Cancer/Radiothrapie 18 (2014) 745752

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Original article

Intensity-modulated whole pelvic radiotherapy provides effective

dosimetric outcomes for cervical cancer treatment with lower
toxicities
La dosimtrie de la radiothrapie conformationnelle avec modulation dintensit
pour le cancer du col utrin permet une diminution de la toxicit
Y. Lv , F. Wang , L. Yang , G. Sun
Department of Radiotherapy, The First Afliated Hospital of Anhui Medical University, 281, Jixi Road, Hefei, Anhui 230022, Peoples Republic of China

a r t i c l e

i n f o

Article history:
Received 19 February 2014
Received in revised form 24 July 2014
Accepted 5 August 2014
Keywords:
Cervical cancer
Intensity-modulated radiotherapy (IMRT)
Bladder lling

a b s t r a c t
Purpose. To compare the efcacy of intensity-modulated radiotherapy, three-dimensional conformal
radiotherapy, and conventional radiotherapy for cervical cancer treatment.
Materials and methods. Whole pelvis intensity-modulated radiotherapy, three-dimensional conformal
radiotherapy, and conventional radiotherapy plans were designed for 16 patients with stage IIB cervical
cancer, each using the prescribed dose of 50.4 Gy/28 fractions. Dosevolume histograms of the target
volume and organs at risk were evaluated.
Results. Compared to the 3D conformal and conventional radiotherapy plans, the intensity-modulated
radiotherapy plan demonstrated superior conformal treatment. The mean planning target volume dose
of all three plans reached the target effective therapeutic dose. The planning target volume dose of the
intensity-modulated radiotherapy plan was signicantly higher than that of either the three-dimensional
conformal radiotherapy or conventional radiotherapy plan (P < 0.05). When more than 30 Gy was administered in intensity-modulated radiotherapy, organs at risk including the small intestine, rectum, bladder,
and bone marrow received a signicantly reduced volume of radiation. In comparison of the average planning target volume doses, signicant volume reductions in irradiation of organs at risk were obtained
with full bladders.
Conclusions. An intensity-modulated radiotherapy plan with appropriate margins encompassing the
primary tumour and potential microscopic pelvic disease reduces the dose to organs at risk without
compromising target coverage. Intensity-modulated radiotherapy is an appropriate denitive treatment
for patients with cervical cancer.
2014 Published by Elsevier Masson SAS on behalf of the Socit franaise de radiothrapie
oncologique (SFRO).

r s u m
Mots cls :
Cancer du col utrin
Radiothrapie conformationnelle avec
modulation dintensit
Remplissage vsical

Objectif de ltude. Comparer lefcacit de la radiothrapie conformationnelle avec modulation

dintensit, de la radiothrapie conformationnelle tridimensionnelle et de la radiothrapie classique dans
le cancer du col utrin.
Matriels et mthodes. Une radiothrapie pelvienne de 50,4 Gy en 28 fractions a t planie pour
16 patientes atteintes dun cancer du col utrin de stade IIB avec chacune des trois techniques. Les rsultats
de la dosimtrie ont t compars avec les histogrammes dosevolume du volume cible et des organes
risque.

Corresponding author.
E-mail address: sunguoping@ahmu.edu.cn (G. Sun).
http://dx.doi.org/10.1016/j.canrad.2014.08.005
1278-3218/ 2014 Published by Elsevier Masson SAS on behalf of the Socit franaise de radiothrapie oncologique (SFRO).

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Y. Lv et al. / Cancer/Radiothrapie 18 (2014) 745752

Rsultats. La radiothrapie conformationnelle avec modulation dintensit a donn les meilleurs rsultats, la dose dlivre dans le volume cible prvisionnel tant suprieure celle atteinte avec les deux
autres techniques (p < 0,05). Ds que la dose dpassait 30 Gy, la dose dlivre par radiothrapie conformationnelle avec modulation dintensit dans lintestin grle, le rectum, la vessie et la moelle osseuse tait
signicativement rduite. Le remplissage vsical aboutissait aussi une diminution de la dose dlivre
dans les organes risque.
Conclusion. Une radiothrapie conformationnelle avec modulation dintensit avec des marges
adquates de la tumeur primaire et des extensions potentielles microscopiques permet une diminution
de la dose dlivre dans les organes risque sans compromettre la couverture de la cible et savre un
traitement appropri du cancer du col utrin.
2014 Publie par Elsevier Masson SAS pour la Socit franaise de radiothrapie oncologique (SFRO).

