Comparison of coplanar and noncoplanar intensity-modulated radiation therapy and helical tomotherapy for hepatocellular carcinoma.
ABSTRACT To compare the differences in dose-volume data among coplanar intensity modulated radiotherapy (IMRT), noncoplanar IMRT, and helical tomotherapy (HT) among patients with hepatocellular carcinoma (HCC) and portal vein thrombosis (PVT).
Nine patients with unresectable HCC and PVT underwent step and shoot coplanar IMRT with intent to deliver 46-54 Gy to the tumor and portal vein. The volume of liver received 30Gy was set to keep less than 30% of whole normal liver (V30<30%). The mean dose to at least one side of kidney was kept below 23 Gy, and 50 Gy as for stomach. The maximum dose was kept below 47 Gy for spinal cord. Several parameters including mean hepatic dose, percent volume of normal liver with radiation dose at X Gy (Vx), uniformity index, conformal index, and doses to organs at risk were evaluated from the dose-volume histogram.
HT provided better uniformity for the planning-target volume dose coverage than both IMRT techniques. The noncoplanar IMRT technique reduces the V10 to normal liver with a statistically significant level as compared to HT. The constraints for the liver in the V30 for coplanar IMRT vs. noncoplanar IMRT vs. HT could be reconsidered as 21% vs. 17% vs. 17%, respectively. When delivering 50 Gy and 60-66 Gy to the tumor bed, the constraints of mean dose to the normal liver could be less than 20 Gy and 25 Gy, respectively.
Noncoplanar IMRT and HT are potential techniques of radiation therapy for HCC patients with PVT. Constraints for the liver in IMRT and HT could be stricter than for 3DCRT.
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ABSTRACT: PURPOSE: To investigate the dosimetric improvements in stereotactic body radiation therapy for patients with larger or central lung tumors using a highly noncoplanar 4π planning system. METHODS AND MATERIALS: This study involved 12 patients with centrally located or larger lung tumors previously treated with 7- to 9-field static beam intensity modulated radiation therapy to 50 Gy. They were replanned using volumetric modulated arc therapy and 4π plans, in which a column generation method was used to optimize the beam orientation and the fluence map. Maximum doses to the heart, esophagus, trachea/bronchus, and spinal cord, as well as the 50% isodose volume, the lung volumes receiving 20, 10, and 5 Gy were minimized and compared against the clinical plans. A dose escalation study was performed to determine whether a higher prescription dose to the tumor would be achievable using 4π without violating dose limits set by the clinical plans. The deliverability of 4π plans was preliminarily tested. RESULTS: Using 4π plans, the maximum heart, esophagus, trachea, bronchus and spinal cord doses were reduced by 32%, 72%, 37%, 44%, and 53% (P≤.001), respectively, and R50 was reduced by more than 50%. Lung V20, V10, and V5 were reduced by 64%, 53%, and 32% (P≤.001), respectively. The improved sparing of organs at risk was achieved while also improving planning target volume (PTV) coverage. The minimal PTV doses were increased by the 4π plans by 12% (P=.002). Consequently, escalated PTV doses of 68 to 70 Gy were achieved in all patients. CONCLUSIONS: We have shown that there is a large potential for plan quality improvement and dose escalation for patients with larger or centrally located lung tumors using noncoplanar beams with sufficient quality and quantity. Compared against the clinical volumetric modulated arc therapy and static intensity modulated radiation therapy plans, the 4π plans yielded significantly and consistently improved tumor coverage and critical organ sparing. Given the known challenges in central structure dose constraints in stereotactic body radiation therapy to the lung, 4π planning may increase efficacy and reduce toxicity.International journal of radiation oncology, biology, physics 03/2013; · 4.59 Impact Factor
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ABSTRACT: Stereotactic body radiation therapy to centrally located or larger lung tumor results in higher toxicities. To over-come this challenge, we implemented a system that automatically selected and optimized noncoplanar beams. As a result, the dose conformality was signifi-cantly improved. Doses to heart, esophagus, trachea/ bronchus tree, spinal cord, and lungs were markedly reduced. The improved dosimetry would allow a planning target volume dose escalation from 50 to 68 Gy or higher to these tumors without exceeding critical organ dose limits. Purpose: To investigate the dosimetric improvements in stereotactic body radiation therapy for patients with larger or central lung tumors using a highly noncoplanar 4p planning system. Methods and Materials: This study involved 12 patients with