ARTICLE IN PRESS

Applied Radiation and Isotopes 61 (2004) 853859

BNCT dose distribution in liver with epithermal

DD and DT fusion-based neutron beams
H. Koivunoroa,*, D.L. Bleuela, U. Nastasib, T.P. Loua, J. Reijonena, K-N. Leunga
a
Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Mail Stop 5R0121, Berkeley, CA 94720, USA
b
Ospedale San Giovanni A.S., Via Cavour 31, 10100 Torino, Italy

Abstract

Recently, a new application of boron neutron capture therapy (BNCT) treatment has been introduced. Results have
indicated that liver tumors can be treated by BNCT after removal of the liver from the body. At Lawrence Berkeley
National Laboratory, compact neutron generators based on 2H(d,n)3He (DD) or 3H(t,n)4He (DT) fusion reactions
are being developed. Preliminary simulations of the applicability of 2.45 MeV DD fusion and 14.1 MeV DT fusion
neutrons for in vivo liver tumor BNCT, without removing the liver from the body, have been carried out. MCNP
simulations were performed in order to nd a moderator conguration for creating a neutron beam of optimal neutron
energy and to create a source model for dose calculations with the simulation environment for radiotherapy
applications (SERA) treatment planning program. SERA dose calculations were performed in a patient model based on
CT scans of the body. The BNCT dose distribution in liver and surrounding healthy organs was calculated with
rectangular beam aperture sizes of 20 cm
20 cm and 25 cm
25 cm. Collimator thicknesses of 10 and 15 cm were used.
The beam strength to obtain a practical treatment time was studied. In this paper, the beam shaping assemblies for DD
and DT neutron generators and dose calculation results are presented.
r 2004 Elsevier Ltd. All rights reserved.

Keywords: BNCT; MCNP; SERA; Liver cancer; Accelerator; Dose calculation

1. Introduction First, human liver cancer patients were treated with

The liver is the most common target of metastases
from many primary tumors (e.g. colorectal cancer,
breast, lung, etc. (Vitale et al., 1986). Primary and
metastatic liver cancers are highly fatal especially after
resection of multiple individual tumors (Allen et al.,
1997). The response rate for nonresectable hepatocel-
lular carcinoma to traditional radiation treatment or
chemotherapy is very poor. However, some current
results indicate that the thermal neutron irradiation of
the whole liver with a 10B compound could be a way to
destroy all the liver metastases (Pinelli et al., 2002).
*Corresponding author. Tel.: +1-510-495-2792; fax: +1-
510-486-5105.
E-mail addresses: koivunor@cc.helsinki.,
hkoivunoro@lbl.gov (H. Koivunoro).
thermal reactor neutrons into an isolated liver, removed
from the patient. Because of the complexity of the
surgical removal of the liver and its high risks of
complications, in vivo liver boron neutron capture
therapy (BNCT), without removing the liver from body,
may be preferable, if a low dose to healthy tissue and
sufcient tumor dose all over the liver can be assured. In
conventional radiotherapy, the tolerance dose (TD 55;
5% probability of complications within ve years) for
liver has been found to be 30 Gy for fractionated (from
1.8 to 2 Gy dose per day) whole liver irradiation (Emami
et al., 1991). BNCT could be considered a favorable
treatment modality, if a tumor dose >30 Gy (W) can be
assured in the liver tumor.
Lawrence Berkeley National Laboratory has devel-
oped compact neutron generators using a 13.56 MHz
radio frequency (RF) discharge to produce deuterium