1. Introduction
Cervical cancer is the third most commonly diagnosed cancer
and was the fourth leading cause of cancer deaths among women
worldwide in 2008 [1]. The majority of patients diagnosed with
cervical cancer received radiation as a treatment component. The
pathological and anatomic characteristics of cervical cancer make it
a good target for radiotherapy. First, squamous cell carcinoma and
adenocarcinoma are sensitive to radiotherapy. Second, tumours are
generally conned to the pelvis during development. Third, the target dose for the tumour can be reached with limited irradiation to
the surrounding organs. Finally, the natural cavity of the vagina
makes it accessible for brachytherapy.
Conventional radiotherapy for cervical cancer is composed
of brachytherapy and external beam radiotherapy. Although
brachytherapy boosts the local dose to the tumour, external beam
radiotherapy aims to reduce the size of the gross tumour and
the presence of microscopic disease in the pelvic area. External
beam radiotherapy targets include primary tumours, subclinical
lesions (parametrical uterine tissue, and vagina), and regional
lymph nodes (common iliac, external and internal iliac, obturator, and presacral nodes) [2]. Because the cervix is localized in
the pelvic centre and surrounded by the bladder, rectum, small
intestine, and vagina, it is difcult to protect these organs at
risk from irradiation using conventional radiotherapy. Grade 3/4
acute radiation proctitis was observed in up to 16.7% of patients
and grade 3/4 acute cystitis occurs in up to 18.3% of patients
receiving conventional radiotherapy [3]. Multicentre data suggest
that complications, including radiation proctitis and cystitis, occur
in 5 to 30% of cervical cancer patients after radiotherapy [4].
Three-dimensional conformal radiation therapy was subsequently
developed to avoid organs at risk irradiation. Conventional 3D conformal radiotherapy is composed of a set of xed radiation beams,
which are shaped using the projection of the target volume and
normally have uniform intensity across the eld. When appropriate, conventional elds can be modied using simple devices,
such as compensating lters or wedges. With advances in new
technologies, including computed tomography (CT), magnetic resonance imaging (MRI), and 3D planning software, radiotherapy
techniques have signicantly improved. More recently, intensitymodulated radiation therapy has been proposed to treat cervical
cancer. The intensity of each beam can be purposely altered
by the summation of hundreds of beamlets in order to satisfy
clinical target goals and normal tissue doses. In addition, the
uence can be adjusted within individual beamlets, the sum of
which represents the entire apertures contribution [5]. Therefore, when individual contributions from each beam are summed,
complex 3D dose clouds can be generated with concave shapes
and steep dose gradients. This results in highly conformal treatment, where the high dose regions of the plan are conned to
the target only, and doses to organs at risk can be minimized.
Intensity-modulated radiotherapy has been shown to reduce

normal tissue irradiation [6] and has been associated with reduced
acute toxicity compared to conventional 3D conformal radiotherapy [611].
One complication in utilizing intensity-modulated radiotherapy for cervical cancers is the interfractional position change of
organs near the cervix. Utilizing intensity-modulated radiotherapy
in mobile organs not only results in underdose to the target but
also presents a high risk of overdose to nearby organs because of
the nature of the steep dose gradient. In general, motion of the
organs is attributable to variations in bladder lling and rectal lling, and the majority of motion occurs in the anteriorposterior
and superiorinferior directions, with mean interfraction movements of 47 mm [1214]. However, it is worth noting that these
are the average distances, and in some instances the distance has
been reported to be as large as 2.8 cm [14]. To avoid complications
of intensity-modulated radiotherapy in cervical cancer patients,
effective control of the clinical target volume position and bladder
lling status is critical [2,15].
With the aim of addressing the inconsistencies that have arisen
based on previous studies, we conducted a dosimetric study to compare conventional radiotherapy, 3D conformal radiotherapy, and
intensity-modulated radiotherapy plans. We performed quantitative dosimetric analyses of irradiation on the tumour target and
organs at risk, including the bladder, rectum, small intestine, and
pelvic bone marrow. In addition, we compared the dosimetric characteristics of targets and organs at risk during different bladder
states.
2. Materials and methods
2.1. Patient selection
Approval for this study was obtained from the local ethics
review board and all patients provided informed consent for study.
Sixteen patients with stage IIB (FIGO staging) cervical carcinoma
that presented to our department from July 2011 to March 2013
were included in the study. All patients were diagnosed by biopsy
with cervical squamous cell carcinoma and were untreated before
commencing the study. The average age of patients was 52 years
(range: 3879 years). They received written and verbal advice on
bladder lling prior to their planning appointment. Patients were
advised to void the bladder and then drink 500 ml of water within
the next 15 minutes. After 30 minutes, proceed with the planned
radiotherapy. This process should be repeated daily prior to each
treatment.
2.2. Methods and protocols
2.2.1. Position
All patients were immobilized using MED-TEC vacuum body
bags (Klarity Medical, Guangzhou, China) while they were in a
supine position with their hands clasped over their head and their

