Review Article

Evolution of Brachytherapy Applicators for the Treatment of

Cervical Cancer
Ankur Mourya, Lalit Mohan Aggarwal, Sunil Choudhary
Department of Radiotherapy and Radiation Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India

Abstract
Brachytherapy applicators have come a long way since Danlos developed early intracavitary applicators to treat cervical cancer patients.
Therefore, this review will help in the neoteric designs of intracavitary applicators. A detailed literature survey of the gynecological brachytherapy
applicators from the era of preloading to conceptual intensity‑modulated brachytherapy applicators has been carried out. Depending on the
extent of the disease and patient anatomy, the selection of brachytherapy applicators plays a pivotal role in the treatment of cervical cancer.
Furthermore, the selection of the applicators is also based on the imaging modalities to be used for applicator reconstruction and treatment
planning. Dose acceleration in the target and reduction in nearby organs at risk can be optimized using an applicator having the capabilities
of intensity‑modulated brachytherapy. Now, three‑dimensional printed applicators are used for patient‑specific tailor‑made treatment and
they are fast replacing the old conventional applicators. Newer advancements in technology have greatly influenced the neoteric designs of
intracavitary brachytherapy applicators.

Keywords: Brachytherapy applicator, brachytherapy device, cervical cancer brachytherapy, gynecologic brachytherapy, three‑dimensional
printing
Received on: 29‑04‑2021 Review completed on: 07-08-2021 Accepted on: 19‑09‑2021 Published on: 31.12.2021

Introduction selection of radioactive sources. In the due course of time,

brachytherapy (BT) applicators have evolved distinctly into
The use of radioactive substances in medicine was started
a high‑end technology modality of radiation therapy, that
when Pierre curie gave a small amount of radium to
incorporates three‑dimensional (3D) imaging and sophisticated
Dr.  Henry Alexander Danlos with a suggestion that it can
planning methods as the standard of care.[5,6]
be used to treat various pathologies conditions. Danlos early
trials motivated the development of the first applicators to fit
the various purposes of surface and intracavity applications. Preloaded Applicators
Subsequently, in 1903, Alexander Gram Bell suggested the use Danlos used radium for treatment in 1901 and developed the
of radium sealed in a glass tube that could be inserted inside first intracavitary applicator [Supplementary Figure 1a].[7,8]
the carcinoma tumor for treatment. He handed over radium applicators to Dr. Wickham with
150 mg of radium. Wickham incorporated the radium into a
Intracavitary irradiation for cervical cancer in the early years
water-resistant varnish that could be melted, poured, or painted
was fraught with complications. However, with clinical
over a variety of flat, square, or round copper receptacles
experience and improvement in the designs of the applicator,
[Supplementary Figure 1b-d].[9]
such complications have diminished and the cure rate of
cancer has improved.[1‑3] The treatment of cervical cancer has
been highly effective with the combination of intracavitary Address for correspondence: Lalit Mohan Aggarwal,
Department of Radiotherapy and Radiation Medicine, Institute of Medical
and external irradiation, for the early and advanced stages.[4] Sciences, Banaras Hindu University, Varanasi ‑ 221 005, Uttar Pradesh,
Sequelae and complications have been reduced to a minimum India.
by the judicious use of correct applicators  (intracavity or E‑mail: lalitm@bhu.ac.in
interstitial), careful placement of the applicators and proper
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DOI: How to cite this article: Mourya A, Aggarwal LM, Choudhary S. Evolution
10.4103/jmp.jmp_62_21 of brachytherapy applicators for the treatment of cervical cancer. J Med
Phys 2021;46:231-43.

© 2021 Journal of Medical Physics | Published by Wolters Kluwer - Medknow 231

 Mourya, et al.: Gynecological brachytherapy applicators

His applicator resembled an inverted umbrella with an was fixed. Vaginal applicators were connected with a flexible
intrauterine stem screwed into the concave inner center of the spring having a rubber coating. Uterus and vaginal applicators
vaginal portion. The stem and the concavity were painted with were not fixed together. In this method, dose prescription was
the radioactive varnish and the whole applicator was covered in terms of mg‑hr, therefore, there was a lack of information
with a sheath of lead for filtration.[9] about the actual dose to the tumor and the organs at risk (OAR).
However, the actual dose was later found to be 6,150 roentgen
These primary practices recognized the use of ionizing
at Manchester Point A.[21]
radiation in medicine and clinicians established their own rules
for the treatment of cervical cancer. The treatment given by
different clinicians was not the same; therefore, Stockholm, Manchester System
Paris, and Manchester Systems were evolved. All these systems Tod and Meredith developed the Manchester system in 1938
have their own applicator design, set of rules for activity and introduced Point A for dose prescription. Initially, Point A
distribution, and dose prescription. was defined as a point 2 cm lateral to the central canal of the
uterus and 2 cm up from the mucus membrane of the lateral
Stockholm System fornix, in the axis of the uterus.[21]
Stockholm system appeared in 1910 and was modified During the era of X‑ray radiographs, dose calculations
subsequently.[10‑12] It consisted of an intrauterine tube and were done with the help of radiographs and localization of
vaginal box applicator made up of rubber and silver/gold. Point A was difficult because the surface of the ovoids was
Intrauterine and vaginal applicators were not connected to not visible. Therefore, they revised this system in 1953 to
each other [Supplementary Figure 2]. A semifixed geometry locate Point A from 2 cm up from the flange or lowest most
combination of both applicators was used during the source of intrauterine tandem and 2  cm lateral from the
intracavitary application with help of gauze packing.[13] The central canal.[22]
vaginal applicator was held against the cervix and lateral fornix In this system, the intrauterine applicator made up of thin
by gauze packing to reduce the rectum and bladder doses. rubber or plastic hollow tubes with the superior end closed
For the treatment of cervical cancer, both applicators were and flange present at the lower end. It was available in three
loaded with radium‑226  (226Ra).[14] The intrauterine rubber lengths 2  cm, 4  cm, and 6  cm, which was used depending
tube and vaginal boxes were preloaded with 30–90 mg and upon the length of the uterus[23]  [Supplementary Figure  4].
60–80 mg radium‑226 radioactive sources of solid linear tubes. Different intrauterine tube lengths were meant for one, two,
Unequal loading of the source was done in the intrauterine tube or three radium tubes.
and vaginal sources. Total mg‑hrs usually ranged from 6500 The vaginal applicators were called ovoids, made up of hard
to 7100 mg‑hr, out of which 4500 mg‑hrs was approximately rubber or plastic with different varying diameters called
in the vagina. The modified Stockholm method used a larger small, medium, and large ovoids. The ovoids were placed at
amount of radium to reduce the treatment time to 10–18 h for each lateral vaginal fornix at the level of the cervix and tied
each treatment.[15] This loose and flexible applicator had the by thread with the help of a rubber spacer or a washer to fix
advantage of easy insertion into the cervix but at the same time them snuggly. A washer was used for intermediate vaginal size
had the possibility of slippage and a change in geometry after and a spacer with large ovoids was used for large size vagina.
insertion. These applicators were preloaded with radioactive
sources; therefore, it was hazardous to handle them. The Manchester applicators were designed in such a way
that Point A received the same dose rate irrespective of the
intrauterine tube and ovoid combination. Therefore, this system
Paris Method and applicators became more popular than previously available
Regaud and its associate at the Institute of Radium Paris applicators. This system also formed the basis of the modern
developed the Paris Method in 1919. [16,17] It consists intracavitary brachytherapy application and dose specification
of two cork colpostat, connected by a transverse metal methods. However, the definition of Point A has been revised
spring and positioned in lateral fornix perpendicular to the with the change in the design of the applicators and techniques.
intrauterine tube.[18] A hollow rubber elastic tube was used Due to this, the comparison of clinical data between different
in the uterine cavity. The intrauterine tube contained three brachytherapy centers became difficult.
sources in the ratio of 1:1:0.5 i.e.  13.33:13.33:6.66  mg
Applicators used in Stockholm, Paris, and Manchester systems
of radium‑226  [Supplementary Figure  3]. Two colpostat
were not fixed to each other. Therefore, applicator geometry
intravaginal cylindrical applicators were loaded with equal
used to change due to the slipping of applicators after insertion
amount (13.33 mg) of two Radium-226 sources.[19,20]
which resulted in the change of spatial dose distribution. All
An equal amount of radium‑226 source was used in the uterus these systems used preloaded Radium applicators which
and vaginal applicator. The treatment used to be completed were hazardous to staff. The treatment time was also longer
in a single fraction to deliver a dose of 7200–8000 mg‑hrs. because of the low dose rate. To overcome these limitations,
The product of source mass and duration in units of mg‑h the development of rigid and fixed geometry preloaded and

