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Journal of Proton Therapy www.protonjournal.org
www.protonjournal.org
Intensity modulated proton therapy versus uniform scanning proton
therapy: Treatment planning study of the prostate cancer in patients with a
unilateral metallic hip prosthesis
Suresh Rana1*, Gary Larson2, Carlos Vargas3,4, Megan Dunn4, Yuanshui Zheng1
1Department of Medical Physics, ProCure Proton Therapy Center, Oklahoma City, Oklahoma, USA
2Department of Radiation Oncology, ProCure Proton Therapy Center, Oklahoma City, Oklahoma, USA
3Department of Radiation Oncology, Mayo Clinic, Phoenix, Arizona, USA
4Proton Collaborative Group (PCG), Warrenville, Illinois, USA
Article history:
Submission: March 15, 2015
First Revision: April 19, 2015
Second Revision: May 5, 2015
Acceptance: May 6, 2015
Publication: May 8, 2015
© Rana. Published by EJourPub.
Cite this article as:
Rana S, Larson G, Vargas C, Dunn M, Zheng Y. Intensity modulated proton therapy versus
uniform scanning proton therapy: Treatment planning study of the prostate cancer in patients
with a unilateral metallic hip prosthesis. Jour Proton Ther 2015; 1:113.
*Corresponding author:
Suresh Rana, MS; Department of Medical Physics, ProCure Proton Therapy Center, Oklahoma City,
USA
Abstract
The purpose of this study is to compare the dosimetric results between the uniform scanning
proton therapy (USPT) and intensity modulated proton therapy (IMPT) plans for the prostate
cancer in patients with a unilateral metallic hip prosthesis. Five prostate cancer cases with left
(n = 3) and right (n = 2) metallic hip prostheses were included in this retrospective study. For
each case, the USPT and IMPT plans were generated using two anterior -oblique beams and one
lateral beam for a total dose of 79.2 Gy(RBE) to be delivered in 44 fractions. For a given case,
the beam parameters, dose prescription, and delivery schema in the IMPT plan were kept
identical to the ones in the USPT plan. The IMPT and USPT plans were compared for various
dosimetric parameters. The mean dose to the target volume was comparable. Both the IMPT
and USPT techniques achieved the target coverage goals. Dose homogeneity was found to be
similar in the IMPT and USPT plans. For both the rectum and bladder, the IMPT plans produced
favorable dosimetric results in the low-, medium-, and high-dose regions when compared to the
USPT plans. For the high dose regions, the rectal V 70 was lower in the IMPT plans by about 3.89
cc when compared to the one in the USPT plans. The rectal V80 in the IMPT plans (1.10 cc) was
almost half than the one in the USPT plans (2.39 cc). In comparison to the USPT plans, the mean
dose to the rectum, bladder, and femoral head were lower in the IMPT plans by about 8.91%,
4.15%, and 41.09%, respectively. Based on the preliminary results of fi ve cases presented in
this study, the IMPT plans provided slightly better dosimetric results compared to the USPT
plans, especially in sparing the rectum and bladder in the low -, medium-, and high-dose
regions, for the treatment of the prostate cancer in patients with a unilateral metallic hip
prosthesis. Future studies need to address the impact of the setup uncertainties and intra -
fraction prostate motion in the IMPT planning of the prostate cancer patients with prosthetic
hip replacements.
Keywords: Proton Therapy; Prostate Cancer; IMPT; Prosthesis; Treatment Planning
Original Article
1. Introduction
Radiation therapy is one of the most commonly used
techniques for the prostate cancer treatment. Among
various radiation therapy techniques, proton therapy has
become a popular option to treat the prostate cancer. A
number of dosimetric studies on the prostate cancer have
compared the results of proton therapy with that of mega -
voltage (MV) X-ray (photon) therapy such as intensity
modulated radiation therapy (IMRT) and volumetric
Rana et al.:Proton therapy planning for prostate cancer patients with metallic hip replacements
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© Rana. Published by EJourPub.
modulated arc therapy (VMAT).1-10 Proton therapy
planning for the prostate cancer typically includes two 180
degree parallel-opposed lateral fields, but such beam
arrangement is not feasible for a complex prostate case,
which involves a metallic hip prosthesis [Figure 1].