centrally located or larger lung tumors previously treated with 7-to 9-field static beam intensity modulated radiation therapy to 50 Gy. They were replanned using volumetric modulated arc therapy and 4p plans, in which a column generation method was used to optimize the beam orientation and the flu-ence map. Maximum doses to the heart, esophagus, trachea/bronchus, and spinal cord, as well as the 50% isodose volume, the lung volumes receiving 20, 10, and 5 Gy were mini-mized and compared against the clinical plans. A dose escalation study was performed to determine whether a higher prescription dose to the tumor would be achievable using 4p without violating dose limits set by the clinical plans. The deliverability of 4p plans was preliminarily tested. Results: Using 4p plans, the maximum heart, esophagus, trachea, bronchus and spinal cord doses were reduced by 32%, 72%, 37%, 44%, and 53% (P .001), respectively, and R 50 was reduced by more than 50%. Lung V 20 , V 10 , and V 5 were reduced by 64%, 53%, and 32% (P .001), respectively. The improved sparing of organs at risk was achieved while also improving planning target volume (PTV) coverage. The minimal PTV doses were increased by the 4p plans by 12% (PZ.002). Consequently, escalated PTV doses of 68 to 70 Gy were achieved in all patients. Conclusions: We have shown that there is a large potential for plan quality improvement and dose escalation for patients with larger or centrally located lung tumors using noncoplanar beams with sufficient quality and quantity. Compared against the clinical volumetric modu-lated arc therapy and static intensity modulated radiation therapy plans, the 4p plans yielded significantly and consistently improved tumor coverage and critical organ sparing. Given the known challenges in central structure dose constraints in stereotactic body radiation therapy to the lung, 4p planning may increase efficacy and reduce toxicity. Ó 2013 Elsevier Inc.
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ABSTRACT: To investigate the feasibility of using intermediate energy 2 MV x-rays for extracranial robotic intensity modulated radiation therapy. Two megavolts flattening filter free x-rays were simulated using the Monte Carlo code MCNP (v4c). A convolution/superposition dose calculation program was tuned to match the Monte Carlo calculation. The modeled 2 MV x-rays and actual 6 MV flattened x-rays from existing Varian Linacs were used in integrated beam orientation and fluence optimization for a head and neck, a liver, a lung, and a partial breast treatment. A column generation algorithm was used for the intensity modulation and beam orientation optimization. Identical optimization parameters were applied in three different planning modes for each site: 2, 6 MV, and dual energy 2/6 MV. Excellent agreement was observed between the convolution/superposition and the Monte Carlo calculated percent depth dose profiles. For the patient plans, overall, the 2/6 MV x-ray plans had the best dosimetry followed by 2 MV only and 6 MV only plans. Between the two single energy plans, the PTV coverage was equivalent but 2 MV x-rays improved organs-at-risk sparing. For the head and neck case, the 2MV plan reduced lips, mandible, tongue, oral cavity, brain, larynx, left and right parotid gland mean doses by 14%, 8%, 4%, 14%, 24%, 6%, 30% and 16%, respectively. For the liver case, the 2 MV plan reduced the liver and body mean doses by 17% and 18%, respectively. For the lung case, lung V20, V10, and V5 were reduced by 13%, 25%, and 30%, respectively. V10 of heart with 2 MV plan was reduced by 59%. For the partial breast treatment, the 2 MV plan reduced the mean dose to the ipsilateral and contralateral lungs by 27% and 47%, respectively. The mean body dose was reduced by 16%. The authors showed the feasibility of using flattening filter free 2 MV x-rays for extracranial treatments as evidenced by equivalent or superior dosimetry compared to 6 MV plans using the same inverse noncoplanar intensity modulated planning method.Medical Physics 04/2014; 41(4):041709. · 2.91 Impact Factor
Hsieh et al. Radiation Oncology 2010, 5:40
Comparison of coplanar and noncoplanar
intensity-modulated radiation therapy and helical
tomotherapy for hepatocellular carcinoma
© 2010 Hsieh et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
Chen-Hsi Hsieh1,6, Chia-Yuan Liu4, Pei-Wei Shueng1,7, Ngot-Swan Chong1, Chih-Jen Chen4, Ming-Jen Chen4, Ching-
Chung Lin4, Tsang-En Wang4, Shee-Chan Lin4, Hung-Chi Tai3, Hui-Ju Tien1, Kuo-Hsin Chen2, Li-Ying Wang9, Yen-
Ping Hsieh10, David YC Huang*11 and Yu-Jen Chen*3,5,6,8
Background: To compare the differences in dose-volume data among coplanar intensity modulated radiotherapy
(IMRT), noncoplanar IMRT, and helical tomotherapy (HT) among patients with hepatocellular carcinoma (HCC) and
portal vein thrombosis (PVT).