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 Mourya, et al.: Gynecological brachytherapy applicators

afterloading applicators were designed. Delclos Mini‑Colpostat Applicator

The stainless steel Delclos Mini‑Colpostat was developed for
Fletcher Family Tandem and Colpostat/Ovoid use in the narrow or tortuous vaginal cavity in 1970. There were
System Applicator no nylon caps that fit over the colpostat to act as spacers for the
vaginal wall. In the original design (for Radium source) they
Fletcher applicators were inspired by the applicators used in
do not have shielding because of a lack of space for radium
the Manchester system but with improved design. Fletcher
tubes. However, shielding was present in the mini‑colpostats
System was established in 1940 and the fletcher applicator
constructed for small cesium sources.[29] The dose to the vaginal
was developed in 1952.[24,25] This applicator was further refined
wall was higher with mini‑ovoid as there was no spacing effect
by Dr.  Herman Suit and Dr.  Luis Delclos.[26,27] Therefore,
because of the absence of nylon caps.
these applicators are called Fletcher Suit Delclos  (FSD)
applicators [Supplementary Figure 5].
Fletcher‑Suit‑Delclos
Fletcher Applicator (Preloaded) The Fletcher‑Suit‑Delclos has two designs mini and FSD.
The Fletcher Suit mini applicator was similar to delclos
These preloaded applicators were made up of stainless steel
mini‑colpostat design for the Cs‑137 source except for partial
with cylindrical shape ovoids. Each ovoid has its discrete
tungsten shielding in the ovoids.[30,31] If the additional 2 cm
tube, which facilitates the movement of the ovoid anteriorly
nylon cap with half‑moon tungsten shielding is added to the
or posteriorly as per the patient’s anatomy. Ovoid tubes were
mini colpostat/ovoid then it was known as FSD ovoid.[32]
held together with a scissors‑type joint to vary the distance To reduce the dose to the vaginal mucosa, additional spacer
between them. caps of 2.5  cm and 3.0  cm were available to fit over the
Tungsten shielding was located on the medial aspects of the colpostat. These spacer caps were used to push vaginal
anterior and posterior ovoids to minimize the dose to the mucosa away from the radioactive sources. Fletcher ovoids
bladder and rectum. However, the disadvantage of the fletcher were independently dilated up to the fornices. Fletcher
applicator was uncertainty in dosimetry due to the presence of family applicators are rigid and might cause perforation in
shielding material in the ovoids. the uterus if a large force is applied for the insertion of the
intrauterine tube.
Afterloading Applicators
Afterloading technique came in the 1960s and practiced by Henschke Applicator
Ulrich Henschke[28] and Suit et al.[26] Henschke afterloading intracavitary applicator was also
inspired by Manchester intracavitary system and came in
1960. [28,33] Henschke developed an afterloading flexible
Fletcher‑Suit Applicator (Afterloading) applicator system, particularly for cobalt 60 sources. It has a
To minimize the radiation hazards to the personnel, the central plastic uterine tube and two spherical plastic ovoids
preloaded Fletcher applicator design was improved by Suit for the lateral vaginal fornices.
in 1960 for the Radium afterloading system and in 1970 to
accommodate the Cesium‑137 radioactive sources. There was Initially, it was designed without shielding material, but
difficulty in afterloading the sources in ovoids because the later on, shielding was added to protect the rectum and
longitudinal axis of the radioactive source was aligned with the bladder [Supplementary Figure 6].[34]
longitudinal axis of the ovoid. To overcome this problem, he The ovoids were made up of nylon having 2  cm diameter
designed the ovoids with square handle. For the smooth passage and with the addition of nylon caps, the diameter could be
of radium sources around the bend at the point where the handle increased to 3 cm. In the ovoids, sources were loaded through
was attached to the ovoid, the radium carrier tube with a double their handles  (tandems) and placed parallel to the central
hinge system was used [Supplementary Figure 5]. There was tandem. Due to different orientations of the sources in ovoids
no cap to close over the radium tube carrier for the ovoids, as and shielding design, the dose distribution was different than
compared to the preloaded applicator. Therefore, loading and FSD applicators.[35]
unloading of the radium carriers with this system was quicker
than standard preloaded Fletcher applicators. However, the Tandem and Ring Applicator
hinge mechanism in the source carrier was fragile, therefore,
The ring and tandem applicator was developed as an
the radium source carrier design was modified and a radium
afterloading device.[36‑38] Its design was an adaptation of the
tube was attached to the end of the wire or spring.
Stockholm tandem‑and‑box technique. At that time metallic
A cervical stopper was used in the central tandem to decide ring applicators existed in variable diameters (26, 30, 34 mm
the length of tandem required to be inserted in the uterus. It diameters). The radius of the ring was measured from center
was also used as an external os marker. of the ring to center of the source) [Supplementary Figure 7].