Y. Lv et al. / Cancer/Radiothrapie 18 (2014) 745752

legs closed naturally. Surface markers were determined using a

stereotactic frame.
2.2.2. Imaging
Prior to CT scan, a Foley catheter was inserted into the patients
bladder and connected to a drainage bag. The bladder was emptied and then approximately 200250 ml saline was relled to the
maximal extent tolerated. A swab soaked with 15% diatrizoate was
placed at the oricium vaginae to aid the delineation. The contrast
agent iohexol (90 ml) was intravenously injected through a highpressure syringe (brand), with an injection rate of 3.0 ml/s. The
rst enhanced pelvic CT scan with a full bladder was performed
from the top edge of the L3 vertebral body to the bottom edge of
the ischial tuberosity, with a thickness of 5 mm. After scanning,
the bladder was emptied and immediately, a second scan with an
empty bladder was acquired under the same conditions. The full
and empty bladder scans were transmitted and registered in the
Topslane Venus treatment planning system (VENUS 5014 software,
Tuoneng Co., Shanghai, China).
2.2.3. Target and organs at risk delineation
Clinical target volume and organs at risk were contoured on
the full and empty bladder scans. The pelvic clinical target volume
contouring guidelines for radiation therapy issued by Radiation
Therapy Oncology Group (RTOG) in combination with 3D distribution patterns of clinical metastatic pelvic lymph nodes were used
as a guide for contouring [1618]. Contouring of target and normal
tissues (bladder, rectum, and small bowel) was performed in each
patient on individual axial CT slices on Eclipse TPS, according to
International Commission on Radiation Units and Measurements
(ICRU) report 50. The same contours were used for both treatment
techniques. The clinical target volume started from the common
iliac artery bifurcation and was composed of the primary tumour,
uterus, adnexaes, part of vagina (the upper half of vagina when no
tumour involvement was observed in the vagina, or two thirds of
the vagina when the upper half vagina was involved), and pelvic
lymph nodes (common iliac, external iliac, internal iliac, obturator, and presacral). The planning target volume was dened as the
clinical target volume plus a 1.0-cm margin.
2.2.4. Development of the treatment plan
Using the three-dimensional radiation TPS, three radiation
treatment plans were designed for therapy with a full bladder: conventional, 3D conformal, and intensity-modulated radiotherapy
plans. Intensity-modulated radiotherapy plans with same conditions were designed for therapy with an empty bladder.
2.2.4.1. IMRT plans consisted of a seven-eld technique. The prescription dose to the whole pelvis of planning target volume was
50.4 Gy in 28 fractions of 1.8 Gy, with each fraction by 6MV-X-ray.
The maximum allowable organs at risk doses were dened as follows: rectal V40 < 50%, bladder V40 < 50%, bone marrow V30 < 50%,
and small intestine V45 < 10%. Because all objectives generally cannot be met in the treatment volume, the objectives were prioritized
as planning target volume, small intestine, rectum, bladder, and
bone marrow.
2.2.4.2. 3D conformal radiotherapy plans consisted of standard foureld irradiation (anteroposterior, posteroanterior, and two lateral
elds). A multileaf collimator was used in order to reduce the volume of normal tissue. Prescription doses of planning target volume
were 50.4 Gy in 28 fractions at 1.8 Gy each with 6MV-X line.
2.2.4.3. Conventional radiotherapy plans consisted of two-eld vertical irradiation. Fields were based on classic bony landmarks. The
superior border was L3/L4, the inferior border was the bottom of

747

the obturator, 1.5 cm lateral beyond the pelvic brim. The same prescription doses of 50.4 Gy in 28 fractions of 1.8 Gy each, with 6MV-X
line with SSD 100 were used to simulate the intensity-modulated
and 3D conformal radiotherapy plans.
2.2.5. Assessment of treatment plans
Intensity-modulated radiotherapy treatment plans must meet
the following two criteria:
at least 95% of the nal planning target volume received 95% of
the dose, and the planning target volume internal dose gradient
was no more than 10%;
all cold spots were out of the radiation eld and no hot spots were
shown in the bladder wall or rectal wall.
2.2.6. Content observation
Isodose curves and dosevolume histograms at cross sections of
the three plans for the lling bladder were generated. The volume
values were determined for planning target volume and organs at
risk dose distribution, and the maximum dose (Dmax ), the minimum
dose (Dmin ), and average dose (Dmean ) were calculated.
The plans were quantitatively evaluated using the dosevolume
histograms generated by the treatment planning system. The
homogeneity index (HI) was dened as:
, where D5, D95, and D50 are the doses received by
HI = D5%D95%
D50%
5, 95, and 50% volume of the planning target volume. Conformity
of high dose around the target was evaluated by calculating the
conformity index (CI) at a given isodose level (e.g., CI = V PTV95%

