The Korean Journal of Hepatology 2011;17:189-198

http://dx.doi.org/10.3350/kjhep.2011.17.3.189 Original Article

The retrospective cohort study for survival rate in patients

with advanced hepatocellular carcinoma receiving
radiotherapy or palliative care
Hyuk Soo Eun, Min Jung Kim, Hye Jin Kim, Kwang Hun Ko, Hee Seok Moon, Eaum Seok Lee,
Seok Hyun Kim, Heon Young Lee, and Byung Seok Lee

Division of Gastroenterology, Department of Internal Medicine, Chungnam National University

College of Medicine, Daejeon, Korea

Background/Aims: This study was conducted to investigate the assessment of treatment efficacy of radiotherapy (RT) and other
therapeutic modalities compared with palliative care only for treatment with advanced hepatocellular carcinoma (HCC).
Methods: From 2002 to 2010, based on the case of 47 patients with advanced HCC, we have investigated each patients'
Child-Pugh's class, ECOG performance, serum level of alpha fetoprotein and other baseline characteristics that is considered to
be predictive variables and values for prognosis of HCC. Out of overall patients, the 29 patients who had received RT were
selected for one group and the 18 patients who had received only palliative care were classified for the other. The analysis in
survival between the two groups was done to investigate the efficacy of RT. Results: Under the analysis in survival, the mean
survival time of total patients group was revealed between 30.1 months and 45.9 months in RT group, while it was 4.8 months in
palliative care group, respectively. In the univariate analysis for overall patients, there were significant factors which affected
survival rate like as follows: ECOG performance, Child-Pugh's class, the tumor size, the type of tumor, alpha fetoprotein,
transarterial chemoembolization, and RT. The regressive analysis in multivariate Cox for total patients. No treatment under
radiotherapy and high level of Child-Pugh's class grade were independent predictors of worse overall survival rate in patients.
In contrast, for the subset analysis of the twenty-nine patients treated with radiotherapy, the higher serum level of alpha
fetoprotein was an independent predictors of worse overall survival rate in patients. Conclusions: We found that the survival of
patients with advanced HCC was better with radiotherapy than with palliative care. Therefore, radiotherapy could be a good
option for in patients with advanced HCC. (Korean J Hepatol 2011;17:189-198)

Keywords: Hepatocellular carcinoma; Radiotherapy; Survival rate; Alpha-fetoprotein; Child-Pugh class

INTRODUCTION second highest mortality rate, showing 16.4% of the total death
caused by cancer only after lung cancer.1 Because it showed
Pursuant to the the data of National Statistical Information relatively advanced stages at diagnosis in a variety of cases,
Service of the Ministry for Health, Welfare and Family Affairs in radical hepatic resection was available only in limited cases and
2009, hepatocellular carcinoma (HCC) is ranked the fourth in the liver cirrhosis as a underlying disease which occurred in many
2,3
incidence rate of cancer like as follws : gastric cancer, colorectal cases along with multiplicity.
cancer and lung cancer. In addition, the annual report of Statistics As radiotherapeutic technology has currently progressed,
Korea on death causes in 2008 showed that HCC recorded the radiotherapy has been conducted continuously in order to

Received January 30, 2011; Revised July 18, 2011; Accepted August 18, 2011
Abbreviations: AFP, alpha fetoprotein; BCLC, Barcelona Clinic Liver Cancer; BMI, body mass index; CR, complete response; CT, computerized
tomography; ECOG, Eastern Cooperative Oncology Group; Gy, grey; HCC, hepatocellular carcinoma; LN, lymph node; MRI, magnetic resonance
image; MV, megavolt; NR, no response; PD, progressive disease; PR, partial response; PVT, portal vein thrombosis; RILD, radiotherapy induced liver
disease; RT, radiotherapy; SD, stable disease; TACE, transarterial chemoembolization; WHO, world health organization
Corresponding author: Byung Seok Lee
Division of Gastroenterology, Department of Internal Medicine, Chungnam National University College of Medicine, 282 Munwha-ro, Jung-gu,
Daejeon 301-721, Korea
Tel. +82-42-280-7125, Fax. +82-42-280-7143, E-mail; [email protected]