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 Mourya, et al.: Gynecological brachytherapy applicators

This applicator has different lengths  (20, 40, 60  mm) and known as Creteil Method. In the Creteil method, the length of
angles (30°, 45°, 60°) of the intrauterine tube. each vaginal source was 0.8 times the diameter of the cervical
impression  [Supplementary Figure  8b]. The radioactive
The ring remained perpendicular to the tandem and having
sources in the vagina were positioned circumferentially at
predictable geometry because the tandem was fixed in the
7 mm from the left and right external lateral walls of the mold.
center of the ring.[39] Acrylic caps cover over the metallic ring
The sources were not loaded in the anterior and posterior region
tube used to reduce the dose to the vaginal mucosa. The ring
to minimize the dose to the bladder and rectum. At the level
applicator is ideal for patients with shallow lateral fornices,
of the vaginal sources, clinicians select the reference isodose
partial or complete loss of the vaginal fornix. The flange is not
to prescribe the dose at 7 mm from the surface of the mold,
used in the ring applicator. The tandem‑ring applicator provides
and 7 mm from the extremity of the intrauterine radioactive
a pear and banana‑shaped isodose distribution in coronal and
source [Supplementary Figure 8c]. Two lead beads are placed
sagittal view that is similar to a tandem‑ovoid applicator.
in the mold, one anterior and the other posterior to the external
The radioactive sources loaded in the ring of the tandem‑ring os. The cervical dose is calculated at the level of these lead
applicator simulates the nearly same dose distribution as sources beads.
loaded in the two ovoids of the tandem‑ovoid applicator. The
The mold applicator delivers personalized tailored treatment,
ring substitutes two ovoids of the tandem‑ovoid applicator.[40]
the vaginal packing is not required, and insertion of the
Insertion of ring applicator is difficult as compared to ovoids
applicator is without anesthesia. The limitation is that one
and especially in a patient with a narrow vagina.[41] The ring has
applicator cannot be used for another patient.
a fixed size inside the patient whereas the separation between
two ovoids can be varied to modify the dose distribution.
Amersham Gynecological Applicator
Mold Applicator Amersham International introduced the Cesium‑137 manual
afterloading system in 1978 and its design was inspired by
Mold technique for intracavitary developed in 1966 at the
the Manchester system applicator.[44,45] It consists of central
Institut Gustave Roussy in Villejuif Cedex, France.[39,42,43] In
tandem, ovoids (fixed to vaginal tandems), flange, washers,
this technique, individualized applicators are designed to adapt
and spacer. These disposable applicators are made up of
to the patient’s anatomy. It consists of a tandem for the uterus
semi‑flexible plastic material [Supplementary Figure 9]. The
and mold for the vaginal part. To prepare the vaginal mold, a
biggest advantage of these applicators was that they could be
thin strip of gauge piece is inserted up to the vaginal fornices
adjusted as per the anatomy of the patient. These applicators
and then an Alginate compound is poured into the vagina.
were inexpensive, sterilized, and disposable. However, they
The Alginate compound becomes rigid after few minutes and
have the problem of rotation inside the patient after insertion.
an impression of a vagina is created. The vaginal mold takes
the impression of the tumor, vagina, and cervix. This vaginal
impression is immersed in liquid plaster. When it dries, the High Dose Rate Applicators
solid plaster is split into two parts and the vaginal impression is The miniature size of the iridium‑192 source facilitated the
removed. The internal surface of the two split parts is covered reduction of the tandem diameter to 3  mm as compared to
with separating varnish. The acrylic applicator is made by 6 mm in the case of the LDR applicator. The smaller diameter
pouring auto‑polymerized synthetic resins (e. g. Palapress). applicator is easy to insert and causes less discomfort to the
When this resin dries, the two plaster pieces are removed and patient. Therefore, many HDR applicators with less diameter
the mold is ready to make the intracavitary applicator. were developed such as tandem and ovoid/Ring, mold
applicator, etc.
The planned locations of the vaginal catheters are drawn on
the surface of the mold, considering the target volume and
patient anatomy. Two plastic vaginal catheters are fixed and Intracavitary‑Interstitial Brachytherapy
immobilized on the internal surface of the molded applicator. Applicators
A hole at the level of the cervical os is made through which
Conventional intracavitary applicators alone are not suitable
the intrauterine catheter is passed.
to deliver adequate dose to the large tumors in the region of
Multiple holes made on the surface of the mold keep it parametrium and lower vagina without crossing the tolerance
immobilized and adhere to the mucosal membrane of the doses of OARs (organs at risk). Therefore, IC‑ISBT applicators
vaginal wall. The holes also help in the circulation of the fluids were developed to give an adequate dose to the bulky
used for vaginal irrigation. Additional holes are drilled at the infiltrative disease, asymmetric tumor growth, and vaginal
distal extremity of the mold for suturing purposes. Radioactive spread.[46,47]
sources are placed through vaginal catheters and intrauterine
Prefabricated perineal templates are also available through
tandem [Supplementary Figure 8a].
which needles are inserted inside the tumor for the treatment
The plastic catheters in vaginal fornices are either parallel of advanced diseases or distorted anatomy. The template allows
or circumferential. If sources are circumferential then it is the insertion of a needle across the entire perineum through a

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 Mourya, et al.: Gynecological brachytherapy applicators