Methods: Nine patients with unresectable HCC and PVT underwent step and shoot coplanar IMRT with intent to
deliver 46 - 54 Gy to the tumor and portal vein. The volume of liver received 30Gy was set to keep less than 30% of
whole normal liver (V30 < 30%). The mean dose to at least one side of kidney was kept below 23 Gy, and 50 Gy as for
stomach. The maximum dose was kept below 47 Gy for spinal cord. Several parameters including mean hepatic dose,
percent volume of normal liver with radiation dose at X Gy (Vx), uniformity index, conformal index, and doses to organs
at risk were evaluated from the dose-volume histogram.
Results: HT provided better uniformity for the planning-target volume dose coverage than both IMRT techniques. The
noncoplanar IMRT technique reduces the V10 to normal liver with a statistically significant level as compared to HT. The
constraints for the liver in the V30 for coplanar IMRT vs. noncoplanar IMRT vs. HT could be reconsidered as 21% vs. 17%
vs. 17%, respectively. When delivering 50 Gy and 60-66 Gy to the tumor bed, the constraints of mean dose to the
normal liver could be less than 20 Gy and 25 Gy, respectively.
Conclusion: Noncoplanar IMRT and HT are potential techniques of radiation therapy for HCC patients with PVT.
Constraints for the liver in IMRT and HT could be stricter than for 3DCRT.
Hepatocellular carcinoma (HCC) is one of the most com-
mon malignancies worldwide  and is the third most
common cause of cancer mortality in the recent year .
The 5-year survival rate of individuals with liver cancer
reported by the American Cancer Society in the United
States is less than 10% despite aggressive conventional
therapy. In addition, comparing 1991 and 2005, liver can-
cer is not only one of the three cancers with an increasing
death rate, but also the fastest growing death rate (27%) in
the United States . Portal vein thrombosis (PVT) is a
common complication in patients with advanced-stage
HCC, occurring in 20%-80% of these patients [4-6]. PVT
may alter the correct evaluation of HCC imaging and also
limits HCC treatment choices . The median survival
time of HCC patients with PVT is approximately 0.7 to
1.6 months without any treatment . Furthermore, PVT
is often a poor prognostic factor for patient survival
Several modalities, including surgical resection ,
transcatheter arterial chemoembolization (TACE) 
and arterial infusion chemotherapy , percutaneous
ethanol injection therapy, microwave coagulation ther-
apy, radiotherapy, and liver transplantation, have been
used in treating HCC . However, there are some limi-
* Correspondence: email@example.com, firstname.lastname@example.org
3 Department of Radiation Oncology, Mackay Memorial Hospital, Taipei, Taiwan
11 Department of Medical Physics, Memorial Sloan-Kettering Cancer Center,
New York, NY, USA
Full list of author information is available at the end of the article
Hsieh et al. Radiation Oncology 2010, 5:40
Page 2 of 8
tations to performing these treatments. For example, sur-
gical treatment can only be performed on highly selected
patients, because there is a potential risk of postoperative
liver failure and early disease recurrence. TACE is consid-
ered a contraindication for HCC patients with main por-
tal trunk obstruction and indwelling catheters or
catheter-related sepsis, which hinder arterial infusion
While the role of radiotherapy was limited in the past
because of poor tolerance of the whole liver to radiation
, some studies show that higher irradiation doses
resulted in a higher survival rates for HCC patients .
Kim DY et al. reported a dose-response relationship
exists between the radiation dose and PVT, where the
objective response of PVT was observed in 3 of 15
patients (20%) with BED < 58 Gy10 and in 24 of 44
patients (54.6%) with BED ? 58 Gy10 . Toya R et al.
 pointed out conformal radiotherapy is effective not
only for tumor response but also for survival of HCC
patients with PVT. We also reported one HCC patient
with PVT who received intensity-modulated radiation
therapy (IMRT) with sorafenib, resulting in a significant
response and improvement . Moreover, radiotherapy
could be an effective treatment choice for selected HCC
patients with PVT .