V PTv
V PTV95%
).
The
monitor
units
(MU)
for
each
plan
and
treatment
time
Vt
were used to assess treatment efciency.
The mean doses of planning target volume and organs at risk
at the different levels of irradiated volumes (V10 , V20 , V30 , V40 , and
V45 ) for three plans organs at risk were determined.
2.2.7. Statistics
All statistical analyses were performed using SPSS 17.0 statistics
software (SPSS, Chicago, IL, USA). All variables were analysed using
paired t-tests, and P < 0.05 was considered statistically signicant.
3. Results
3.1. Comparison of planning target volume among the three
radiotherapy plans
At the same prescription dose of 50.4 Gy, the mean planning
target volume dose of the intensity-modulated, 3D conformal, and conventional radiotherapy plans were 5077.01 5.00,
5015.51 45.77, and 4790.64 175.97 cGy, respectively (Table 1).
The mean planning target volume dose of all three plans reached
the effective target therapeutic dose. The planning target volume
dose of the intensity-modulated radiotherapy plan was signicantly higher than those of the 3D conformal and conventional
radiotherapy plans (P < 0.05).
As shown in Fig. 1 in the intensity-modulated radiotherapy plan,
the concave shape of the 95% isodose curve is similar to that of
the target. However, in the 3D conformal and conventional radiotherapy plans, the 95% isodose curves are a square shape, and the
majority of the bladder, rectum, small intestine, and bone marrow
were covered.
The homogeneity index and conformity index for these patients
are shown in Table 1. The mean homogeneity indexes for intensitymodulated, 3D conformal, and conventional radiotherapies were
1.02, 1.14, and 1.26, respectively. The target dose conformity was
determined by comparing the volume of the planning target volume with the volume encompassed by 95% isodose body. The mean

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Y. Lv et al. / Cancer/Radiothrapie 18 (2014) 745752

Table 1
Distribution of planning target volumes according to the radiotherapy technique for cervix cancers.
Volumes cibles prvisionnels selon la technique de radiothrapie du cancer du col utrin.
Intensity-modulated radiotherapy
Dmax (cGy)
Dmin (cGy)
Dmean (cGy)
Homogeneity index
Conformity index
Monitor units

5740.74
3256.21
5077.01
1.02
0.89
662.50

73.93
373.77
5.00
0.02
0.03
78.85

3D conformal radiotherapy
5286.15
3854.22
5015.51
1.14
0.54
255.50

122.75*
353.06
45.77
0.05
0.05
9.25

Conventional radiotherapy
5331.44
1256.24
4790.64
1.26
0.36
229.75

138.16*
1477.65
175.97
0.04
0.01
29.42

n = 16,  s; P < 0.05 for all paired comparisons in each variable group, except for comparison between two groups; *P = 0.251.

conformity indexes 95% were 0.89, 0.54, and 0.36 for the intensitymodulated, 3D conformal, and conventional radiotherapy plans,
respectively. Compared to 3D conformal and conventional radiotherapy, intensity-modulated radiotherapy provided signicantly
better homogeneity and target dose conformity. The average numbers of monitor units delivered by the three plans were 662.5, 255.5,
and 229.75, respectively (Table 1). Thus, intensity-modulated
radiotherapy increased the treatment time and reduced the efciency of machine.
3.2. Organs at risk dose distribution of the three plans
The mean doses to organs at risk, including the bladder, rectum,
small intestine, and bone marrow, were compared among the three
plans (Table 2). The intensity-modulated radiotherapy plan was
superior to the 3D conformal and conventional radiotherapy plans,

with statistically signicant lower mean doses to the organs at risk.

The dosevolume parameters among these plans were compared
in individual organs at risk.

3.3. Bladder
In comparisons of the volume of intensity-modulated radiotherapy to the 3D conformal and conventional radiotherapy plans for
the bladder, signicant differences were observed from the 20 Gy
dose level (P < 0.05), and a signicant volume reduction was shown
from the 30 Gy level (Table 3). At the 30, 40, and 45 Gy levels,
volume reductions of 12.48, 28.59, and 34.70% were observed compared to 3D conformal radiotherapy, whereas reductions of 20.57,
55.06, and 69.22% were observed compared to conventional radiotherapy.

Fig. 1. Axial views of isodose distribution in radiotherapy for cervical cancer. A. Intensity-modulated radiotherapy. B. 3D conformal radiotherapy. C. Conventional radiotherapy.
Isodoses de radiothrapie du cancer du col utrin. A. Radiothrapie conformationnelle avec modulation dintensit. B. Radiothrapie conformationnelle tridimensionnelle.
C. Radiothrapie classique.

