Feasibility and efficacy of helical tomotherapy in cirrhotic patients with unresectable hepatocellular carcinoma
Huang et al. World Journal of Surgical Oncology
Feasibility and efficacy of helical tomotherapy in cirrhotic patients with unresectable hepatocellular carcinoma
Chun-Ming Huang 1 3
Ming-Yii Huang 0 1 3
Jen-Yang Tang 0 1
Shinn-Cherng Chen 2 4
Liang-Yen Wang 2 4
Zu-Yau Lin 2 4
Chih-Jen Huang 0 1 3
0 Department of Radiation Oncology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University , Kaohsiung , Taiwan
1 Department of Radiation Oncology, Kaohsiung Medical University Hospital , 100 Tzyou 1st Road, Kaohsiung , Taiwan
2 Division of Hepatobiliary Medicine, Department of Internal Medicine, Kaohsiung Medical University Hospital , Kaohsiung , Taiwan
3 Cancer Center, Kaohsiung Medical University Hospital , Kaohsiung , Taiwan
4 Department of Internal Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University , Kaohsiung , Taiwan
Background: This study is to evaluate the toxicity and outcomes of helical tomotherapy (HT) in patients treated for unresectable hepatocellular carcinoma (HCC). Results: There was a complete response in 2 patients (5.2 %), partial response in 18 patients (47.4 %), stable disease in 13 patients (34.2 %), and progressive disease in 5 patients (13.2 %). The median overall survival was 12.6 months, and 1- and 2-year overall survival rates were 56.2 and 31.7 %, respectively. Eastern Cooperative Oncology Group (ECOG score, p = 0.008), Child-Pugh classification (p = 0.012), albumin (p = 0.046), and hemoglobin (p = 0.028) were significant parameters that predicted primary tumor response to radiotherapy in multivariate analysis. ECOG score (p = 0.012), Child-Pugh class (p = 0.026), and response to radiotherapy (p = 0.016) were independent prognostic factors for overall survival in multivariate analysis. Responders had better overall survival than non-responders (23.6 vs. 5.8 months, p < 0.001). The 1- and 2-year overall survival rates for responders were 68.3 and 57 %, respectively, while for non-responders, they were 0 %. The 1- and 2-year local control rates were 88.2 and 82.3 %, respectively. Five patients (13.2 %) had grade 3 or greater liver toxicity, and one patient (2.6 %) had a grade 3 gastric ulcer. No treatment-related liver failure or death was documented in this study. Conclusions: Radiotherapy using HT seems to be a safe and effective treatment option for unresectable HCC patients. This study indicates that HT is a feasible treatment even in patients without good performance status and hepatic function reservation.
Helical tomotherapy; Hepatocellular carcinoma; Survival; Cirrhosis
Hepatocellular carcinoma (HCC) is the fifth most
frequently diagnosed cancer in men and the second reason of
cancer-related mortality in the world . In women, it is
the seventh most common cancer and sixth leading cause
of cancer death. Because of the prevalence of hepatitis B
and C, the incidence of HCC is particularly high in East
Asia and Africa . Complete surgical resection and
hepatic transplantation is considered a curative therapy for
HCC, but only less than 15 % of patients with HCC are
indicated for curative surgery because of tumor extent or
compromised hepatic function [3, 4]. It remains
challenging to treat patients with unresectable HCC, and most of
them have dismal prognosis. Several other treatment
modalities for patients with unresectable HCC, including
percutaneous ethanol injection (PEI), radiofrequency
ablation (RFA), and transcatheter arterial chemoembolization
(TACE), seem to be more effective in smaller tumors and
are contraindicated in patients with portal vein tumor
thrombosis (PVTT), ascites, or biliary obstruction.