0969-8043/$ - see front matter r 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.apradiso.2004.05.043
 ARTICLE IN PRESS
854 H. Koivunoro et al. / Applied Radiation and Isotopes 61 (2004) 853859
and/or tritium ions from plasma. RF-discharge yields a
high fraction of monoatomic ion species (for DD, D+-
ions and for DT, 50% of D+ and 50% T+-ions) in the
ion beam. The ions are accelerated to an energy of
120 keV or higher to impinge the beam on a titanium
coated copper or aluminum target where 2.45 MeV DD
or 14.1 MeV DT neutrons are generated through fusion
reactions. These neutrons can be moderated to thermal
or epithermal energies. The gamma component in these
moderated neutron beams is produced by purely
secondary reactions in the moderator and can be
minimized with the appropriate material selection.
Earlier theoretical studies of DD or DT fusion
reaction based neutron generators have produced
moderator and reector congurations for brain tumor
BNCT (Verbeke et al., 2000).
A study of in vivo BNCT with a DD and a DT
fusion based neutron generator has been performed. The
neutron source and various congurations of beam
shaping assemblies (BSA) were modeled with MCNP
(Briesmeister, 2000) in order to obtain an optimal
epithermal neutron beam. A neutronphoton source
for simulation environment for radiotherapy applica-
tions (SERA) (Wessol et al., 2001) was created from the
results of MCNP simulations. Rectangular beam sizes of
20 cm
20 cm and 25 cm
25 cm and collimator thick-
nesses of 10 and 15 cm were used. BNCT dose
distributions were calculated with SERA in the liver
and surrounding organs modeled based on CT-scans of
the body.
2. Materials and methods
2.1. DD and DT fusion neutron source modeling for
sera calculations
The BSAs were modeled with the MCNP code to
generate the DD and DT source for the SERA
calculation. The modeled source was a cylindrical
tandem axial neutron generator. The area of the conical
target was 250 cm2. With a 25% duty cycle and 150 kW
beam power, the power density at the target is 150 W/
cm2. This source geometry allows increased neutron
source brightness and leads to a neutron yield B1012 n/s.
With the same parameters, B1014 n/s DT neutron yield
can be obtained.
DD fusion neutrons have energies of B2.45 MeV
and DT fusion neutrons energies of B14 MeV. These
neutrons need to be moderated to the optimal neutron
energy spectrum for BNCT. Moderating the neutrons to
near the optimal energy of 10 keV is performed in two
stages. In an earlier study (Koivunoro et al., 2004), the
best results were achieved with iron and FluentalTM
moderator materials. FluentalTM (69% AlF3/30% Al/
1% LiF) is a neutron moderator material developed at
VTT in Finland (Auterinen and Hiismaki, 1993). The
material combination of FluentalTM is ideal to decrease
the neutron ux to the desired energy range of B10 keV
without over-moderation. First, a 20 cm for DD and
28 cm for DT layer of iron was used to decrease the
fast neutron energy in the range of 12.45 MeV or
114.1 MeV. Second, a 30 cm layer for DD neutrons or
a 34 cm layer for DT neutrons of FluentalTM was used
to decrease the neutron ux in the range of >100 keV.
The fusion neutron sources give isotropic neutron
yields from the target and thus, the neutrons need to be
guided to the beam aperture direction with the reector
materials. In this study, lead was used as a reector
material for both DD and DT neutrons, though with
the bismuth collimator, spectra calculations gave ap-
proximately the same results. A benet of both of these
materials is that new gamma particles are not created in
the neutron collisions and they absorb existing gammas
from the beam. After moderation, neutrons were
collimated with a 5 cm layer of bismuth and a 5 cm
layer of lithiated-polyethylene (on the surface). These
collimator materials were chosen based on the literature
(Seppala 2002; Burn et al., 2002). Lithiated polyethylene
was used as shielding to absorb low-energy neutrons.
The rectangular beam aperture size was 25 cm
25 cm.
Energy spectra in air at the collimator output with these
beam shaping assemblies are shown in Fig. 1.
The resulting neutron source was tallied at a 5 cm
depth inside the collimator with the surface source write
(SSW) option (Briesmeister, 2000). A body-sized phan-
tom was placed in front of the beam aperture to account
for the source component resulting from back scattering
from the patient. A cross-sectional picture of the MCNP
model created for the source calculation study is shown
in Fig. 2. The neutron and photon energy and angular
distributions data were used to create the source-le in
the SERA program. In addition to the neutron and
photon source, a 5 or 10 cm layer of the enriched
lithiated-polyethylene collimator was included in the
SERA source le.
2.2. Patient modeling
A patient model was created with the SERA program
using trans-axial body CT scans (FOV=369 cm

