Comparison of Dose Distribution
between Intensity Modulated Radiation Therapy and Dynamic Arc Therapy in and
out-of-Field for Prostate Cancer Treatment
Aymen
Ben Abdennebi, Guillaume Auzac, Jean Chavaudra, Mounir Besbes, Damien Llanas,
Rodrigue Allodji, Yungan Tao, Pierre Blanchard, Attila Veres, Andr¨¦ Bridier,
Dimitri Lefkopoulos, Florent De Vathaire, Ibrahima Diallo
Aymen
Ben Abdennebi, Guillaume Auzac, Jean Chavaudra, Damien Llanas, Yungan Tao,
Pierre Blanchard, Andr¨¦ Bridier, Dimitri Lefkopoulos, Florent De Vathaire, Institut Gustave
Roussy, Villejuif, F-94805, France
Aymen
Ben Abdennebi, Damien Llanas, Rodrigue Allodji, Florent De Vathaire, Ibrahima
Diallo, Inserm, CESP -
U1018, Radiation Epidemiology Team, F 94807, Villejuif, France
Aymen
Ben Abdennebi, Damien Llanas, Rodrigue Allodji, Florent De Vathaire, Ibrahima
Diallo, Univ. Paris XI,
Villejuif, F-94800, France
Attila
Veres, Equal-Estro Laboratory, Villejuif, F-94805, France
Aymen
Ben Abdennebi, Mounir Besbes, Univ. de Tunis El Manar Facult¨¦ des Sciences de Tunis,
2092 El Manar Tunis
Mounir
Besbes, Institut
Salah-Azaïz Tunis 1006
Correspondence
to: Ibrahima DIALLO, Cesp-Inserm U1018, Equipe 3,
Epid¨¦miologie des cancers: radio carcinog¨¦n¨¨se et effets iatrog¨¨nes des
traitements. Institut Gustave Roussy 114, rue EdouardVaillant, F94805 Villejuif
Cedex. Ibrahim.DIALLO@gustaveroussy.fr
Telephone:
+33 (1) 42-11-49-18 Fax: +33 (1)
42-11-53-15
Received: July 26, 2013
Revised: September 28, 2013
Accepted: September 30, 2013
Published
online: October 18, 2013
ABSTRACT
AIM: The aim of this study is to compare intensity modulated radiation therapy
(IMRT) and dynamic conformal arc therapy (DAT) for prostate cancer treatments.
METHODS: Doses received by in-field and out-of-field organs were estimated for both
techniques. We have selected ten patients with prostate cancer and we simulated
their treatment using IMRT and DAT. A 6-beams (6MV) ballistic was used for the
IMRT treatment, whereas a 4-arc (6MV) ballistic was used for the DAT. Dose
volume histograms (DVHs) were computed. For both techniques, Planning Target
Volume (PTV), Planning Organ at Risk Volume (PRV) and Remaining Volume at Risk
(RVR), as well as estimates of the dose out-of-field for thirteen anatomical
sites were analyzed and compared. The out-of-field dose evaluation was
performed using experimental data from previous work.
RESULTS: The mean absolute RVR volume, included between 2-45 Gy for IMRT, was about
1500 cm3 larger than with DAT. On the other hand, IMRT significantly
increased the irradiated volume of the rectum wall in the dose range 2 to 60 Gy
and also significantly increased the irradiated volume of the bladder wall.
However, IMRT significantly reduced the dose to the femoral heads, as compared
to the DAT. For both techniques, the dose to the PTV remained similar. For the
thirteen out-of-fields anatomical sites evaluated, IMRT provided doses about 5%
higher than DAT.
CONCLUSIONS: DAT improves the dosimetric parameters of the
prostate cancer treatment by reducing the doses not only to the PRV¡¯s but also
to the RVR while keeping the same PTV coverage.
© 2013 ACT. All rights reserved.