With advances in radiotherapy modalities, such as
three-dimensional conformal radiotherapy (3DCRT) and
IMRT, delivering a good radiation dose to the tumor tar-
get volume while sparing the critical organs appears
achievable [19,21,22]. With the development of confor-
mal assays, radiation therapy could be an effective choice
for selected HCC patients with PVT . Rotational
IMRT modalities, including helical tomotherapy (HT)
, VMAT (Volumetric intensity modulated arc ther-
apy)  and the others, are new image-guided intensity-
modulated radiotherapy. These complex rotational IMRT
machines can deliver highly conformal dose distributions
and possess the ability to spare critical organs in a greater
extent [19,24]. We evaluated various radiation plans for
HT and IMRT as they are currently used at our depart-
ment. Due to IMRT can preserve acceptable target cover-
age and better spare nonhepatic organs among HCC
patients than 3DCRT . Therefore, we selected differ-
ent IMRT planning strategies rather than 3DCRT to com-
pare to HT in our study.
The purpose of this study was to define the potential
impact of HT and to compare the differences in dosimet-
ric indicators among coplanar and noncoplanar IMRT
and HT among HCC patients with PVT previously docu-
mented to have at least partial responses to recannular-
ization and to have undergone repeated TACE after
A retrospective study was performed for nine patients
with unresectable HCC and PVT underwent step and
shoot coplanar IMRT to treat the tumor and portal vein
between January 2007 and June 2007, eight of them were
men. Patients with at least partial response to RT, docu-
mented by identifiable recannularization using CT imag-
ing or abdominal ultrasound, and could be subjected to
receive repeated TACE after RT were retrospectively
enrolled. All patients had stage IIIA HCC (American
Joint Committee on Cancer Staging, 6th edition), chronic
hepatitis B carriers and underwent TACE before and
after IMRT, with an interval of at least 30 days between
the two modalities.
(a) Planning CT and Volume definitions
All patients were immobilized using Alpha Cradle®
(Smithers Medical Products, Inc. North Canton, OH,
USA) in supine position with arms elevated above head to
provide a fixed position during CT scan and radiation
therapy. Two series of axial CT images, with and without
contrast enhancement, with 5-mm contagious slice thick-
ness including whole liver and kidneys were acquired for
each patient. Targets were delineated on non-contrast
images under the aids by contrast ones. Treatment plan-
ning was performed by using non-contrast images. All
patients were treated using coplanar static IMRT. No
respiratory control or abdomen compression was applied
during the treatment, and the organ motion was taken
into account in planning-target volume (PTV). Gross
tumor volume (GTV) was defined as the hepatic tumor
volume plus PVT visualized by contrasted CT images.
GTV was expanded by 0.5 cm to create clinical target vol-
ume (CTV). A non-uniform three dimensional (3D) mar-
gin, 0.5 cm radically and 1.5 cm cranial-caudally was
applied to CTV for creating PTV. The normal liver vol-
ume was defined as the total liver volume minus the GTV.
(b) Dose prescription and planning objectives
The prescription dose was 44.8 to 54.0 Gy depended on
the ratio of PTV volume and nonirradiated liver volume
. When nonirradiated liver volume was < 1/3, 1/3-1/2
or >1/2 of liver volume, the delivered dose could be 40,
44.8-50.4 or 50-66 Gy, respectively. No patient was given
radiation to the entire liver. Treatment was delivered once
daily with 1.6 - 1.8 Gy, 5 fractions per week by a 6-MV
linear accelerator (Varian 2100IX, Varian Medical Sys-
tems, Palo Alto, CA, USA).
For planning objectives, the mean hepatic dose and
dose to30% volume of liver was kept less than 30 Gy (V30
< 30%) [18,27-29]. Given that HT is a rotational treat-
ment, volumes of low-dose distributed regions for OARs
were generally greater . Thus, volume of normal liver
Hsieh et al. Radiation Oncology 2010, 5:40
Page 3 of 8
received 10 and 20 Gy (V10, V20) were also investigated
for a comparison. For OARs, mean dose to stomach,
spleen, kidneys and maximum dose to spinal cord were
assessed. The maximum doses were specified as maxi-
mum dose to 1% volume, denoted as D1% . According
to TD5/5 (the tolerance dose leading to 5% complication
rates at 5 years), the mean dose to at least one side of kid-
ney was kept below 23 Gy, and 50 Gy as for stomach .