Y. Lv et al. / Cancer/Radiothrapie 18 (2014) 745752

749

Table 2
Mean dose to organs at risk according to the technique for cervix cancer radiotherapy.
Dose moyenne aux organes risque pour la radiothrapie du cancer du col utrin selon la technique.
Organs at risk

Intensity-modulated radiotherapy

Bladder
Rectum
Small intestine
Bone marrow, left
Bone marrow, right

3863.20
3879.22
2514.43
2308.56
2347.71

48.12
140.14
160.63
77.29
88.35

3D conformal radiotherapy

Conventional radiotherapy

4461.86 294.71
4307.68 89.08
3044.07 319.17*
3117.39 186.29
3219.35 156.08#

5122.21
5196.60
3545.35
3292.62
3361.30

76.41
77.82
688.19*
121.95
245.38#

Doses are expressed in centigrays; n = 16,  s; P < 0.05 for all paired comparisons in each variable group, except for comparison between two groups; *P = 0.198; # P = 0.372.

3.4. Rectum
In the rectum, signicant differences (P < 0.05) and volume
reduction was shown from 30 Gy (Table 3). At the 30, 40, and 45 Gy
levels, reductions of 10.84, 24.82, and 25.92% were found compared
to 3D conformal radiotherapy, whereas reductions of 13.36, 58.40,
and 70.11% were observed compared to conventional radiotherapy.
3.5. Small intestine
At low radiation levels (10 Gy), although a larger volume of small
intestine was irradiated in intensity-modulated radiotherapy than
in the 3D conformal and conventional radiotherapy plans, no statistical signicance was obtained (P > 0.05). However, the irradiated
volume of small intestine was lower in the intensity-modulated
radiotherapy plan when patients received more than 20 Gy and
signicant differences were found from 30 Gy (P < 0.05; Table 3).
3.6. Pelvic bone marrow
The volume of irradiation to both sides of the pelvic bone marrow is compared in Table 3. Intensity-modulated radiotherapy

was superior to 3D conformal and conventional radiotherapies in

reducing volume to the pelvic bone marrow. Although reduced
irradiated volumes were observed in both sides when comparing intensity-modulated to 3D conformal radiotherapy at the 10 Gy
dose level, signicantly higher volumes were obtained compared
to the conventional radiotherapy plan (P < 0.05). However, signicantly reduced volumes were observed on both sides at doses from
20 to 45 Gy (P < 0.05).
3.7. Planning target volume mean dose of the
intensity-modulated radiotherapy plan in full and empty bladders
To elucidate the effect of bladder lling on intensity-modulated
radiotherapy, the planning target volume dose distribution and
dose to organs at risk were compared in 16 patients with full and
empty bladders.
With respect to the Dmax , Dmin , and Dmean , there were no signicance differences between full and empty bladders (P > 0.5)
(Table 4). However, irradiation to bladder, rectum, and small intestine was reduced with full bladder (Table 5). When dosevolume
histograms for these organs were compared, inconsistent results

Table 3
Comparison of the dosevolume parameters of organs at risk according to the technique for cervix cancer radiotherapy.
Paramtres dosevolume des organes risque pour la radiothrapie du cancer du col utrin, selon la technique.
Organs at risk

Intensity-modulated radiotherapy

Bladder
V10 *
V20
V30
V40
V45

3D conformal radiotherapy

Conventional radiotherapy

100.00
99.08
79.43
44.94
30.78

0.00
0.43
3.11
1.94
3.87

100.00
100.00
91.91
73.53
65.48

0.00
0.00#
6.34
13.68
15.82

100.00
100.00
100.00
100.00
100.00

0.00
0.00#
0.00
0.00
0.00

Rectum
V10 *
V20 *
V30
V40
V45

99.9
99.65
86.64
41.60
29.89

0.20
0.79
10.02
8.98
6.77

100.00
100.00
97.48
66.42
55.81

0.00
0.00
3.29#
3.55
6.02

100.00
100.00
100.00
100.00
100.00

0.00
0.00
0.00#
0.00
0.00

Small intestine
V10 *
V20 *
V30
V40
V45

91.24
64.69
32.40
10.87
5.80

5.04
9.32
4.01
1.84
1.56

89.99
80.53
50.22
21.48
17.72

6.04
6.14
13.91#
7.21
6.03

78.44
72.43
68.04
61.87
53.88

14.46
15.75
16.77#
14.68
13.43

Bone marrow, left

V10
V20
V30
V40
V45

87.32
60.93
26.75
4.60
1.20

3.92
4.99
3.83
2.63
1.16

92.70
81.99
62.50
23.88
17.09

2.24
4.98
6.62*
4.89
3.66

74.10
67.88
66.10
57.85
42.90

3.02
3.30
3.08*
3.72
4.29

Bone marrow, right

V10
V20
V30
V40
V45

87.88
61.45
26.76
6.38
1.57

3.39#
2.78
5.10
2.02
0.99

91.87
83.19
62.76
26.96
20.48

1.02#
2.49
3.89
6.07
6.77

73.74
68.82
66.47
60.62
48.60

5.78
6.16
6.06
5.49
6.16

Expressed in percent; n = 16,  s; *P > 0.05 for all paired comparisons in each variable group, except for comparison between two therapies ( P < 0.05). P < 0.05 for all paired
comparisons in other variable groups, except for comparison between therapies; # P > 0.05; *P = 0.246;  P = 0.055; P = 0.305.