Copyright Ⓒ 2011 by The Korean Association for the Study of the Liver
The Korean Journal of Hepatology∙pISSN: 1738-222X eISSN: 2093-8047
190 The Korean Journal of Hepatology Vol. 17. No. 3, September 2011

prevent the recurrence and to increase the survival rate after criteria of HCC were hepatic nodules which were confirmed
4
nonsurgical treatments of advanced HCC. Radiotherapy is through liver ultrasonography and others, alpha fetoprotein
applied to HCC patients who cannot be treated with surgical (AFP) of over 200 ng/mL and findings which were appropriate to
resection or with a radical treatment such as a locoregional HCC in one of the contrast-enhanced dynamic computerized
treatment and transarterial chemoembolization (TACE). It is tomography (CT) and contrast-enhanced dynamic magnetic
mainly executed for patients with liver function of A or upper B resonance image (MRI). When AFP was less than 200 ng/mL,
in Child-Pugh's classification, and its response rate and median the patients were diagnosed as HCC, who showed appropriate
survival time were reported to be 40-90% and 10-25 months, features to HCC in two or three out of three imaging studies of
respectively.4 The indication of radiotherapy for safe treatment, the contrast-enhanced dynamic CT, the contrast-enhanced
which provokes only a few side effects, is that the volume of dynamic MRI and the hepatic angiography. Those results were
5
the tumor is less than one third of the total liver volume. based on the criteria which were provided by “Practice guideline
Furthermore, the indications of extended radiotherapy show that for management of HCC 2009” jointly under the definition of the
it is less than two thirds or 70% of the total liver volume6,7 and Korean Liver Cancer Study Group and National Cancer Center.22
that the volume irradiated with 30 Gy is less than 60% of the total Out of the 47 patients, 29 were selected by excluding patients
8
liver volume in dose-volume analysis. Providing a high-dose with distant metastasis. They completed their scheduled
irradiation as a local irradiation, not the whole liver irradiation, radiotherapy for one or more lesions among primary HCC, local
has been identified, which has been continuously reported that lymph node metastasis and portal vein thrombosis sites without
the combination therapy of radiotherapy and chemotherapy or early discontinuance or delay from December 2005 to September
9-11
TACE for HCC works favorably. What is more, in case of the 2009. Except for them, the other 18 received only palliative care.
patients who are not under other treatments or associating with Under the definition of WHO, palliative care means the cases of
portal vein thrombosis,12-15 radiotherapy was safe and effective receiving only passive treatments to improve the survival rate
16
to raise the survival rate. The radiotherapy had the effect of after the diagnosis of HCC.23 It enables patients to improve the
relieving cancer pain, improving symptoms through the decrease quality of life, assisting them from physical, mental and spiritual
of lesions, lengthening the survival time in the circumstances aspects until they face death, which leads them to accept the
with the biliary obstruction of a tumor associated with death as a normal process with reducing distress and pain rather
17,18
jaundice, and extending the survival time in patients with than lengthening their life artificially.
19
abdominal lymph node metastasis. However, even now it is not The clinical and biochemical data of patients at diagnosis were
uncommon that only best palliative care can be maintained when investigated, which included the existence of ascites and hepatic
it is hard to treat advanced HCC actively or when the general encephalopathy and Child-Pugh's classification based on
condition of a HCC patient is not appropriate. As a result, this albumin, prothrombin time and total bilirubin. Others were also
study is focused on analyzing whether radiotherapy leads to a examined as followings: AFP, hepatitis B, hepatitis C,
significant difference in the survival rate, comparing not only Eastern Cooperative Oncology Group (ECOG) score,24 body
advanced HCC patients who have underwent treatments based mass index (BMI), and the history of smoking and drinking.
on radiotherapy but also with those who have received only According to the causes of liver cirrhosis, patients were
conservative ones. classified into alcoholic, hepatitis B- and hepatitis C- related
and idiopathic one. Liver cirrhosis was diagnosed by
PATIENTS AND METHODS synthesizing the degree of decompensated features of the
former liver, such as ascites, hepatic encephalopathy, jaundice
Patients and upper gastrointestinal bleeding, the results of clinical and
The critical point of this retrospective research was the clinicopathological examinations and medical references which
medical record of overall 47 patients under advanced HCC of were suggested as portal hypertension on endoscopy. As
Barcelona Clinic Liver Cancer (BCLC) stage C or D diagnosed shown in Table 1, the characteristics of the total subjects are
at Chungnam National University Hospital from January 2002 to summarized significantly in the pattern of classification.
20
March 2010. The patients who recorded C in Child-Pugh's
classification or with a diffuse tumor were excluded.21 Diagnosis
 Hyuk Soo Eun, et al. Survival rate on radiotherapy compared with palliative care in HCC 191

Table 1. Patients’ characteristics

Characteristics Total patients (n=47) Radiotherapy (n=29) Palliative care (n=18) P-value
Age (years, mean±S.D.) 63.3±9.4 62.2±9.2 64.9±9.7 0.353
<60, n (%) 15 11 (73.3%) 4 (26.7%)
0.343
≥60, n (%) 32 18 (56.2%) 14 (43.8%)
Gender 0.473
Male, n (%) 37 24 (64.9%) 13 (35.1%)
Female, n (%) 10 5 (50.0%) 5 (50.0%)
ECOG performance 0.009
1 40 28 (70.0%) 12 (30.0%)
2 7 1 (14.3%) 6 (85.7%)
Alcohol drinking 0.130
Yes 28 20 (71.4%) 8 (28.6%)
No 19 9 (47.4%) 10 (52.6%)
Smoking (packyears) mean±S.D. 14.7±17.1 16.6±18.3 11.8±14.8 0.357
2
BMI (kg/m ) mean±S.D. 23.5±3.1 24.3±3.1 22.3±2.8 0.033
HBsAg 0.763
Positive 28 18 (64.3%) 10 (35.7%)
Negative 19 11 (57.9%) 8 (42.1%)
Anti-HCV 0.025
Positive 6 1 (16.7%) 5 (83.3%)
Negative 41 28 (68.3%) 13 (31.7%)
Liver cirrhosis 37 21 (56.8%) 16 (43.2%) 0.277
Etiology of cirrhosis 0.088
HBV 25 16 (64.0%) 9 (36.0%)
HCV 4 0 (0%) 4 (100.0%)
Alcoholic 6 4 (66.7%) 2 (33.3%)
Idiopathic 2 1 (50.0%) 1 (50.0%)
Child-Pugh's class 0.010
A 34 25 (73.5%) 9 (26.5%)
B 13 4 (30.8%) 9 (69.2%)
Data represents patients number (%). Pearson's chi-squared test, the independent two-sample t-test, or Fisher's exact test were used
for statistical analysis.
SD, standard deviation; ECOG, Eastern Cooperative Oncology Group; HBsAg, hepatitis B viral antigen; Anti-HCV, anti-hepatitis C viral
antibody; HBV, hepatitis B virus; HCV, hepatitis C virus.

Types of HCC Multinodular and single nodular ones consist of two or more
In order to identify the most important variables on this separated nodules and single nodule, respectively. In addition,
research, the types of HCC were divided into massive, multino- HCC was analyzed into classifying under the size of the tumor
dular, and single nodular ones by following the classification and the existence of portal vein thrombosis. The size of the tumor
21
of Yuki et al Regardless of the existence of a satellite nodule, was measured on CT image, which was done for single nodular
the massive type can be defined into a large single mass. HCC with the longest diameter of the nodules and for
192 The Korean Journal of Hepatology Vol. 17. No. 3, September 2011

Table 2. Tumor characteristics and treatments

Characteristics Total patients (n=47) Radio-therapy (n=29) Palliative care (n=18) P-value
Tumor type 0.215
Massive 8 3 (37.5%) 5 (62.5%)
Multinodular 26 16 (61.5%) 10 (38.5%)
Single nodular 13 10 (76.9%) 3 (23.1%)
The number of tumor 0.365
<5 28 19 (67.9%) 9 (32.1%)
≥5 19 10 (52.6%) 9 (47.4%)
The size of tumors (cm) <0.001
<5 23 20 (87.0%) 3 (13.0%)
≥5 24 9 (37.5%) 15 (62.5%)
Okuda stage <0.001
1 28 23 (82.1%) 5 (17.9%)
2 12 3 (25.0%) 9 (75.0%)
3 7 3 (42.9%) 4 (57.1%)
BCLC stage 0.003
C 39 28 (71.8%) 11 (28.2%)
D 8 1 (12.5%) 7 (87.5%)
AFP (ng/mL)
Mean 7669.2±28 046.3 3221.1±9128.4 10731.6±32 880.8 0.759
<200 30 20 (66.7%) 10 (33.3%)
0.533
≥200 17 9 (52.9%) 8 (47.1%)
Lymph node 0.739
Yes 13 9 (69.2%) 4 (30.8%)
No 34 20 (58.8%) 14 (41.2%)
Potal vein thrombosis 1.000
Yes 28 17 (60.7%) 11 (39.3%)
No 19 12 (63.2%) 7 (36.8%)
TACE <0.001
Yes 25 25 (100.0%) 0 (0%)
No 22 4 (18.2%) 18 (81.8%)
Chemo-therapy 0.069
Yes 6 6 (100.0%) 0 (0%)
No 41 23 (56.1%) 18 (43.9%)
Operation 0.018
Yes 9 9 (100.0%) 0 (0%)
No 38 20 (52.6%) 18 (47.4%)
Data represents patients number (%). Pearson's chi-squared test or Mann-Whitney U-test were used for statistical analysis.
BCLC, Barcelona Clinic Liver Cancer; AFP, alpha fetoprotein; TACE, transarterial chemoembolization.

