Radiotherapy and Oncology xxx (2015) xxx–xxx

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Radiotherapy and Oncology

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Individualised 3D printed vaginal template for MRI guided

brachytherapy in locally advanced cervical cancer
Jacob Christian Lindegaard ⇑, Mikkel Lænsø Madsen, Anders Traberg, Bjarne Meisner,
Søren Kynde Nielsen, Kari Tanderup, Harald Spejlborg, Lars Ulrik Fokdal, Ole Nørrevang
Department of Oncology, Aarhus University Hospital, Denmark

a r t i c l e i n f o a b s t r a c t

Article history: Intracavitary–interstitial applicators for MRI guided brachytherapy are becoming increasingly important
Received 16 November 2015 in locally advanced cervical cancer. The 3D printing technology enables a versatile method for obtaining a
Accepted 8 December 2015 high degree of individualisation of the implant. Our clinical workflow is presented and exemplified by a
Available online xxxx
stage IVA cervical cancer with superior dose distribution.
Ó 2015 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology xxx (2015) xxx–xxx
Keywords:
Image guided brachytherapy
3D printing
Locally advanced cervical cancer
Intracavitary–interstitial brachytherapy

MRI guided adaptive brachytherapy is state of the art in the
treatment of locally advanced cervical cancer [1]. New ambitious
planning aims and dose–volume constraints are being established
as accumulating data are showing how these parameters can be
used to widen the therapeutic window. To satisfy these goals,
new techniques based on combined intracavitary–interstitial (IC/
IS) applicators have been developed and feasibility studies have
shown that these techniques are safe [2–4], providing not only
excellent dose distributions [5] but also improved clinical results
[6,7].
New commercial MRI compatible applicators for the IC/IS
approach such as the Vienna [5] and Utrecht [8] applicator are
now available from the vendors, but only in certain standard sizes,
which may be problematic especially in cases with narrow vaginal
conditions. Also these new applicators do not readily allow for
guidance of individualised oblique needle tracks in terms of angu-
lations and insertion points in the vagina.
In this technical note we present our clinical workflow based on
a 3D printed vaginal template, which combined with a conven-
tional vendor based tandem applicator and plastic needles repre-
sents a new, fast and cheap avenue for individualised IC/IS BT in
cervical cancer.
⇑ Corresponding author at: Department of Oncology, Aarhus University Hospital,
Nørrebrogade 44, Building 5, DK-8000 Aarhus C, Denmark.
E-mail address: jacolind@rm.dk (J.C. Lindegaard).
Materials and methods
The clinical workflow is exemplified by a case concerning a
locally advanced cervical cancer involving the posterior bladder
wall, infiltrating right proximal parametrium and the left parame-
trium to the pelvic wall causing hydronephrosis (FIGO stage IVA).
The patient was treated with external beam radiotherapy (EBRT),
weekly cisplatin and MRI guided pulsed dose rate (PDR)
brachytherapy (BT). The dose of EBRT was 45 Gy/25 fractions
delivered with RapidArcÒ technique (Varian).
BT was initiated with a preplanning tandem-ring implant (BT0)
performed in the fifth treatment week using the 26 mm Varian
plastic tandem and ring applicator (Fig. 1A). Two definitive
implants (BT1 and BT2) were then performed in weeks 6 and 7.
MRI (3T T2 weighted) with the BT applicator in situ, complete con-
touring of target and organs at risk as well as treatment planning
(BrachyVisionTM) were performed for all 3 implants. In the actual
clinical case a CT scan was also performed for BT1 and BT2 to ease
the identification and reconstruction of the oblique needles. The
planning aim was to reach a D90 of CTV-HR >90 Gy EQD2 using
20 hourly pulses of PDR for each definitive implant (Table 1).
The design of the individualised vaginal template was based on
the rendering of the Varian 26 mm plastic ring (Fig. 1B). However,
the ring channel itself was discarded and replaced with 8 guiding
holes interspaced by 45°, for implanting needles in parallel to the
tandem. Treatment planning utilising virtual parallel and oblique
needles was performed to define additional guiding holes in the
virtual vaginal template including points of insertion in the vagina
and angle and implantation depths towards the tumour extension.

http://dx.doi.org/10.1016/j.radonc.2015.12.012
0167-8140/Ó 2015 Elsevier Ireland Ltd. All rights reserved.

Please cite this article in press as: Lindegaard JC et al. Individualised 3D printed vaginal template for MRI guided brachytherapy in locally advanced cervical
cancer. Radiother Oncol (2015), http://dx.doi.org/10.1016/j.radonc.2015.12.012
2 3D printing for cervix cancer brachytherapy

A B

D C

Fig. 1. Workflow for design, production and use of a 3D printed vaginal template in locally advanced cervical cancer: (A) Preplanning of virtual needle positions and tracks
based on T2 weighted 3T MRI scan with a tandem-ring applicator in situ (BT0). (B) Design of the virtual template in SolidWorks based on DICOM information transferred from
BrachyVisionTM. (C) Dummy run assembly and subsequent autoclaving of the 3D printed vaginal template. (D) Implant performed for BT1. A second implant (BT2) using the
same template was performed one week later.

Table 1
Dose–volume histogram parameters, prescribed dose and planning aims in terms of cumulative dose of external beam radiotherapy (EBRT) and brachytherapy (BT) expressed as
equivalent dose in 2 Gy fractions (EQD2). EBRT was 45 Gy/25 fractions and each BT fraction was delivered using pulsed dose rate BT employing 20 pulses, 1 pulse per hour. EQD2
was calculated using a/b = 3 for organs at risk, a/b = 10 for tumour. The repair halftime was estimated to be 1.5 h.

Variable* BT0 (Gy) BT1 (Gy) BT2 (Gy) EBRT + BT1+2 (GyEQD2) Planning aim (GyEQD2)
GTVBT D98 26.7 24.7 22.3 102 >95
CTVHR D98 17.2 17.6 17.3 83 >75
CTVHR D90 20.5 21.0 21.0 94 >90
CTVIR D98 10.2 10.1 9.1 63 >60
Bladder D2 cm3 13.8 16.2 17.1 85# <80
Rectum D2 cm3 7.4 9.5 9.0 61 <65
Sigmoid D2 cm3 7.5 10.1 7.0 59 <65
Bowel D2 cm3 7.2 2.7 3.0 47 <65
ICRU Recto-vaginal point 11.2 11.8 7.7 63 <65
#
Constraint deliberately surpassed due to bladder involvement.
*
Defined according to the ICRU89 GEC ESTRO report [1].

The delineation of the tandem and the needles was coherently
exported in Dicom-format from the treatment planning system.
The exported file was read by an in–house MATLAB-software.
The software transformed the string like delineation of the applica-
tors and needles into a tube like representation, which was written
as a file in the STL-file format. The STL-file could be imported into
computer aided design software (SolidWorks) where the final
design of the vaginal template for 3D printing was performed.
The vaginal template was 3D printed (Fig. 1C) by use multijet
printing (ProjetÒ 3510 SD, 3D Systems) in 2 copies in biocompati-
ble material (VisijetÒ M3 Crystal, 3D Systems). The printing time
was 9 h and was performed over night. After a dummy assembly
the vaginal template was autoclaved and ready for clinical use.
Production time for the vaginal template from the BT0 procedure
until ready for clinical use was 3 days. The 3D printed vaginal tem-
plate was approved by our hygiene unit before clinical use was
initiated.
The implantation of the 3D printed applicator at BT1 and BT2
was in principle similar to the ordinary tandem and ring proce-
dure. With the patient in general anaesthesia and with trans-
abdominal ultrasound guidance the uterine channel was dilated
and the tandem was inserted. The vaginal template was then
applied and attached to the tandem. The second copy of the vaginal
template was available at the operating table to help correct iden-
tification of the guiding holes. For the clinical case presented here 8
parallel and 5 oblique needles in 2 layers and angles (22–47°) were
then implanted to a depth of 1–5 cm according to the preplan
(BT0). The implant procedure including time for anaesthetizing
the patient was about 45 min.
At BT1 the radial distance from the centre of the tandem to the
periphery of the CTV-HR at the left pelvic wall measured 4.6 cm
(Fig. 1D). The volume of GTVBT and CTV-HR at BT1 was 15 cm3
and 45 cm3, respectively. Treatment planning followed our normal
protocol using the same planning aims and dose–volume con-
straints as used with the tandem-ring combined with needles
(Table 1). Loading of the needles was kept at maximal 20% of a
standard loading time for an IC standard stopping position [9].
However, stopping positions in needles inside the template at ‘‘ring
level” were allowed to have a standard loading time. Stopping
positions clearly inside the GTVBT were also allowed to go higher
than 20% if needed.
During PDR-BT treatment it was possible to keep the patient
free of pain by use of ordinary per oral pain medication. Morphine
and tranquilisers were given just before the removal of the appli-
cator. There was no significant bleeding or other acute toxicities
associated with the procedure. At first follow-up 3 months after

Please cite this article in press as: Lindegaard JC et al. Individualised 3D printed vaginal template for MRI guided brachytherapy in locally advanced cervical
cancer. Radiother Oncol (2015), http://dx.doi.org/10.1016/j.radonc.2015.12.012
 J.C. Lindegaard et al. / Radiotherapy and Oncology xxx (2015) xxx–xxx
treatment complete remission was found both by MR and gynaeco-
logical examination in general anaesthesia.
Results and discussion
The acquisition of a quality 3D printer was instrumental for the
implementation of the technology in our already established clin-
ical workflow [7] allowing us to design and print the individualised
MRI compatible templates within a few days without delaying the
definitive BT implants or prolonging overall treatment time. With
an in house 3D printer the production price for each template is
low and allows for single use of the vaginal template, which is also
to be preferred from a hygienic perspective. It is important to note
that the 3D printed vaginal template is not a BT applicator per see
as it is only used as guidance for commercially available applica-
tors with no direct contact to the radioactive source.
Small vaginal dimensions sometimes found in nulliparous and/
or elderly are often prohibitive for applying a ring applicator with
needle cap. In practice we have experienced that the 3D printed
vaginal template is easy to handle even in narrow conditions pro-
viding repeatedly precise needle guidance also for the oblique nee-
dles as substantiated by the similarity of the obtained physical
doses at BT1 and BT2 (Table 1). Correct identification of the needle
guiding holes during implantation can be challenging even having
the second copy of the template available outside the patient and
we are experimenting with colour coding of the holes. The small
diameter of the vaginal template is in our experience more com-
fortable for the patients during PDR treatment and easier to
remove afterwards than our ring applicators with caps for needle
guidance.
The planning aims and dose–volume constraints used (Table 1)
reflect the current results of the multicentre studies retroEmbrace
and Embrace. These constraints are now being implemented in the
forthcoming Embrace II protocol. The presented clinical case with
extreme involvement of the parametrium demonstrates that these
planning aims are realistic if combined IC/IS techniques are
employed. The 3D vaginal template technique further catalyses
the possibilities for obtaining optimal dose distributions by image
guided adaptive BT without the use of additional parametrial boost
by EBRT with all its inherent problems [10]. The vaginal template
has also an added value in clinical cases that in principle could
be treated by a pure IC technique. This involves the possibility to
move the loading of stopping positions from the vagina directly
into the cervix and tumour tissue itself, thereby reducing the like-
lihood of development of significant vaginal morbidity arising from
hyperdose sleeves overlapping vaginal mucosa [11]. Moreover the
parallel needles close to the tandem allow for specific targeting of
the GTVBT with a boost within the boost. Based on the preliminary
results of the Embrace study this seems to be important for local
control [12]. The drawback of the vaginal template is evidently that
it always requires insertion of needles.
Until now we have only been working with a circular vaginal
template. Individualised shaping of the template using for instance
ellipsoid or superellipsoid shapes could be explored including split
templates for more easy removal after treatment. Other clinical
Please cite this article in press as: Lindegaard JC et al. Individualised 3D printed vaginal template for MRI guided brachytherapy in locally advanced cervical
