Download dosimetric influence of uterus position in cervix cancer high

DOSIMETRIC INFLUENCE OF UTERUS POSITION
IN CERVIX CANCER HIGH-DOSE-RATE BRACHYTHERAPY
M.T. GEORGESCU1,2, V.G. MOLDOVEANU1, B.V. ILEANU3, R. ANGHEL1,2
1
2
Institute of Oncology “Prof. Dr. Al. Trestioreanu” Bucharest, Romania
University of Medicine and Pharmacy “Carol Davila” Bucharest, Romania
3
Bucharest University of Economic Studies, Romania
Received June 30, 2015
Brachytherapy is an integrating component for the treatment of locally advanced
cervical cancer. While most women present anteverted or intermediary position
uterus, only 20–25% have retroverted uterus. We evaluated 418 high-dose-rate
brachytherapy plans of patients diagnosed with biopsy proven cervical cancer.
Urinary bladder and rectal points were identified on the orthogonal digital X-ray
images according to ICRU Report no.38. The brachytherapy plans were divided
according to uterus position into three groups, anteverted, intermediary and
retroverted, respectively. The statistical analysis of the dosimetric data confirmed that
uterus axis influences radiation doses received by the urinary bladder and rectum.
Key words: brachytherapy, cervix cancer, uterus position, rectum, urinary bladder,
high-dose-rate, orthogonal simulator, image-guided, ultrasound,
individualized applicator.
1. INTRODUCTION
Cervical cancer is the fourth most common cancer in women, and the seventh
overall, with an estimated 528,000 new cases in 2012. There were an estimated
266,000 deaths from cervical cancer worldwide in 2012, accounting for 7.5% of all
female cancer deaths. In Romania, considered the country with the highest World
Age-Standardized incidence rates for cervical cancer from Europe, this malignancy
represents, after breast cancer, the second most common cause of cancer death in
women [1]. Starting the early 1900’s, radiotherapy is currently being used with
curative intent in the management of cervical cancer. Because brachytherapy boost
to external beam radiotherapy showed increased 5 year PFS, compared to external
beam radiotherapy (EBRT) alone [2, 3], it became an integrating component for the
treatment of locally advanced cervical cancer (stages IB2 to IVA) [4].
Rom. Journ. Phys., Vol. 61, Nos. 9–10, P. 1557–1566, Bucharest, 2016
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Regarding its axis and position, the uterus assumes anteverted position in
50% women, retroverted position in 25% women whilst the rest have midposed
uterus [5]. For patients with gynecologic malignancies undergoing uterine
brachytherapy, uterus position and axis are essential to the depth-dose parameters
and of the procedure risks. The purpose of this study was to evaluate how the
position and axis of the uterus, in cervix cancer biopsy proven patients, influence
radiation exposure for the organs at risk during HDR intrauterine brachytherapy
procedure.
2. MATERIALS AND METHODS
We evaluated the medical records of 723 patients with uterine cancer treated
in our department between January 2013 and December 2014. From those, 218
patients were enrolled in this study based on the following inclusion criteria:
biopsy-proven cervical cancer, stage IB1-IVB (according to International
Federation of Gynecology and Obstetrics (FIGO) 2009 staging guidelines) and
preoperative radiotherapy. Pre-therapeutic examination consisted of: initial clinical
examination, complete blood count, liver and renal function assessment, chest
X-ray and abdominopelvic CT/MRI. Uterine axis and position were also assessed
clinically and radiological.
2.1. TREATMENT SCHEME
All patients underwent pelvic EBRT using a four-field box technique with
CT-based treatment planning to a median total dose of 50.4 Gy (37.8 Gy–60.4 Gy).
Thirty two patients needed para-aortic nodal radiotherapy. For 78 patients
concurrent weekly Cisplatin chemotherapy was used. After EBRT completion all
patients received HDR 192Ir brachytherapy using GammaMedplus iX HDR
afterloader unit.
2.2. BRACHYTHERAPY PROCEDURE
Each procedure started by the insertion of a Foley catheter into the urinary
bladder and the inflation of the catheter balloon with contrast and normal saline
(7.0 ml). Before applicator positioning, cervical hysterometry was done, using a
straight hysterometer with graduated cursor. The applicators used for the
brachytherapy procedure were Fletcher-Suit Delcos-Style Applicator Set (Fig. 1)
and Ring Applicator (Fig. 2). After applicator positioning, appropriate vaginal
packing was done, in order to fix the applicator and also to push the bladder and
rectum away from the vaginal applicators, and an endorectal catheter was inserted.