Given the risks of radiation-induced liver disease (RILD)
and even liver failure and low tolerance of whole liver
irradiation, radiotherapy (RT) has played a limited role in
managing advanced HCC with conventional RT
techniques . The limitation is more prominent in HCC
patients with underlying liver cirrhosis, which is prone to
decompensated liver disease. With the advent of
intensitymodulated radiotherapy (IMRT) and image-guided
radiotherapy (IGRT), higher tumoricidal dosage could be more
safely and precisely delivered to liver tumor and might
theoretically increase local tumor control [6, 7]. Emerging
evidence has shown that partial liver irradiation with
three-dimensional conformal radiation therapy (3D-CRT)
resulted in low toxicity and long-term tumor control in
patients with unresectable HCC [8, 9]. However, the
treatment techniques, fractionation, and total doses of RT for
patients with HCC have varied greatly within different
Helical tomotherapy (HT) uses modulated treatment
apertures (defined by dynamic multi-leaf collimator) and
dose rate to improve target conformality, dose
homogeneity, and normal tissue sparing compared to 3D-CRT
and/or IMRT. The on-board megavoltage computed
tomography (CT) detection allows for daily setup
verification, which can minimize planning target margins and
irradiated normal tissues. With integrating IGRT with
IMRT, HT could deliver higher dose to the relatively
large tumor without increasing the normal tissue
damage. However, there have been a few clinical reports
regarding oncologic outcomes and tolerance of HCC
patients receiving HT. This retrospective study aimed at
evaluating the efficacy and toxicity of HT for cirrhotic
patients with unresectable HCC.
The diagnosis of HCC was made according to
histopathology (n = 13) or the typical radiologic features in a
cirrhotic liver with or without an elevated serum
alphafetoprotein (AFP) level (n = 25). Typical images to
diagnose the presence of HCC in a mass lesion greater than
2 cm in greatest dimension with hypervascularity were
taken. Unresectable tumor was defined by extensive
tumor, major vascular invasion, or a poor medical
condition that disallows surgical resection. The inclusion
criteria in this study were primary HCC confirmed by
biopsy or imaging, patients considered unresectable,
and age >18 years. Patients who had extrahepatic
metastases, Eastern Cooperative Oncology Group (ECOG)
score ≧3, Child-Pugh class C disease or double cancer
were excluded. Sixty-four HCC patients treated with
HT were enrolled in our hospital between March 2008
and February 2011. Among them, 26 patients were
excluded; 17 patients had evidence of distant metastases,
5 did not complete the planned RT, 2 had prior abdominal
irradiation, and 2 had other malignancies. Finally, 38
patients were evaluated in the current study. Written
informed consent was obtained from all the patients, and
this retrospective study was approved by the Institutional
Review Board of Kaohsiung Medical University Chung-Ho
Memorial Hospital (KMUH-IRB-20120155).
CT simulation was performed for each patient with 5-mm
slice thickness without contrast medium. All patients were
immobilized with a posterior vacuum-lock body fixation
device and an anterior vacuum-sealed cover sheet to
reduce respiration movement. To further diminish liver
motion by breathing, all patients were educated to breathe
shallowly and not to fight with the compression of
anterior cover sheet. The gross tumor volume (GTV), including
PVTT, was delineated according to contrast-enhancing
tumor exhibiting on diagnostic CT or magnetic resonance
imaging (MRI) images. The whole intrahepatic tumor was
included in the GTV with physician’s concern about
tumor size, preserved liver function, and the irradiated
volume of the liver. A margin of 1 to 1.5 cm was added to
the GTV to cover microscopic tumor extension. Another
0.5 to 1 cm radical margin and 1 to 1.5 cm craniocaudal
margin were added to count for organ motion and setup
errors (planning target volume (PTV)). The entire liver
was contoured, and the normal liver volume was defined
as the whole liver volume minus the GTV. Treatment
planning was generated using Tomotherapy planning software,
version 4.0 (Tomotherapy, Madison, WI). Total prescribed
dose depended on the individual physician’s decision .
HT was delivered once per day, five times a week. Before
each treatment, a megavoltage CT scan was performed to
correct the displacement of tumors and internal organs
automatically or manually.