Prostate cancer cases involving a metallic prosthesis are
very rare at our institution. The Task Group (TG) 63 of
American Association of Physicists in Medicine (AAPM)11
recommends avoiding beam passing through the metals
such as hip prostheses that are composed of high -Z
materials. Hence, proton therapy planning for a prostate
cancer case with a unilateral metallic hip prosthesis may
need to include at least one oblique field in addition to the
lateral field.
Tang et al.1and Trofimov et al.4demonstrated the
feasibility of using non-parallel-opposed lateral fields in
proton therapy planning for the prostate cancer. Tang et
al.1showed that the anterior-oblique proton fields are
superior in reducing dose to the anterior rectal wall in the
high-dose regions when compared to the bilateral fields.
Similar result was reported by Trofimov et al.4showing
anteriorly angled lateral proton fields can reduce the rectal
dose when compared to two parallel-opposed lateral
fields. Both the studies of Tang et al.1and Trofimov et al.4
included the prostate cases which did not include a
metallic hip prosthesis. To date, there are only two
published studies7, 12, which address the proton therapy
for the prostate cancer patients with a metallic hip
prosthesis. Rana et al.7demonstrated that the
combination of one lateral and two oblique fields in the
uniform scanning proton therapy (USPT) provides
dosimetric advantage over the VMAT. Cuaron et al.12
reported the clinical results with acceptable normal tissue
toxicities for the prostate patients treated with the
anterior-oblique proton beams.
Figure 1: Axial CT slice showing the clinical target volume
(CTV), planning target volume (PTV), rectum, bladder,
femoral head, and metallic hip prosthesis in a prostate
cancer case.
Proton therapy community is showing increasing interest
in intensity modulated proton therapy (IMPT), which is a
more advanced proton therapy technology, compared to
the uniform scanning (US) and double scattering (DS)
proton therapy. In US and DS proton therapy, the
treatment planning is based on a 3D conformal approach,
which utilizes beam specific apertures and compensators.
By contrast, the IMPT plans can be generated using single
field optimization (SFO) and multiple field optimization
(MFO) techniques. For the SFO-IMPT, the treatment plan is
optimized such that each field covers the target volume;
whereas for the MFO-IMPT, the treatment plan
optimization involves the sum of multiple fields producing
uniform dose coverage to the target volume.
In a more recent study by Kirk et al.13, the authors found
that the IMPT plans are more conformal than the USPT
plans, but differences in the organs at risk (OAR) doses
among various proton plans were not significant. Existing
proton therapy treatment planning studies on the prostate
cancer reported either the US technique involvin g a
metallic hip prosthesis7, 12 or the IMPT techniques but with
no involvement of a metallic hip prosthesis 3, 13, 14, 15. The
purpose of this study is to compare the dosimetric results
between the USPT and MFO-IMPT plans (hereafter
referred as IMPT plans) for the prostate cancer in patients
with a unilateral metallic hip prosthesis.
2. Materials and Methods
A total of 5 prostate cancer cases with unilateral left (n =
3) or right (n = 2) metallic hip prostheses were selected
for this retrospective study. All 5 cases are included in the
Proton Collaborative Group (PCG) research study (REG01 -
09, WIRB Protocol #20091082). Patients were treated
using the USPT technique at our institution (ProCure
Proton Therapy Center, Oklahoma City) between January
2012 and December 2014. The IMPT planning on five
cases was done for a comparative purpose.
2.1 Simulation
Computed tomography (CT) simulation was done on a
General Electric CT Scanner (GE Healthcare, Waukesha,
WI) by immobilizing patients in a supine position using the
vac-lok system (CIVCO Medical Solutions, Kalona, IA, USA).
Each patient had fiducial markers placement within the
prostate. Per institutional protocol, all patients were
instructed to drink 16 to 24 oz of water to maintain a full
bladder prior to the CT simulation and during treatment.
Additionally, 100 cc of saline was inserted into the rectum
of each patient. The CT dataset with slice thickness of 1.25
mm were then transferred to the treatment planning
station for the contouring and planning.