perforated template and shapes the isodose to encompass the of the MUPIT applicator, Benidorm Template was developed
tumor volume and spare the OAR. with MR compatible titanium needles.[50]
Commonly used early IC‑ISBT applicator for gynecological
interstitial implantation are the Syed‑Neblett template and the Syed‑Neblett Gynecological Template
Martinez Universal Perineal Interstitial Template (MUPIT). A. M. Nisar Syed and David Neblett introduced initially
Modern IC‑ISBT applicator are Utrecht, Vienna, Split Ring, a butterfly‑shaped template for interstitial gynecological
Venezia, Geneva etc. brachytherapy.[51] It consists of two thick lucite plates which are
joined each other by Allen head screws. On the plate, one large
Martinez Universal Perineal Interstitial and several small holes are grooved. Small holes are grooved
in five concentric circles, one on the periphery of the vaginal
Template obturator and the other four on the template.[52]
MUPIT was developed for a multi‑site single template for
A large hole is for the insertion of the plastic vaginal obturator
an intracavitary‑interstitial applicator having an Octagon
having 2 cm diameter and 15 cm length and it can accommodate
shape. Initially, it consisted of a flat template, cover
interstitial needles (Syed‑Neblett Gyn Template, Best Medical
plate, and obturators made up of acrylic material having
International, Virginia, USA)  [Supplementary Figure  10e].
multiple holes. However, currently, it is made up of
Inside the vaginal obturator, a hole is present for the insertion
polyphenyl sulfone (PPSU) (MUPIT, Elekta AB, Stockholm,
of the intrauterine tandem. The intrauterine tandem is fixed
Sweden) [Supplementary Figure 10a-d].[48]
to the vaginal guide by tightening a screw. In this template,
Three large holes are located along the vertical central axis of the conventional intravaginal ovoids are replaced with interstitial
template for the passage of Foleys catheter (upper one), vaginal needles, which are implanted through paravaginal and
obturator (middle one), and rectum obturator (lowermost). The parametrial tissue. This template is available with 15 or 17
size of the rectal and vaginal obturators is the same (13 cm in gauge stainless needles. Small doughnuts shaped rubber
length and 2.5 cm in diameter). There are holes in the four O‑rings are placed surrounding the guide needle holes to
corners of the template to suture it to the patient. immobilize the needles. Rubber O‑rings are flattened when the
There are multiple holes  (guide holes) in the template at a Allen head screws in the lucite plates are tightened.[53]
1.25 cm distance from each other for the insertion of the trocar In another technique, the steel needles are lubricated by dipping
needles for transperineal insertion. The even and odd horizontal in alcohol and inserted in the guide holes of the template. After
row consists of two different angles for guide holes. In odd a few minutes of insertion, the alcohol evaporates and the
horizontal rows, guide holes are perpendicular to the template needles get fixed at their respective position due to friction.
used for straight placement of the needles, which allows a
The use of this template is easy as compare to MUPIT but it
volume extending 4 cm to either side of the midplane.
does not have the provision of oblique needles. Therefore,
Even horizontal rows, guide holes are 13° laterally outward the tumor coverage is limited as compare to MUPIT.
oblique angle to the template allows wider volume coverage Patients with locally advanced cervical cancer unsuitable
of parametrial or pararectal tissue with the prevention of for conventional ICBT can be treated with ISBT using these
ischium perforation during procedure. Even rows having perineal templates.[54,55]
oblique needles allow a volume extending 7 cm to either side
of the midplane. Computed Tomography/Magnetic Resonance
The vaginal obturator [Supplementary Figure 10c] is used to Compatible Applicators
treat the vaginal surface, and it can be loaded with stainless
Image‑guided brachytherapy is becoming popular for the
steel needles to encompass disease from the fornix to the
treatment of cervical cancer and treatment planning is done
introitus. In case of intact uterus, both intrauuterine tandem
on the images obtained with computed tomography  (CT)
and interstitial needles along with vaginal obturator are used
and/or magnetic resonance imaging  (MRI). Therefore, the
to deliver high dose to the cervix.
requirement for CT/MR compatible brachytherapy applicators
The tumor coverage is better with MUPIT and it avoids has increased. However, metallic applicators and inbuilt shields
a central low dose area, in cases where an intrauterine inside the ovoids generate streak artifacts on CT images. Image
tandem applicator cannot be inserted because of fibrosis or quality is also deteriorated due to beam hardening and photon
advanced‑stage disease. starvation. Reconstruction of applicator and contouring of
structures on deteriorated images affect the quality of planning.
However, the delineation of OAR and CTV during the planning
becomes difficult as CT images have artifacts due to metallic To address the issue of streak artifacts in CT images, some
needles.[49] The length of the stainless steel trocar needles is authors used applicators made up of low atomic‑number
only 20 cm that limits its ability to reach beyond the cervix and materials as it minimizes photoelectric interactions and the
needles are not MRI compatible. To overcome these limitations subsequent sudden attenuation discontinuity at the tissue/

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 Mourya, et al.: Gynecological brachytherapy applicators

applicator interface. Therefore, FSD applicators were in T2W images produced by metal fiducial markers and
constructed using acrylic material with afterloaded shields.[56] blooming artifacts in proton density weighted  (PDW)
Distortion in acquired CT images happened when the metal images.[5,65] The artifacts from titanium applicators improve at
components of ovoids interfere with 3D‑imaging modalities. the tip of the tandem and its source–pathway reconstruction
The shielded applicator overcome these issues by incorporated when T1‑weighted MR images are used with minimal slice
removable shielding in the ovoids. thickness.[64]
For CT compatible applicator, Week’s et al. made tandem and Modern CT/MR Applicators use strong composite fiber tubing
ovoids of black anodized aluminum and the handles were of and plastic to avoid image distortion in CT and MR images. The
stainless steel.[57] The external dimensions of the ovoids were applicator‑modeling module available in the treatment planning
the same as those of mini Delclos ovoids. To avoid the artifacts system is used to reconstruct the applicator as per its actual
from tungsten shielding in the ovoids, the CT scan of the dimensions. Catheters containing copper sulphate  (CuSO4)
patients were taken without shielding material. are clearly visible in plastic applicators on T1W and T2W MR
Images. Phantom study on MR and CT images of the titanium
The use of low Z (atomic number) material to design a uterine
applicator/needles help to evaluate the applicator geometry
tandem becomes difficult because these materials are not as
relative to the artifact pattern generated on MR images.[66]
strong as high atomic numbers metals. Therefore, material like
Modern designs of Henschke  [Figure  1a], Ring  [Figure  1b],
PPSU or Epoxy Polyvinyl ester polyester glass fiber is used
and Fletcher applicators are now compatible with miniature
for CT/MRI compatible applicator that makes the intrauterine
HDR sources as compared to LDR sources. The modern
tube of less diameter (4 mm) in proximal portion for the HDR
Fletcher [Figure 1c], Fletcher Shielded (Elekta AB, Stockholm,
applicator.
Sweden)  [Figure  1d], and Ring applicators  (Elekta AB,
Modified values of CT window and level were used in standard Stockholm, Sweden) [Figure 1e], are made CT/MRI compatible
shielded FSD applicators, to reduce the appearance of the by changing using the appropriate material. Other Advance
artifact on the CT image for delineation of the bladder and gynecological applicators are Vienna Applicator  (Elekta
rectum boundaries with respect to implanted applicator.[58] AB, Stockholm, Sweden), Vienna II Applicator,[67] Utrecht
Metal artifact reduction (MAR) algorithm based on Projection Applicator  (Elekta AB, Stockholm, Sweden), Split Ring
interpolation methods and hybrid approaches were used to Applicator  (Eckert & Ziegler BEBIG, Berlin, Germany),
minimize the metal artifacts produced by the applicator.[59,60] MAC  (Mick‑Alektiar‑Cohen) Applicator  (Eckert & Ziegler
BEBIG, Berlin, Germany), Venezia Applicator  (Elekta
The image based CT planning complemented with MRI
AB, Stockholm, Sweden), Geneva Applicator  (Elekta AB,
has benefited over a CT‑only methodology.[61] As the use
Stockholm, Sweden), Ring Tulip Applicator (Eckert & Ziegler
of MRI‑assisted brachytherapy has improved local control
BEBIG, Berlin, Germany), and 3D printed applicators.
and overall survival.[62] However, CT and MRI compatible
Brief details of various Gynecological Applicators shown in
applicators with the absence of ferromagnetic materials are
Supplementary Table 1.
required for imaging. Therefore, applicators made up of
graphite, plastics, titanium, etc., are used.
Vienna Applicator
Applicator reconstruction of titanium applicators is more
challenging than that of plastic applicators due to artifacts. The Vienna applicator is a modified form of ring applicator
having multiple holes in the ring tube to implant needles
The size and appearance of the artifacts in MR images also
parallel to the intrauterine tandem and the circular ring is fixed
depend upon the magnetic field strength, the orientation of the
to the cervix through the tandem. The holes in the ring of the
metal applicator relative to the main magnetic field, magnetic
Vienna applicator have a 2 mm diameter, which is at a distance
susceptibility, and the pulse sequence parameters.[63] The
of 2 mm from the surface of the outer ring. The number of
shields in the ovoids create magnetic susceptibility artifacts due
holes for the needles increases with an increase in the diameter
to perturbations in the homogeneity of the applied magnetic
of the ring [Figure 1f].
field, resulting in image distortion. The susceptibility artifacts
caused by the titanium metallic tandem can be substantial There are nine holes in 30  mm and 34  mm diameter ring
with spin‑echo sequences with short echo times.[64] Bloom whereas six holes are there in 26 mm diameter ring The Outer
or ballooning artifacts at the tip of the tandem applicator diameters of the rings are 42.5 mm, 46.5 mm, and 38.5 mm
may introduce geometric uncertainties in the applicator respectively. Titanium needles of 20–24 cm length are used
reconstruction. In addition, the diameter of an applicator may for the interstitial implant with these templates. The tip of
appear 2 times larger than its original diameter. the needle is placed 5 mm or more above the tumor because
the needle tip is blind up to 5 mm and the radioactive source
The Orthopedic metal artifacts reduction (O‑MAR) sequence
cannot be placed there.[68]
with view angle tilt  (VAT) and slice encoding for metal
artifacts reduction sequence  (SEMAC) is used to improve With the help of interstitial needles in the Vienna applicator,
the delineation of the titanium brachytherapy applicator in asymmetric changes in the isodose distribution can be made
MR images. O‑MAR also minimizes susceptibility artifacts for better dose conformity depending upon the location of the

