Introduction
High-dose rate vaginal cuff brachytherapy (HDR-VBT),
either administered independently or in conjunction
with external beam radiotherapy (EBRT), constitutes a frequently employed treatment modality following hysterectomy
for the management of gynecologic malignancies.[-] This treatment regimen is typically applied to
patients diagnosed with endometrial carcinoma in pathological
Stages I-III disease in combination with EBRT for those with more advanced disease or alone in early
stage with low-grade histology.[,] In light of the affirmative
outcomes from previous studies, the utilization of
HDR-VBT has obtained a notable increase.[-]
With the development of imaging technology, especially
the utilization of computed tomography (CT),
there has been substantial interest in implementing
three-dimensional (3D) treatment planning for intracavitary
brachytherapy in recent years. Currently, approximately
80% of treatment plans are structured in
3D format, with up to 75% exclusively executed during
the initial application.[] The guidelines provided by
the American Brachytherapy Society (ABS) recommend
a customized treatment plan established once for
each patient and applied consistently for all treatment
sessions because customizing treatment plans for every
treatment session would be mostly time-consuming,
incurring additional technical expenses, and likely not
yield discernible improvements in patient outcomes.
[-] Therefore, fixed geometry applicator using
assumes to prevent potential variations in applicator
position between treatment sessions, or radiographs
or other measures are taken to ensure that the applicator
remains in the same position within the vagina
and relation to the bladder and rectum for each application
is recommended. However, the necessity for
routinely calculating bladder and rectal doses during
the administration of VBT alone has been a subject of
inquiry. This is due to the relatively low dose delivered
to normal tissues and the overall low treatment-related
complications. In ABS, guideline-specific parameters
and standardized bladder filling conditions for patients
undergoing VBT were not definitively established. Furthermore,
the optimal indicators for quantifying the
radiation dose to the bladder during VBT are not clear.
Numerous studies have conducted assessments of
3D conformal treatment plans in patients diagnosed
with cervical and endometrial cancers.[-] These
studies involved the dosimetric comparison of some
features between 2D and 3D plans. The manipulation
of internal anatomical parameters has been the subject
of an extensive investigation to gauge its influence on
the radiation dose administered to both target and normal
tissue during VBT. The effect of bladder fullness on
dose distribution has been thoroughly examined within
the context of both cervical and endometrial cancer,
yielding conflicting results.[-] Despite the available
data on bladder fullness during BRT with intact
uterus, the delivery of BRT through a vaginal cylinder
remains a topic infrequently addressed in 3D imagebased
dosimetric studies.[,] In a prospective study, Stewart et al.[] found that augmenting bladder filling
heightened the maximum bladder dose and the volume
of the bladder receiving ≥ 70% of the prescribed
dose. Nevertheless, this maneuver displaced the nearest
bowel away from the vaginal cylinder. Another study
by Hung et al.[] illustrated that bladder filling, while
effective in reducing radiation exposure to the small
bowel, did not adversely impact the dose to the bladder,
rectum, or sigmoid colon. Additionally, Kobzda et
al.[] observed that the dose to the empty bladder was
lower compared to the distended bladder, and the doses
to the intestine rose comparatively when the bladder
was empty as opposed to when it was full. Hoskin et
al.[] employed urinary catheterization to ensure consistent
bladder-filling states before VBT. A comparison
between a full bladder and an empty bladder has shown
that bladder fullness reduces D50% values of the bladder
and decreases the dose to the small intestine. Despite
the multifaceted considerations pertaining to VBT
treatment planning, a definitive correlation between radiation
dose and clinical outcomes remains unclear.
Consequently, there has been a lack of standardization
regarding bladder filling and dose estimation,
which hinders the establishment of routine clinical
practices in 3D treatment planning. The utilization of
3D treatment with either an empty or full bladder varies
among radiation therapy centers. It is considered
appropriate to simulate treatment planning for vaginal
cuff brachytherapy with an empty bladder and rectum.
Nevertheless, the practice of employing a Foley catheter
to empty the bladder in each treatment fraction
can potentially impact the risk of infection, treatment
compliance, and the overall quality of life for patients.