Key words: Intensity
Modulated Radiation Therapy (IMRT); Dynamic Arc therapy (DAT); Remaining Volume
at Risk (RVR); Dose out-of-field; Planning Organ at Risk Volume (PRV)
Abdennebi AB,
Auzac G, Chavaudra J, Besbes M, Llanas D, Allodji R, Tao YG, Blanchard P, Veres
A, Bridier A, Lefkopoulos D, De Vathaire F, Diallo I. Comparison of Dose
Distribution between Intensity Modulated Radiation Therapy and Dynamic Arc
Therapy in and out-of-Field for Prostate Cancer Treatment. Journal of Tumor 2013;
1(6): 43-49 Available from: URL: http://www.ghrnet.org/index.php/JT/article/view/519
INTRODUCTION
Report 83 from the
International Commission on Radiation Units and Measurements (ICRU)[1],
introduced the concept of Remaining Volume at Risk (RVR), allowing a convenient
global risk assessment of the dose delivered to a given patient. Today
commercial treatment planning systems¡¯ (TPS) accuracy has been improved to
calculate the dose to the Planning Target Volume (PTV) and its immediate
vicinity, but do not allow to suitably calculate as well the peripheral dose
outside the irradiated volume. To assess the risk of second cancers[2],
the whole patient volume must be considered: the PTV, the Planning Organs at
Risk Volumes (PRV) and the RVR. Prostate cancer is a frequent tumor for which
radiotherapy is a major treatment. The ballistic of external beam radiotherapy
for prostate cancer has changed dramatically during the last decades from
two-dimensional (2D) to three-dimensional (3D) conformal techniques, and then
to intensity modulated radiation therapy (IMRT), Volumetric Modulated Arc
Therapy (VMAT) and dynamic conformal arc therapy (DAT).
Studies based on the results
of the epidemiological survival suggested an increase in the development of a
secondary cancer in the bladder and rectum after radiotherapy for prostate
cancer[3-5] and the role of hyper/hypo-fractionation is still
discussed[6,7]. Other recent studies[8,9] have shown that
stereotactic techniques for prostate cancer increase patient comfort and
improve quality of life. IMRT has been shown to significantly increase the
pelvic volume receiving doses under the 15 Gy isodose, but to reduce the
irradiated volume of the rectum in the dose range of 5 to 40 Gy and also to
significantly reduce the irradiated volume of bladder and femoral heads[10].
The dose coverage in the PTV remains similar for all three RT techniques. The
objective of the current study is to compare IMRT and DAT radiotherapy
techniques for prostate cancer treatment performed at the Institut Gustave
Roussy. We have evaluated the dose distribution in the PTV and PRV¡¯s in the
immediate and distant vicinity of the PTV, as well as the delivered dose to the
RVR for both techniques to assess risk factors for secondary cancers.
MATERIALS AND METHODS
Patients¡¯ selection
The study focused on
data from ten patients treated by RT at the Institut Gustave Roussy (IGR)
between 2012 and 2013. The patients¡¯ selection scheme was such as to include 10
individuals for whom the type of RT was IMRT or DAT. Anatomical characteristics
of the patients were derived from clinical parameters, namely age, size and
body mass index.
The BMI was calculated by
using the following formula:
BMI (kg/m2)=
More details on anatomical
characteristics of the population are presented in table 1.
Computed tomography (CT) scan technique
Patient data for
treatment planning were acquired using the same CT-scan (Siemens sensation
40 open). A CT-scan was performed in the treatment position exploring about
29 cm of the pelvic region. In total, 97 slices were recorded with a thickness
of 3 mm.
Volume delineation
Target volumes were
defined as the clinical target volume CTV-1 prostate and seminal vesicles, and
CTV-2 prostate only. According to the current local policy for daily IGRT
treatment using fiducial markers, PTVs are defined with a margin of 5 mm around
the CTV in all directions. For prostate radiotherapy PRV¡¯s are usually rectum,
rectal wall, bladder, bladder wall and femoral heads. These structures were
delineated by the same physician to maintain consistency in the definition of
volume.
The mean volume of PTV-1 was
150 cm3 (ranging from 90 cm3 to 245 cm3) and
the mean volume of PTV-2 was 130 cm3 (ranging from 74 cm3
to 210 cm3). The mean volumes of the rectum, bladder and the femoral
heads for the ten patients, as calculated by the TPS, were 70 cm3
(ranging from 43 cm3 to 114 cm3), 275 cm3
(ranging from 172 cm3 to 330 cm3), and 160 cm3
(ranging from 132 cm3 to 190 cm3), respectively.
Dose prescription
Ten patients with
localized prostate cancer and different PTV-1 and PTV-2 volumes were included
in this study. For each patient, a clinical IMRT and a clinical DAT have been
planned, considering a total dose of 78 Gy to the prostate (2 Gy per fraction).
Total delivered dose represents the cumulated dose to the prostate for the two
PTVs irradiation. The first treatment phase aims at delivering a 46 Gy dose to
the prostate and seminal vesicles. In the second phase, a 32 Gy dose is
delivered to the prostate only.