369 cm and matrix size 512
512 pixels) of a patient
taken at the Radiological Department of Cuneo
Hospital in Italy. Only 46 (0.5 cm thick) CT slices were
available, and the length of the body had to be increased
to ensure relevant dose delivery (with o2% error) from
surrounding tissues. It has been shown, that signicant
disturbance due to phantom size occurs, if the phantom
is less than 6 cm smaller than the beam aperture (if the
irradiated object is larger than that) (Koivunoro et al.,
2003). Also, to gain accurate backscatter in the
measurement point, 5 cm of tissue in each direction is
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H. Koivunoro et al. / Applied Radiation and Isotopes 61 (2004) 853859
Fig. 1. Neutron ux (per source neutron) of DD and DT fusion neutron sources after moderation. Moderation was done with 20 cm
of iron and 30 cm of Fluental with DD neutrons and 28 cm of iron and 34 cm of FluentalTM with DT neutrons.
Fig. 2. Cross-section of moderator and lter assembly with a
tissue phantom as used in MCNP simulations for SERA
calculations.
needed to correspond to the real situation (with o3%
error). Patient model length was increased by adding 21
copies of the most cranial slice and 12 copies of the most
855
inferior slice into the model. In addition to the liver,
some of the surrounding healthy organs (skin, lungs,
heart, kidney, spleen, vertebral body, spine, lungs and
ribs) were included in the model. The rest of the tissue
was modeled as an average soft tissue. Material
compositions of the tissues were dened according to
ICRU report 46 (International Commission on Radia-
tion Units and Measurements, 1992) with 5 ppm of B-10.
The liver comprises 30 CT slices, meaning the height of
the liver in this model is 15 cm. The deepest depth from
the skin was B12 cm in the liver model.
2.3. Dose calculation
In dose calculation, boron concentrations reported for
boronophenylalanine-fructose (BPA-F) in liver and liver
tumors were used (Pinelli et al., 2002). The boron
concentration of the healthy liver tissue was assumed to
be 8 ppm (mg/kg) and of the tumor tissue 48 ppm,
creating a concentration difference of 1:6 between the
healthy liver and the tumor tissue. The weighting factors
commonly used in BNCT were used as an estimate for
dose calculations, because the relative biological effec-
tiveness (RBE) and compound biological effectiveness
(CBE) factors in liver are unknown. To calculate
biological dose, weighting factors 1, 3.2 and 3.2, (wg
wN and wfast n ) for gamma dose (Dg ), nitrogen dose (DN )
and fast (or hydrogen) dose (Dfast n ) were used. To
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856 H. Koivunoro et al. / Applied Radiation and Isotopes 61 (2004) 853859

calculate biological boron dose (DB ), caused by boron
capture reactions, a weighting factor (wB ) of 1.3, for
boron in tissue and 3.8 for boron in tumor were used
(Coderre and Morris, 1999). With these dose weighting
factors, the total weighted dose can be expressed in units
Gy (W) (Savolainen et al., 1999) and it was calculated
according to equation
DW wg Dg wB DB wN DN wfast n Dfast n :
Dose calculations were performed with a
20 cm
20 cm and a 25 cm
25 cm rectangular beam
aperture and with 10 and 15 cm aperture thicknesses.
Aperture size and thickness was varied adjusting the
collimator in the SERA source le. Dose calculations
were performed with the single beams and combination
of three beams of same size varying beam angle.
The linear quadratic approach (Hall, 1994) was used
to calculate the tolerance dose for single fraction whole
liver irradiation from the TD 55 of 30 Gy for fractionated
(2 Gy fractions) irradiation. With this method, a
tolerance dose of 10 Gy for single-fraction whole liver
irradiation can be found. However, the healthy tissue
dose in BNCT rapidly decreases with depth in tissue and
thus less than two-thirds of the organ volume is covered
by >50% isodose. The TD 55 for one-third of the liver
volume in fractionated irradiation is reported to be
50 Gy (Emami et al., 1991). The corresponding tolerance
dose of single-fraction irradiation is then calculated to
be 13.65 Gy. Based on these evaluations, the maximum
dose to the healthy liver in this study was limited to a
safe value of 12.5 Gy (W).
The body was placed as close to the beam as possible,
in practice from 0.6 to 1.5 cm distance. The beam
centerline was located 1 cm higher than the center of the
liver, because the deepest parts of the liver are located in
the higher half of the organ. In every SERA simulation,
8 million particles were simulated. The dose for neutrons
and photons was plotted on the beam axis. In addition,
the isodose contours were printed over the CT images
and dose volumes in liver were calculated for tumor dose
and healthy tissue dose.
3. Results
3.1. Independent beams
Table 1 shows beam parameters (treatment time,
maximum tumor dose and tumor dose at 12 cm with
single beam) with each independent beam. The highest
tumor dose with both DD and DT neutron source was
obtained with a 20 cm rectangular beam and a 15 cm
thick collimator. The deepest penetration with both the
DD and DT neutron source was obtained with a
25 cm rectangular beam and a 15 cm thick collimator,
when doses of 11 Gy (W) and 10 Gy (W) at 12 cm depth
were obtained for DD and DT beams, respectively.
When the collimator length was increased from 10 to
15 cm, the treatment time was increased by 70110%,
but the maximum tumor dose was increased only by
1015% with the DD source and 13% with the DT
source. With a 15 cm collimator, the tumor dose at
12 cm depth was increased by 624% with DD
neutrons and 011% with DT neutrons. The depth
dose proles of the DT and DD beams (eld #2) with
25 cm rectangular beam and 15 and 10 cm collimators
are shown in Figs. 3(a) and (b), respectively.
3.2. Combination of three beams
Doses and dose volumes for combined beams with the
maximum healthy tissue dose of 12.5 Gy (W) are shown