Prescribing tumor dose to the 95 % isodose line to
encompass the PTV was required. The organs at risk used in
current study were (1) spinal cord: maximum dose ≤45 Gy;
(2) kidneys: mean dose to bilateral kidneys must be <15
Gy, and no more than 30 % of the volume of kidney
can receive ≥20 Gy; (3) liver: mean normal liver dose
must be ≤28 Gy, and no more than 30 % of normal liver
can receive ≥30 Gy (V30 < 30 %); and (4) stomach and
small bowels: maximum dose ≤45 Gy.
Follow-up and response evaluation
The tumor response was evaluated by contrast-enhanced
CT scans or MRIs at 3 to 6 months after the completion
of RT. The response evaluation to criteria in solid tumors
(RECIST) was used to determine the tumor response after
because of contraindications for other treatment
modalities. The characteristics of the 38 patients are
shown in Table 1.
Table 1 Baseline characteristics of patients
No. of patients (%)
23 (60.5)/15 (39.5)
10 (26.3)/28 (73.7)
irradiation . A complete response (CR) represented a
complete disappearance of the irradiated tumor. Partial
response (PR) represented at least a 30 % reduction of
tumor in the greatest dimension. Progressive disease (PD)
was defined as at least a 20 % increase of tumor in the
greatest dimension, and stable disease (SD) was defined as
any tumor volume change other than PR or PD. Patients
with CR or PR after RT were defined as responders, and
non-responders represented patients with SD or PD. Local
control was defined as image-based absence of disease
progression. Patients with CR, PR, or SD were categorized
as a condition of local control of disease.
Treatment associated side effects were evaluated weekly
during RT and at each follow-up visit after treatment. Late
toxicity was determined when toxicity occurred 3 months
after the completion of treatment. The toxicity was assessed
according to Radiation Therapy Oncology Group toxicity
criteria . Radiation-induced liver disease was defined as
the development of nonmalignant ascites without disease
progression and an anicteric increase in the
alkalinephosphatase level at least twofold or in the transaminase
level at least fivefold after RT .
Chi-square test, Fisher’s exact test, or t test was used to
determine the association between tumor response and
various parameters. Parameters with a p value less than
0.05 in univariate analysis were further evaluated in
multivariate analysis, using logistic regression model.
The overall survival (OS) was calculated from the start
of RT to the date of death or last follow-up visit. Time
to local failure was defined from the beginning of the
treatment until progression. Rates were estimated using
the Kaplan-Meier method and compared the effect of
each variable on the survival using the log-rank test.
Parameters with a p value less than 0.05 in univariate
analysis were further evaluated in multivariate analysis,
using Cox regression hazard model. Data analyses were
conducted with the JMP software (version 9.0, SAS
Institute Inc., Cary, NC). Results were considered significant
at p values < 0.05.
Thirty-one men and 7 women were enrolled. The
median patient age was 67 years (range, 45–85). All
patients had liver cirrhosis. 27 patients (71.1 %) were
Child-Pugh class A, and 11 patients (28.9 %) were class
B. There were 24 patients (63.2 %) with portal vein
tumor thrombosis. Twenty-nine patients underwent
median 3 cycles (range, 1–9) of TACE (range, 1–9), and
18 patients received PEI or RFA, but all of them
experienced poor treatment response or disease progression.
HT was delivered as the first treatment for 3 patients
AJCC tumor stage
PVTT portal vein tumor thrombus, ECOG Eastern Cooperative Oncology Group,
TACE transcatheter hepatic arterial chemoembolization, PEI percutaneous
ethanol injection, RFA radiofrequency ablation, AJCC American Joint
Committee on Cancer
Table 2 Summary of tomotherapy
RT duration (days)
BED10 biologic effective dose, RT radiation therapy
The median RT dose was 54 Gy (range, 46–71.8 Gy).
Because of different doses per fraction used in the study,
the biologically effective doses (BED) were also assessed
and are summarized in Table 2. The mean volume of
PTV was 241.2 cm3 (range, 44.8–722.4), and the mean
normal liver volume was 987.7 cm3 (range, 391.5–1515.4).
The mean normal liver V30 was 12.8 % (range, 3–27 %).