2.2 Contouring
The clinical target volume (CTV) was contoured by the
radiation oncologist. The CTV included either the prostate
and seminal vesicles (n = 3) or the prostate only (n = 2).
The planning target volume (PTV) expansion among these
5 clinical cases, however, varied slightly with a setup
technique (i.e., 5 mm uniform expansion with a rectal
balloon and no fiducial markers; 3 mm posterior and 5 mm
Rana et al.:Proton therapy planning for prostate cancer patients with metallic hip replacements
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© Rana. Published by EJourPub.
elsewhere for high-risk cases with fiducial markers and
saline injection into the rectum). For a comparative
purpose in this study, we used a 5 mm uniform PTV
expansion around the CTV, and each case was re -planned
with the USPT, which was then compared to the
corresponding IMPT plan using the same PTV ( i.e., 5 mm
uniform expansion around the CTV). The OARs such as the
rectum, bladder, and femoral head as well as the streaking
artifacts were contoured too. All the artifacts were
overridden by relative stopping power values, which were
obtained by sampling the tissues in the CT dataset.
2.3 Treatment planning
Proton plans were generated in the XiO treatment
planning system (TPS), version 5.00 (CMS Inc., St. Louis,
MO, USA). Our XiO TPS used the beam commissioning data
that were measured on an IBA Cyclotron (IBA, Louvain-la-
Neuve, Belgium). The uniform scanning proton beam is
scanned laterally with a constant frequency in order to
deliver a uniform dose for a near rectangular scanning
area, whereas the IMPT modulates the dose in the beam
direction and lateral to the beam direction. For each
prostate case in this study, dose prescription to the PTV
was 79.2 Gy(RBE) with a daily fractional dose of 1.8
Gy(RBE) (i.e., 44 fractions).
Proton dose calculations were done using a pencil beam
algorithm16 with a grid size of 3 mm × 3 mm × 3 mm.
Treatment planning was done based on the same CT
calibration curve, which has a maximum relative stopping
power of 2.5 (obtained from the linear extrapolation).
However, beam angles were chosen so that the beam did
not pass through the metal device, thus the actual stopping
power of hip implants did not have an effect on the dose
calculations.
For both the USPT and IMPT, the treatment planning goal
was to minimize the dose to the OARs as much as possible
while maintaining dose to 99% of the CTV more than 98%
of the prescription dose (CTV D99 > 98%) and dose to
98% of the PTV volume more than 95% of the prescription
dose (PTV D98 > 95%).
2.3.1 USPT planning
USPT plans were generated using three fields: lateral (left
or right), left-anterior-oblique (LAO), and right-anterior-
oblique (RAO). The lateral field was weighted 50% ,
whereas each oblique field was weighted 25%. Beam
angles in each case were selected such that the bea m
entrance through a metallic hip prosthesis and rectum was
avoided. The isocenter of each proton field was placed at
the center of the PTV. For each beam in the USPT plans, the
distal and proximal ranges were calculated based on the
uncertainties of 2.5% of proton range for the CT to
stopping power ratio conversion inaccuracy plus an
additional 2 mm to account for a systematic range
uncertainty. The margins for the aperture were 0.8 − 1.0
cm and range compensators had a smearing distance of 1.2
cm. Tapering was not used for the compensators. The
beam delivery schema in the USPT plans was such that the
lateral field was delivered daily, whereas the LAO and RAO
fields were delivered alternatively.
2.3.2 IMPT planning
IMPT plans were generated by optimizing all three fields
together by applying dose-volume constraints to the PTV,
rectum, and bladder. The rectal and bladder constraints
used during plan optimization were as follows: V50 Gy(RBE) <
30%, V70 Gy(RBE) < 15%, V79.2 Gy(RBE ) < 5%. Since the XiO TPS
does not have a feature to generate a beam-specific PTV
margin based on the range uncertainty calculations,
especially for the anterior-oblique beams, the PTV (a 5 mm
uniform expansion from the CTV) was chosen as the
optimization volume. The calculated range of each layer
was adjusted by applying a shift (i.e., 2.5% of water
equivalent path length [skin edge to the distal and
proximal edges of the CTV] plus 2 mm) to account for the
range uncertainties along the beam direction. For a given
case, the IMPT plan had the same beam parameters (e.g.,
distal and proximal ranges), isocenter, outlined structures,
and delivery schema as in the corresponding USPT plan.