236 Journal of Medical Physics  ¦  Volume 46  ¦  Issue 4  ¦  October-December 2021

 Mourya, et al.: Gynecological brachytherapy applicators

disease. Patients treated with this applicator show better dose split ring. Each cap contains 10 equally spaced holes in the
distribution in target while limiting the dose to OARs (bladder inner and outer ring through which the interstitial needles
and rectum).[69] However, if the tumor is extended to lateral are inserted to cover the large tumors [Figure 1i]. It has the
parametrium then it is difficult to cover it with this applicator advantages of a ring applicator as well as ovoids. The ring is
because interstitial needles are parallel to intra‑uterine tandem. split into two, therefore insertion is easy and space between
This problem has been addressed in the Vienna‑II applicator. two halves of the ring can be increased to modify the dose
The modified form of the Vienna‑1 applicator is called the distribution.
Vienna‑II applicator and it has an additional cap, which is
fixed below the vaginal ring [Figure 1g]. This cap allows the Mick‑Alektiar‑Cohen Applicator
insertion of interstitial needles into the distal parametrium/ MAC applicator design consists of a vaginal cylinder,
lateral pelvic wall in an oblique direction of 20° angles relative intrauterine tandem, and template for the insertion of the
to the tandem for appropriate dose coverage.[67] interstitial needle. It has holes in the concentric circles
As compared to MUPIT trocar needles, the round point‑shaped for the placement of the needles in a straight and oblique
needles are used in the Vienna applicator to minimize tissue direction [Figure 1j] to treat disease in the region of the cervix,
damage and discomfort to the patient. vagina, and parametrium.

Utrecht Applicator Venezia Applicator

The Utrecht applicator is a tandem‑ovoid‑based intracavitary It is a hybrid applicator with capabilities of intracavitary and
as well as an interstitial CT/MR compatible brachytherapy interstitial brachytherapy and was introduced in 2017.[73,74]
applicator.[70] It consists of an intra‑uterine tube, a cervical Patients with large or asymmetric tumor can be treated
stopper, and two ovoids. The applicator is made up of effectively with this hybrid applicator.[75]
polyphenylsulfone. The intrauterine and ovoid tubes contain
It consists of an intrauterine tube, interstitial lunar‑shaped
glass fiber. Each ovoid has five holes at 15° angles so that
ovoids when connected together form a ring. The posterior
the plastic interstitial needle can be placed nearly parallel to
portion of each lunar ovoid consists of alphabetic letter
the tandem. Ovoids act as a template for the placement of
numbering from A to H for placing straight and oblique
the plastic needle. Each ovoid has three holes in the lateral
interstitial needles alternatively [Figure 1k].
direction at 7 mm apart from each other, one each in ventral
and dorsal direction [Figure 1h]. On average 6 needles per BT Below the Lunar ovoids, a cap (resembling cylinder) can be
fraction are sufficient to achieve the planning objectives.[71] attached to treat the vaginal wall disease. Perineal template
attachable with Venezia applicator helps to spread the needle
Split Ring Intracavitary Applicator across the vaginal extension. The perineal template helps in
implanting the needles in the desired geometry.[76] Venezia
The Split Ring Applicator can be used as a ring applicator or
applicator assembly is fixed quickly without screws. A fixation
it can be split into different symmetric or asymmetric diameter
clamp is used to fix the uterine and lunar ovoid tandems. Venezia
distances as per patient anatomical variations of the vaginal
applicator is compatible with ultrasound, X‑ray, CT, and MR
canal and shape. Insertion of this applicator is easier than ring
imaging modalities. The insertion of the Venezia applicator is
applicator. For a narrow vagina, each split ring can be inserted
easy and it significantly improves dose coverage to the tumor
independently and splayed laterally producing an inter‑ring
diameter between 3.5 and 7.0 cm. while at the same time sufficiently spares organs at risk.

The applicator is made up of medical‑grade titanium alloy with

6% aluminum and 4% vanadium. The patients with titanium
Geneva Applicator
applicator can safely undergo both CT and MRI scanning for Its design is inspired by Henschke, Rotterdam,Standard
treatment planning. Fletcher and Utrecht applicators. The cervical stopper is
integrated with the central tandem, which avoids the chances
It has disposable/reusable build‑up silicon rubber caps to of its slippage from the intrauterine tandem. To treat the
fit a wide variety of anatomies. The intrauterine tandem has asymmetric disease around the ovoid region, an interstitial
different sizes (2–8 cm) to accommodate the different uterine template is provided beside the ovoid to accommodate the
lengths. An adjustable rectal retractor having a lever‑like interstitial needles [Figure 1l]. This applicator has the facility
mechanism to depress the rectal wall removes the need for to insert a flexible interstitial tube through the cervical stopper
packing. in place of the uterine tandem. It has a rotating and click
Ellis interstitial caps placed over the split ring applicator help mechanism to fix the applicator assembly, which is quicker
in improving the tumor coverage and prevent normal structure than the screw mechanism. It provides distortion‑free images
rupturing from the interstitial needle.[72] The custom interstitial with different imaging modalities, as it has no metallic parts
caps are independently attached to the upper surface of each and screws.

Journal of Medical Physics  ¦  Volume 46  ¦  Issue 4  ¦  October-December 2021 237

 Mourya, et al.: Gynecological brachytherapy applicators

a b c d e f g

h i j k l m
Figure 1: Modern computed tomography or magnetic resonance imaging compatible applicator. (a) Henschke computed tomography compatible
applicator*. (b) Ring computed tomography compatible applicator*. (c) Fletcher computed tomography/magnetic resonance imaging compatible
applicator*. (d) Fletcher shielded computed tomography/magnetic resonance imaging compatible applicator*. (e) Ring computed tomography/magnetic
resonance imaging compatible applicator*. (f) Vienna applicator*. (g) Vienna II applicator.[67] (h) Utrecht applicator*. (i) Split ring applicator #.[72] (j) MAC
applicator #. (k) Venezia applicator*. (l) Geneva applicator*. (m) Ring tulip applicator #. *: Elekta AB, Stockholm, Sweden, #: Eckert & Ziegler BEBIG,
Berlin, Germany. Permission was obtained from Elekta, Eckert & Ziegler Bebig to reproduce the figures for publication.