The maximum dose was kept below 47 Gy for spinal cord
(c) Description of IMRT and helical tomotherapy techniques
All targets and OARs were delineated on Eclipse V7.3.10
planning system (Varian Medical System, Palo Alto, CA,
USA) and then transferred to Helical Hi-Art Tomother-
apy (Tomotherapy, Inc., Madison, Wisconsin, USA) via
Digital Imaging and Communications in Medicine
(DICOM) protocol. The dose by IMRT was calculated
using the Eclipse system. In Eclipse plans, 5-field gantry
arrangement for coplanar and noncoplanar static step
and shoot IMRT was designed in all cases. Minimum
monitor units (MU) for each segment was set to 5 with
no more than 40 segments were allowed for each plan.
For HT plans, the field width, pitch, and modulation fac-
tor [32,33] used for the treatment planning optimization
were 2.5 cm, 0.32 and 3.5, respectively. The dose con-
straints and the penalties were adjusted accordingly dur-
ing the optimization process. The dose calculation matrix
resolution was 3.0 mm for Eclipse system and 4.0 mm for
HT. The inverse planning systems performed iterations
during optimization process, which were multi-resolu-
tion dose calculation for Eclipse-IMRT but algebraic iter-
ation for HT. For final dose calculation, HT employed
employed Analytical Anisotropic Algorithm.
(d) Conformity index (CI) and Uniformity index (UI)
The dose to PTV has been estimated by DVH after nor-
malization. Dose conformity and homogeneity to the
PTV and OARs represent the ability to fulfill dose-vol-
ume histogram objectives. The conformity index (CI) was
originally proposed by Paddick  to evaluate the tight-
ness of fit of the planning target volume to the prescrip-
tion isodose volume in treatment plans as follows,
algorithms and Eclipse
where VPTV is the volume of PTV, VTV is the treated vol-
ume enclosed by the prescriptiond isodose surface, and
TVPV is the portion of the PTV within the prescribed iso-
dose volume. The CI approximates unity means lesser
dose to normal tissues and higher dose to target volume.
The uniformity index (UI) was defined as D5%/D95%,
where D5% and D95% were the minimum doses delivered to
5% and 95% of the planning target volume as previously
reported . The greater HI indicates the poorer inho-
Differences in actuarial outcomes between the three
groups were calculated using one-way ANOVA with post
hoc multiples comparisons. The differences were consid-
ered significant at p < 0.05. All analyses were performed
using the Statistical Package for the Social Sciences, ver-
sion 12.0 (SPSS, Chicago, IL, USA).
Target Volume Coverage, Conformity and Uniformity Index
The average CTV and normal liver volume for the nine
patients was 614.4 ± 323.4 ml (range, 154.5-1170.9 ml)
and 1294.8 ± 372.9 ml (range, 895.4-2125.8 ml), respec-
tively. The isodose distributions in axial, sagittal and cor-
onal views obtained with coplanar IMRT, noncoplanar
IMRT and HT in one representative patient were shown
in Fig. 1. Fig. 2 shows dose volume histograms (DVHs) for
the PTV of one representative patient using coplanar,
noncoplanar IMRT and HT planning techniques. In gen-
eral, the PTV coverage and comformity was better in HT
plan. The similar results were obtained for other patients.
For target coverage, 95% of CTV, 90% and 95% of PTV,
all achieved at least 99% of the prescribed dose were
listed, respectively. There were no significant differences
of coverage for CTV and PTV between three different
techniques. (Table 1) The mean score of CI showed no
significant difference between the HT and IMRT plan-
ning. However, a better uniformity index provided by HT
than both IMRT plans was noted (p < 0.05) (Table 1). The
UI and CI for each individual patient were plotted in Fig.
3 and in Fig. 4, respectively.
The radiation doses for OARs obtained by coplanar
IMRT, noncoplanar IMRT and HT were summarized in
Table 1. There were no significant differences between
both IMRT techniques and HT for the mean doses of
liver. The low dose region of liver for HT plans were
higher for V10 than others (p value < 0.05). There was a
trend for noncoplanar IMRT and HT that both tech-
niques provided lower V20 and V30 than coplanar IMRT.
For other OARs, there were no significant differences
between both IMRT and HT plan for spinal cord, kidneys
and stomach (Table 1).
Compared with both IMRT techniques, tomotherapy
provides better uniformity. The noncoplanar IMRT tech-
nique reduced the normal liver volume receiving 10 Gy to
a statistically significant level as compared to tomother-
apy. The constraints for V30 of the liver for coplanar
CI = (/ ) /(/)
PTVPV PV TV
Hsieh et al. Radiation Oncology 2010, 5:40
Page 4 of 8
IMRT vs. noncoplanar IMRT vs. tomotherapy might be
reconsidered as 21% vs. 17% vs. 17%, respectively.