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Table 4
Comparison of planning target volume dose distribution between intensitymodulated radiotherapy of cervical cancer with a full bladder and an empty bladder.
Radiothrapie avec modulation dintensit du cancer du col utrin : comparaison des
volumes cible prvisionnels avec vessie pleine ou vide.
Plans

Dmax (cGy)

Dmin (cGy)

Dmean (cGy)

Full bladder
Empty bladder
t
P

5740.74 73.93
5719.91 65.91
0.478
0.654

3257.21 373.77
3329.74 356.85
-0.668
0.541

5077.01 5.00
5081.12 7.91
-2.327
0.080

n = 16,  s; represents paired-sample t-tests; P indicates P-value, and values less

than 0.05 were considered statistically signicant.

were obtained. Irradiation volumes with full bladder were signicantly reduced at V40 and V45 in the bladder and at V20 and V30 in the
small intestine. Notably, volumes at V40 and V45 of the small intestine were reduced with full bladder but no statistical signicance
was observed. The mean dose to the pelvic bone marrow showed no
statistical signicance (P = 0.080) between full and empty bladders
at various volume levels.
4. Discussion
Based on the dosimetric analyses in this study, intensitymodulated radiotherapy demonstrated superior conformal treatment compared to 3D conformal and conventional radiotherapies.
Intensity-modulated radiotherapy provided signicantly superior
planning target volume coverage as well as signicantly lower irradiation doses to organs at risk including the small intestine, rectum,
bladder, and bone marrow. When comparing the effect of bladder lling, no differences were observed in the planning target
volume average dose between full and empty bladders. However,
the irradiated volume of bladder, rectum, and small intestine were
signicantly reduced with a full bladder.
The use of intensity-modulated radiotherapy for the treatment of gynaecologic malignancies has increased signicantly in

recent years [5]. Many studies have reported dosimetric benets of

intensity-modulated radiotherapy in cervical cancer, which benets the small intestine, rectum, bladder, and bone marrow [1922].
However, conicting reports have shown intensity-modulated
radiotherapy is inconsistent reducing the irradiated volume of
organs at risk [14,2328]. A meta-analysis pooled from 13 articles compared intensity-modulated to 3D conformal radiotherapy
treatment plans and found that although there was signicant
volume reduction in the small intestine and rectum when receiving high dose radiation, no statistically signicant decreases in
bladder or bone marrow volume was obtained [29]. However,
these studies are partly retrospective, with variations in relative organs at risk planning prioritization. Thus, nal comparisons
are difcult without uniform planning constraints, and, intensitymodulated radiotherapy treatment for gynaecologic malignancies
is not yet generally recommended by the National Comprehensive
Cancer Network (NCCN) [29]. In this study, we compared planning target volume coverage and irradiation volume to organs at
risk in 16 patients receiving intensity-modulated, 3D conformal,
or conventional radiotherapy plans. Intensity-modulated radiotherapy demonstrated superior conformal treatment compared to
the two other techniques. The isodose curve formed a concave
U shape tightly focal on the target, demonstrating a signicant
advantage over conventional radiotherapy, which formed a square
shape covering the majority of the bladder, rectum, small intestine,
and bone marrow. In addition, intensity-modulated radiotherapy
provided signicantly better homogeneity and target dose conformity compared to the two other techniques. Moreover, dosimetric
advantages are observed when the irradiated volume to organs
at risk is compared among the three plans. Organs at risk were
preferentially spared with the intensity-modulated radiotherapy
plan because of the use of conformal avoidance (i.e., limiting
the radiation dose below the designated threshold limit). Signicant differences were shown in these organs receiving more than
30 Gy, and the reductions became more apparent in organs with
higher irradiation volume. Numerous studies have demonstrated

Table 5
Comparison of dose distribution to organs at risk between intensity-modulated radiotherapies of cervical cancer with a full and an empty bladder.
Radiothrapie avec modulation dintensit du cancer du col utrin : comparaison des distributions de doses aux organes risque avec vessie pleine ou vide.
Organs at risk and bladder state

V10 (%)

V20 (%)

V30 (%)

V40 (%)

V45 (%)

Dmean (cGy)