Tulip Applicator shielding material is not moved relative to the source or

surrounding Tissue.
Any existing conventional applicator can be converted into a Tulip
applicator with an add‑on 3D printed kit to facilitate intracavitary Direction‑modulated brachytherapy applicator
as well as interstitial application [Figure 1m]. A Needle Guide Tungsten alloy shielded grooved rod inserted in tandem is
system is attached distally to the conventional ring or ovoid tubes. used with 192Ir source in direction‑modulated brachytherapy
The interstitial needle template attached to the proximal portion applicator.[77] The uterine tandem of DMBT is a 5.4‑mm diameter
of the ring or ovoid work together with the distal needle guide tungsten alloy rod having 6 peripheral grooves (separated by
to ensure that the implanted needles cover the target areas in the 60° equidistant angles) wrapped inside a 0.3‑mm thick bio‑safe
cervix or parametrium and remain at their place during treatment. thermoplastic sheath [Figure 2]. Along the length of the central
It has the advantage of putting the interstitial needles parallel to tandem, the source travels through these six symmetric grooves.
the intrauterine tube as well as oblique at desired angles. Thin plastic tubes fitted into each groove are connected to
each transfer tube for source movement as per programming
Intensity‑modulated brachytherapy
of TPS. The tip of the tandem is sealed with polyether ether
Intensity‑modulated intracavitary brachytherapy is achieved
ketone material.[78,79] The dynamic single‑channel shields
with the help of a shielded applicator or radiation source and
with narrow beam widths in the polar and azimuthal direction
it could be static or dynamic.
give rise to anisotropic distributions. DMBT gives directional
Static intensity‑modulated brachytherapy dose profiles in the transverse and longitudinal tandem axis as
In S‑IMBT, the intensity at a point is modulated through compared to conventional tandem‑ring applicators that produce
inbuilt static shielding design or by optimizing the dwell isotropic dose distribution. Artifacts formed in CT images are
time and position. It can be achieved by direction‑modulated reduced digitally with MAR Algorithm.[80] Monte Carlo‑based
brachytherapy  (DMBT) applicator  (Fletcher‑shielded algorithm or TG‑186 algorithm is required for planning to take
applicator, MUPIT, Venezia, Vienna, etc.). In S‑IMBT, care of heterogeneity produced by the tungsten shielding.[81]

238 Journal of Medical Physics  ¦  Volume 46  ¦  Issue 4  ¦  October-December 2021

 Mourya, et al.: Gynecological brachytherapy applicators

curved applicator. Dose conformity with H‑RSBT and

S‑RSBT are similar, but the treatment time is less with
H‑RSBT.[85] The inner applicator wall contains six equally
spaced helical keyways that firmly delineate the emission
direction of the partial radiation shield as a function of
depth in the applicator [Figure 3d].
The above techniques of RSBT are conceptually proposed for
eBT source with shielded applicators and very few patients
a b have been treated with unshielded applicators.[86] However, the
Figure 2: Direction‑modulated brachytherapy. (a) Axial view of flute style [Figure 4] shielded applicator may be used to achieve
direction‑modulated brachytherapy applicator (b) Actual image of intensity‑modulated brachytherapy with radioactive sources.[87‑89]
direction‑modulated brachytherapy applicator without plastic sheath[78]
D‑IMBT has been demonstrated with a rotating MRI‑compatible
flute style shielded applicator for different radioactive sources
Dynamic intensity‑modulated brachytherapy such as 192Ir, Selenium‑75 (75Se), and Yttrium‑169 (169Yb). 75Se
In D‑IMBT, shielding material changes its direction relative and 169Yb sources increase the modulation potential of IMBT
to the radiation source or surrounding tissue and it can be because their average photon energies are less than Ir‑192.
achieved by the following methods.
Rotation shield brachytherapy Three‑Dimensional Printed Applicator
The Rotation shield brachytherapy consists of electronic 3D printers are used to design customized brachytherapy
brachytherapy (eBT) source, which can be shielded inside the
applicators or some parts of applicators to be assembled
applicator. A  partially shielded Xoft Axxent eBT source is a
with commercially available applicators. [90,91] 3D printed
miniature X‑ray source that is sheathed in a 5.4 mm diameter
brachytherapy applicators are designed [Figure 5a‑d] from the
water‑cooled catheter. The tube can be operated between 20 and
dimensions estimated from physical examination and imaging
50 kVp, at a standard operating voltage of 50 kV and tube current
of the patient.[92,93] A material used for 3D printed applicator
of 300 µA. The eBT sources were used to check the feasibility
should be biocompatible, sterilizable, CT/MR‑compatible,
of dose distribution in S‑RSBT  (Single‑shield rotating shield
and have dose‑attenuation properties similar to water.[94] Sekii
brachytherapy), D‑RSBT (Dynamic rotating shield brachytherapy),
et al.[95] designed interstitial templates with a 3D printer using
H‑RSBT  (Multi Helixrotating shield brachytherapy), and
medical images of vaginal tumors. They used Polycarbonate/
P‑RSBT (Paddle rotating shield brachytherapy) applicator.
acrylonitrile‑butadiene‑styrene  (PC‑ABS) polymer alloy
a. In S‑RSBT, inside the applicator, at each dwell position,
material for the template.
the partial tungsten shield of 0.5  mm thickness is
rotated to numerous angular locations around the eBT Radiation attenuation properties of 3D printed brachytherapy
source.[82] The treatment time is more as compared to the applicators with different infill percentages of thermoplastic
conventional ICBT/IS‑ICBT technique and it dependents materials should be studied to see its impact on dose
upon the selection of azimuthal shield emission (ASE) distribution.[96] Biocompatibility of 3D printed devices can be
angle [Figure 3a] assured by using United States Pharmacopeia (USP) Class VI
b. D‑RSBT uses two independent layers of rotating tungsten or ISO standard 10993 certified materials.[97]
alloy shields (each 0.5 mm thick) and each shield has an 3D printed applicators are beneficial for cervical patients,
opening of 180° ASE angle.[83] During the treatment, both whose anatomy falls outside the range of currently available
tungsten shields can be rotated to achieve an azimuthal commercial applicators. The limitation of customized 3d
emission angle of less than 180° to modulate the radiation printed applicators is that they can’t be used for another patient.
beam. Due to the variable AES facility in D‑RSBT, more
conformal dose distribution can be achieved as compared Limitations of the review
to single shield S‑RSBT that uses the same ASE during In the literature, there are not enough studies available
the treatment [Figure 3b] related to IMBT and 3D printed applicator. Therefore, their
c. P‑RSBT uses a set of independently operated Tungsten comparison with the conventional brachytherapy applicator
alloy shield paddles. Intensity modulation is achieved could not be carried out in this review. With the advent
by the insertion/retraction of these paddles and rotation/ of technology, heterogeneity exists in the design of the
translation of the whole applicator [Figure 3c]. The set gynecological applicators, loading of the radioactive sources,
of shield paddles can move in  (close) and out  (open) radionuclide, shielding design, and imaging. Therefore, this
independently to block and expose the radiation source[84] review lacks in comparative dosimetric study based on depth
d. H‑RSBT is achieved using the linear translational dose, isodose curve, the effect of heterogeneity, and different
motion of the source and shield combination inside a radionuclide sources.