Radiotherapy for treating HCC patients has been lim-
ited to palliation purpose in the past experiences due to
the low tolerance of the whole liver to radiotherapy
[36,37] despite HCC being reported as a radiosensitive
cancer in clinical investigations . Nevertheless, the
radiation dose is the most significant factor associated
with tumor response for HCC patients. Troublesomely, as
the irradiation doses deliver to the liver increased,
hepatic toxicity has become a problem . The encour-
aging results confirm 3DCRT is an effective modality, not
only for tumor response but also for survival in HCC
patients who are not suitable for other treatment modali-
ties [17,18,20]. Cheng et al.  reported that IMRT
offers the better potential of increasing the dose confor-
mality to the tumor and reducing the dose to the sensitive
structures than 3DCRT does for HCC patients with PVT.
Therefore, highly conformality delivered by radiotherapy
to HCC patients with PVT cause better tumor control
and lower toxicities to normal liver. In the current study,
noncoplanar IMRT and HT are compatible with coplanar
IMRT in V95 of CTV and PTV. (Table 1) There are no
significant differences of CI between HT and both IMRT
techniques. However, a trend for more stable conformal-
ity for each individual patient provided by HT than both
IMRT is noted in Fig. 4. HT provides better uniformity
than both IMRT techniques. (Table 1) The UI for each
individual patient were plotted in Fig. 3. In addition, the
dose-volume histogram for HT had a steeper slope. (Fig.
2) Where the differences among the treatment tech-
niques are clear: suggesting that HT provides higher uni-
formity within the planning target volume than both
IMRT techniques. In summary, HT provides better uni-
formity for PTV coverage than both IMRT techniques.
There is a trend for more stable conformality for each
individual patient provided by HT than both IMRT. Nev-
ertheless, both IMRT techniques and HT have similar
coverage for V95 of CTV and PTV.
Figure 1 Isodose distributions of prescribed dose of 46.4 Gy to PTV for different treatment techniques. A, D and G showed the isodose axial,
coronal and sagittal views for coplanar IMRT plan respectively. B, E and H were the isodose axial, coronal and sagittal views for noncoplanar IMRT plan.
The helical tomotherapy plan was shown in C, F and I.
Hsieh et al. Radiation Oncology 2010, 5:40
Page 5 of 8
There are several models used to predict liver toler-
ance, one is the normal tissue complication probability
(NTCP) and another one is maximum tolerable dose
(MTD). The NTCP model shows that the mean liver dose
is the most significant predictor of RILD, with a threshold
dose of 31 Gy. The University of Michigan Medical Cen-
ter reported that the mean hepatic dose was a strong pre-
dictor of subsequent radiation-induced liver disease
(RILD) and no cases of RILD were observed when the
mean liver dose was less than 31 Gy (BED = 30 Gy10 in 2
Gy/fraction) . A mean dose to normal liver smaller
than 23 Gy (4-6 Gy/fraction) or 30 Gy (2 Gy/fraction)
could be safe parameters for RILD prevention as reported
by Liang et al.  and Kim et al. , respectively (Table
2). The MTD model is based on PTV and liver volume in
equal fractions. The concepts of dose constraints for nor-
mal organs are extrapolated from the critical volume
model  as well as the known constraints on partial
liver resection that have indicated that up to 80% of the
liver can be safely removed in a patient with adequate
liver function . In addition, the constraint of 700 cc or
35% of normal liver to receive less than 15 Gy, as no sig-
nificant instances of RILD have been reported .
Additionally, Yamada et al.  reported that deteriora-
tion of liver function was observed in all patients with
V30 > 40%. Chen JC et al. suggested that V30 < 42% could
avoid RILD . (Table 2) In current study, coplanar
IMRT, noncoplanar IMRT and HT provide V30 data as
21%, 17% and 17%, respectively. In the other words, non-
coplanar IMRT and HT could be considered as another
potential choice for HCC patients with PVT as compared
with coplanar IMRT because they can achieve similar
dose to the tumor with comparable UI and CI but a rela-
tively low mean dose and V30 to the normal liver. Liang et
al.  reported the tolerable liver volume percentages
with 3DCRT planning with hypofractionation (4-6 Gy)
was 35% for V25 (= V29 Gy10) and 28% for V30 (= V35
Gy10). (Table 2) In current study, coplanar IMRT provides
similar results for the V10, V20 and V30 of normal liver
as 3DCRT planning as compared to the previous report
Figure 2 Dose-volume histogram of planning-target volume for
one representative patient undergoing coplanar intensity-mod-
ulated radiotherapy (IMRT), noncoplanar IMRT, and helical tomo-
Figure 3 The uniformity index (UI) for each individual patient un-
dergoing coplanar intensity-modulated radiotherapy (IMRT),
noncoplanar IMRT, and helical tomotherapy.