TPS dose calculation
In the present
study, dose distributions for the PTV, RVR and PRV¡¯s were calculated with the
treatment planning system Konrad (4.1 version, Siemens) for IMRT (Step and
Shoot) treatment, while arc therapy treatment plan calculations were performed
using iPlan TPS (iPlan Cranial 3.0 software, BrainLab, Germany). Both TPS are
based on the Pencil beam algorithm for dose calculation and have been compared
on basic data. DAT ballistic is composed of four coplanar 6 MV dynamic arc beams:
PTV-1 is treated by 2 arc beams from 20 to 150 degrees and from 210 to 340
degrees approximately (these angulations are adapted according to patient
anatomy). The same angulations of the two previous arc beams are used to
irradiate the PTV-2. IMRT ballistic is composed of six coplanar 6 MV beams with
gantry angles of 25¡ã, 70¡ã, 135¡ã, 225¡ã, 290¡ã and 335¡ã.
According to ICRU report 83,
the PTV dose was assessed with recommended parameters such as median dose (D50%),
which represents the prescribed dose, near maximum dose (D2%) and
near minimum dose (D98%). Note that VDGy is the percentage of organ
volume exceeding D Gy and Dx% is the minimum dose to x% of the
organ¡¯s volume. In accordance with the ICRU 83 guidelines, the homogeneity
index (HI) was calculated by using the following equation: HI=
. The
analysis of RVR and PRV¡¯s was made according to ICRU 83 recommendation as well. The IMRT and
DAT results of all analyses were based on the data of the mean dose volume
histograms of the patients¡¯ selection.
Calculation limits of the TPS and estimated dose
out-of-field
In order to verify
the calculation limits of the TPS and dose estimates, dose measurements were
performed on the Novalis Tx™ linear accelerator (Varian Medical Systems,
Palo Alto, CA, USA). 6 MV photon beams were used for the tests. The doses
were measured with thermoluminescent dosimeters type TLD-700 (Harshaw Chemical
Company, Cleveland, OH). The dosimeters were read on a PCL-3 (FIMEL, Velizy,
France) automated reader. A water tank of 100 cm ¡Á 50 cm ¡Á 30 cm dimensions was
used for dose to water measurements. The tank was filled with water up to 20
cm. A special holder was designed for the TLD capsules, allowing their
positioning at different depths, outside the irradiation field. This support
facilitates a reproducible positioning of the capsules. The distance between
the source and water surface (SSD) was set to 100 cm. Measurements were
performed using four different field sizes: 5 cm ¡Á 5 cm, 10 cm ¡Á 10 cm, 15 cm ¡Á 15 cm and 20 cm ¡Á 20 cm. The measurement points were spaced with a constant
step of 5 cm, up to 30 cm from the central axis of the beam. From this
position, the measurement points were separated with a 10 cm step, up to 70 cm
from the central axis of the beam, at depth of 10 cm in the water tank. All
TLDs were prepared and read by Equal-Estro Laboratory (Estro-Equal, Villejuif,
France), which is a European reference in the use and analysis of TLDs[11-13].
For each irradiation technique, dose estimated to the organs distant from PTV
for the patients¡¯ selection was performed using experimental data from previous
work[2,10,14,15].
Statistics
Friedman test was
used to compare DVHs of the two techniques at each dose level. Statistical
analyses were performed using SPSS 17.0 for Windows[16].
RESULTS
Dose volume calculations by the TPS for
RVR
Figure 1 presents
the results of the dose distribution in RVR. This distribution shows that DAT
reduces the dose in the RVR volume as compared to the IMRT. On average, the
indicator V10Gy is 35% for IMRT and 29% for DAT. The volume covered
by isodose 15 Gy reaches 30% and 22% for IMRT and DAT respectively. The volume
covered by various isodose surfaces below 30 Gy with the IMRT and DAT is 16%
and 8% respectively. Similarly, the comparison between the two radiotherapy
techniques shows that the 5 Gy isodose covers more volume of the RVR with the
IMRT than with the DAT, since the percent of volume covered by this isodose is
53% for IMRT versus 43% for DAT. Figure 2 shows that IMRT irradiates a larger
volume of the RVR with lower doses than DAT. The mean absolute RVR volume
included between 2-45 Gy for the IMRT is about 1500 cm3 larger than
when using DAT. In this dose range, the mean relative volume increase with
IMRT, as compared with DAT, is 32%. The difference between the two techniques
is statistically significant, as shown by the Friedman statistical test.