The mean dose to normal liver was 17.6 Gy (range, 6–28),
and the average V10, V18, and V40 of normal liver were
64.6, 32.7, and 6.4 %, respectively. The mean doses to the
right kidney, left kidney, small bowel, and stomach were
8.6, 3.2, 4.6, and 6.7 Gy, respectively.
Tumor response rates
Median follow-up time was 17.2 months (range, 7–46).
All patients were evaluable for the tumor response.
There was CR in 2 patients (5.2 %), PR in 18 patients
(47.4 %), SD in 13 patients (34.2 %), and PD in 5 patients
Table 3 Predictive factors for local control
Age (≤67/>67) years
ECOG score (0–1/2)
Child-Pugh class (A/B)
AFP (≤400/>400) ng/ml
Albumin (>3.6/≤3.6) g/dL
Hemoglobin (>11/≤11) g/dL
BED (>65.5/≤65.5) Gy10
RT duration (≤37/>37) days
(13.2 %). The objective tumor response rate was 52.6 %.
Univariate analysis showed that ECOG score, Child-Pugh
classification, albumin, hemoglobin, mean BED, and mean
RT duration were statistically significant predictors of
tumor response. ECOG score (p = 0.008), Child-Pugh
classification (p = 0.012), albumin (p = 0.046), and hemoglobin
(p = 0.028) remained significant in multivariate analysis.
The 1- and 2-year local control rates were 88.2 and
82.3 %, respectively. Patients with Child-Pugh B, AFP >
400 ng/ml, albumin ≤ 3.6 g/dL, hemoglobin ≤ 11 g/dL, or
BED ≤ 65.5 Gy10 were more likely to relapse. In
multivariate analysis, a higher BED remained significantly
associated with a lower risk of relapse (hazard ratio (HR) = 0.78;
95 % confidence interval (CI), 0.69–0.92; p = 0.023). AFP
(HR = 0.81; 95 % CI, 0.74–0.93; p = 0.011) and Child-Pugh
classification (HR = 0.85; 95 % CI, 0.69–0.98; p = 0.022)
were also associated with higher risk of local failure.
Results are presented in Table 3.
Survival analysis and predictors of survival
At the time of analysis, 31 patients had died and 7
patients remained alive. The median survival time was 12.6
months (range, 3.6–40.9), with 1- and 2-year survival
rates of 56.2 and 31.7 %, respectively.
On the log-rank test, poor ECOG score, Child-Pugh
class B, albumin ≤ 3.6 g/dL, and response to RT were
significant unfavorable prognostic factors for overall survival.
In Cox regression analysis, ECOG score (p = 0.012),
ChildPugh class (p = 0.026), local tumor control (p = 0.011), and
response to radiotherapy (p = 0.016) were independent
prognostic factors for overall survival (Table 4). For patients
achieving tumor response (CR + PR), the median survival
time was 27.8 ± 8.5 months, which was much higher than
6.2 ± 2.8 months of non-responders. The 1- and 2-year
overall survival rates for responders were 68.3 and 57 %,
Hazard ratio (95 % CI)
Hazard ratio (95 % CI)
PVTT portal vein tumor thrombus, HCC hepatocellular carcinoma, ECOG Eastern Cooperative Oncology Group, BED biologically effective dose, RT radiation therapy,
RT duration (days)
Table 4 Predictive factors for overall survival
PVTT portal vein tumor thrombus, HCC hepatocellular carcinoma, ECOG Eastern
Cooperative Oncology Group, BED biologically effective dose, SD standard
deviation, AFP Alpha-fetoprotein
Fig. 1 Overall survival rates according to the response of tumor.
Responders had significantly better survival than non-responders (p < 0.001)
respectively, while those without response were 0 % (Fig. 1).
Patients remained local control after RT had significantly
longer median survival time than patients with progressive
disease (13.2 vs. 7.3 months, p = 0.007; Fig. 2).