Figure 4 The conformal index (CI) for each individual patient un-
dergoing coplanar intensity-modulated radiotherapy (IMRT),
noncoplanar IMRT, and helical tomotherapy.
Hsieh et al. Radiation Oncology 2010, 5:40
Page 6 of 8
. In the mean time, the noncoplanar IMRT and tomo-
therapy techniques reduced more than 10% for V20 and
V30 of normal liver, respectively. (Table 1) Compared
with IMRT, HT has an additional dose superior and infe-
rior to the target volume (Fig. 1) due to the thicker fan
beam thickness . Although HT shows greater confor-
mity in the axial view as the dose was delivered rotation-
ally with higher intensity modulation can be achieved.
However, HT had greater V10 than the other modalities
noted in the current study. (Table 1) The potential risk of
radiation toxicities caused by low dose off-targets even
with highly conformal radiotherapy has been reported
. Careful considerations should be taken into account
for the larger low-dose regions to avoid unexpected side
effects. According to our results and the guidelines of
reducing the potential risk of RILD, we suggest that the
constraints for the liver in the V30 for coplanar IMRT vs.
noncoplanar IMRT vs. tomotherapy could be reconsid-
ered as 21% vs. 17% vs. 17%, respectively. Using IMRT or
HT, the constraints for mean dose to the normal liver
could be reconsidered as below: when delivering 50 Gy
and 60-66 Gy to the tumor bed, the mean dose to the nor-
mal liver could be less than 20 Gy and 25 Gy, respectively.
The constraints for liver could be more tighten than those
used in 3DCRT when we used IMRT or HT for HCC
patients with PVT.
The rates of gastrointestinal complications linked to
doses of < 40 Gy, 40-50 Gy, > 50 Gy were 4.2%, 9.9%, and
13.2%, respectively . Both IMRT techniques and HT
had similar dosimetric effects for OARs. Theoretically,
these advantages allow these techniques to push the
higher radiation dose to the tumor and keep relatively
lower radiation dose to OARs (Table 1).
The applications for reducing liver motion are not used
in the current study. To reduce the motion of liver in
radiotherapy, several strategies have been reported. The
application of four-dimensional computed tomography
(4D CT) using an external respiratory signal to acquire
difference phases of CT images could improve the dose
coverage for target volumes . Further use of abdomi-
nal compression was showed effectively in reducing liver
tumor motion, yielding small and reproducible excur-
sions in three dimensions . Case et. al.  showed
that the change in liver motion amplitude was minimal
over the treatment course and no apparent relationships
with the magnitude of liver motion and intrafraction
Table 1: Comparison of dosimetric parameters for irradiation of portal vein thrombosis and target volumes and normal
organs at risk (OARs) by using different treatment techniques.
Coplanar IMRT Noncoplanar IMRT Tomotherapy
CTVV95% (%)98.72 ± 1.90 99.98 ± 0.0299.97 ± 0.07
PTVV90% (%)99.44 ± 1.07 99.54 ± 0.6199.84 ± 0.17
V95% (%)98.83 ± 0.7498.71 ± 1.28 99.17 ± 0.64
UI 1.10 ± 0.021.11 ± 0.03 1.04 ± 0.02#,*
CI 1.16 ± 0.071.14 ± 0.061.13 ± 0.04
Normal liver V10 (%)64.81 ± 17.86 51.91 ± 21.56 72.51 ± 13.31*
V20 (%)41.36 ± 13.99 32.62 ± 14.9532.78 ± 9.18
V30 (%)21.10 ± 7.9017.17 ± 8.8517.00 ± 6.10
mean (Gy)18.23 ± 3.1116.14 ± 4.6117.93 ± 2.83
Stomachmean (Gy)11.68 ± 5.479.90 ± 6.1813.19 ± 6.05
Right Kidney mean (Gy) 5.07 ± 4.996.32 ± 5.089.00 ± 8.94
Left Kidney mean (Gy)2.1 ± 3.032.36 ± 2.915.00 ± 5.27
Spinal cordD1% (Gy)20.98 ± 7.51 20.12 ± 9.0822.53 ± 3.31
The Vx is the percentage of normal liver volume that receives ≥ × Gy in the total normal liver volume.