Bladder
Full bladder
Empty bladder
t
P

100.00 0.00
100.00 0.00

99.08 0.43
99.38 0.49
0.964
0.389

79.43 3.11
82.78 6.05
0.847
0.445

44.94 1.94
49.12 4.28
3.472
0.029

30.78 3.87
37.42 5.08
4.577
0.010

5863.20 48.12
4000.70 115.10
3.589
0.023

Rectum
Full bladder
Empty bladder
t
P

99.91 0.20
100.00 0.00
1.000
0.374

99.65 0.79
99.44 1.25
1.000
0.374

86.64 10.02
87.32 11.05
0.306
0.775

41.60 8.98
45.51 9.39
1.428
0.226

29.89 6.77
30.78 7.52
0.425
0.693

3579.22 140.14
3960.25 132.42
6.126
0.004

Small intestine
Full bladder
Empty bladder
t
P

91.24 5.04
90.98 4.40
0.466
0.665

64.69 9.32
67.46 8.74
5.481
0.005

32.40 4.01
41.44 4.00
8.124
0.001

10.87 1.84
16.41 7.00
2.356
0.078

5.80 1.56
8.57 4.02
2.266
0.086

2514.43 160.63
2693.55 163.80
4.777
0.009

Bone marrow, left

Full bladder
Empty bladder
t
P

87.68 3.49
88.10 4.33
0.316
0.756

59.39 1.28
57.63 2.55
1.978
0.067

24.91 4.61
24.14 3.87
1.817
0.089

5.64 1.59
6.17 1.31
1.185
0.255

1.94 1.15
1.85 0.47
0.425
0.677

2330.55 84.32
2297.68 94.78
0.869
0.425

Bone marrow, right

Full bladder
Empty bladder
t
P

89.05 2.92
87.68 1.67
0.302
0.766

59.88 3.09
59.18 3.49
1.118
0.281

27.45 5.53
25.42 4.26
1.861
0.082

7.74 1.29
6.74 1.58
1.509
0.152

2.25 1.00
2.53 0.79
0.862
0.402

2369.39 71.63
2303.89 98.22
1.497
0.195

n = 16,  s; t represents paired-sample t-tests; P indicates P-value, and values less than 0.05 were considered statistically signicant.

Y. Lv et al. / Cancer/Radiothrapie 18 (2014) 745752

dosimetric benets of intensity-modulated radiotherapy in gynaecologic cancers, manifested predominantly in benets to the small
intestine, rectum, and bladder [19,20,22,23,30]. In a study comparing intensity-modulated radiotherapy with conventional four-eld
whole pelvis radiotherapy, there was no difference in the average
target volume, but intensity-modulated irradiation signicantly
reduced the dose to organs at risk at the V50 , V45 , V40 , and V30 levels [31]. There was an apparent difference in V50 in most patients:
84% (bladder), 58% (small intestine), 54% (sigmoid), and 84% (rectum). In another study, van de Bunt et al. also concluded that
intensity-modulated radiotherapy is superior in sparing organs at
risk (bladder, small intestine, and rectum) compared to conventional and conformal treatment, particularly when the volume is
greater than 30 Gy [32].
Radiation-induced bone marrow damage is dependent on both
dose and volume [33,34]. Bone marrow is extremely sensitive to
radiotherapy with histopathologic changes evident in doses as low
as 4 Gy and complete hypoplasia with doses higher than 50 Gy
[34]. In a phase 2 postoperative study, Klopp et al. reported that
limiting the volume of bone marrow in pelvic intensity-modulated
radiotherapy with cisplatin therapy reduced rates of hematologic
toxicity and improved tolerance to chemotherapy in cervical cancer patients [35]. Their results suggested that the volume of bone
marrow receiving 40 Gy and the median dose to bone marrow
correlated with higher rates of grade 2 or above toxicity among
patients receiving weekly cisplatin. Reducing radiation to the bone
marrow relieves hematologic toxicity and minimizes neutropenia and anaemia, thus ensuring anti-tumour therapy progress. In
addition, it reduces the cost of treatment by obviating the need
for blood transfusions and growth factors [35]. Application of
highly conformal intensity-modulated radiotherapy reduces bone
marrow irradiation. With the goal of sparing bone marrow, several studies have applied intensity-modulated radiotherapy plans
that included the bone marrow as an additional treatment planning constraint in patients with cervical and endometrial cancer
[21,36]. When comparing organs at risk sparing with the conventional or intensity-modulated radiotherapy, bone marrow-sparing
plans signicantly reduced irradiation to the bladder, small intestine, and rectum, but also further reduced pelvic bone marrow
irradiation at low volumes. In one study, bone marrow-sparing
intensity-modulated radiotherapy reduced the pelvic bone marrow
volume receiving a dose superior to 16.4 Gy. Bone marrow-sparing
intensity-modulated radiotherapy reduced the volume of ilium,
lower pelvis bone marrow, and small intestine receiving doses
superior to 27.7, 18.7, and 21.1 Gy, respectively. In addition,
bone marrow-sparing intensity-modulated radiotherapy reduced
the volume of lumbosacral spine bone marrow at all dose levels in all patients [21]. In another study, bone marrow-sparing
intensity-modulated radiotherapy treatment plans demonstrated
a signicant reduction in the volume of bone marrow receiving
more than 40% (18 Gy) of the prescription dose (45 Gy) compared
with both conventional intensity-modulated radiotherapy and
four-eld treatment. On average, bone marrow-sparing intensitymodulated radiotherapy resulted in only 60% of the bone marrow
volume irradiated to more than 50% of the dose compared with
87.4% (P < 0.001) of the bone marrow volume in a four-eld plan and
75.7% (P < 0.003) of the volume in an intensity-modulated radiotherapy plan [36]. In our study, the maximum allowable dose for
bone marrow was dened as V30 < 50% in the intensity-modulated
radiotherapy plan. Although bone marrow volume was assigned
a last objective priority, the bone marrow objective was reached
and intensity-modulated radiotherapy signicantly reduced irradiated volume of both sides of bone marrow at doses from 20 to
45 Gy (P < 0.05). Our results indicate that using a well-designed
plan, intensity-modulated radiotherapy can reduce bone marrowsparing to low volumes.