The toxicities for all patients during RT and 2–3 months
afterward are summarized in Table 5. Most of the acute
gastrointestinal toxicities were self-limited. In terms of
hepatic toxicities, five patients (13.2 %) experienced
Common Terminology Criteria for Adverse Events (CTCAE)
grade 3 or higher transaminase elevation and four of them
simultaneously suffered from grade 3 or higher bilirubin
elevation. One patient experienced RILD according to
prior definition, and transaminase levels of the patient
returned to normal under supportive care at 3 months
after completion of RT. Normal liver volume for this
patient was 423.6 cm3, and lesion size was 9.6 cm in
diameter. RT parameters were as follows: prescription dose was
56 Gy in 25 fractions, mean dose to normal liver was 26.8
Gy, and V30 was 26.5 %. For gastrointestinal toxicities,
only one patient experienced a gastric ulcer bleeding at
4 months after RT, but after proton pump inhibitor
therapy, he recovered from the ulcer. Four patients had
CTCAE grade 1 or 2 gastroduodenitis or ulcers, and all of
them were transient. There was no treatment-related liver
failure or death in this study.
The indication of RT for patients with unresectable HCC
has yet to be defined. HCC is a radiosensitive tumor, but it
is within a considerably radiosensitive organ. In the past,
RT has been considered as palliative and potentially toxic
for HCC patients with underlying cirrhosis. Preservation
of liver function and achievement of tumor control are
equally important for their prognosis . Combining
intensity-modulated and image-guided radiotherapies, HT
Fig. 2 Patients remained local control after radiotherapy had significantly longer median survival time than patients with progressive disease
(13.2 vs. 7.3 months, p = 0.007)
can deliver highly conformal radiation dose to liver tumors
while sparing most of the normal liver parenchyma to
reduce hepatic toxicity. In this study, low incidence of severe
liver dysfunction was observed in HCC patients with
underlying cirrhosis receiving HT and objective tumor
regression after RT was associated with better prognosis.
For unresectable HCC patients receiving 3D-CRT, some
studies reported tumor response rates ranged from 40 to
72.7 % [15–18]. Kong et al.  reported an objective
response rate of 72.7 % to HT in 22 unresectable HCC
patients. However, only 8 of 20 patients (36.4 %) had PVTT
and may be biased to a high response rate. Kim et al. 
reported that an objective response rate for primary liver
tumors after 3D-CRT was 54.3 %, and for PVTT, a
response rate was 39.0 %. Kang et al.  treated 27 HCC
patients with IMRT and reported an objective response
rate of 44.4 %. The study included 18 cases (66.6 %) with
PVTT. Patients with HCC invading portal vein seem to
have lower response rates to RT compared with values
observed in patients with primary HCC. In our study, HT
Table 5 Adverse events in the study
No. of patients with CTCAE grade (%)
CTCAE Common Terminology Criteria for Adverse Events, AST aspartate
aminotransferase, ALT alanine aminotransferase
was delivered to 38 patients with unresectable HCC
and 24 patients (63.2 %) had PVTT. We found a CR
rate of 5.2 % (2/38), a PR rate of 47.4 % (18/38), and an
objective response rate of 52.6 %. With relatively higher
proportion of patients with PVTT, the response rate of
our study is still encouraging.
The survival rate in our study is relatively low
compared with values previously reported. Kong et al. 
reported that 1- and 2-year overall survival rates were 86.4
and 69.1 %, for 22 HCC patients treated with
tomotherapy. McIntosh et al.  performed IMRT using HT in 22
HCC patients with or without PVTT. The 1 year overall
survival was 73 % for patients with Child-Pugh class A
disease and 11 % for patients with Child-Pugh class B
disease. Kim et al.  treated 70 HCC patients with or
without PVTT by 3D-CRT and reported 1- and 2-year
overall survival rates of 43.1 and 17.6 %, respectively. In
our study, the 1- and 2-year overall survival rates were
56.2 and 31.7 %, respectively. The relatively low survival
rates might be due to inclusion of a larger proportion of
patients with poor prognostic factors such as PVTT,
ECOG scale 2, and Child-Pugh class B disease. It might be
those adverse factors that prompted physicians and
patients to choose HT, aiming to reduce treatment toxicity
with adequate tumor ablation dosage. Although this
overall survival rate seems relatively low, it is not a low value
when considering that most of the patient population in
our study had advanced HCC and adverse factors.