V90 and V95 mean volume covered by 90% and 95% of prescribed dose, respectively.
UI: Uniformity index; CI: Conformal index.
#: The p value is < 0.05 for comparing tomotherapy with coplanar IMRT.
*: The p value is < 0.05 for comparing tomotherapy with noncoplanar IMRT.
Hsieh et al. Radiation Oncology 2010, 5:40
Page 7 of 8
time. The application of 4D CT and abdominal compres-
sion may thus increase the coverage of target volume and
reduce the motion uncertainty in radiation therapy.
To sum up, our results suggest that noncoplanar IMRT
and HT are potentially effective techniques of radiation
therapy for HCC patients with PVT. Constraints for the
liver in IMRT and HT could be stricter than for 3DCRT.
Further clinical studies of HT and noncoplanar IMRT
applied to HCC patients with PVT are warranted.
We have no personal or financial conflict of interest and have not entered into
any agreement that could interfere with our access to the data on the research,
or upon our ability to analyze the data independently, to prepare manuscripts,
and to publish them.
All authors read and approved the final manuscript. CHH, CYL and PWS carried
out all CT evaluations, study design, target delineations and interpretation of
the study. CHH drafted the manuscript. CJ C, CCL, TEW, SCL, MJC and KHC took
care of patients. HCT, NSC and HJT made the treatment planning and carried
out all plans comparisons and evaluations. DYCH and YJ C participated in man-
uscript preparation and study design. LY W and YPH gave advice on the work
and carried out statistical analysis.
1Department of Radiation Oncology, Far Eastern Memorial Hospital, Taipei,
Taiwan, 2Department of Surgery, Far Eastern Memorial Hospital, Taipei, Taiwan,
3Department of Radiation Oncology, Mackay Memorial Hospital, Taipei, Taiwan
, 4Department of Gastrointestinal Division, Mackay Memorial Hospital, Taipei,
Taiwan, 5Department of Medical Research, Mackay Memorial Hospital, Taipei,
Taiwan, 6Institute of Traditional Medicine, School of Medicine, National Yang-
Ming University, Taipei, Taiwan, 7Department of Radiation Oncology, National
Defense Medical Center, Taipei, Taiwan, 8Graduate Institute of Sport Coaching
Science, Chinese Culture University, Taipei, Taiwan, 9School and Graduate
Institute of Physical Therapy, College of Medicine, National Taiwan University,
Taipei, Taiwan, 10Department of Healthcare Administration, Asia University,
Taichung, Taiwan and 11Department of Medical Physics, Memorial Sloan-
Kettering Cancer Center, New York, NY, USA
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Received: 2 February 2010 Accepted: 23 May 2010
Published: 23 May 2010
This article is available from: http://www.ro-journal.com/content/5/1/40© 2010 Hsieh et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Radiation Oncology 2010, 5:40
Table 2: The parameters of predicted helical tomotherapy plan within mean 30 Gy to normal liver of hepatocellular
carcinoma compared with selected published series.
Published seriesModality Mean Tumor dose
/fraction size (Gy)
V30 (%)Suggested mean dose (Gy) of
normal liver under
Dawson et al. 3DCRT 52.5/1.5-1.65 30 Gy10
30 GyKim et al. 3DCRT54/2
Cheng et al. 3DCRT50/1.8-2 42%
Liang et al. 3DCRT50/4-635% 28 Gy10
Yamada et al. 3DCRT57/240%
IMRT Coplanar IMRT50.4/1.821%20 Gy
IMRTNoncoplanar IMRT 50.4/1.8 17%20 Gy
HTTomotherapy 50.4/1.817%20 Gy
Abbreviations: 3DCRT = Three-dimensional conformal radiotherapy; HT = Helical tomotherapy; V30 = percent volume of normal liver with
radiation dose more than 30 Gy; X Gy10 = a biologic effective dose (BED) of X Gy10 as the α/β ratio = 10 in daily fraction of 2 Gy; OARs = Organs
Hsieh et al. Radiation Oncology 2010, 5:40
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Cite this article as: Hsieh et al., Comparison of coplanar and noncoplanar
intensity-modulated radiation therapy and helical tomotherapy for hepato-
cellular carcinoma Radiation Oncology 2010, 5:40