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Fig. 1 – Iridium source Fletcher-Suit-Delcos applicators with half-ovoid pair colpostats.
Fig. 2 – Iridium source Ring applicator (left) and Ring & Tandem Combination Applicator Set (right).
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Following that, orthogonal radiographs were taken in supine position
(anteroposterior and lateral views) for conventional planning using a Simulix X-ray
machine. On the X-ray images geometrical reconstruction of the applicator and
point A, bladder and rectal reference points were identified (Fig. 3).
Fig. 3 – Orthogonal digital anteroposterior (left) and lateral (right) X-ray images.
Treatment planning was done using BrachyVision treatment planning system
and the reference points were identified according to International Commission on
Radiation Units and Measurements (ICRU) 38 protocol. Dwell positions
optimization was used in order to minimize the dose to rectal and bladder points
(Fig. 4).
Fig. 4 – Isodose distribution obtained with Fletcher applicator (left) and Ring applicator (right).
2.3. STATISTICAL ANALYSIS
Statistical analysis was done using IBM-SPSS v 20.0 software package. The
three groups were compared two by two, calculating the means of two variables
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using two-sample t-test. To assess the equality of variances for all variables
calculated for the three groups, Levene’s test for the homogeneity of variance was
used [6, 7]. Statistical analysis was completed by non-parametric Mood
Independent Median Sample Test [8] as cited in [9], for mean and maximum values
for the variables implied in the analysis.
3. RESULTS
There were analyzed 419 brachytherapy plans. The median number of
applications per patient was 2 (range, 1–4 applications), while the median
prescribed dose per fraction was 7.5 Gy (range, 5–30 Gy). According to uterine
axis, plans were categorized into group 1 (n = 51.78%), where uterus position was
anteverted, group 2 (n = 39.63%), of patients with midposed uterus, and group 3
(n = 8.59%), of patients with retroverted uterus (Fig. 5).
36
166
217
Group 1 (anteverse)
Group 2 (intermediary)
Group 3 (retroverse)
Fig. 5 – Brachytherapy plans.
The mean ICRU bladder point doses were the following: 239.7 cGy (median
238.9 cGy), 219.2 cGy (median 223 cGy) and 191.8 cGy (median 178.85 cGy),
respectively, for group 1 (anteverted uterus), group 2 (intermediary uterus) and
group 3 (retroverted uterus), respectively. We also calculated the maximum ICRU
bladder point doses for the three groups and we identified the following results:
333.4 cGy (median 339 cGy) for group 1, 307.8 cGy (median 313.25 cGy) and
259.6 cGy (median 260.2 cGy) for groups 2 and 3, respectively.
The same variables were calculated for the ICRU rectal point’s doses. The
following results were obtained when calculating mean ICRU rectal point doses:
137.8 cGy (median 136.3 cGy), 146.5 cGy (median 145.85 cGy) and 190.1 cGy
(median 190.7 cGy), respectively, for groups 1, 2 and 3, respectively. We also
calculated maximum ICRU rectal point doses for the three groups and the results
were as follows: 298.3 cGy (median 306 cGy) for group 1, 315 cGy (median 321.8
cGy) for group 2, and 399.7 cGy (median 407.7 cGy) for group 3.
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By statistical analysis of the resulted data we identified that for the mean
ICRU bladder points there is a major decrease of dose starting from the highest
values for brachytherapy plans of group 1, through the ones in group 2 and to the
brachytherapy plans of the retroverted uterus ones (Fig. 6). Also, we have observed
that the maximum ICRU bladder dose follows the same descending trend as the
mean ICRU bladder dose.
Fig. 6 – Dosimetric comparison for ICRU bladder point radiation doses.
Regarding mean and maximum ICRU rectal points Fig. 7 shows an increase
of radiation doses received starting brachytherapy plans from group 1, through the
ones from group 2, the highest values corresponding to the brachytherapy plans
from group 3.
Fig. 7 – Dosimetric comparison for ICRU rectal point radiation doses.