Several studies have reported that primary tumor
response was significantly associated with overall survival of
patients with HCC following RT [15, 16, 18]. In our study,
patients achieving objective tumor response (CR + PR)
had a median survival of 27.8 ± 8.5 months, while
nonresponders had a median survival of 6.2 ± 2.8 months. The
1- and 2-year overall survival rate for responders was 68.3
and 57 %, respectively, while non-responders had dismal
overall survival rates. This finding supports that RT can be
one of the treatment options in unresectable HCC
patients who failed to respond to previous treatments. It is
also crucial to identify clinical or molecular parameters
that can predict liver tumor response after RT.
A dose-response relationship in RT for HCC was shown
in some studies. A higher radiation dose was associated
with a higher response rate [20–22] and a higher survival
rate [16, 17]. Some studies failed to show the correlation
between radiation dose and survival [15, 23]. In our
studies, we used BED to analyze the correlation between
radiation dose, tumor response, and patient survival because of
a variety of fraction sizes ranging from 1.8 to 2.4 Gy. The
response rates in patients receiving ≤65.5 Gy10 and >65.5
Gy10 were 44.4 and 59.1 %, respectively (p = 0.547).
However, the mean BED of 65.1 ± 18.5 Gy in primary tumor
responders was significantly lower than that of 70.1 ± 16.8
Gy in non-responders (p = 0.045). The mean duration of
RT in tumor responders was shorter than that in
nonresponders (36.8 vs. 42.4 days, p = 0.045). As a whole, a
higher BED with a shorter period of RT seemed to result in
higher tumor response rate. Patients receiving >65.5 Gy10
or completing RT ≤37 days had longer median survival
than their respective counterparts. However, it might be
due to the small sample size and heterogeneity in
studied cases that these differences were not statistically
In addition to BED, ECOG score 2, Child-Pugh class
B, hypoalbuminemia, and anemia were factors associated
with poor RT response in our study. Increasing evidence
has shown that the presence of a systemic inflammatory
response correlates with poor prognosis in patients with
advanced cancer . A simple inflammation-based scoring
system, combining C-reactive protein and serum albumin,
is associated with prognosis in patients undergoing cancer
treatments [25, 26]. In our study, hypoalbuminemia was
not only associated with non-response to RT but also with
a low survival rate. Therefore, correction of status of
hypoalbuminemia in HCC patients might be beneficial.
Anemia is common in cancer patients and is considered
to induce tumor hypoxia, which can contribute to
radioresistance. In addition, numerous studies have shown that
anemia is an independent adverse predictor for overall
survival and local control at various tumor sites [27–29].
We found that patients with hemoglobin >11 g/dL had
better primary tumor response rates following RT
(61.1 vs. 23.1 %, p = 0.035). Median survival rate in
patients with hemoglobin >11 g/dL was 9.5 months, which
was longer than 6.6 months in patients with hemoglobin ≤
11 g/dL. However, the difference failed to show statistical
significance due to small sample size.
Table 6 Comparison of the literatures for helical tomotherapy in patients with unresectable hepatocellular carcinoma
Reference No. Fraction Total dose (Gy)
McIntosh  20 2.5 50
PVTT(−) 60 %
50 (range, 45–60) PVTT(+) 100 % CR 14.3
PVTT(+) 36.4 % CR 18.2
Current study 38 1.8–2.4
54 (range, 46–71.8) PVTT(+) 63.2 % CR 5.2
PVTT(−) 63.6 % PR 54.5
PVTT(−) 36.5 % PR 47.4
RT radiation therapy, PVTT portal vein tumor thrombus, N/A no data, CR complete response, PR partial response, SD stable disease, RILD radiation-induced liver
disease, GI gastrointestinal
a1-year overall survival rate (%)
The potential acute toxicities of HCC patients
undergoing RT are gastrointestinal complications such as appetite
loss and gastroduodenal ulcer or bleeding and hepatic
toxicity such as RILD, which was considered the most
dismal toxicity due to high fatality. In our study,
gastrointestinal toxicities we encountered were manageable. The
incidence of RILD ranged from 0 to 15.4 % [8, 9, 15], and
in our study, RILD was found in one patient (2.6 %),
which was low compared with values previously reported.