Journal of Medical Physics  ¦  Volume 46  ¦  Issue 4  ¦  October-December 2021 239

 Mourya, et al.: Gynecological brachytherapy applicators

a b c d
Figure 3: Dynamic IMBT (D‑IMBT) applicators design based on electronic sources. (a) S‑RSBT applicator design.[82] (b) D‑RSBT.[83] (c) P‑RSBT.[84] (d) H‑RSBT.[85]
IMBT: Intensity‑modulated brachytherapy, RSBT: Rotational shield brachytherapy, S‑RSBT: Single‑shielded RSBT, D‑RSBT: Dynamic RSBT, P‑RSBT:
Paddle RSBT, H‑RSBT: Multihelix RSBT

infancy, and the rigorous testing of applicators used with

clinical results is required.
The future of gynecological applicator belongs to an in‑house
3D printed applicator as per the patient anatomy, extension,
and location of the disease. Applicators with capabilities
of intracavitary and interstitial brachytherapy with a robust
mechanism of rectum and bladder retractions are the need of
the hour.
Financial support and sponsorship
Figure 4: D‑IMBT a rotating MRI‑compatible flute style shielded applicator Nil.
with radioactive source.[88] D‑IMBT: Dynamic intensity‑modulated
brachytherapy
Conflicts of interest
There are no conflicts of interest.

References
1. Holschneider  CH, Petereit  DG, Chu  C, Hsu  IC, Ioffe YJ, Klopp AH,
et al. Brachytherapy: A critical component of primary radiation therapy
for cervical cancer: From the Society of Gynecologic Oncology (SGO)
and the American Brachytherapy Society  (ABS). Brachytherapy
2019;18:123‑32.
2. Gill BS, Kim H, Houser CJ, Kelley JL, Sukumvanich P, Edwards RP,
et al. MRI‑guided high‑dose‑rate intracavitary brachytherapy for
a b c d
treatment of cervical cancer: The University of Pittsburgh experience.
Figure 5: Designs of three‑dimensional printed applicator. (a) Patent Int J Radiat Oncol Biol Phys 2015;91:540‑7.
specific vaginal applicator.[93] (b) Tandem with three‑dimensional 3. Viswanathan AN, Beriwal S, De Los Santos JF, Demanes DJ, Gaffney D,
printed needle cap.[91] (c) Multichannel vaginal cylinder with interstitial Hansen J, et al. American Brachytherapy Society consensus guidelines
needle.[92] (d) Tandem and ring with parallel and oblique needles  for locally advanced carcinoma of the cervix. Part  II: High‑dose‑rate
brachytherapy. Brachytherapy 2012;11:47‑52.
4. Karlsson  J, Dreifaldt  AC, Mordhorst  LB, Sorbe  B. Differences
Conclusions in outcome for cervical cancer patients treated with or without
brachytherapy. Brachytherapy 2017;16:133‑40.
A detailed review of the gynecological brachytherapy 5. Dimopoulos JC, Petrow P, Tanderup K, Petric P, Berger D, Kirisits C,
applicators from the era of preloading to afterloading et al. Recommendations from Gynaecological  (GYN) GEC‑ESTRO
applicators and conceptual intensity‑modulated brachytherapy Working Group (IV): Basic principles and parameters for MR imaging
within the frame of image based adaptive cervix cancer brachytherapy.
applicators have been presented. The role of imaging in Radiother Oncol 2012;103:113‑22.
brachytherapy has increased; therefore, neoteric applicators 6. Nomden CN, de Leeuw AA, Roesink JM, Tersteeg RJ, Moerland MA,
try to fulfill the challenge of compatibility with all available Witteveen  PO, et al. Clinical outcome and dosimetric parameters
imaging modalities. Interstitial brachytherapy helps in covering of chemo‑radiation including MRI guided adaptive brachytherapy
with tandem‑ovoid applicators for cervical cancer patients: A  single
the advanced stage tumor; hence, gynecological applicators institution experience. Radiother Oncol 2013;107:69‑74.
having capabilities of intracavitary as well as interstitial 7. Becquerel H, Curie P. Action physiologique des rayons du radium.
brachytherapy are much in demand. Compt. Rend. Acad. Sci. 1901;132:1289-91.
8. Del Regato JA. Brachytherapy. Front Radiat Ther Oncol 1978;12:5‑12.
Recently, intensity‑modulated brachytherapy  (IMBT) with 9. Mould RF. A century of x-rays and radioactivity in medicine With
shielded applicators or sources have been investigated. emphasis on photographic records of the early years. United States:
Theoretically, it has been demonstrated that IMBT decreases Institute of Physics Publishing; 1993.
10. Heyman  J. The so‑called Stockholm method and the results of
the dose to OARs and increases target coverage as compare treatment of uterine cancer at the radiumhemmet. Acta Radiol
to conventional brachytherapy. IMBT may help in the dose 1935;16:129‑48.
escalation in cervical cancer; however, this technique is in 11. Radium treatment of uterine cancer. Arch Gynecology 1918;108:229-474.