The layer spacing was set to 8 mm for all cases. The
available spot positions for each beam in the XiO TP S are
defined by a three-dimensional rectangular grid passing
through the beam isocenter, within the target boundaries.
2.4 Plan evaluation
USPT and IMPT plans were compared based on the dose -
volume histograms (DVH) results generated in the XiO
TPS. The absolute dose normalization mode available in
XiO was applied in all the IMPT and USPT plans. The CTV
and PTV were evaluated for the mean dose and dose
coverage. The PTV was also evaluated for the homogeneity
index (HI). The rectum and bladder were evaluated for the
mean dose, and the relative volume (in percentage) of the
structure receiving 70, 50, and 30 Gy(RBE) (V70, V50, and
V30, respectively). Additionally, the rectum and bladder
were evaluated for the absolute volume (in cc) of the
structure receiving 75, 79.2, and 80 Gy(RBE) (V75, V79.2 , and
V80, respectively). The femoral head was evaluated for the
mean dose.
5% 95% (1)
D D
HI Prescription Dose
where, D5% and D95% represent the doses to 5% and 95% of
the PTV, respectively.
Rana et al.:Proton therapy planning for prostate cancer patients with metallic hip replacements
4Volume 1, Issue 1, 2015 Journal of Proton Therapy
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© Rana. Published by EJourPub.
Table 1: Comparison of the dosimetric parameters in the IMPT and USPT plans for a prostate cancer case with a metallic hip
prosthesis. The results are averaged over five analyzed cases
IMPT
USPT
CTV
Mean Dose (Gy(RBE))
80.42 ± 0.27
80.24 ± 0.43
D99 (%)
100.91 ± 0.59
100.36 ± 0.76
PTV
Mean Dose (Gy (RBE))
80.37 ± 0.11
80.24 ± 0.23
D98 (%)
98.50 ± 1.43
97.99 ± 1.41
V95 (%)
99.62 ± 0.44
99.47 ± 0.61
HI
0.02 ± 0.01
0.03 ± 0.02
Rectum
Mean Dose (Gy(RBE))
15.76 ± 4.79
17.97 ± 7.21
V30 (%)
21.71 ± 6.68
24.83 ± 10.24
V50 (%)
14.53 ± 5.08
18.22 ± 8.08
V70 (%)
7.12 ± 3.50
10.08 ± 5.70
V75 (cc)
5.83 ± 4.21
9.42 ± 7.09
V79.2 (cc)
2.25 ± 2.50
4.54 ± 4.41
V80 (cc)
1.10 ± 1.54
2.30 ± 2.90
Bladder
Mean Dose (Gy(RBE))
24.19 ± 10.91
25.23 ± 11.16
V30 (%)
34.94 ± 18.43
37.76 ± 20.37
V50 (%)
18.34 ± 7.87
19.91 ± 8.23
V70 (%)
9.52 ± 4.21
11.90 ± 4.70
V75 (cc)
20.49 ± 12.07
28.45 ± 16.71
V79.2 (cc)
10.20 ± 7.86
16.04 ± 10.31
V80 (cc)
6.44 ± 6.68
8.76 ± 6.44
Femoral
Mean Dose (Gy(RBE))
18.59 ± 3.25
31.43 ± 1.52
Abbreviations: CTV = clinical target volume; PTV = planning target volume; IMPT = intensity modulated proton therapy
plan; USPT = uniform scanning proton therapy; V95 of PTV = relative volume of the PTV receiving x% of the prescription dose;
Vxfor the rectum and bladder = volume (in % or cc) of the structure receiving x Gy (RBE); DX= dose at x% (relative volume) of
the PTV; HI = homogeneity index
Figure 2: Rectal and bladder volume (in cc) receiving at least 70, 75, 79.2, and 80 Gy (RBE) (V70, V75, V79.2, and V80,
respectively) in five prostate cancer cases with a unilateral metallic hip prosthesis.
Rana et al.:Proton therapy planning for prostate cancer patients with metallic hip replacements
5Volume 1, Issue 1, 2015 Journal of Proton Therapy
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© Rana. Published by EJourPub.