cancer. Radiother Oncol (2015), http://dx.doi.org/10.1016/j.radonc.2015.12.012
3
indications such as vaginal cancer and vaginal recurrences of
endometrial cancer are currently being investigated. At the
moment we are also engaged in creating a user-friendlier interface
between the treatment planning system and the 3D printer. In our
view, it is foreseeable that commercially available treatment-
planning systems in a near future may have features for direct
export of a virtual template for 3D printing, which then could be
produced either in house or delivered by a 3D printing company
within a short production time.
Conflict of interest statement
Jacob Lindegaard has received a honorarium from Varian Medical
Systems. There are no other conflicts of interest of the authors.
Acknowledgements
This work is supported by research grants from the Danish Can-
cer Society and CIRRO—the Lundbeck Foundation Center for Inter-
ventional Research in Radiation Oncology.
References
[1] International Commission on Radiation Units and Measurements, ICRU Report
89. Prescribing, recording, and reporting brachytherapy for cancer of the
cervix. J ICRU, In press.
[2] Fokdal L, Tanderup K, Hokland SB, et al. Clinical feasibility of combined
intracavitary/interstitial brachytherapy in locally advanced cervical cancer
employing MRI with a tandem/ring applicator in situ and virtual preplanning
of the interstitial component. Radiother Oncol 2013;107:63–8.
[3] Dimopoulos JC, Kirisits C, Petric P, et al. The Vienna applicator for combined
intracavitary and interstitial brachytherapy of cervical cancer: clinical
feasibility and preliminary results. Int J Radiat Oncol Biol Phys 2006;66:83–90.
[4] Petric P, Hudej R, Music M. MRI assisted cervix cancer brachytherapy pre-
planning, based on insertion of the applicator in para-cervical anaesthesia:
preliminary results of a prospective study. J Contemp Brachyther
2009;3:163–9.
[5] Kirisits C, Lang S, Dimopoulos J, Berger D, Georg D, Potter R. The Vienna
applicator for combined intracavitary and interstitial brachytherapy of cervical
cancer: design, application, treatment planning, and dosimetric results. Int J
Radiat Oncol Biol Phys 2006;65:624–30.
[6] Pötter R, Dimopoulos J. Clinical outcome of protocol based image (MRI) guided
adaptive brachytherapy combined with 3D conformal radiotherapy with or
without chemotherapy in patients with locally advanced cervical cancer.
Radiother Oncol 2011;100:116–23.
[7] Lindegaard JC, Fokdal LU, Nielsen SK, Juul-Christensen J, Tanderup K. MRI-
guided adaptive radiotherapy in locally advanced cervical cancer from a Nordic
perspective. Acta Oncol 2013;52:1510–9.
[8] Jurgenliemk-Schulz IM, Tersteeg RJ, Roesink JM, et al. MRI-guided treatment-
planning optimisation in intracavitary or combined intracavitary/interstitial
PDR brachytherapy using tandem ovoid applicators in locally advanced
cervical cancer. Radiother Oncol 2009;93:322–30.
[9] Tanderup K, Nielsen SK, Nyvang G, et al. From point A to the sculpted pear: MR
image guidance significantly improves tumour dose and sparing of organs at
risk in brachytherapy of cervical cancer. Radiother Oncol 2010;94:173–80.
[10] Lindegaard JC, Tanderup K. Counterpoint: time to retire the parametrial boost.
Brachytherapy 2012;11:80–3.
[11] Kirchheiner K, Nout RA, Tanderup K, et al. Manifestation pattern of early-late
vaginal morbidity after definitive radiation (chemo)therapy and image-guided
adaptive brachytherapy for locally advanced cervical cancer: an analysis from
the EMBRACE study. Int J Radiat Oncol Biol Phys 2014;89:88–95.
[12] Tanderup K, Kirisits C, Kirchheiner K, et al. Dose response and dose effect of
IGABT in cervix cancer. Radiother Oncol 2015;115:59–60.