In this study, our primary objective was to ascertain
the influence of a Foley catheter on bladder fullness
and its subsequent effects on the doses received
by critical organs and target volumes in post-operative
endometrial or cervical cancer patients undergoing
vaginal cuff brachytherapy with an empty bladder.
Methods
Patients
A dosimetric examination was conducted on twenty
patients diagnosed with post-operative endometrial or
cervical cancer. These patients had undergone three-dimensional
vaginal HDR-BRT using a multi-channel cylinder
applicator between January 2020 and May 2021.
All patients had previously undergone total abdominal
hysterectomy, and a subset of them had received EBRT before BRT treatment. The characteristics of the patients
are presented in Table 1. Ethical approval for this
study was obtained from the institutional review board.
This study has been conducted in accordance with the
principles outlined in the Helsinki Declaration.
Simulation and Insertions
Before the delivery of brachytherapy (BRT), a thorough
gynecologic examination was conducted to evaluate
the condition of the vaginal vault and to ascertain
the appropriate applicator diameter. To prepare for the
procedure, patients were required to undergo a laxative
or enema regimen to empty the intestinal contents.
Subsequently, after voiding the bladder, two simulation
CT scans were performed: first, without a Foley catheter
and after then, with the insertion of a 16-French
Foley catheter with 7 mL of saline filling the balloon.
Intracavitary BRT was carried out using plastic
multichannel cylinder applicators that were compatible
with CT imaging, and these applicators were selected
to accommodate cylinders customized to suit
each patient's anatomy in diameters ranging from 2.5
to 3.5 cm. The cylinder was sheathed with a lubricated
condom and positioned anatomically to prevent any pressure on the bladder anteriorly or the rectum posteriorly.
The applicator was securely fastened in place
using a universal applicator clamping device located
beneath the patient. Consistently, the same applicators
were used throughout the treatment course. Moreover,
before each BRT session, the applicator"s position was
verified through radiographs to ensure it remained in
the same location as during the initial application.
The CT simulation was performed to cover the entire
length of the vaginal applicator, scanning the region
of interest in the pelvic region from the L4/L5 interface
to the lower border of the ischial tuberosity. A CT scan
with 2.5-mm thick slices was carried out adhering to the
established departmental protocol. Notably, no oral or
intravenous contrast agents were employed during the
planning CT. The patients were positioned in the supine
posture with their legs fully extended during both simulation
and treatment procedures. During planning, target
volumes and critical organs such as the rectum, bladder,
sigmoid colon, and small bowel were outlined according
to the relevant guidelines on the CT scan slices acquired
for treatment planning. Each organ was contoured by
outlining its entire structure. The rectum was defined as the colonic segment extending from the rectosigmoid
junction to the anal verge. The sigmoid colon was characterized
as the bowel section extending proximal to the
rectum, marked by a transition to a vertical orientation.
The designation of small bowel encompassed all individual
loops of the intestines, excluding the rectum and
sigmoid colon, up to the level of the inferior sacroiliac
joints. This delineation included individual loops of the
bowel as visualized during the CT simulation process.
Treatment Planning and Delivery
All patients received treatment using a Nucletron Flexitron
model with an Iridium-192 source HDR afterloader,
manufactured by ELEKTA Medical Systems in
the UK. The treatment planning was performed using
the Oncentra Brachy version 4.6.3 treatment planning
system software. Multichannel vaginal cylinders
were employed for all insertions to target the proximal
one-third, approximately 3?5 cm of the vagina, adhering to the recommendations of both ABS and Groupe
Européen de Curiethérapie and European Society for
Therapeutic Radiology and Oncology (GEC-ESTRO).
[,,] HDR irradiation with an iridium-192 source
was prescribed to a depth of 0.5 cm from the surface of
the cylinder. The dose per fraction ranged from 5 to 6
Gy for all patients. The treatment plans were optimized
using the Inverse Planning Simulated Annealing technique
to ensure the delivery of 100% of the prescribed
dose to the designated prescription point. The treatment
plan that was approved during the planning CT
scan with the Foley catheter in place was transferred to
the CT scan without the Foley catheter, and DVH parameters
were assessed separately (Fig. 1a, b). For both
plans, values such as D90, D95, and D98 for High-Risk
Clinical Target Volume (HRCTV) were recorded. Additionally,
the doses to critical organs, including the
bladder, rectum, and sigmoid, were documented separately
for volumes of 0.1 cc, 1 cc, and 2 cc. All treatment
plans adhered to the GEC-ESTRO recommendations,
ensuring that doses to 2 cc of the organs at risk other
critical organs (OARs) met the criteria of D2cc for the
rectum, sigmoid, and small bowel below 5 Gy and for
the bladder below 7 Gy, respectively.
Fig. 1: Three dimensional HDR-VBT treatment plan of one endometrium cancer patient. (a) 3D-BRT plan with Foley
catheter, (b) 3D-BRT plan without Foley catheter.
HDR-VBT: High-dose rate vaginal cuff brachytherapy; 3D-BRT: Three dimensional brachytherapy.
Statistical Analysis
Statistical analysis was performed using (SPSS v20.0;
SPSS Inc., Chicago, IL, USA). The doses of the target
volume (HRCTV) and critical organs were compared
between the treatment plan without the Foley catheter
and the decay-and-treat method plan with the inserted
Foley catheter. Paired sample t-tests were performed
to assess the significance of differences in volumes and
doses between the brachytherapy (BRT) plans. Results
are presented as mean values along with their standard
deviations unless otherwise specified. The statistical
significance was considered for p<0.05.
Results
The median age of the patients was 60 years (35?79).
The median ECOG performance score was 1 (0?2) and
75% (n=15) had additional comorbidities. Half of the
patients were obese, and the median body mass index
(BMI) in all patients was 34 kg/m2 (20-40). The features
of patients are summarized in Table 1.
Table 1: Patient and tumor characteristics
Vaginal cuff BRT was applied to 16 patients diagnosed
with endometrial cancer and 4 patients with
cervical cancer with SCC histology. Median 50.4 Gy
(45?50.4 Gy) external RT was applied to 12 patients
with a total of 15 Gy BRT boost in 3 fractions. A total of 27.5 Gy HDR-BRT in 5 fractions was applied to 8
early-stage endometrial cancer patients.
Concerning DVH parameters volumes of HRCTV
and organs at risk were summarized in Table 2. All
critical organ doses were within limits and intestine
doses were notably low. No significant difference was
found between target and critical organ volumes when
the DVH parameters of the plan with and without the
Foley catheter were evaluated. In addition, the mean
and specified cc volumes of OARS such as D0.1, D1,
D2cc, and also mean and D90, D95, and D98 doses of
HRCTV were summarized in Tables 3 and 4. No statistically
significant difference was found between the
two plans in terms of target and critical organ doses.
Table 2: Volumes of HRCTV and organs at risk
Table 3: Dosimetric analysis of HRCTV
Table 4: Dosimetric analysis of organs at risk
Discussion
In our study, we observed no statistically significant
differences between the BRT plans with or without the
insertion of a Foley catheter in terms of the doses of
organs at risk, including the bladder, rectum, sigmoid,
and small bowel, as well as HRCTV doses.
The use of 3D VBT treatment planning, particularly
concerning bladder filling and the optimal planning
schedule, still lacks a consensus. There have been
a limited number of studies investigating the impact of
bladder distention on OAR doses in patients who have
undergone hysterectomy and received HDR-VBT. In a study conducted by Hoskin et al.,[] it was determined
that infusing the bladder with 100 mL of liquid resulted
in a significant 57.5% reduction in the exposure of the
small bowel within the high-dose treatment region, as
assessed on CT slices through the cranial-most dwell
positions, compared to cases with a voided bladder.
However, it is noteworthy that this study relied on 2D
measurements of bladder height, and as such, volumetric
parameters of the bladder were not considered, and
doses to the sigmoid colon and small bowel were not
evaluated. In contrast, Kobzda et al.[] discovered that
the dose to the empty bladder was lower than when the
bladder was full (4.6 Gy, range: 3.1?5.6 Gy, vs. 4.9 Gy,
range: 3.9?5.9 Gy; p<0.05). Furthermore, the doses to
the bowels increased proportionally when the bladder
was empty compared to when it was full (4.6 Gy, range:
2.5?7.3 Gy, vs. 4.1 Gy, range: 1.3?5.7 Gy; p<0.05).
The study by Hung et al.[] explored the dosimetric
impact of bladder distension in 3D treatment
planning for post-operative gynecologic cancer patients
undergoing vaginal brachytherapy. Their study
found no statistically significant differences in rectum,
sigmoid, or bladder dosimetry between treatments
with an empty bladder (indwelling catheter) and a full
bladder (180 mL of sterile water). However, they did
observe a significant reduction in mean small bowel D2cc and small bowel D50% when treating with a full
bladder. As a result, they recommended the preference
for vaginal cylinder brachytherapy with a distended
bladder, citing the dosimetric advantage to the small
bowel. In a prospective trial conducted by Stewart et
al.,[] they assessed radiation doses to normal tissues
during VBT and studied the impact of non-invasive
bladder filling on normal tissue dosimetry using CT
imaging. Their findings revealed that both the volume
and surface area of the bladder receiving radiation
were significantly smaller when the bladder was
empty compared to when it was full. Therefore, they
suggested that, whenever feasible, patients undergoing
HDR-VBT should be treated with an empty bladder.
They highlighted the shift in focus from urinary catheterization,
previously a common method for bladder
emptying during low-dose rate VBT, to patient comfort
and practicality in outpatient HDR treatments. Although
their study did not assess the dosimetry of the
sigmoid and small bowel, they reported a significant
increase in the cylinder-to-bowel distance from 0.575
to 1.16 cm with an empty to full bladder. The study by
Guler et al.[] demonstrated that a combination of a
distended bladder and an empty rectum before vaginal
vault brachytherapy could lead to increased bladder
doses, potentially resulting in lower doses to the
sigmoid colon and small bowel. However, the impact
of bladder distention on gastrointestinal and genitourinary
toxicities remains uncertain. As a result, it may be
adequate to implement appropriate bowel preparation
before each therapeutic session, particularly in highvolume
patient clinics, without the need for bladder
distension. It is important to note that this concept is
tentative and requires further validation through additional
dosimetric and clinical investigations.
Our study had several limitations. First, the contouring
of OARs on CT scans, particularly the rectum,
sigmoid, and small bowel was challenging to distinguish
the borders due to the lack of oral contrast. To minimize
variability and standardize volume delineation,
a single dosimetric contoured all OARs. Additionally,
the study was limited by the relatively small number of
patients analyzed, which restricts the generalizability
of the results. Finally, it is essential to acknowledge that
this investigation was designed as a dosimetric study
and did not incorporate clinical outcomes.
Conclusion
In conclusion, our study suggests that, for vaginal cuff
brachytherapy, an empty bladder appears to be suitable in terms of both critical organ doses and HRCTV coverage.
Additionally, our study revealed that the doses
to the small intestine were notably low. It implies simply
voiding the bladder before treatment sessions to be
sufficient and the use of a Foley catheter for bladder
emptying may not be necessary. However, it is important
to note that this study was primarily designed as
a dosimetric analysis. To establish its clinical implications
more conclusively, further studies are needed to
support and validate these findings.
Peer-review: Externally peer-reviewed.
Conflict of Interest: All authors declared no conflict of interest.
Ethics Committee Approval: The study was approved by
the Ankara University Human Research Ethics Committee
(no: İ07-505-23, date: 21/08/2023).
Financial Support: None declared.
Authorship contributions: Concept - S.D.B., Y.B.; Design
- S.A., Y.A.; Supervision - S.A., S.D.B.; Funding - S.D.B.,
O.C.G.; Materials - Y.B., Y.A.; Data collection and/or processing
- Y.B., Y.A.; Data analysis and/or interpretation -
O.C.G., Y.B.; Literature search - S.D.B., O.C.G.; Writing -
S.A., S.D.B.; Critical review - S.A., O.C.G.
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