Table 1
Effect of collimator size and thickness on treatment time (TT) and tumor dose in a patient model while maximum healthy tissue dose is
limited to 12.5 Gy (W)

Collimator dimensions Field # TT [min] Dtumor max (Gy(W)) Dtumor at 12 cm (Gy(W))

2
Width [cm ] Thickness [cm] DD DT DD DT DD DT

1 2010 36 63.9 74.8 6.4 6.2

20
20 10 2 2183 42 61.7 73.5 8.4 8.6
3 1883 28 65.7 72.8 5.4 5.5
1 3809 65 71.8 74.6 7.5 6.8
20
20 15 2 4251 72 71 75.3 8.9 9.0
3 3465 58 72.5 75.2 6.1 5.5
1 1578 30 61.2 73.3 6.7 7.4
25
25 10 2 1765 33 60.4 72.1 8.9 9.2
3 1507 28 62.4 72.4 5.5 5.4
1 2932 51 70.6 73.1 8.0 8.2
25
25 15 2 3255 56 69.2 72.8 11 10.1
3 2707 46 70.2 72.3 6.4 6.3
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in Table 2. When three beams of different angles were achieved with the 25 cm beam and 15 cm collimator,
used, the highest tumor dose with the DD neutron while all the other collimator combinations gave same
source was achieved with the 20 cm beam with both the higher tumor dose. Total liver volume was calculated to
collimators. With the DT source, smallest dose was be 1778 cm3. The largest liver volume (58% and 57%)
was covered with the 25 cm beam and 15 cm collimator
thickness with the DD and DT beams. Total liver
80
Tumor Dose D-T
isodose contours over the CT slice where liver has the
70 Tissue Dose D-T deepest depth from the skin, with the 25 cm beam and
Gamma Dose D-T
60 Fast Dose D-T 15 cm collimator thickness, are shown in Fig. 4 for both,
Tumor Dose D-D the DD and DT beams.
Dose [Gy (W)]

50 Tissue Dose D-D

Gamma Dose D-D
Fast Dose D-D
40

30 4. Discussion
20
In this study, higher boron concentrations and CBE
10
values in skin and intestinal epithelium were not taken
0 into account. Studies have predicted a CBE factor of 2.5
0 2 4 6 8 10 12 14
for skin (Coderre and Morris, 1999) and close to that of
Depth in tissue [cm]
skin for oral mucosa, but for intestinal epithelium, the
Fig. 3. Depth dose distributions in a patient model for DT CBE factor is unknown. Boron concentration for skin is
and DD neutron source with 25 cm beam with 15 cm thick reported to be 1.5 times that of blood (Coderre and
collimator. Morris, 1999). Using a CBE factor of 2.5 instead of 1.3,

Table 2
Treatment time (TT), maximum tumor dose (Dtumor max), isodose value of 30 Gy(W) tumor doses, and liver volume covered by dose of
greater than 30 Gy (W), when four different combinations of three beams were used. Maximum healthy tissue dose was limited to
12.5 Gy (W)

Maximum tissue dose 12.5 Gy(W)

Collimator dimensions TT (min) Dtumor max (Gy(W)) 30 Gy(W) isodose Liver volume covered

Width (cm2) Thickness (cm) DD DT DD DT DD DT DD DT

20
20 10 4448 63 70 71 43 42 57% 52%

20
20 15 7508 128 70 71 43 42 58% 56%
25
25 10 3493 68 68 71 44 42 58% 41%
25
25 15 5538 94 69 70 44 43 58% 57%

