Internal motion of the vagina after hysterectomy for gynaecological cancer

Abstract

The purpose of this study was to investigate position changes of the vagina after hysterectomy for early stage cervical or endometrial cancer and their impact on CTV-PTV margins. We also studied their correlation with surrounding organ filling.
Fifteen patients underwent T2-weighted MR scans before and weekly during the course of their EBRT. The vaginal CTVs and the surrounding organs were delineated. PTV margins were derived from the boundaries of the CTVs in the main directions and correlated with changes in the volumes of organs at risk. Additionally we investigated the impact of margin sizes on CTV coverage.
The vaginal CTVs change their position in the pelvis during time with a maximum in anterior-posterior direction. The 95% confidence level was 2.3 cm into the anterior or posterior direction, 1.8 cm to left or right and 1.5 cm towards the cranial. With a homogenous 1.5 cm CTV-PTV margin ≥5% inadequately covered vaginal CTV was seen in only 3.3% of the measurements. This increased to 20.6% with a margin of 1.0 cm. Concerning the impact of organ filling on vaginal position changes we found the only significant correlation with rectal volume and shift of the vagina towards anterior-posterior.
To accommodate the changes in the position of the vaginal CTV inhomogeneous PTV margins should be generated with the largest size in the anterior-posterior direction. The position shifts were only weakly related to the volume of the rectum and not at all to the volumes of other parts of the bowel and the bladder.

Full text

Gynaecological radiotherapy
Internal motion of the vagina after hysterectomy for gynaecological cancer
Ina M. Jürgenliemk-Schulz
a,
⇑
, Malgorzata Z. Toet-Bosma
a
, Gérard A.P. de Kort
b
, Henk W.R. Schreuder
c
,
Judith M. Roesink
a
, Robbert J.H.A. Tersteeg
a
, Uulke A. van der Heide
a
a
Department of Radiation Oncology;
b
Department of Radiology; and
c
Department of Gynaecologic Oncology, University Medical Center Utrecht, Utrecht, The Netherlands
article info
Article history:
Received 24 December 2009
Received in revised form 20 October 2010
Accepted 26 October 2010
Available online 13 December 2010
Keywords:
Gynaecological cancer
Post-operative margins
Organ motion
MRI
abstract
Background and purpose: The purpose of this study was to investigate position changes of the vagina after
hysterectomy for early stage cervical or endometrial cancer and their impact on CTV–PTV margins. We
also studied their correlation with surrounding organ filling.
Materials and methods: Fifteen patients underwent T2-weighted MR scans before and weekly during the
course of their EBRT. The vaginal CTVs and the surrounding organs were delineated. PTV margins were
derived from the boundaries of the CTVs in the main directions and correlated with changes in the vol-
umes of organs at risk. Additionally we investigated the impact of margin sizes on CTV coverage.
Results: The vaginal CTVs change their position in the pelvis during time with a maximum in anterior–pos-
terior direction. The 95% confidence level was 2.3 cm into the anterior or posterior direction, 1.8 cm to left
or right and 1.5 cm towards the cranial. With a homogenous 1.5 cm CTV–PTV margin P5% inadequately
covered vaginal CTV was seen in only 3.3% of the measurements. This increased to 20.6% with a margin
of 1.0 cm. Concerning the impact of organ filling on vaginal position changes we found the only significant
correlation with rectal volume and shift of the vagina towards anterior–posterior.
Conclusion: To accommodate the changes in the position of the vaginal CTV inhomogeneous PTV margins
should be generated with the largest size in the anterior–posterior direction. The position shifts were only
weakly related to the volume of the rectum and not at all to the volumes of other parts of the bowel and the
bladder.
Ó2010 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 98 (2011) 244–248
Treatment of choice for endometrial cancer and early stage cer-
vical cancer is surgery, often consisting of hysterectomy. In the
case of adverse prognostic factors for local or loco-regional recur-
rence, surgery is followed by radiotherapy (RT) or chemoradiation
in order to increase control rates and outcome [1–4]. In the case of
adverse prognostic factors like parametrial infiltration, pelvic node
pathology or lymph-vascular space involvement, external beam
radiotherapy (EBRT) is often preferred over vaginal brachytherapy
[1]. Conventionally, EBRT is delivered by large treatment portals
encompassing parts of the vagina and the draining lymphatics, as
well as the organs at risk located in the pelvis. Control rates are
acceptable with these techniques but treatment related toxicity
Pgrade 3 (3–25%) is not negligible [1,5–9]. With the development
of image guidance and treatment planning technology in RT, more
conformal treatment portals can be produced. Especially multileaf
collimators and intensity modulated radiotherapy (IMRT) tech-
niques allow dose tailoring to the defined target volume with the
potential to spare the surrounding organs and to increase the tar-
get dose [10–19].
However, in the case of a highly conformal treatment set up
precise information on the position changes of the RT target during
the course of the treatment is mandatory [20–26]. A pitfall in this
respect can be internal target motion induced by variations in in-
tra-abdominal organ filling. For advanced stage cervical cancer,
primarily treated with (chemo)radiation, target position changes
during the course of the treatment and their impact on treatment
margins have been investigated [21–23].
The purpose of this study was to investigate position changes of
the vagina after hysterectomy for early stage cervical or endome-
trial cancer and their impact on CTV–PTV margins. We also studied
their correlation with surrounding organ filling.
Materials and methods
Fifteen patients with gynaecological cancer, treated at our
department between March 2007 and September 2007, were en-
rolled in the study. Thirteen patients had cancers originating from
the uterine corpus and two patients had cervical cancer. Staging
was performed according to the International Federation of Gyne-
cology and Obstetrics (FIGO) classification [27]. All patients had
FIGO stage I disease.
0167-8140/$ - see front matter Ó2010 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.radonc.2010.10.026
⇑
Corresponding author. Address: Department of Radiation Oncology, University
Medical Center Utrecht, Heidelberglaan 100, 3548 CX Utrecht, The Netherlands.
E-mail address: i.m.schulz@umcutrecht.nl (I.M. Jürgenliemk-Schulz).
Radiotherapy and Oncology 98 (2011) 244–248
Contents lists available at ScienceDirect
Radiotherapy and Oncology
journal homepage: www.thegreenjournal.com

In accordance with our treatment protocol patients were trea-
ted conventionally with 3–4 treatment fields (bilateral portals
combined with either AP/PA fields or one single PA field) to a total
of 46 Gy in 23 fractions of 2 Gy, irradiating the proximal part of the
vagina (vaginal clinical target volume CTV)), the parametria and
the draining lymphatics (up to the level of L5/S1). Patients were
treated in prone position. To prevent any rotation of the hip, a knee
cushion for alignment of the legs was used in each fraction. No fur-
ther immobilization devices were used. No special measures were
taken to minimize the variation in rectum and bladder filling.
Each patient underwent a CT scan (CT aura, Philips Medical Sys-
tems, Best, The Netherlands). Contiguous 3 mm slices were made
from the iliac crest to the ischial tuberosities. In order to accurately
delineate the regions of interest, MR images were made using a
1.5T MRI scanner (Gyroscan NT Intera, Philips Medical Systems,
Best, The Netherlands). Patients were scanned in the treatment po-
sition, using a flat tabletop insert. Because of its superior soft-tis-
sue contrast, MRI was used to delineate the target volumes as
well as organs at risk (OAR). All 15 patients underwent MR imaging
before treatment and weekly during EBRT. The first week MRI was
performed after about 10 Gy, the second week MRI after about
20 Gy, third week MRI after about 30 Gy and the fourth week
MRI after about 40 Gy. Images were acquired using a Synbody coil
according to the following protocol: axial Proton Density images
(TE 20 ms, TR 1960 ms) with 6.6 mm thick slices of the whole
abdomen and pelvis; axial, sagittal and coronal T2-weighted
images (TE 100 ms, TR 3000 ms), with 4.5 mm thick slices from
the body of L5 to the ischial tuberosities. The images were taken
without additional vaginal markers, contrast agents or vaginal
fillings.
We used the planning CT scan as the frame of reference for the
MRI data sets of all time points. Therefore, we registered the MRI
data sets to the CT scan using a mutual information-matching algo-
rithm (VTK CISG Registration Toolkit, Kitware, York). While the ori-
ginal MRI datasets were used, we extracted a dataset containing
only the bony anatomy obtained from the CT using a threshold
algorithm. This dataset was used so that the bony anatomy of
the CT and each of the five MRI datasets could be matched. Struc-
tures contoured on the five MR images were transferred to the CT
or MRI coordinate frame using the transformation and image fu-
sion functionality available in our in-house developed contouring
software package Volume tool [31]. In an earlier study, we showed
that the registration accuracy was on average 1.0–1.4 mm [22]. The
analysis of the internal motion was carried out using the five sets
of delineations overlayed on the CT scan. For display purposes
the delineations were overlayed on the pre-treatment MRI scan.
A radiation oncologist delineated the outer contour of the prox-
imal vagina (vaginal CTV) on the T2-weighted pre-treatment and
first to fourth week MR images (Fig. 1). The vaginal CT as contoured
here is part of the total post-operative CTV. Parametria, surgical
bed and draining lymphatics are not part of this investigation. Con-
touring was performed on the axially sliced datasets using also the
information of the sagittal and coronal images to define the exten-
sion of the vagina wall in 3 dimensions. In clinical practice the vag-
inal CTV is defined as vaginal vault and proximal vagina. Depiction
of the lower vagina and especially the introitus without using
intravaginal contrast is difficult on MRI. We, therefore, set the cau-
dal border of the vaginal volume to the cranial border of the ramus
inferior of the Os pubis. This bony reference is used as an indicator
for the inferior treatment field border in our clinical practice. A
radiologist specialized in gynaecologic
oncology and a gynaecologic oncologist reviewed the delin-
eated vaginal CTVs. The following critical organs were delineated
using the outer organ wall: bladder, rectum, sigmoid and bowel
(bowel up to the level of the aorta bifurcation). Vaginal volumes
were calculated for 14 patients, one case was excluded because
of persisting haematoma.
We have chosen a relatively simple and pragmatic approach to
analyze the vaginal position changes, along the lines of Van de
Bunt et al. [22]: for each of the four weekly MRI scans an inhomo-
geneous margin was generated around the pre-treatment CTV
encompassing the boundaries of the weekly CTV in the six main
directions (anterior, posterior, left lateral, right lateral, superior
and inferior) (Fig. 1). A consequence of this approach is that a mar-
gin of zero in a given direction does not imply the absence of a
shift, but that the boundary of the new volume lies inside the
pre-treatment volume.
We used the margin sizes derived for the weekly MRI scans as a
surrogate for the shift of the target to assess the impact of variation
in organ-filling. To this end a margin in the posterior (P) direction
is interpreted as positive, in the anterior (A) direction as negative.
Similarly left lateral (L) is positive, right lateral (R) negative and
cranial positive (S). As the caudal margin was related to the bony
anatomy of the pelvis in all the cases we considered the margin
to be zero in this direction. Points with a margin equal to zero
are removed from this analysis because the value of zero only
means that the new structure fell within the pre-treatment
structure.
A paired t-test was used to compute the differences in vaginal
volume between the MRI scans taken in different weeks. A least
square linear regression is performed to study the correlation be-
tween margin sizes and change in rectum, sigmoid, and bladder
volume.
Results
Vaginal and OAR volumes
Post-operative vaginal volumes were easily depicted on the T2
weighted MRI scans before and during radiotherapy and were cal-
culated for 14 patients and five moments. The calculated 70 vol-
umes appeared to be quite comparable with on average 24.9 cm
3
(SD 7.6). We did not see significant changes during the course of
treatment with on average 23.6, 24.4, 26.0, 24.3 and 23.3 cm
3
be-
fore treatment and in week 1, 2, 3 and 4, respectively. One of the
15 patients was excluded from this analysis because of post-oper-
ative haematoma in the vagina vault and an initial vaginal volume
of 98 cm
3
, which is about 4 times the volume that we saw in the
other patients (Fig. 2C). For calculated volumes of rectum, sigmoid
and bladder we noticed a decrease from pre-treatment on average
106.7, 142.0 and 153.6 cm
3
to 50.9, 99.6 and 115.3 cm
3
in week 4.
Treatment margins
The impact of vaginal shifts on the coverage of the vaginal vol-
ume is depending on the chosen treatment margins. In order to
Fig. 1. (A) Transversal view of the pre-treatment vaginal CTV (red) and four CTVs at
later time points. The generic PTV, which encloses the pre-treatment en all intra-
treatment CTVs is indicated in yellow; (B) analogous for the sagittal direction.
I.M. Jürgenliemk-Schulz et al. / Radiotherapy and Oncology 98 (2011) 244–248 245

determine these margins we used the 4 intra-treatment MRIs for
all 15 cases. Around each of the pre-treatment vaginal CTVs inho-
mogeneous margins were derived to accommodate the changes in
the position of the vaginal CTVs and to generate the PTVs on the
weekly MRI scans (Fig. 1). This results in 60 margin sizes in the
anterior–posterior, left and right lateral, and cranial directions. In
these margin sizes the influence of internal organ motion as well
as variations in vaginal shape is included. Generic margin sizes that
allow complete coverage of 90% and 95% of the vaginal volumes
are within the ranges of 1.9–1.1 cm and 2.3–1.5 cm, respectively,
and most pronounced in the anterior–posterior direction (2.3 and
1.9 cm anterior–posterior, 1.8 and 1.1 cm left and right and
1.5 cm cranial).
With homogenous CTV–PTV margins of 1.0 and 1.5 cm, as of-
ten used in clinical practice, we found that vaginal volumes were
not completely covered in 53.3% (32 of 60) and 20.0% (12 of 60)
of the intra-treatment situations, respectively. With a margin of
1.0 cm there was quite some amount of vaginal volume that was
covered inadequately, up to 5% in 31.7% (19 of 60) of the
measurements, more than 5% in 20.6% (13 of 60), respectively
(Fig. 3). With a margin of 1.5 cm in all directions the amount
of inadequately covered volume was lower, up to 5% in 16.7%
(10 of 60) of the measurements, more than 5% in only 3.3% (2
of 60), respectively.
Impact of organ filling
Concerning the relation between organ filling and vaginal shifts
we found no correlation with changes in bladder, sigmoid and bo-
wel volumes. The only significant (p< 0.001) but weak correlation
(correlation coefficient 0.44) was observed between variations in
rectum filling and vaginal motion towards anterior or posterior
(Fig. 4). We noticed a trend towards decreased rectal filling over
time resulting in a volume reduction from pre-treatment
Fig. 2. Changes in volume and position of vaginal CTVs (green contours), T2 weighted sagittal MRI before and in the last week of treatment. (A) Stable volume, no vaginal
motion, despite changes in rectum and bladder filling. (B) Vaginal motion and deformation due to changes in organ filling. (C) Substantial volume reduction due to resorption
of post-operative haematoma.
0
10
20
30
40
50
60
0102030
% Vaginal CTV outside PTV
Frequency
10mm
15mm
Fig. 3. Influence of clinically accepted CTV–PTV margins on percentage of vaginal
CTV coverage.
-3
-2
-1
0
1
2
3
4
5
-200 -150 -100 -50 0 50 100
volume change rectum [cm3]
ant-post shift vagina [cm]
post
ant
Fig. 4. Correlation of rectal volume changes and vaginal shifts. Point 0 indicates
rectal volume and vagina position on the pre-treatment MRI. With decreasing rectal
volumes there is a trend towards larger shifts into the dorsal direction. Abbrevi-
ations: post = posterior, ant = anterior.
246 Internal motion of the vagina after hysterectomy for gynaecological cancer

106.7 cm
3
(SD 45.0) to 50.9 cm
3
(SD 20.9). As indicated in Fig. 2B
vaginal volumes, and mainly their cranial part, tend to move into
the posterior direction if the rectal volume decreases. The required
CTV–PTV margins into the posterior direction from pre-treatment
to week 1, week 2, week 3 and week 4 were on average 1.0 cm
(SD 0.8), 1.3 cm (SD 0.9), 1.1 cm (SD 0.8), 1.5 cm (SD 1.0), respec-
tively. There were no significant relations between organ filling
and vaginal shifts towards left–right or cranial (correlation coeffi-
cients between 0.25 and 0.03).
Discussion
For patients with cervical or endometrial cancer, post-operative
EBRT of the pelvic region is often part of their curatively intended
treatment [1–3]. The beneficial effect on tumour control, however,
has to be balanced against EBRT related side effects, mainly on
bladder and bowel (large and small) [5–9]. Modern radiotherapy
techniques, such as IMRT, offer more conformality with potential
in either dose escalation or organ at risk sparing. However, the
more conformal treatment portals are the more precise the dose
is tailored to the target volume, the better one has to be informed
about volume or position changes of the target during the course of
the treatment. In post-operative radiotherapy for cervical or endo-
metrial cancer risk reduction on tumour recurrence in the vagina is
one of the intentions. The proximal part of the vagina is defined as
CTV and needs to be identified for treatment planning purposes.
MR images are preferable over CT scans in the case of gynaecolog-
ical cancers [28–30] and we, therefore, used MR images for con-
touring purposes. The vaginal volumes as calculated from the
delineations on T2 weighted scans were overall comparable and
stable on the weekly MRI’s with small standard deviations. We no-
ticed one exceptional case of post-operative haematoma in which
MRI provided additional information for the clinical treatment
planning. The dimension of this haematoma would have been
underestimated without image guidance (Fig. 2C).
But precise information about the shape and extension of the
treatment target before starting highly conformal radiotherapy is
not enough. Information on position changes during the course
of the treatment is also needed. On the one hand, as indicated in
Fig. 1B, the shape of the vaginal CTV can vary over time with some
deformations especially in the region of the vagina vault. On the
other hand the vagina (and especially the vault) moves within
the pelvis during the course of EBRT. A CTV–PTV margin of
2.3 cm towards anterior–posterior would allow complete vaginal
coverage in 95% of the operated and non-operated cases. These
shifts are in the same order of magnitude as the position changes
of the CTVs when the primary tumour is still in situ. For primary
cervical cancers we are informed in this respect by studies from
Chan et al. [21], Van de Bunt et al. [22] en Taylor et al. [23], which
show that essential changes in target positions occur during the
course of radiotherapy. The magnitude of the primary CTV shifts
lie in the order of 1–2.5 cm with variations into the different direc-
tions and maximum towards anterior–posterior. Based on a study
of Kerkhoff et al. [32] it can even be expected that position changes
occur within a single EBRT fraction. In order to investigate which
margins might accommodate the post-operative vaginal position
changes we used the approach as described by van de Bunt et al.
[22]. This approach is easily applicable in the commercially avail-
able planning software. More advanced methods that allow adap-
tive individualisation for deformable treatment targets are
published by Wright et al. [33] and Redpath and Muren [34].
Additional to the directions and magnitude of the vaginal CTVs
shifts, we investigated their relation to the filling status of the sur-
rounding organs. Only in case of the rectum we found a significant
although weak correlation between CTV shift and organ volume.
The smaller the rectal volume was the more pronounced was the
shift towards posterior. A weak correlation between target volume
shifts and rectal volume changes is also documented by van de
Bunt et al. [22]. In contrary, for prostate, a strong relation is found
between target volume position and rectal volume changes [35].
The difference between a strong and weak correlation might be
due to the limited number of patients that have been investigated
in our study. We found no correlation between bladder, sigmoid or
bowel filling and the position of the vagina in the pelvis. This might
be due to the fact that the complex movements and volume
changes of these organs are related to each other. In the example
in Fig. 2A the bladder filling has increased between the two mo-
ments of investigation. The bowel loops have shifted and the rec-
tum filling has changed, but in the end the vaginal CTV stays in
the same place. In Fig. 2B, however, all the differences in organ fill-
ing and position changes shift the vagina top towards posterior.
These findings help to understand that the measures that are taken
to control bladder or rectum fillings do not necessarily reduce po-
sition shifts of the radiation targets in the small pelvis in all pa-
tients in the same way and do not necessarily allow a safe
reduction of treatment margins.
Given herein the presented magnitude of the vaginal shifts one
can expect that clinically accepted CTV–PTV generic margins of
about 1.0 cm without reliable position verification measures might
be too small for an adequate irradiation of the CTVs. And indeed,
with 1.0 cm in all directions we found more than 5% of the CTV ly-
ing outside the PTV in 20.6% of the measurements. With a margin
of 1.5 cm the situation was improved with only at two moments
more that 5% of the CTV was inadequately covered. In how far this
lack of coverage might have impact on the tumour control proba-
bility has not been investigated in this study. It anyhow indicates
the need for appropriate position verification procedures during
the course of treatment to reduce a possible risk, especially when
highly conformal treatment techniques are used.
Conclusion
In gynaecological patients after hysterectomy we found sub-
stantial position shifts of the proximal part of the vagina on five
consecutive MRIs during the course of post-operative radiother-
apy. These shifts were only weakly related to rectal volume and
not at all to the volumes of other parts of the bowel and the blad-
der. To accommodate the position changes of the vaginal CTV inho-
mogeneous PTV margins should be generated with a maximum in
the anterior–posterior directions.
Conflict of interest statement
No conflict of interest exists for the work presented here.
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248 Internal motion of the vagina after hysterectomy for gynaecological cancer