240 Journal of Medical Physics  ¦  Volume 46  ¦  Issue 4  ¦  October-December 2021

 Mourya, et al.: Gynecological brachytherapy applicators

12. Heyman  J. The technique in the treatment of cancer uteri at Nucletron applicators. Med Dosim 1995;20:201‑7.
radiumhemmet. Acta Radiol 1929;10:49‑64. 38. Wester, U. Report on modifications of the Cervitron II afterloading
13. Heyman  HV. Technique and results in the treatment of carcinoma apparatus. Stockholm (Sweden): Statens Straalskyddsinstitut; 1975.
of the uterine cervix at “Radiumhemmet,” Stockholm. From 39. Gerbaulet A, Potter R, Haie-Meder C. Cervix cancer. In: Gerbaulet A,
“Radiumhemmet,” Stockholm; Chief: Professor Gösta Forssell. BJOG Potter R, Mazeron JJ, Meertens H, Van Limbergen E, editors. The GEC
Int J Obstet Gynaecol 1924;31:1‑19. ESTRO handbook of brachytherapy. Brussels: ESTRO; 2002. p. 301-
14. Berven E, Heyman J, Thoroeus R. The technique at radiumhemmet in 63.
the treatment of tumours except cancer uteri. Acta Radiol 1929;10:1‑71. 40. Noyes WR, Peters NE, Thomadsen BR, Fowler JF, Buchler D, Stitt J,
15. Walstam R. The dosage distribution in the pelvis in radium treatment of et al. Impact of “optimized” treatment planning for tandem and ring,
carcinoma of the cervix. Acta Radiol 1954;42:237‑50. and tandem and ovoids, using high dose rate brachytherapy for cervical
16. Swanberg H. Regaud’s technic in cervical cancer: Use of new radium cancer. Int J Radiat Oncol 1995;31:79-86.
applicator. Radiology 1929;12:435‑46. 41. Nag S, Erickson B, Thomadsen B, Orton C, Demanes JD, Petereit D. The
17. Murdoch J. Dosage in radium therapy. Br J Radiol 1931;4:256‑84. American Brachytherapy Society recommendations for high‑dose‑rate
18. Fichardt T. The Pretoria method in radiotherapy of cancer of the cervix brachytherapy for carcinoma of the cervix. Int J Radiat Oncol Biol Phys
uteri. S Afr Med J 1962;36:303‑10. 2000;48:201‑11.
19. Mazeron  JJ, Gerbaulet  A. The centenary of discovery of radium. 42. Pierquin B, Marinello G, Mege JP, Crook J. Intracavitary irradiation of
Radiother Oncol 1998;49:205‑16. carcinomas of the uterus and cervix: The Créteil method. Int J Radiat
20. ICRU Report 38. Dose and Volume Specification for Reporting Oncol 1988;15:1465‑73.
Intracavitary Therapy in Gynecology;1985. Available at: https://doi. 43. Magné N, Chargari  C, SanFilippo  N, Messai  T, Gerbaulet  A,
org/10.1093/jicru/os20.1.Report38. [Last accessed on 2021 October Haie‑Meder  C. Technical aspects and perspectives of the vaginal
28]. mold applicator for brachytherapy of gynecologic malignancies.
21. Tod  MC, Meredith  WJ. A  dosage system for use in the treatment of Brachytherapy 2010;9:274‑7.
cancer of the uterine cervix. Br J Radiol 1938;11:809‑24. 44. Law  RC, Mohamed AS, Maguire  RB. Treatment time for Amersham
22. Tod M, Meredith WJ. Treatment of cancer of the cervix uteri, a revised caesium‑137 manual afterloading system. Comput Biol Med
Manchester method. Br J Radiol 1953;26:252‑7. 1992;22:337‑49.
23. Radium Based Manchester Applicator Design. Available from: https:// 45. Joslin C, Flynn A, Hall E. (2001) Principle and Practice of Brachytherapy:
www.orau.org/ptp/Library/Radium/Radium.Radon.pdf.  [Last accessed Using after Loading Systems. London: Joanna Koster; 2001.
on 2021 Jun 15]. 46. Nandwani  PK, Vyas  RK, Neema  JP, Suryanarayan  UK, Bhavsar  DC,
24. Fletcher GH. Cervical radium applicators with screening in the direction Jani KR. Retrospective analysis of role of interstitial brachytherapy using
of bladder and rectum. Radiology 1953;60:77‑84. template  (MUPIT) in locally advanced gynecological malignancies.
25. Yordy  JS, Almond  PR, Delclos  L. Development of the M. D. J Cancer Res Ther 2007;3:111‑5.
Anderson Cancer Center gynecologic applicators for the treatment 47. Martinez  A, Edmundson  GK, Cox  RS, Gunderson  LL, Howes  AE.
of cervical cancer: Historical analysis. Int J Radiat Oncol Biol Phys Combination of external beam irradiation and multiple‑site perineal
2012;82:1445‑53. applicator  (MUPIT) for treatment of locally advanced or recurrent
26. Suit  HD, Moore  EB, Fletcher  GH, Worsnop  R. Modification of prostatic, anorectal, and gynecologic malignancies. Int J Radiat Oncol
Fletcher ovoid system for afterloading, using standard‑sized radium Biol Phys 1985;11:391‑8.
tubes (milligram and microgram). Radiology 1963;81:126‑31. 48. Martinez  A, Cox  RS, Edmundson  GK. A  multiple‑site perineal
27. Delclos  L, Fletcher  GH, Sampiere V, Grant WH 3rd. Can the Fletcher applicator (MUPIT) for treatment of prostatic, anorectal, and gynecologic
gamma ray colpostat system be extrapolated to other systems? Cancer malignancies. Int J Radiat Oncol Biol Phys 1984;10:297‑305.
1978;41:970‑9. 49. Velmurugan  T, Sukumar  P, Krishnappan  C, Boopathy  R. Study of
28. Henschke  UK. “Afterloading” applicator for radiation therapy of dosimetric variation due to interfraction organ movement in High Dose
carcinoma of the uterus. Radiology 1960;74:834. Rate Interstital (MUPIT) brachytherapy for gynecologic malignancies.
29. Delclos  L, Fletcher  GH, Moore  EB, Sampiere  VA. Minicolpostats, Pol J Med Phys Eng 2010;16:85‑95.
dome cylinders, other additions and improvements of the Fletcher‑suit 50. Rodriguez Villalba  S, Richart Sancho  J, Otal Palacin  A,
afterloadable system: Indications and limitations of their use. Int J Perez Calatayud  J, Santos Ortega  M. A  new template for MRI‑based
Radiat Oncol Biol Phys 1980;6:1195‑206. intracavitary/interstitial gynecologic brachytherapy: Design and clinical
30. Haas  JS, Dale Dean  R, Mansfield  CM. Fletcher‑Suit‑Delclos implementation. J Contemp Brachytherapy 2015;7:265‑72.
gynecologic applicator: Evaluation of a new instrument. Int J Radiat 51. Feder BH, Nisar Syed AM, Neblett D. Treatment of extensive carcinoma
Oncol 1983;9:763‑8. of the cervix with the “transperineal parametrial butterfly.” Int J Radiat
31. Haas  JS, Dale Dean  R, Mansfield  CM. Dosimetric comparison of the Oncol 1978;4:735‑42.
fletcher family of gynecologic colpostats 1950‑1980. Int J Radiat Oncol 52. John  B, Scarbrough  EC, Nguyen  PD, Antich  PP. A  diverging
1985;11:1317‑21. gynecological template for radioactive interstitial/intracavitary implants
32. Ling CC, Spiro IJ, Kubiatowicz DO, Gergen J, Peksens RK, Bennett JD, of the cervix. Int J Radiat Oncol 1988;15:461‑5.
et al. Measurement of dose distribution around Fletcher‑Suit‑Delcos 53. Paley PJ, Koh WJ, Stelzer KJ, Goff BA, Tamimi HK, Greer BE. A new
colpostats using a Therados radiation field analyzer (RFA‑3). Med Phys technique for performing Syed template interstitial implants for anterior
1984;11:326‑30. vaginal tumors using an open retropubic approach. Gynecol Oncol
33. Aronowitz JN. Afterloading: The technique that rescued brachytherapy. 1999;73:121‑5.
Int J Radiat Oncol Biol Phys 2015;92:479‑87. 54. Pinn-Bingham M, Puthawala AA, Syed AMN, Sharma A, DiSaia
34. Mohan R, Ding IY, Martel MK, Anderson LL, