Introduction
Intracavitary vaginal brachytherapy (BT) can be administered
either alone or after external beam radiotherapy (EBRT) in the adjuvant treatment of patients who have
undergone surgery for cervical and endometrial cancer.
[,] In intracavitary vaginal BT applications, the organs
at risk (OARs) affected by radiotherapy (RT) include the bladder, rectum, sigmoid colon, and small bowel.
Reducing the potential side effects associated with BT is
highly dependent not only on the quality of the application
and the administered dose but also on the quality
of the computerized treatment planning (TP) for BT.
Computerized TP enables the delivery of an adequate
dose to the clinical target volume (CTV) while restricting
the doses to the OARs. Compared to single-point
optimization, more optimal dose distributions can be
achieved through various optimization strategies, including
manual optimization, geometric optimization
(normalized to a point or line), graphical optimization,
and inverse planning volumetric optimization.[-]
In the literature, there exists only one study that
compares inverse planning volumetric optimization
with forward planning reference line (RL) optimization
in vaginal cuff BT. In Bahadur et al.[]s study, the
coverage of the CTV and the doses received by OARs,
specifically in terms of 2 cc volumes (D2cc) (maximum
radiation dose delivered to the most exposed 2 cc of a
specified organ or tissue in a RT treatment plan) were
compared among forward planning techniques using 2
conventional optimization methods (optimization at a
single point 0.5 cm proximal to the apex of the stump
applicator and optimization at the RL drawn 0.5 cm
away from the lateral aspect of the applicator) and the
inverse planning technique utilizing volume optimization.
However, in that study, the line in the RL optimization
is a straight uncurved line and does not adequately
represent the dose received by the vaginal vault.
Given that the vaginal cuff is not solely represented by
the vaginal side walls, an accurate comparison between
RL optimization and volumetric optimization necessitates
that RL covers both the curved apex and straight
side walls of the vaginal cuff. Thus, our study aims to
compare inverse planning using vaginal cuff CTV optimization
with forward planning using RL optimization
(RL created by combining 8 points at 0.5 cm from the
apex and side walls of the vaginal cuff surface) in terms
of CTV dose-volume parameters and OAR doses. As
the first study comparing forward planning using an
accurate RL optimization technique with inverse planning
using volumetric optimization, our aim is to elucidate
which optimization technique proves more relevant
for routine clinical applications in vaginal cuff BT.
Methods
The study was conducted according to the guidelines
of the Declaration of Helsinki and approved by
Non-interventional Research Ethics Committee (No:
2019/13-21, Date: 22/05/2019).
This retrospective study used CT scans of 20 patients
with cervical and endometrial cancer who underwent
adjuvant EBRT (4500 cGy) followed by 3D BT (3x600
cGy). Our study aimed to compare the doses obtained
from volumetric optimization and RL optimization in
vaginal cuff BT using the stump applicator. The Varian
ARIA Oncology Information System for Radiation
Oncology (OIS for RO) server and Varian BrachyVision
v.11.0 Brachytherapy Treatment Planning System
were utilized for data management and BT planning,
respectively. GammaMedplus iX HDR Afterloader System
housing 192Iridium radioactive source was used for
treatment delivery in BT.
In vaginal cuff BT, stump applicator with the largest
diameter suitable for the patient"s vaginal width had
been inserted. In the CT slices obtained, vaginal length
was measured in sagittal sections from the vaginal apex to
the vaginal entrance. Vaginal cuff CTV's length was taken
as one third of the measured vaginal length. Vaginal cuff
CTV volume was delineated by adding a 0.5 cm margin
to the cylindrical applicator contour in all directions and
cropping the cylindrical applicator contour from the CTV
contour. For RL length determination, the vaginal cuff
CTV length was considered from the sagittal CT sections.
The midline of the stump applicator in the coronal plane
was selected as the section to draw RL, and the RL was
drawn symmetrically on both sides of the applicator with
a total of 8 points located 0.5 cm away from the applicator.
Figure 1 illustrates the creation of the RL for each case.
Fig. 1. Determining the reference line in the computed tomography sections.
In inverse planning using volumetric optimization,
dose-volume parameter criteria for the CTV were
determined as follows: D98%≥85%, D90%≥100%,
V100%≥92.5% and D50%/D90%≥1.5 (DX%: minimum
dose expressed in percentage received by a
volume of a structure, V100%: percentage of CTV
receiving 100% of the defined dose). In inverse planning
using volumetric optimization, the biological
equivalent dose in terms of 2 Gy per fraction (EQD2)
according to α/β=3 that 2 cc volumes of OARs would
receive were restricted ensuring they did not exceed
recommended limits. In the light of GEC-ESTRO recommendations,
OAR D2cc EQD2 cumulative doses
for bladder, sigmoid, rectum and bowel were set as
≤9000 cGy, ≤7000 cGy, ≤7000 cGy and ≤7000 cGy,
respectively.[] In inverse planning, all criteria (CTV
and OARs) were given equal priority, and no user
intervention was made during volumetric optimization
in any plan. Figure 2 illustrates 3D view of CTV
and OARs contoured for inverse planning using volumetric
optimization. RL optimization aims to ensure
dose consistency along the RL without consideration of dose to OARs during optimization. Inhomogeneity
correction was not performed in BT planning. After
dose calculation was made in RL, the dose-volume
parameters of the vaginal cuff CTV and OARs were
examined through Dose Volume Histogram (DVH).
Comparisons were made between the two optimization
techniques (volumetric and RL optimization) in
terms of OAR (bladder, rectum, sigmoid, and bowel) D2cc doses. In addition, two optimization techniques
were compared in terms of CTV dose-volume parameters
(D90%, D50%/D90% and V100%).
Fig. 2. (a) CTV contour in 3D, (b) CTV and OAR contours in 3D.
CTV: Clinical target volume; OAR: Organs at risk.
Given the number of cases included in the study
was below 30, statistical analysis was performed using
non-parametric tests (Wilcoxon Signed-Rank test comparing
two paired samples) with SPSS software. The p
value of <0.05 was considered statistically significant.
Results
The stump applicator diameters used in our study
were 3 and 3.5 cm. It was found that the craniocaudal
length of CTV varied between 2.5 and 4 cm
across cases.
Cross-sectional images illustrating the dose distributions
of inverse planning volumetric optimization
and forward planning RL optimization are presented
in Figure 3.
Fig. 3. (a) Cross-sectional images of the dose distribution obtained by reference line optimization, (b) cross-sectional images
of the dose distribution obtained with volumetric optimization.
Table 1 displays the statistical comparison of OAR
EQD2 total (EBRT+BT) doses obtained through volumetric and RL optimization across all cases (Table 1).
Table 1 Statistical comparison of OAR EQD2 total
(EBRT+BT) doses obtained through inverse
planning volumetric optimization and forward
planning RL optimization
In Table 1, it is seen in general that statistically significantly
lower doses were obtained from volumetric optimization
for all OARs compared to RL optimization.
Table 2 presents the statistical comparison of CTV
dose-volume parameters, including D90%, V100%,
and D50%/D90%, obtained through volumetric and
RL optimization (Table 2). Across all cases, D90% and
V100% parameters obtained from RL optimization are
observed to be statistically significantly higher compared
to volumetric optimization. Conversely, D50%/
D90% parameter (recommended to be as low as possible
below the 1.5 threshold value) obtained from volumetric
optimization is statistically significantly lower
compared to RL optimization.
Table 2 Statistical comparison of CTV dose-volume parameters
D90%, V100% and D50%/D90% obtained
through inverse planning volumetric optimization
and forward planning RL optimization
Mean total reference air kerma (TRAK) was 3213±323
(2526-3573) cGy.cm2 and 3071±306 (2246-3507) cGy.
cm2 for RL and volumetric optimization, respectively.
Range of dwell times was 16-119.8 seconds, and 9.3-73.3
seconds for RL and volumetric optimization, respectively.
Discussion
In vaginal cuff BT, geometrical line optimization,
graphical, or inverse planning volumetric optimization
have been shown to achieve more optimal dose distribution
compared to geometrical single-point optimization.[-] However, a standardized approach has not
yet been established in this regard.
In Bahadur et al.[]s study, CTV and OAR dosevolume
parameters were compared using three different
optimization techniques in BT TP. In their series,
26 patients were administered three fractions of 400
cGy as BT after a total dose of 4500 cGy EBRT. The
three techniques included normalization to a single
reference point positioned 0.5 cm away from the vaginal
vault towards cranial direction, optimization to the
RL created 0.5 cm away from only the lateral wall of the
vagina, and inverse planning volumetric optimization
using dose-volume criteria for CTV and OARs.
In our study, we compared CTV and OAR dosevolume
parameters using two different optimization
techniques: Inverse planning volumetric optimization
and forward planning RL optimization. In our series,
20 patients had been treated with three fractions of 600
cGy BT following a total dose of 4500 cGy EBRT
Bahadur et al.[] study compared inverse planning
volumetric optimization with forward planning RL optimization;
however, their RL was not curved in accordance
with the shape of vaginal cuff and thus did not represent
the apex of vaginal cuff. However, since the vaginal
cuff is not solely represented by the vaginal side walls, an
appropriate comparison necessitates RL covering both
the vaginal apex and vaginal side walls completely. In our
study, RL was created by combining 8 symmetrical points
0.5 cm away from the apex and side walls of the vaginal
cuff surface. The superiority in our study is the formation
of a curved RL similar to the shape of CTV. To our
knowledge, our study is the first one to compare forward
planning RL optimization and inverse planning volumetric optimization in vaginal cuff BT with an accurate
methodology, and it aims to determine the more relevant
optimization technique for clinical routine applications.
Although the optimization criteria for CTV and
OARs in inverse planning volumetric optimization differed
between the two studies, equal priority was given
to all criteria in both studies. Bahadur et al.[] found
that among 3 different optimizations, inverse planning
volumetric optimization provided the best CTV dose
coverage. In our study, criteria including D98%≥85%,
D90%≥100%, V100%≥92.5%, and D50%/D90%≤1.5
for CTV were provided for all cases in both volumetric
and RL optimizations. Although RL was statistically
significantly superior in D90% and V100% parameters
of CTV, volumetric optimization was statistically significantly
superior in D50%/D90%.
Since CTV dose-volume criteria were met in all
cases in our study, the choice between optimization
methods is unlikely to create a disadvantage in terms
of disease control.
In Bahadur et al.[]s study, RL optimization provided
the lowest dose among 3 different optimizations
for OARs. In our study, it was observed that the limit of
D2cc EQD2≤7000 cGy was exceeded in only 1 case for
the rectum in the volumetric optimization and in 3 cases
in the RL optimization. It should be noted that 7500
cGy - which is the most recommended upper dose limit
- was not exceeded in these 4 cases. Unlike Bahadur
et al.[]s study, our study showed that volumetric optimization
could provide statistically significantly lower
doses for OARs compared to RL optimization. This difference
in the sparing of OARs between the two studies
is attributed to differences in RL shape and location as
well as OAR optimization criteria.
Recently, Rovirosa et al.[] reported the results of a
dosimetric study on HDR 3D planning in vaginal cuff BT.
In that study, it is concluded that prescribing at 5 mm and
the use of an applicator diameter of 3.5 cm is the most
adequate for CTV coverage with a lower vaginal mucosa
dose. In our study, we also preferred drawing the reference
line at 5 mm distance from the vaginal surface for
RL optimization, and we contoured the vaginal cuff CTV
with a thickness of 5 mm for inverse planning volumetric
optimization. In terms of applicator diameter, we also
preferred using the largest stump applicator diameter
suitable for the patient's vaginal width. Thus, the applicator
diameter was 3.5 cm in relevant patients in our series.
When multichannel applicators are used instead of
single channel applicators in vaginal BT, the choice of
optimization method becomes even more important.
In a study performed by Carrara et al.,[] different treatment planning optimization methods were compared
in vaginal HDR BT with multichannel applicators.
IO methods were more effective in reducing hot
spots to the vaginal mucosa compared to forward optimization
methods.
It should be noted that when time required for different
optimization methods is considered, geometric
optimization (normalized to a point or line) and
graphical optimization usually are more advantageous
than IO methods. Especially in busy clinics with high
workload, selection of optimization method may also
be influenced by this time factor.
Limitations of the study
The limitation of the study is the number of patients
included in the study being less than 30.
Conclusion
Consequently, while both volumetric and RL optimizations
meet the determined criteria for CTV, this is not
always the case for OARs. In RT, adherence to the "As
Low As Reasonably Achievable" (ALARA) principle
for OARs is essential, aiming to minimize OAR dose
exposure. In this context, the resultant significant difference
in favor of inverse planning volumetric optimization
regarding OARs supports the use of this optimization
technique for routine clinical applications in
vaginal cuff BT with the stump applicator.
Ethics Committee Approval: The study was approved by
the Dokuz Eylül University Non-interventional Research
Ethics Committee (no: 2019/13-21, date: 22/05/2019).
Informed Consent: Informed consent was obtained from
all participants.
Conflict of Interest Statement: The authors have no conflicts
of interest to declare.
Funding: The authors declared that this study received no
financial support.
Use of AI for Writing Assistance: No AI technologies utilized.
Author Contributions: Concept - S.S., Ş.K., K.A., A.N.D.;
Design - S.S., Ş.K., K.A., A.N.D.; Supervision - K.A., A.N.D.;
Materials - S.S., Ş.K., A.N.D.; Data collection and/or processing
- S.S., Ş.K., K.A., A.N.D.; Data analysis and/or interpretation
- S.S., Ş.K., K.A., A.N.D.; Literature search - S.S.,
Ş.K., K.A., A.N.D.; Writing - S.S., Ş.K., K.A., A.N.D.; Critical
review - S.S., Ş.K., K.A., A.N.D.
Acknowledgments: The authors would like to thank Doğa
Yıldırım for her help in translating this manuscript.
Peer-review: Externally peer-reviewed.
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