751

Due to its special anatomical position, the cervix easily moves

and is subject to the impact of surrounding organs, such as the
lling state of the bladder and rectum. Due to the repetition of
radiation treatments, variations in patient positions usually take
place throughout the entire treatment process, and thus, the physical status of the internal organs changes as well. In addition,
cervical tumour regression during treatment should also be considered. Mobile organs compromise the efcacy of therapy and
increase irradiation to the organs at risk. In order to deliver an
adequate dose to achieve sufcient efcacy for treatment as well
as minimize organs at risk irradiation, several different methods
are used to compensate for the discrepancies occurring in each
fraction [37]. However, further studies are needed to evaluate
these methods. Bladder lling has been proposed to overcome
these issues during cervical cancer radiotherapy [15,23,32,38].
However, a reproducible bladder lling protocol has not been
developed due to individual differences in patients, poor compliance with bladder lling instructions, and the inability to ll
the bladder within a specied time [14,32]. However, bladder
lling remains a feasible method. Although consistency in bladder lling is not always achieved, patients can still benet from
it, particularly regarding organs at risk sparing [23,39]. In our
study, three steps were applied to avoid position changes. First,
we applied a catheter to rell the bladder during CT imaging for
treatment planning. Second, an immobilized body bag was used
to constrain the motion. Third, all patients were instructed to
strictly follow the bladder lling instructions. Although no differences were found in average planning target volume doses
between full and empty bladders, signicant reductions in irradiation to the bladder, small intestine, and rectum were obtained
for full bladder Our results suggest that bladder lling may limit
the volume amount of the bladder and intestine in the treatment area and help reduce the radiation dose to the organs at
risk.
It is worth noting that the strength of this study is that all
patients recruited were stage IIB patients with no operation after
radiotherapy. The homogeneous pathology background made our
results more predominant in comparison of efcacy and toxicity of
intensity-modulated radiotherapy and avoided background inconsistency resulting from other published series with mixed clinical
situations and sometimes mixed diseases.
Intensity-modulated radiotherapy plans also have advantages
regarding toxicity, predominantly in terms of gastrointestinal,
hematologic, and genitourinary toxicity [24,28]. Due to the potential for complications during the long-term follow-up period, we
were not able to include clinical outcomes in this report. However, a prospective study is now underway at our hospital to
compare the clinical outcomes of these patients. Another limitation of this study is we did not measure organ motion, which may
result in treatment inconsistencies. Our results suggest that wellplanned intensity-modulated radiotherapy benets cervical cancer
patients in areas with limited resources. Moreover, clinicians
should be aware that new image-guided radiotherapy techniques
will improve the accuracy of radiation eld placement and reduce
exposure to healthy tissue during radiation treatments, which is
benecial to patients.
In summary, we have demonstrated the dosimetric superiority of intensity-modulated radiotherapy over conformal and
conventional radiotherapies in the treatment of cervical cancer.
Intensity-modulated radiotherapy provided signicantly superior
planning target volume coverage as well as signicantly lower irradiation to organs at risk, including the small intestine, rectum,
bladder, and bone marrow. It is anticipated that this reduction
in normal tissue irradiated volume will translate into overall
reductions in acute as well as late treatment-related toxicities.

752

Y. Lv et al. / Cancer/Radiothrapie 18 (2014) 745752

Disclosure of interest
The authors declare that they have no conicts of interest concerning this article.
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