3. Results
Table 1 provides the dosimetric results in the IMPT and
USPT plans. The results are averaged over five analyzed
cases. Figure 2 shows the rectal and bladder volume (cc)
receiving 75, 79.2, and 80 Gy(RBE) in each case analyzed
in this study.
3.1 Target volume
The mean CTV doses in the IMPT (79.5 Gy (RBE)) and
USPT (79.5 Gy (RBE)) plans were comparable. The mean
PTV doses in the IMPT and USPT were also almost
identical (80.4 Gy (RBE) vs. 80.3 Gy (RBE)). Dose
homogeneity was found to be similar in the IMPT (HI =
0.02) and USPT (HI = 0.03) plans. Both the IMPT and USPT
plans met coverage goals for the CTV (D99 > 98%) and PTV
(D98 > 95%).
3.2 OARs
3.2.1 Low-dose region
IMPT plans produced slightly smaller volumes of the
bladder being irradiated to the low dose (V30 ) when
compared to the USPT plans (34.9% vs. 37.8%). Similarly,
the rectal volume exposed to 30 Gy (RBE) was smaller in
the IMPT plans (21.7%) when compared to the USPT plans
(24.8%).
3.2.2 Medium-dose region
The V50 evaluation shows that the IMPT plans produced
lower values when compared to the USPT plans for both
the rectum (14.5% vs. 18.2%) and bladder (18.3% vs.
19.9%).
3.2.3 High-dose region
IMPT plans were better at reducing the bladder and rectal
volume exposed to higher-dose (V70, V75 , V79.2, and V80)
when compared to the USPT plans. For example, the rectal
V70 was lower in the IMPT plans (7.12%) when compared
to the one in the USPT plans (10.1%). The rectal V 80 in the
USPT plans (2.39 cc) was almost twice than the one in the
IMPT plans (1.10 cc).
3.2.4 Mean dose
The mean dose to the bladder and rectum were slightly
lower in the IMPT plans (24.2 Gy (RBE) and 15.8 Gy (RBE),
respectively) than in the USPT plans (25.2. Gy (RBE) and
18.0 Gy (RBE), respectively). The mean femoral head dose
was also found to be lower in the IMPT plans (18.6 Gy
(RBE) vs. 31.4 Gy (RBE))
4. Discussion
In this study, we assessed the dosimetric impact of proton
therapy planning techniques for the prostate cancer
patients with metallic hip replacements. Both the IMPT
and USPT techniques met the target coverage goals. Dose
homogeneity within the PTV as well as the mean dose to
the CTV and PTV were comparable too. Dosimetric results
of the OARs, however, demonstrated that the IMPT is
slightly better than the USPT in sparing the rectum and
bladder in the low-, medium-, and high-dose regions while
maintaining excellent target coverage. For the IMPT
planning, we applied dose-volume constraints to the OARs
during plan optimization process, which helped in
reducing dose to the rectum and bladder in the IMPT
plans.
Cuaron et al.12 reported the clinical results of the prostate
cases, which were treated using USPT. The findings of
Cuaron et al.12 are encouraging in the sense that the
patients treated with the anterior-oblique beams had no
biochemical or distant failures with acceptable low
toxicities. However, the reported median follow-up was
6.4 months12, and further follow-up will be crucial in
determining long term outcome and toxicities. Several
studies have correlated the dosimetric results to the rectal
toxicities. For example, Michalski et al.17 reported that the
small rectal volumes receiving a high dose (e.g. V 70) were
the most critical predictors of late toxicity. Cozzarini et
al.18 and Fiorino et al.19 have reported the late rectal
bleeding associated with the lower doses. The rectal dose-
volume results from our study demonstrated that the
IMPT is capable of further decreasing the rectal dose when
compared to the USPT, thus the IMPT has a potential of
further reducing the rectal toxicities. For the bladder, the
QUANTEC20 recommends V70 < 35%, and both the
techniques (IMPT and USPT) were able to meet the
criteria.
In this study, the PTV in each case was expanded by 5 mm
from the CTV. Although we used a range uncertainty in the
beam direction, we were unable to generate a beam-
specific PTV margin based on the range uncertainty
calculations, especially for the anterior-oblique beams.
Current literature21 shows no common consensus on the
use of range uncertainty, which may depend on the
treatment delivery unit, treatment planning system,
patient anatomy, and tumor location. A review article by
Paganetti21 reported that the Massachusetts General
Hospital uses the range uncertainty 3.5% + 1 mm, whereas
the MD Anderson Proton Therapy Center and Loma Linda
University Medical Center use range uncertainty 3.5% + 3
mm. These range uncertainties are different from the
recommended range uncertainty at our center (2.5% + 2
mm). The consensus on range uncertainties for different
disease sites is yet to be reached among different proton
centers.
Treatment plans in this study were generated in an ideal
scenario assuming that (i) the patient anatomy will remain
identical to the CT simulation during the entire course of
the treatment, (ii) bladder filling does not vary daily, and
(iii) daily setup variations are minimal. Ho wever, in a more
Rana et al.:Proton therapy planning for prostate cancer patients with metallic hip replacements
6Volume 1, Issue 1, 2015 Journal of Proton Therapy
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© Rana. Published by EJourPub.
realistic situation, the prostate cancer treatments are
susceptible to inter- and intra-fraction motions. The daily
change in the bladder filling can also affect the penetration
depth of anterior-oblique beams. Figure 3 shows the axial
CT slice of an obese case with a substantial abdominal
adipose mass, which can produce a considerable challenge
to the reproducibility of setup in the path of anterior-
oblique beams. The combination of day-to-day variations
in the setup of the soft abdominal tissue and bladder filling
can substantially affect the penetration in tissue for
anterior-oblique beams, and result in a geometric miss of
the target. In the case of IMPT, the misalignment of
inhomogeneous doses from individual beams may result in
target underdose. Since our study is limited by the
retrospective design, the effect of an intra-fraction
prostate motion on the USPT and IMPT prostate plans was
not investigated.
Figure 3: Proton beams arrangement for the prostate
cancer case with a metallic hip prosthesis.
A number of studies22, 23 have recommended to perform
robust plan optimization for the IMPT planning in order to
ensure sufficient target coverage and improved normal
tissue sparing. Several studies have reported that the
dosimetric quality of the IMPT plans is more sensitive to
the treatment setup and delivery uncertainties .13, 22, 23 The
current version of our XiO TPS does not provide robust
optimization feature. Hence, we were unable to evaluate
the dosimetric impact of setup and treatment
uncertainties on the daily I MPT planned dose
distributions. The IMPT plans were generated by
optimizing a lateral field (44 fractions) and two anterior -
oblique fields (each field 22 fractions) together; however,
the daily dose in the IMPT plans include dose
contributions from 2 fields (one lateral and other anterior -
oblique field) only. The main reason to use a schema of 2
fields per day in the IMPT plans was to maintain the same
delivery schema as in the USPT plans. In the next study, we
aim to investigate the dosimetric impact of IMPT
optimization technique and delivery schema on a daily
fractional dose for the prostate cancer plans. Also, the
robustness of the IMPT planning based o n the range
uncertainties and treatment setup variations needs to be
addressed in the future studies. Another limitation of our
work is the limited number of cases presented in this
study. Since the prostate cases with metallic hip
replacements are rare at our institution, it is most likely
that a multi-institutional study will be needed to include a
large number of such cases. Further studies with a large
number of prostate cancer cases with metallic hip
replacements are warranted in order to determine th e
dosimetric advantages of the IMPT plans over the USPT
plans.
5. Conclusion
Based on the preliminary results of five cases presented in
this study, the IMPT plans provided slightly better
dosimetric results compared to the USPT plans, especially
in sparing the rectum and bladder in the low-, medium-,
and high-dose regions, for the treatment of the prostate
cancer in patients with a unilateral metallic hip prosthesis.
Future studies need to address the impact of the setup
uncertainties and intra-fraction prostate motion in the
IMPT planning of the prostate cancer patients with
prosthetic hip replacements.
Conflict of Interest
The authors declare that they have no conflicts of interest.
The authors alone are respo nsible for the content and
writing of the paper.
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