Dose volume calculations with the TPS
for PRV¡¯s
Figure 3 presents
the mean dose volume histogram results for PRV¡¯s of the patients¡¯ selection and
shows that, for rectum wall, DAT significantly reduces the volume of irradiated
rectum wall receiving 2 to 60 Gy compared with the IMRT (p-values 0.02).
DVH of the rectal wall shows that the volume receiving at least 60 Gy increases
with IMRT as compared with DAT by 27%. For the bladder wall DAT significantly
reduces the volume of irradiated bladder wall, as compared to the IMRT (p-values
0.02): the mean relative volume increases with IMRT, as compared with DAT, by
55%. However, the IMRT significantly reduces the irradiated volume of femoral
heads, compared to the DAT (p-values 0.02). For PTVs, no significant difference
was observed in the doses delivered to the 98%, 50% and 2% of the PTVs volume
between the two techniques of irradiation. For PTV-1 the homogeneity indexes
for IMRT and DAT were 0.30 and 0.34 respectively. For PTV-2 the homogeneity
indexes for IMRT and DAT were 0.07 and 0.05 respectively.
Calculation limits of the TPS and
estimated dose out-of-field
Figure 4 compares
the dose profiles obtained experimentally by TLD measurements and those from
TPS calculations, for a 10 cm¡Á10 cm field size at a depth of 10 cm in water. The TLD
measurements were performed up to 70 cm from the central axis of the beam. For the 10 cm¡Á10 cm field size, for distances between 5
cm and 10 cm from the central axis, we observed that the calculations of both
of the TPS overestimate the dose outside the field with an average of 1.5%.
This overestimation increases with distance and reaches 2% at 13 cm from the central
axis. Table 2 shows the magnitudes of the estimated doses to a selection of
thirteen anatomical sites near and distant to the field edge, processing with
IMRT and DAT for the patients¡¯ selection. The analysis of these results shows
that the estimated doses with IMRT are slightly higher than with DAT. In a
region distant from the fields¡¯ edge, the ratio between the estimated mean
doses for both techniques
(DIMRT/DDAT) varies between 1.01 and 1.10. The maximum ratio was estimated for the
right eye located at a distance of approximately 68 cm from the PTV. The
minimum ratio was estimated for the spleen located at a distance of
approximately 33 cm from the PTV. The mean of estimated doses ratio (DIMRT/DDAT) between IMRT and DAT is almost equal to 1.05 for all PRV's at a
distance from the PTV.
DISCUSSION
The present work
compares IMRT and DAT for prostate cancer treatments. Doses received by
in-field and out-of-field organs were assessed for both techniques. Regarding
the ten selected patients, DVHs were computed for PRV¡¯s and RVR for both
techniques, and the dose delivered to thirteen selected out-of-field anatomical
sites were analyzed and compared.
Our study shows that for the
same coverage of PTV, and for satisfactory dose constraints conformance to the
PRV¡¯s, the IMRT technique increases the dose to the rectum and bladder as well
as for RVR and out-of-field organs. In the
dose range from 2 to 45 Gy, the mean relative volume is increased with the IMRT
by 35%, compared to the DAT technique and for the thirteen out-of-fields
anatomical sites evaluated, the ratio between the estimated doses for both
techniques varied between 1.01 to 1.10, DAT providing lower doses. These
results are consistent with data of previous publications comparing dose
distribution between IMRT and DAT for prostate cancer[17]. Indeed
Metwaly et al[17] have shown that DAT significantly reduces
the irradiated volume of the rectum and bladder, compared to IMRT for the same
coverage of PTV and a recent work[18] has shown that DAT provided
dose distributions at almost the same level of conformity and homogeneity as
IMRT, with treatment times shorter by about 45%.
We focused on the analysis
of the dose received by PRV's, as well as low-dose irradiated volume because of
the long-term risk of secondary cancers. Regarding clinical consequences for
second malignant neoplasms after radiotherapy for prostate cancer, some
clinical data suggest that irradiated prostate cancer patients have an
increased risk of radiation induced malignancy. Brenner et al[19]
showed that the risk of a secondary malignancy of any type was significantly
greater after radiotherapy than after surgery, by about 6%, although the
majority of clinical evidence is based on older RT techniques[20,21].
For recent techniques, such as IMRT and DAT, clinical studies examining second
primary cancers often have relatively low patient numbers and short durations
of follow up[4,5,22,23].