Fig. 4. Isodose contours for total liver tissue dose with the three-beam irradiation of (a) DT and (b) DD beams. Beam diameter of
25 cm and collimator of 15 cm was used. The ratio of three elds are 3 (F1), 3 (F2) and 4 (F3).
 ARTICLE IN PRESS
858 H. Koivunoro et al. / Applied Radiation and Isotopes 61 (2004) 853859
the boron concentration of 12 ppm instead of 8 ppm and
the correct nitrogen composition of tissue (4.2) instead
of that of liver (3), the skin dose increases by B20%
compared to results reported here. With DD beams
and a 10 cm collimator, which create a tissue depth dose
peaking at the skin, this would lead to higher than
12.5 Gy skin dose and treatment time and tumor dose
would decrease from that which reported here.
In the worst case, the CBE factor for intestinal
epithelium might be 4, causing an increase of B30% to
the intestinal dose. In our study, some of the intestines
are covered by the 80% isodose, when dose to intestinal
epithelium would be higher than our healthy tissue limit.
(12.5 Gy (W)
1.3
0.8=13 Gy (W)). However, TD 55
for fractionated intestine irradiation (Emami et al.,
1991) is somewhat higher than that for liver (5040 Gy
vs. 4030 Gy for one-third and whole liver irradiations,
respectively) and thus may lead to a safe intestinal dose.
For a more accurate study of the dose to the liver and
surrounding sensitive organs, the CBE factors for each
organ needs to be determined.
5. Conclusions
When healthy liver dose is limited to 12.5 Gy (W),
tumor dose greater than 30 Gy (W) is possible to deliver
only 58% of liver volume with the DD or the DT
beams. Overall, treatment times with DD neutron
source of neutron yield 1012 n/s were not feasible (all
>25 h). DD neutron yield should be increased to
3
1013 n/s to obtain realistic treatment time of B12 h.
With DT neutron source of yield 1014 n/s, treatment
times were acceptable (3072 min with single beam and
63128 min with 3 beams of different direction). Results
show that a tumor dose of 30 Gy (W) cannot be achieved
in the whole liver volume with any of these beam
combinations and boron concentrations in the tumor
and tissue presented here. In order to obtain greater
than 30 Gy (W) tumor dose all over the liver (greater
than 15% isodose), the average healthy tissue dose must
be 21 Gy (W) and the maximum dose (to B12% of total
liver volume) 36 Gy (W).
A further aid is to try to enhance the tumor to tissue
boron concentration ratio by the loco-regional infu-
sion (Zanon et al., 2001) of the NCT compounds. If
this method can be applied to BNCT and if the boron
compound can be located more selectively to liver
metastases when infused through hepatic artery, higher
healthy tissue to tumor tissue boron concentration ratio
can be attained. Three times higher boron concentration
ratio than used in this study (i.e. 18:1) is needed while
the boron concentration in healthy tissue remains
constant (8 ppm), to cover nearly all of the liver volume
with greater than 30 Gy (W) dose. In this case, the
maximum tumor dose would be B200 Gy (W), when
>30 Gy (W) dose would be reached at the 15% isodose.
Acknowledgements
This work is supported by Department of Energy
under Contract No. DE-AC03-76SF00098 the Compag-
nia di San Paolo Foundation (NCT Turin Project), and
the Finnish Cultural Foundation. The authors would
like to thank Dr. Tiina Seppala of Boneca Corp. Finland
and Dr. Charles Wemple of INEEL for their assistance
with the SERA program.
References
Allen, B.J., Wallace, S.A., Carolan, M.G., 1997. Can epither-
mal boron neutron capture therapy treat primary and
metastatic liver cancer? In: Larsson, B., Crawford, J.,
Weinreich, R. (Eds.), Advances in Neutron Capture
Therapy Vol. I, Medicine and Physics. Elsevier, Amsterdam,
pp. 118.
