV edge was
covered by isodose curve from 70% to 90%. (B) Three-

Y. X. CHEN ET AL. 162
dimensional graph of planar implantation and dose distri-
bution on TPS.
no tumor or only accumulative metal granule shadow
detectable by imaging analysis. 2) Partial response (PR)
was defined as the shrinkage of tumor with the P value
decreasing by ≥50% compared to the pre-procedure
value. 3) No change (NC) was defined as a P value de-
crease of <50% or increase of <25% compared to the
pre-procedure value. 4) Progression of disease (PD) was
defined as a P value increase of ≥25% or the appearance
of new tumor foci. Local control rate (LCR) was calcu-
lated as cases of (CR + PR)/total × 100%. We com-
pared the products (P) of two largest and perpendicular
diameters within the tumor under CT examination before
and after the procedure.
3. Results
3.1. Implantation of 125I Radioactive Seeds
A total of 34 brachytherapies and 60 lung metastatic le-
sions were performed on the 29 patients, among which,
29 were successful at the first time, achieving the TPS
criteria, and 5 didn’t reach the TPS criteria, followed by
additional implantations. The total number of implanted
seeds was 493, with an average of 8.2 per tumor. The
satisfactory rate of seed implantation was 94.1% (32/34).
3.2. Treatment Efficacy
Months are counted from the first time of 125I brachy-
therapy and the median duration of follow-up was 11
months (range, 6 - 17 months). The local control rates
after 3, 6, 10 and 15 month were 86.2, 71.4, 60.9 and
50.0% respectively. The 15-month survival rate of our
study is 48.3% (14/29) excluding 4 patients who were
alive without evidence of recurrence at 11, 11, 12 and 14
months. At the time of writing, ten patients are alive
without evidence of recurrence at 11 - 15 months. The 10
patients presented good control of local tumor and no
systemic recurrence and survived throughout the fol-
low-up period. Eleven patients died of multiple hemato-
genous metastases 5 - 15 months after brachytherapy.
Among the 29 patients, 125I brachytherapy was repeated
in 6 patients because of local residue or local progression
of the lymph node. The clinical responses of patients to
brachytherapy were summarized in Table 1.
3.3. Side Effects
Several complications related to the procedure occurred
during or after brachytherapy. A small amount of local
hematoma occurred in 5 patients that involved applicator
insertion through the lung, probably because of injury of
small lung vessels. Four patients presented pneumotho-
rax with pulmonary compression of 30% - 40% after the
procedure and recovered after drainage. During the fol-
low-up, two patients had minor displacement of radioac-
tive seeds. Severe complications such as massive bleed-
ing and radiation pneumonitis did not occur.
4. Discussion
Extrahepatic metastases of HCC have been reported in
25 to 65 percent of autopsy series, with lung, bones, and
regional lymph nodes as the most commonly involved
sites and the most common site of metastasis is lung [2].
The prognosis of patients with extrahepatic metastases
remains poor. In two studies, the median survival time
was less than 7 months and the 1-year survival rate was
as low as 25% [11,12]. Although we recognize that our
study was small and had limited follow-up periods, the
survival rates seem promising. The 15-month survival
rate of our study is higher than the 1-year survival rate of
the above two studies. The results of our study seem bet-
ter compared with the above reports. At the time of this
writing, particularly encouraging is the outcome of 10
patients who are alive without evidence of recurrence for
11 - 15 months after 125I brachytherapy. For these pa-
tients, 125I brachytherapy has been curable treatment so
far. However, eleven patients died during follow-up. All
the 11 patients had multiple hematogenous metastases at
the time of follow-up, which resulted in death.
In our study, 125I brachytherapy for lung metastases is
not indicated if any uncontrollable recurrent foci are
recognized at the primary site. In these cases of HCC,
however, intrahepatic recurrences often occur and are not
regarded to be well controllable by re-resections or other
local treatments. In this series, we excluded patients with
a history of intrahepatic recurrences as candidates for 125I
brachytherapy when the intrahepatic recurrent tumors
could not be well controlled.
The success of 125I brachytherapy depends on the ac-
curate placement of radioactive seeds within a known
volume of tumor [13]. Using CT guidance, an image of
the implant volume can be seen and the position of each
implant needle can be adjusted to ensure proper place-
ment. In our study, the positions of the seeds are deter-
mined to provide a good dose distribution including a
Table 1. Clinical effectiveness of 125I brachytherapy on lung
metastasis.
Local control efficacy
Follow-up
time (months)
No. of
patients CRPR NC PD
Local control rate
(%)
(CR + PR)/Total
%
3 29 205 2 2 86.2%
6 28 164 3 5 71.4%
10 23 122 4 5 60.9%
15 14 6 1 1 6 50.0%

Y. X. CHEN ET AL. 163
Note—Months are counted from the time of ablation session. Four patients
who were alive without evidence of recurrence at 11, 11, 12 and 14 months
at the time of writing were excluded at 15 months of follow-up time.
minimum peripheral dose coverage, a uniform dose dis-
tribution, and the protection of surrounding tissues since
methods for calculating optimal seed locations are avail-
able [14,15]. The relative coordinates of the seeds are
then used for seed implantation within the lesions. Seeds
and spacers are ejected from the needle when the depth
of the needle specified by the plan is reached. Achieving
this desired seed placement is left to the surgeon, who
must take into account tissue deformations during the
implant process [16,17]. Also inserting and retracting a
needle in soft tissues cause the tissues to move, stretch
and deform. This displacement and distortion of the tu-
mor during the implantation result in misplaced seeds
[17].
During the procedure, with the guidance of CT, the
vital blood vessels and organs surrounding the tumor can
be clearly displayed, allowing better control of implant-
ing applicator and reducing the risk of damaging impor-
tant blood vessels. No severe complications such as mas-
sive bleeding occurred during procedure, suggesting it is
a safe procedure. To avoid radioactive damage on im-
portant organs such as vital blood vessels, the distance
between implanted seeds should not be less than 10 mm
to prevent accumulative radioactivity as a result of two
closely positioned seeds. A route with minimal invasion
into the lung tissue should be selected to reduce the risk
of inducing pneumothorax. After procedure, it is better to
keep patient hospitalized for 3 - 5 days and prospectively
prescribe antibiotics and hemostatics to reduce the inci-
dence of bleeding and infection.
Our study also had limitations that we only included
29 patients and followed them up for a maximum of 17
months. More cases and longer follow-up are desired for
future survival analysis. We also expect to carry out fur-
ther study on combining this local approach with sys-
temic approach for tumor treatment.
In summary, the application of 125I brachytherapy in
treating lung metastasis from hepatocellular carcinoma is
still in the developing stage. In this study, we found that
125I brachytherapy has satisfactory short- to mid-term
effect on controlling local lung metastasis, without se-
vere complications such as massive bleeding or other
complications associated with routine radiotherapy such
as bone marrow arrest, radiation pneumonitis, digestive
response or hair loss. Our study indicates that 125I bra-
chytherapy is a promising treatment for lung metastasis
from hepato- cellular carcinoma.
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Abbreviations:
Hepatocellular carcinoma (HCC)
Computed tomographic (CT)
Treatment planning system (TPS)
Matched peripheral dose (MPD)
Dose-volume histogram (DVH)
Planning target volume (PTV)
World Health Organization (WHO)
Complete response (CR)
Partial response (PR)
No change (NC)
Progression of disease (PD)
Local control rate (LCR)
Products (P)