In the present work,
concerning PRV¡¯s, compared to the DAT, the mean dose in the bladder and the
rectum increases with IMRT by about 10 % and 7 % respectively. Currently, the
literature regarding the risk of second cancer after DAT technique is
dramatically rare due to the novelty of the technique, the short experience in
clinics and the short follow-up of the patients treated by DAT. However, many
long-term studies can be found, discussing effects of IMRT. For example,
according to Patil et al, the incidence of radiation-induced
malignancies after IMRT was 0.10 and 3.42 per 10,000 person-years for the
bladder and rectum respectively[24]. Furthermore, Brenner et al[19]
showed in their study that the risk of a second solid tumor dramatically
increased especially to the bladder and rectum at 10 years or more after
diagnosis.
Regarding femoral heads, the
mean dose increases with DAT by about 15 %, compared to the IMRT. A study
showed that the femoral heads fractures are very rare event (<0.5%) and
stated on the difficulty of establishing a dose-response relationship and
define recommendations[25]. Emami et al[26] showed
a risk of complications lower than 5% concerning femoral heads. Bedford et
al[27] recommended V52Gy lower than 5%. In our study
the two techniques respected these recommendations.
In our study, for the
thirteen out-of-fields anatomical sites evaluated, the IMRT provided doses of
about 5% higher than DAT. However, at present, there are limited data in the
literature regarding out-of-field dose, especially for modern radiation therapy. In the
case of prostate cancer, in this context, Tao et al[10]
estimated the out-of-field doses for thyroid organ with the IMRT using photon
energies around 20 MV. Our results were similar, with a mean deviation of 7%.
In the same way Kry et al showed that use of lower photon energies could
minimize the out-of-field doses obtained by the IMRT (step-and-shoot)[28].
Our dose estimation method matches the results of the previous out of field
dosimetry studies within a difference of 3% to 7% in accordance to the distance
from the field edge[29].
It is important to estimate
dose distribution out-of-field to evaluate the effect of low doses on normal
tissues, especially for long-term effects such as second primary cancers. For
example, to assess the likelihood of risk of second cancer in out-of-field
organs, Bednarz et al calculated the lifetime attributable risk (LAR), which is
defined as the probability that an irradiated individual will develop a cancer
during their lifetime[30]. These results showed for the class of age
of patients included in this study that the IMRT technique LAR values as a
function of exposure organ and age were 1.6¡Á10-9 for thyroid,
1.89¡Á10-6 for lung, 2.45¡Á10-6 for spleen, 3.92¡Á10-7
for liver, 2.39¡Á10-6 for pancreas and 3.31¡Á10-6 for
kidneys, which is reassuring.
In out-of-field regions,
according to Murray et al[31] the increased volume of normal
tissue receiving low doses with IMRT has also been thought to contribute to
increase radiation induced second primary cancers risk in normal tissues.
Therefore in the long-term, patients who are treated with DAT are likely to
develop less secondary cancers than those treated with the IMRT technique. That
is why the DAT technique for prostate cancer may increase the benefit risk ratio
compared to IMRT.
CONCLUSION
DAT improves
dosimetric parameters for treatment of the prostate cancer although PTV
coverage is kept the same compared to the IMRT. This is done by reducing the
dose not only to the organs at risk but also to the RVR, especially between 2
and 45 Gy. Furthermore, through this technique, the organs out of the field
receive lower doses. However, the DAT increases the dose to the femoral heads
and high doses (>60 Gy) to the rectum. Indeed, modern techniques are well
suited for the radiotherapy treatment of the prostate cancer; nonetheless,
regarding to the low dose distributions, the assessment of the dose received at
distance from the treated volume and the volume of RVR should be evaluated to
investigate the possible correlation with second cancers. Moreover, more
long-term follow-up, with higher number of patients, will be needed to assess
the effects of DAT technique.
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Peer reviewers: Nihal
Mohamed, Department of Urology, Mount Sinai Medical Center, 1 Gustave Levy
Place, Box 1272, New York, NY 10029, the United States; Guila Delouya,
CHUM-Hôpital Notre-Dame, D¨¦partement de Radio-Oncologie, 1560 Sherbrooke est,
Montr¨¦al, Quenec, H2L 4M1, Canada; H¨¦ctor R Contreras, Program of Physiology
and Biophysics, Institute of Biomedical Sciences, Faculty of Medicine,
University of Chile, Av Independencia 1027, Santiago, Chile.
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