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The differences, visible in the figures presented above, were tested using the
methods presented in the Statistical analysis paragraph. By testing the mean and
maximum doses of irradiation for the urinary bladder and rectum between the three
groups, the differences proved to be statistically significant, independent of
Levene’s Test for Equality of Variances. Also, by using t-test for equality of means
between the three groups, grouped into pairs of two, statistically significant
differences at a threshold value of 1% were obtained between the anteverted uterus
(group 1) and retroverted uterus brachytherapy plans (group 3) for both ICRU
rectal and bladder point doses.
The statistically significance between groups given by the position of uterus
was sustained by the results when Mood Median Test was applied.
4. DISCUSSIONS
The purpose of our study was to identify if uterine position is an important
factor in the distribution of the mean and maximum rectal and bladder ICRU 38
point doses.
Our data confirm that uterine position is responsible for differences of the
mean and maximum ICRU rectal and bladder point doses between all the three
brachytherapy plans groups.
Brachytherapy is an integral part of the treatment of cervical cancer. The
imaging modality and the methods used for the reconstruction of the applicators are
the main factors influencing the treatment planning for the delivery of radiation.
Currently, orthogonal radiographs are used for treatment planning in our
institution. Although published in 1985, the ICRU Report no. 38 recommendations
[8] remain as the main reference and guideline for the brachytherapy of cervical
cancer [9]. After the publication ICRU tumor and organ at risk (bladder and
rectum) reference points were used for the definition of the doses in conventional
brachytherapy plans. Over the past two decades multiple studies [10, 11, 12]
critically reviewed and challenged the ICRU 38 recommendations for intracavitary
brachytherapy in cervical cancer.
While most literature studies referring to cervix cancer brachytherapy are
focusing on the significance image acquisition has for the treatment planning, there
are limited literature data referring to the influence that the patients anatomy has
for it.
Current literature studies [12, 13, 14, 15] that suggest the introduction of the
image-guided brachytherapy procedure for the treatment of cervix cancer are
comparisons between CT/MRI-based volumetric calculations and ICRU referencepoint estimates of the radiation doses delivered to the bladder and rectum during
this procedure. All these showed that compared to the image-guided technique, 2D
brachytherapy underestimates the radiation dose to the organs at risk and
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overestimates the radiation dose to the target volume. Considering this we expect
that for the three groups from the current study the differences regarding the
maximum bladder and rectal point doses are higher.
To our knowledge, there has been limited published data or literature
available regarding the dosimetric comparison of uterine position and its influence
on brachytherapy treatment planning in cervical cancers. Referring to uterine axis
during radiotherapy, Huh et al. [16] published in 2004 a study in which at patients
with cervical cancer, during radiation treatment positional changes of the uterus
were detected. Other authors such as Taylor P. [17] have also found that large
movements of the uterus can occur in both superoinferior and anteroposterior
directions during radiotherapy. Mayr et al. [18] conducted a study on
brachytherapy management by ultrasound-guided applicator placement for patients
with retroverted uterus, the technique resulting in acceptable outcome and
complication rates. Referring to the ultrasound guidance for the applicator
placement Sahinler I. et al. [19], as well as Small W Jr. et al.’s literature review
[20] found that due to the high rate of uterine perforation, undetected by orthogonal
radiographs, the use of real-time ultrasound should be considered for all uterine
tandem insertions.
The present study brings forward the need for the evolution from the ICRU
Report 38 point-based brachytherapy to an image based brachytherapy in the
treatment of cervical cancer. Currently there exists a full range of brachytherapy
products for the treatment of cervix cancer patients; therefore we would
recommend ultrasound assessment of uterine position before applicator placement
in order to improve the therapeutic outcome.
5. CONCLUSIONS
Our study suggests that uterine axis is an important factor in brachytherapy
treatment planning. ICRU no. 38 rectal and bladder mean and maximal point doses
varied according to uterus position, the rectum receiving significantly higher doses
in case of retroverted uterus. Due to the limitations of the orthogonal X-rays in
evaluating brachytherapy treatment planning rectal and bladder point doses we
consider that continuing to use point A dose prescriptions is neither acceptable nor
desirable. By considering patient anatomy, individualized applicator geometry and
treatment planning, image-guided brachytherapy can be improved to personalized
brachytherapy, which lowers even further the dose to the organs of risk with
significantly dose distribution in the target volume.
Acknowledgements. This work received financial support through the project entitled “CERO
– Career profile: Romanian Researcher”, grant number POSDRU/159/1.5/S/135760, co financed by
the European Social Fund for Sectoral Operational Programme Human Resources Development
2007–2013.
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