multinodular one with the sum of the two longest diameter of the portal vein invasion of the subjects are presented in Table 2.
nodules. Each size was classified into two groups of less than 5
cm and 5 or more than 5 cm. Meanwhile, portal vein thrombosis Treatments of HCC
was examined through CT or hepatic arteriography. The detailed While clinical trials are under way for this study, 29 patients
HCC which is related to morphologic classification, stages and have underwent radiotherapy for HCC, including both of patients
 Hyuk Soo Eun, et al. Survival rate on radiotherapy compared with palliative care in HCC 193

who have received only radiotherapy and those with TACE, diagnosis date to the death of date for patients expired, and from
hepatic resection, chemotherapy or combination therapy. Out of the diagnosis date to the date of the last follow-up for surviving
the 29 patients, 24 were treated only with radiotherapy during the patients. To compare basic characteristics of the radiotherapy
treatment, while the others were done with radiotherapy and and the palliative care groups, Pearson's chi-squared test and
chemotherapy. 28 patients received other treatments before independent two-sample t-test were performed. When the cases
radiotherapy, and 17 got an additional treatment after it. For with an expected frequency of less than 5 was over 25% of the
TACE, according to priority of treatment procedures, a catheter contingency table, Fisher's exact test was applied. As the
was inserted to the hepatic artery through arteriopuncture of the variation of AFP was severer in standard deviation compared to
ingunial area, the combination of 10 ml lipiodol and 50 mg its mean value, Mann-Whitney U-test or a non-parametric test
doxorubicin as antitumor agents was injected into the hepatic was used. The survival rate was analyzed with Kaplan-Meier
artery selectively, and then gelfoam was injected lastly. method, and a log-rank test was conducted to compare and
The dose for radiotherapy was not only determined by analyze the survival curve by each factor. To exclude the
individualizing patients under their general conditions and correlation among factors which influence the survival rate
stages, but they were also irradiated by using a 10 megavolt significantly, multivariate analysis was performed with Cox
(MV) linear accelerator. The patients under the radiotherapy regression analysis, using Cox’s proportional hazard model. A
were irradiated with daily dose of 2Gy for five days per week. P-value of <0.05 was considered to be significant statistically.
Overall exposure dose was 45.9±10.6Gy in average, and 3D
conformal radiotherapy was utilized for the irradiation. The RESULTS
radiotherapy was performed for one patient as initial treatment
and for the other 28 ones as rescue therapy. Clinical and clinicopathological characteristics
The number of all the patients registered for this study was
Evaluation of response to treatment totally 47, who were 37 males and 10 females under the average
Response to the treatment was evaluated through CT for a of 63.3±9.4 years old. At the time of diagnosis on HCC, 37
follow-up in 6-8 weeks after the radiotherapy. There were four (78.7%) patients had liver cirrhosis. Out of the liver cirrhosis
significant cases associated with the size of tumor and portal vein patients, 24 (64.9%) and 13 (35.1%) were recorded as A and B
thrombosis. The definitions for each case are followed: in Child-Pugh's classification, respectively.
Complete response (CR) was tabulated without any tumor and As shown in Table 1, BMI was not different significantly
portal vein thrombosis. Partial response (PR) was measured into between the radiotherapy and the conservative treatment groups
the decrease in the longest diameter of the largest nodule or the by recording 24.3±3.1 kg/m2 and 22.3±2.8 kg/m2, respectively.
sum of the longest diameter of the largest two nodules by over As for morphological characteristics of tumors, massive,
50%. No response (NR) was defined into the decrease by less multinodular and single nodular types were found in 8 (17.0%),
than 50% or no change and the increase in the number of lumps. 26 (55.3%) and 13 (27.7%) patients each. The mean AFP was
Progressive disease (PD) was classified as the increase in the size 7669.2±28 046.3 ng/mL (1.5-175,000 ng/mL). While AFP of 12
of a tumor by over 25%.25,26 The responder group was the patients was within the normal range (<10 ng/mL), AFP of 18
addition of CR and PR groups and the non-responder group was patients was over 200 ng/mL (Table 2).
25
that of NR and PD groups.
Comparison of characteristics between the
Statistical analysis radiotherapy and the palliative care groups, and
The frequency and proportion of patients receiving each response to radiotherapy
treatment modality were calculated and tabulated with SPSS When the 29 patients undergoing radiotherapy were compared
®
version 13 (SPSS Inc.) for statistical analysis. The results were and analyzed with the 18 receiving only palliative care, the rate
presented with mean value and standard deviation, and, if of patients who recorded two points in ECOG performance status
necessary, percent (%) was used with each individual number. was significantly higher (P=0.009), the rate of hepatitis C
Overall survival time was defined as the period from the patients was also higher (P=0.025) and the grade in Child-Pugh's
194 The Korean Journal of Hepatology Vol. 17. No. 3, September 2011

classification was higher (P=0.010), in the palliative care group group recording two points of ECOG performance status
than in the radiotherapy group. In addition, patients with a large showed much shorter survival period than that with one point
tumor were observed more frequently in the palliative care group and the difference was significant statistically (8.0 vs. 34.0)
(P<0.001) and both of Okuda and BCLC stages were advanced (P=0.005). As the mean survival time of the groups with
in the palliative care group (P<0.001, P=0.003). Except for them, Child-Pugh's classification A and B was respectively 38.4
as shown in Table 1 and 2, the other factors did not have any and 9.8 months, higher grade was significantly associated
significant differences statistically between the two groups. The with shorter survival time (P<0.001). The mean survival time
radiotherapy group was divided into the responder group under of the groups with the size of a tumor nodule of less than 5 cm
CR (n=4, 13.8%) and PR (n=7, 24.1%) and the non-responder and over 5 cm was 46.6 and 11.5 months each, so the group
group under NR (n=8, 27.6%) and PD (n=10, 34.5%), including with a larger nodule had shorter survival time (P<0.001). In
11 (37.9%) and 18 (62.1%) out of the 29 patients, respectively. addition, the mean survival time of the massive type and
the multinodular type was reduced significantly, comparing
Survival analysis to that of the single nodular type (7.5 vs. 33.1 vs. 42.0 months)
The follow-up period for overall patients to be observed was (P=0.010). The group with AFP of over 200 ng/mL had
25.0 (1-110) months in average. The mean survival time of significantly shorter survival time than that with AFP of less
the total patients was 30.1 (19.8-40.4) months, and that of the than 200 ng/mL (12.8 vs. 37.5 months) (P=0.023). For the other
radiotherapy and the palliative care groups recorded 45.9 factors except for them, there was no significant difference in the
(32.0-59.8) and 4.8 (2.0-7.6) months, respectively (P<0.001). survival time (Table 3).
Univariate analysis of all the subjects revealed that the After dividing the radiotherapy and the palliative care groups

Table 3. Univariate analysis of overall survival of all patients (n=47)

Variable N Mean survival (months) P-value
Age (years) <60/≥60 15/32 31.2/30.2 0.938
Sex M/F 37/10 30.3/29.0 0.978
BMI ≤23.0/>23.0 18/29 31.4/30.9 0.979
ECOG 1/2 40/7 34.0/8.0 0.005
Child-Pugh's class A/B 34/13 38.4/9.8 <0.001
The number of tumor <5/≥5 28/19 24.3/40.5 0.265
Tumor size (cm) <5/≥5 23/24 46.6/11.5 <0.001
Type of tumor Massive/multi-nodular/single nodular 8/26/13 7.5/33.1/42.0 0.010
AFP (ng/mL) <200/≥200 30/17 37.5/12.8 0.023
Portal vein thrombosis Yes/No 28/19 23.0/40.7 0.101
Radiotherapy Yes/No 29/18 45.9/4.8 <0.001
TACE Yes/No 25/22 48.1/10.0 <0.001
Alcohol drinking Yes/No 28/19 27.5/34.5 0.788
HBsAg Yes/No 28/19 33.4/24.9 0.664
Anti-HCV Yes/No 6/41 15.8/31.5 0.395
Liver cirrhosis Yes/No 37/10 28.2/33.4 0.415
Operation Yes/No 9/38 46.8/26.2 0.107
Chemotherapy Yes/No 6/41 42.2/27.9 0.224
Kaplan-Meier method or log-rank test were used for statistical analysis.
BMI, body mass index; ECOG, Eastern Cooperative Oncology Group; AFP, alpha fetoprotein; TACE, transarterial chemoembolization; HBsAg,
hepatitis B viral antigen; Anti-HCV, anti-hepatitis C viral antibody.
 Hyuk Soo Eun, et al. Survival rate on radiotherapy compared with palliative care in HCC 195

into Child-Pugh's classification A and B groups, respectively As shown in Table 5, the partial analysis for 29 patients
(RT-A, RT-B, palliative care-A and palliative care-B) the undergoing radiotherapy by univariate analysis showed that the
survival analysis was conducted. The mean survival time of higher an AFP level was, the shorter survival time was
RT-A, RT-B, palliative care-A and palliative care-B groups was significantly (P=0.039). Likewise univariate analysis, multiple
49.7, 26.5, 7.3 and 2.3 months, respectively (P<0.001) (Fig. 1). regression analysis which was conducted only for the
According to multiple regression analysis through Cox radiotherapy group also revealed that the group with AFP of over
regression model with the total subjects, the outcome in Table 4 200 ng/mL had shorter survival time significantly, as shown in
shows that patients recording a lower grade in Child-Pugh's Table 6.
classification and undergoing radiotherapy showed significantly
longer survival time even after adjusting significant factors DISCUSSION
which were observed in univariate analysis.
This is a retrospective study which analyzed the survival rate
by comparing the groups undergoing radiotherapy and only
palliative care with HCC patients. As mentioned before, the total
subjects of this study had HCC on the advanced stages, and the
radiotherapy group received various treatments before and after
radiotherapy.
For most patients with advanced HCC, it is difficult to
treat them actively due to their poor general conditions or
performance status. If radical treatment is performed for these
patients excessively, the risk of death following hepatic failure
can increase easily. That's the reason why non-radical treatments
are applied. In the radiotherapy group, most patients underwent
radiotherapy as rescue therapy (28 out of 29, 96.6%). Because of
Figure 1. Comparison of overall survival of patients with
advanced hepatocellular carcinoma treated with radiotherapy or it, the response rate of this study or 37.9% was slightly lower than
palliative care based on Child-Pugh classes A and B (Kaplan-Meier that observed overall in previous studies applying the irradiation
method, log-rank test, P<0.001). of a similar dose or 40-60%.4,12,27

Table 4. Multivariate analysis of overall survival of all patients (n=47)

Variables Wald Hazard ratio (95% confidence interval) P-value
Gender (female vs. male) 1.03 1.74 (0.60-5.03) 0.310
Age (<60 vs. ≥60) 0.02 1.07 (0.46-2.49) 0.879
ECOG (1 vs. 2) 0.27 0.76 (0.27-2.15) 0.602
AFP (ng/mL) (<200/≥200) 2.55 2.00 (0.86-4.52) 0.110
TACE (No vs. Yes) 0.81 0.55 (0.15-2.01) 0.367
Radiotherapy (No vs. Yes) 7.40 0.12 (0.03-0.55) 0.007
Tumor size (cm) 0.78 1.65 (0.54-5.02) 0.378
Type of tumor 1.04 0.600
Single nodular vs. massive 0.46 1.62 (0.40-6.47) 0.499
Single nodular vs. multinodular 0.01 0.95 (0.34-2.66) 0.922
Child-Pugh's class (A vs. B) 5.58 3.15 (1.22-8.18) 0.018
Cox regression analysis was used for statistical analysis.
ECOG, Eastern Cooperative Oncology Group; AFP, alpha fetoprotein; PVT, portal vein thrombosis; TACE, transarterial chemoembolization.
196 The Korean Journal of Hepatology Vol. 17. No. 3, September 2011

Table 5. Univariate analysis of overall survival of the subset analysis of the 29 patients treated with radiotherapy (n=29)
Variable N Mean survival (months) P-value
AFP (ng/mL) <200/≥200 20/9 53.4/21.2 0.039
Alcohol drinking Yes/No 20/9 36.9/66.6 0.088
RT target Main-mass/PVT/LN/Main mass+PVT+LN 11/12/5/1 68.4/29.8/26.8/67 0.064
RT response CR/PR/NR/PD 4/7/8/10 49.0/57.3/28.8/42.4 0.236
RT response category Responder/non-responder 11/18 61.9/36.6 0.064
Kaplan-Meier method or log-rank test were used for statistical analysis.
AFP, alpha fetoprotein; PVT, portal vein thrombosis; LN, lymph node; CR, complete response; PR, partial response; NR, no
response; PD, progressive disease; RT, radiotherapy.

Table 6. Multivariate analysis for overall survival for the subset analysis of the 29 patients treated with radiotherapy (n=29)
Variables Wald Hazard ratio (95% confidence interval) P-value
Gender (female vs. male) 0.12 1.26 (0.34-4.75) 0.730
Age (<60 vs. ≥60) 1.49 0.54 (0.20-1.46) 0.222
AFP (ng/mL) (<200/≥200) 4.96 3.30 (1.15-9.42) 0.026
Cox regression analysis was used for statistical analysis.
AFP, alpha fetoprotein.

Because radiotherapy for HCC utilized the irradiation to was conducted. However, TACE did not produce any significant
the whole liver in the past, there were many limitations in effect on the improvement of the survival rate in the patients who
determining a therapeutic dose due to hepatic failure and side were selected on this study.
effects of irradiation of over a certain dose. However, it was Although basic characteristics of the two groups were largely
found that high-dose irradiation to a localized part of the liver did different in this study, it was only a limitation of a retrospective
17,28,29
not provoke hepatotoxicity, and that the therapeutic dose study reviewing the medical record, and the result was considered
could be raised by deciding the range for the therapy selectively. to be unavoidable except for a well-designed prospective study.
In particular, for 3D conformal radiotherapy which was provided Death causes in most cases were hepatic failure, upper
for most patients in this study, it is well known that it improves gastrointestinal bleeding and hemorrhage caused by ruptured
the survival rate of patients with advanced HCC associated with tumor following hepatic metastasis of HCC, portal vein
embolism by increasing its therapeutic effect, declining thrombosis and secondary portal hypertension. Like this,
side effects and reaching the target radiation dose effectively whether radiotherapy for much advanced HCC patients is helpful
11,13,25
compared to conventional radiotherapy. in boosting the survival rate could be clinically controversial, this
Meanwhile, the combination of TACE and local radiotherapy study was conducted based on the assumption. Multivariate
has been applied continuously to primary HCC which cannot be regression analysis with the total subjects found that lower grade
resected, and its positive outcomes of enhancing the survival rate in Child-Pugh's classification or a representative factor as an
12,30
have been reported. In particular, antitumor agents, which index of liver function and general condition before treatment
were used during TACE to tumor cells on the tumor margin, was associated significantly with longer survival time and
work as radiosensitizers not only to increase the effect of radiotherapy increased the survival time as well. Multivariate
radiotherapy but also to make TACE available by improving regression analysis, as partial analysis with the 29 patients
4
portal vein thrombosis. In this study, 26 patients out of total 29 undergoing radiotherapy, revealed that higher AFP was a
ones in the radiotherapy group (89.7%) underwent TACE before prognostic factor related to the decrease of the survival rate. The
and after radiotherapy, which was considered to affect their finding was the same as that of previous studies reporting that
31-33
survival rate significantly. As the mechanism was mentioned, increased AFP would be associated with poor prognosis.
multivariate analysis including both of TACE and radiotherapy When the results of multivariate analysis of the two groups were
 Hyuk Soo Eun, et al. Survival rate on radiotherapy compared with palliative care in HCC 197

put together, the survival rate of advanced HCC were associated 2. Dusheiko GM, Hobbs KE, Dick R, Burroughs AK. Treatment of small
hepatocellular carcinomas. Lancet 1992;340:285-288.
with all internal and external factors related to treatments for
3. Mori W. Cirrhosis and primary cancer of the liver. Comparative study in
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