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REVIEW ARTICLE

Three-Dimensional Dosimetry of the Full and Empty


Bladder in High Dose Rate Vaginal Cuff Brachytherapy
Justyna D. Kobzda, MSc,* Ewa Cikowska-Wozniak, PhD,* Magdalena Michalska, PhD,*
and Roman Makarewicz

Objectives: The objectives of the study were to assess the bladder doses during vaginal cuff
brachytherapy and to examine the effect of bladder filling on normal tissue dosimetry by
means of computed tomography.
Materials and Methods: A total number of 45 women were enrolled in a prospective
clinical trial. Patients were treated with the application of a single-line source vaginal cylinder.
All the patients were asked to consume 400 mL of water 40 minutes before computed to-
mography scans were taken. For each patient, 2 treatment plans were performedVone with
full bladder and the other one when the bladder was emptied. A dose-volume histogram
and the equivalent of 2-Gy dose for full and empty bladder were calculated. Doses to the
bowels in 2 states of the bladder were estimated.
Results: Thirty-five patients received a lower dose to the empty bladder than to the filled
organ. The average dose difference was 0.5 Gy. Ten patients received a lower dose to the
full bladder than to the empty one. However, in this case, the difference amounted only to
0.2 Gy on average. Dose parameters (the maximal dose received by 0.1 cm3 of tissue and
the maximal dose received by 2 cm3 of tissue) were lower in the empty state, but the
volumetric parameters (the percent of bladder volume receiving Q50% of the prescribed
dose and the percent of bladder volume receiving Q80% of the prescribed dose) were higher
in the empty state of the bladder. Doses to the bowels seemed to be higher in the empty
bladder. However, none of the doses exceeded the limitations.
Conclusions: The results have shown that in most cases, the dose to the empty bladder
is lower than when the bladder is full. Simultaneously, the doses to the bowels increase
proportionally in the empty state of the bladder comparing to the full organ. Protection of
the bowels, which are more radiosensitive, suggests treating the patients in the full state of
the bladder. Early and late bowel toxicity should be investigated to establish clear standards
of treatment.
Key Words: Vaginal cuff brachytherapy, HDR brachytherapy

Received September 17, 2013, and in revised form February 18, 2014.
Accepted for publication February 18, 2014.
(Int J Gynecol Cancer 2014;24: 923Y927)

E ndometrial carcinoma is 1 of the most common gyneco-


logic malignancy in Poland. The standard treatment of
oophorectomy with or without the application of lymph node
dissection. The implementation of adjuvant radiation for sur-
endometrial cancer is hysterectomy and bilateral salpingo- gical stage I patients with intermediate risk factors has been

*International Oncotherapy Centre, Poznan; and Chair and Clinic Nicolaus Copernicus University in Torun, Bydgoszcz, Poland.
of Oncology and Brachytherapy, Centre of Oncology in Bydgoszcz, Address correspondence and reprint requests to Justyna D. Kobzda,
Copyright * 2014 by IGCS and ESGO MSc, International Oncotherapy Centre, 28 Czerwca 1956r. 223/229
ISSN: 1048-891X Str. 61-485 Poznan, Poland. E-mail: justyna.kobzda@gmail.com.
DOI: 10.1097/IGC.0000000000000127 The authors declare no conflicts of interest.

International Journal of Gynecological Cancer & Volume 24, Number 5, June 2014 923

Copyright 2014 by IGCS and ESGO. Unauthorized reproduction of this article is prohibited.
Kobzda et al International Journal of Gynecological Cancer & Volume 24, Number 5, June 2014

a controversial subject over the years. However, studies show to ABS and GEC-ESTRO recommendations5). The high dose
that radiation therapy is an effective treatment strategy.1 Ex- rate (HDR) dose, delivered by iridium 192 source, was pre-
ternal beam radiotherapy has usually been reserved for the scribed to the depth of 0.5 cm from the cylinder surface.
patients with high (915%) recurrence rate, whereas vaginal
brachytherapy has been used in cases with low or medium
recurrence rate.2 Recently, highYdose rate brachytherapy has AIM
replaced lowYdose rate treatment in most centers. The ad- The implementation of 3-dimensional (3D) technique
vantage of this modality is primarily related to the convenience provides the opportunity to record doses to organs at risk.6
of an outpatient administrator. The objectives of this study were to assess the bladder tissue
The most common applicators are the vaginal cylinders doses during vaginal cuff brachytherapy (VBT), to examine
with different diameters, adjusted to the size of the vagina. In the effect of bladder filling on normal tissue dosimetry by
some cases, 2 ovoids or a ring applicator can be used to reach means of computed tomography (CT), and to suggest stan-
the most upper part of the vagina.3 Recently, a new method dards of treatment.
with the application of an intravaginal balloon applicator has
been introduced.4 This technique was developed to keep the
best conformity and dose coverage in accordance with the MATERIALS AND METHODS
anatomy of the patient. A total number of 45 women were enrolled in a pro-
In this study, the vaginal cylinders were used for all spective clinical trial. The choice of patients was done on the
insertions to treat the proximal one third of the vagina (according basis of clinical diagnosis (patients with endometrial cancer

FIGURE 1. Dose distribution in empty (A) and full (B) bladder state. Isodose lines: V50, V75, V90,
V100, and V150.

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3D Dosimetry of Bladder in
International Journal of Gynecological Cancer & Volume 24, Number 5, June 2014 HDR Brachytherapy

after surgery with all FIGO stages). Patients were treated with Differences between the volumes of full and empty blad-
the application of a single-line source vaginal cylinder ap- der calculated in the treatment planning system were significant
plicator to deliver a dose of 6 Gy per fraction at the depth of (Table 2). The mean volume of the full bladder was approxi-
0.5 cm from the applicator surface. The total dose was 24 Gy mately 3.5 times bigger comparing to the empty organ.
in 4 fractions when brachytherapy alone was used or 18 Gy For evaluation reasons, the following values were taken
in 3 fractions when brachytherapy was combined with external into account for both full and empty bladder: percent of
beam irradiation. Qualification for brachytherapy as monother- bladder volume receiving greater than or equal to 50% of the
apy or adjuvant therapy with external beam radiotherapy (EBRT) prescribed dose (V50), percent of bladder volume receiving
was done on the basis of FIGO stage after surgery, grading, greater than or equal to 80% of the prescribed dose (V80),
information about lymph nodes, and other prognostic factors. D0.1 cc, and D2 cc. To show insignificant differences in the
The cylindersdiameters varied within the range of 2.5 to 3.5 cm. doses to the rectum, the approximation for the values of the
The widest cylinder that the patient could tolerate was inserted doses to the rectum are estimated more precisely comparing
to ensure the optimal coverage of treatment volume. to the rest of the data.
All the patients were asked to apply Laxantia 1 day before The evaluation of the bladder showed differences in
every fraction to provide a minimal filling and at the same doses between empty bladder (EB) and full bladder (FB). The
time possibly maximal stability of the rectum and bowels. The outcome presented in Table 2 describes the average values
imaging protocol was standardized, and CT scans with full gathered from all the results. From the outcomes, 2 groups
and empty bladder were performed on the same day for each have been distinguished. In the first group, 35 patients re-
patient. The position of the patient at the time of CT imaging ceived a lower dose to EB than to FB. In all these cases, the
and treatment delivery was the same (patient lying on the difference reached 0.5 Gy on average. In the second group, 10
back with knees bent). To provide a sufficient filling of the patients received a lower dose to FB than to EB. However, the
bladder, patients were asked to consume 400 mL of water difference amounted only to 0.2 Gy on average. D0.1 cc rep-
40 minutes before the CT scans were taken. No contrast was resents the maximal dose received by the organ in accordance
used to visualize the bladder during imaging. After perform- with GEC-ESTRO recommendations.5 The evaluation of this
ing the first set of CT scans, the patients were asked to empty parameter showed again the higher values for FB in most cases.
the bladder, and CT imaging was repeated. For the rectum and bowels (including the sigmoid), only
Both sets of CT images were transferred to the 3D D2 cc was taken into account. The goal of this evaluation was
Flexiplan Planning System (Nucletron, An Electa Company, to verify if these organs change their position significantly
Veenendaal, the Netherlands). The bladder, rectum, bowels, and because of the different filling of the bladder. The results
clinical target volume (CTV) were contoured in 3 dimen- showed only slight differences in the doses to the rectum
sions by 1 physician and checked by another. For preserving
the same conditions in all cases, the contouring protocol was TABLE 1. Patients characteristics
standardized, and the following rules were set in place: the blad-
der was delineated in the empty and full state as a whole organ; Characteristics No. Patients
the rectum and bowels (including the sigmoid) were contoured
within the whole length of the cylinder and 2 cm above it. Age
A dose volume histogram was generated. The volumes e60 26
of the bladder receiving at least 100% or more, 90% or more, 960 19
80% or more, and 50% or more of the dose were reported FIGO stage
(a dose distribution for exemplary patient is shown in Fig. 1).
IA 11
Measurements of the maximal dose received by 2 cm3 of
tissue (D2 cc, a factor which has been correlated with the IB 22
risk of late adverse effects) and the maximal dose received by II 8
0.1 cm3 of tissue (D0.1 cc, a representation of maximal dose III-IV 4
received by the organ) for the bladder were recorded ac- Tumor grade
cording to GEC-ESTRO recommendations. For the rectum G1 19
and bowels (small bowels and sigmoid), D2 cc was calculated.
All dosimetric parameters were summed, and the mean G2 22
values were calculated. The differences in bladder volume in G3 4
the full and empty state were compared using the t test. Treatment schedule
45 Gy/50.4Gy EBRT + 18 Gy BT 36
24 Gy BT only 9
RESULTS
Cylinder diameter, cm
A cylinder size of 2.5 cm was used in 4 cases, 3.0 cm in
23 cases and 3.5 cm in 18 patients. All patients received 6 Gy 2.5 4
per fraction to the upper one third of the vagina (the active 3 23
length of the cylinder was 3 cm). Patients characteristics by 3.5 18
means of age, FIGO stage (2009), and tumor grade are shown BT, brachytherapy; EBRT, external beam radiotherapy.
in Table 1.

* 2014 IGCS and ESGO 925

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Kobzda et al International Journal of Gynecological Cancer & Volume 24, Number 5, June 2014

TABLE 2. Mean dosimetric values in full and empty bladder state


Mean Dosimetric Values
According to Bladder
Filling (VBT Only) Full Bladder Empty Bladder P
3
Mean volume (range), cm 229.7 (53.4Y663.4) 65.3 (28.4Y379.0) G0.05
V50 (range), % 10.1 (3.1Y22.3) 17.7 (3.7Y33.9) G0.05
V80 (range), % 1.5 (0Y5.2) 3.6 (0Y11.3) G0.05
Physical dose for a EQD2 for a Physical dose for a EQD2 for a
single fraction, Gy single fraction, Gy single fraction, Gy single fraction, Gy
D0.1 cc (range), Gy 6.4 (5.0Y8.8) 12 (8.0Y20.8) 6.0 (4.5Y7.6) 10.8 (6.8Y16.1) G0.05
D2 cc (range), Gy 4.9 (3.9Y5.9) 7.7 (5.4Y10.5) 4.6 (3.1Y5.6) 7.0 (3.8Y9.6) G0.05
D2 cc for rectum (range), Gy 3.60 (2.5Y5.6) 4.75 (2.7Y9.5) 3.55 (2.4Y5.3) 4.65 (2.6Y8.9) 0.41
D2 cc for bowels (range), Gy 4.1 (1.3Y5.7) 5.8 (1.1Y9.9) 4.6 (2.5Y7.3) 7.0 (2.8Y15.0) G0.05

(3.60 Gy for FB and 3.55 for EB on average). For bowels, we vaginal failures (1.8%). Similar results were obtained by other
achieved an average difference of 0.5 Gy (4.1 Gy for FB and authors.8 They emphasized an extremely low risk rate of toxicity.
4.6 Gy for EB). Moreover, the randomized trial comparing vaginal brachytherapy
As a representation of biological dose received by the alone to pelvic irradiation (PORTEC 2) published in 2010
bladder, rectum, and bowels, the equivalent of 2-Gy dose proved that brachytherapy is effective in ensuring vaginal
(EQD2) was calculated (>/A = 3). The limitations for OARs control and should be a treatment of choice for patients with
follow again the GEC-ESTRO recommendationsVless than endometrial carcinoma of high-intermediate risk.2 Most data
90 Gy for bladder and less than 75 Gy for the rectum and in the literature on HDR brachytherapy show a very favorable
bowels in the whole treatment (EBRT + BT).5 The total EQD2 rate (0%Y1%) of significant complications (Alektiar et al10).
(EBRT + BT) calculated for full and empty bladder is shown These low rates of toxicity were obtained as a result of close
in Table 3. We protectively assumed that a bladder receives a attention paid to total doses, fraction doses, length of vagina
full prescribed dose from EBRT in 3D technique (for 45 Gy/25 treated, and references points. The optimal state of bladder
fractions: EQD2, 43.2 Gy; for 50.4 Gy/28 fractions: EQD2, filling was rarely taken into account.
48.4 Gy). The mean dose for the bowels was estimated after Our data show that for the bladder, the empty state is
the evaluation of 15 EBRT plans and amounted 25 Gy (for slightly more advantageous. However, this organ is consid-
25 fractions: EQD2, 20 Gy; for 28 fractions: EQD2, 22.4 Gy). ered the most radioresistant from all the OARs in this area.
Doses to the rectum did not show any significant dif-
ferences (Table 2), which brings to the conclusion that the
DISCUSSION states of the bladder did not affect the position of this organ.
Vaginal cuff brachytherapy is a simple outpatient pro- Bowels are the most unstable organ for dosimetric eval-
cedure, which consists in the application of a highYdose rate uation because of their constant peristaltic movements. This
brachytherapy method. This radiotherapy technique allows for makes it impossible to define a clear location of the bowels
the minimization of the rate of toxicity. In a large retrospective within the time between CT simulation and treatment. There-
study made by Horowitz et al,7 highYdose rate brachytherapy fore, a dosimetric evaluation of the bowels should be read as
was yielded to 164 surgically staged patients with stage IA, an estimation. However, few regularities have been observed.
IB, and II (FIGO 2009) to provide excellent rates of local In most cases, the position of the bowels differed in full and
control. Their overall failure was 8.4% with only 3 pelvic or empty state of the bladder, which was clearly observed on the

TABLE 3. Total EQD2 for full and empty bladder (calculated for EBRT + BT or BT alone)
EQD2 for Bladder EQD2 for Bowels
Total Dose (EBRT + BT) (>/A = 3), Gy (>/A = 3), Gy
45 Gy EBRT + 18 Gy BT (mean dose for D2 cc of FB + range) 66.4 (59.3Y74.7) 37.5 (23.4Y49.8)
45 Gy EBRT + 18 Gy BT (mean dose for D2 cc of EB + range) 64.2 (54.5Y72.1) 41.0 (28.3Y65.1)
50.4 Gy EBRT + 18 Gy BT (mean dose for D2 cc of FB + range) 71.6 (64.5Y79.9) 39.9 (25.8Y52.2)
50.4 Gy EBRT + 18 Gy BT (mean dose for EB + range) 69.4 (59.7Y77.3) 43.4 (30.7Y67.5)
24 Gy BT only (mean dose for D2 cc of FB + range) 31 (21.5Y42) 23.3 (4.5Y39.7)
24 Gy BT only (mean dose for D2 cc of EB + range) 28 (15.1Y38.5) 28 (11.0Y38.5)

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Copyright 2014 by IGCS and ESGO. Unauthorized reproduction of this article is prohibited.
3D Dosimetry of Bladder in
International Journal of Gynecological Cancer & Volume 24, Number 5, June 2014 HDR Brachytherapy

CT scans. The more the bladder was filled, the further the full organ. Protection of the bowels, which are more radio-
bowels were pushed aside from the cylinder. The dosimetric sensitive, suggests treating the patients in the full state of
data show (Table 2) that the dose to the bowels in the empty the bladder. However, early and late bowel toxicity should
state of the bladder was higher comparing to the full state be investigated to establish clear standards of treatment. To
(0.5 Gy of average difference). Thus, the full state of the control and evaluate the dose to OAR, CT-based VBT should
bladder was more favorable for the bowels, which are more be used. The outcomes confirm the other studies.
radiosensitive and should be better protected. However, looking
at EQD2 (Table 3), we see that none of the doses exceeded
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