Auterinen, I., Hiismaki, P., 1993. Design of an epithermal
neutron beam for the TRIGA reactor at otaniemi,
Proceedings of the CLININCT BNCT Workshop, TKK-
F-A718, Helsinki, p. 14.
Briesmeister, J.F. (Ed.), 2000. MCNP-a general Monte Carlo
N-particle transport Code. Version 4C, LA-13709 M.
Burn, K.W., Casalina, L., Daffara, L., Nava, E., Petrovich, C.,
Gualdrini, G., Fiorani, O., Perrone, A., Rosi, G., 2002.
Design of an epithermal facility for treating patients with
brain glioma at the TAPIRO fast reactor at ENEA
Casaccia. Research and development in neutron capture
therapy. In: Sauerwein, W., Moss, R., Wittig, A. (Eds.),
Proceedings of the 10th International Congress on Neutron
Capture Therapy, Essen, Germany, September 813, 2002.
Monduzzi Editore, Bologna, pp. 129134.
Coderre, J.A., Morris, G.M., 1999. Review: the radiation
biology of boron neutron capture therapy. Radiat. Res. 151,
18.
Emami, B., Lyman, J., Brown, A., Coia, L., Goitein, M.,
Munzenrider, J.E., Shank, B., Solin, L.J., Wesson, M., 1991.
Tolerance of normal tissue to therapeutic irradiation. Int. J.
Radiat. Oncol. Biol. Phys. 21, 109122.
Hall, E.J., 1994. Radiobiology for the Radiologist 4th Edition..
Lippincott Williams & Wilkins, Philadelphia, PA.
International Commission on Radiation Units and Measure-
ments, 1992. Photon, Electron, Proton and Neutron
Interaction Data for Body Tissues Report No 46, ICRU,
Bethesda, MD.
Koivunoro, H., Auterinen, I., Kosunen, A., Kotiluoto, P.,
Seppala, T., Savolainen, S., 2003. Computational study of
the required dimensions for standard sized phantoms in
boron neutron capture therapy dosimetry. Phys. Med. Biol.
48 (21), N291300.
Koivunoro, H., Lou, T.-P., Reijonen, J., Leung, K.-N., 2004. A
D-D/D-T Fusion based neutron generator system for liver
BNCT. Proceedings of the Sixth International Topical
 ARTICLE IN PRESS
H. Koivunoro et al. / Applied Radiation and Isotopes 61 (2004) 853859
Meeting on Nuclear Applications of Accelerator Technol-
ogy, AccApp03, June 15, 2003. San Diego, California,
USA.
Pinelli, T., Zonta, A., Altieri, S., Fossati, F., Bruschi, P.,
Ferrari, C., Prati, U., Roveda, L., Ngnitejeu Tata, S.,
Zonta, C., Barni, S., Chiari, P., Nano, R., 2002. TAOrMI-
NA: from the rst idea to the application on the human
liver. In: Sauerwein, W., Moss, R., Wittig, A. (Eds.),
Proceedings of the 10th International Congress on Neutron
Capture Therapy, Essen, Germany, September 813 2002,
Research and Development in Neutron Capture Therapy.
Monduzzi Editore, Bologna, pp. 10651072.
Savolainen, S., et al., 1999. Dosimetry chain for the treatments
of glioma patients in the epithermal neutron beam at the
Finnish BNCT facility (FiR 1). Med. Biol. Eng. Comput. 37
(Suppl. 1), 388389.
Seppala, T., 2002. FIR 1 Epithermal neutron beam model
and dose calculation for treatment planning in neutron
capture therapy. Report series in physics, University of
859
Helsinki. HU-P-D103. ISBN 952-10-0570-X. http://ethesis.
helsinki./.
Verbeke, J.M., Vujic, J., Leung, K.-N., 2000. Neutron beam
optimization for boron neutron capture therapy using the
D-D and D-T high-energy neutron sources. Nucl. Technol.
129 (2), 257.
Vitale, G.C., Heuser, L.S., Polk Jr., H.C., 1986. Malignant
tumors of the liver. Surg. Clin. North Am. 66, 723.
Wessol, D.E., Wemple, C.A., Wheeler, F.J., Cohen, M.T.,
Rossmeier, M.B., Cogliati, J., 2001. SERA:simulation
environment for radiotherapy applications. Users Manual,
Version 1C0. INEEL External Report. http://www.cs.
montana.edu/Bbnct/.
Zanon, C., Grosso, M., Clara, R., Alabiso, O., Chiappino, I.,
Miraglia, S., Martinotti, R., Bortolini, M., Rizzo, M.,
Gazzera, C., 2001. Combined regional and systemic
chemotherapy by a mini-invasive approach for the treat-
ment of colorectal liver metastases. Am. J. Clin. Oncol. 24
(4), 354359.