Several studies correlated various dose-volumetric
parameters with the risk of RILD. These included the mean dose
to the normal liver, percentage of the normal liver volume
receiving ≥30 Gy, percentage of the total liver volume
receiving ≥30 Gy, and the normal tissue complication
probability estimates [30–32]. However, the RT technique used
in these studies was mainly 3D-CRT. It might be
inappropriate to apply these findings to patients receiving IMRT,
which has smaller radiation dose in the liver compared
with 3D-CRT . There is a need of further
investigations about the impact of IMRT on RILD.
3D-CRT and IMRT are able to deliver a conformal
radiation dose to cover the target volume while sparing
the critical organs appears attainable [7, 33]. Rotational
IMRT modalities, such as HT, are modern image-guided
intensity-modulated RT techniques. These complex
rotational IMRT machines are able to deliver highly
conformal dose distributions and can spare critical organs
to a greater extent [14, 15, 19]. Several data have shown
that HT has dosimetric advantages over IMRT based on
comparisons in treatment planning. However, there have
been few reports on clinical outcomes for HCC patients
undergoing HT. We present our data and compare it
with other published studies. Table 6 summarizes the
treatment outcomes and toxicity of previously published
studies using HT in the treatment of HCC patients.
Some limitations exist in the current study. First,
because this was a retrospective study, heterogeneity of study
population and dose fractionation schedules were present.
The tumor response to RT might be influenced by
fractionated RT dose, but no consensus has been reached on a
standard radiation dose fractionation schedule for patients
with HCC until now. Thus, further research on optimal
fraction size and total dose should be conducted. Second,
the sample size was small and this may minimize the
detection of small but clinically important parameters. Third,
the follow-up period was not long. Therefore, long-term
toxicity and quality of life of patients receiving HT for
HCC cannot be evaluated.
Using HT to treat patients with unresectable HCC, we
found that treatment response and overall survival rates
were good with a manageable toxicity even in patients
with poor performance status and PVTT. For responders,
the median survival duration was 27.8 months with 1- and
2-year overall survival rates of 68.3 and 57 %, respectively.
The promising results indicate that stricter patient
selection will maximize potential benefits of unresectable HCC
patients receiving RT. Further large-scale, prospective
randomized studies are needed to address the efficiency and
optimal dose fraction schedules of RT.
AFP: alpha-fetoprotein; BED: biologically effective dose; CT: computed
tomography; CR: complete response; ECOG: Eastern Cooperative Oncology
Group; GTV: gross tumor volume; HCC: hepatocellular carcinoma; HT: helical
tomotherapy; IMRT: intensity-modulated radiotherapy; IGRT: image-guided
radiotherapy; OS: overall survival; PEI: percutaneous ethanol injection;
PVTT: portal vein tumor thrombosis; PR: partial response; PD: progressive
disease; RT: radiotherapy; RILD: radiation-induced liver disease; RFA: radiofrequency
ablation; SD: stable disease; TACE: transcatheter arterial chemoembolization;
3D-CRT: three-dimensional conformal radiotherapy.
The authors declare that they have no competing interests.
CMH and CJH participated in the design of the study, performed the statistical
analysis and interpretation of data, and drafted the manuscript. SCC, LYW, and
ZYL recruited patients to the study. MYH, JYH, and CJH are radiation oncologists
who contributed to treat the patients. All authors read and approved the final
The authors acknowledge the contribution to data collection made by the
Hepatobiliary Cancer Group from the Cancer Center of Kaohsiung Medical
University Hospital. This study was supported by grants from the Excellence for
Cancer Research Center Grant through the funding by the Ministry of Health and
Welfare, Executive Yuan, Taiwan, Republic of China (MOHW103-TD-B-111-05), the
Kaohsiung Medical University Hospital (KMUH101-1 M67), Taiwan.
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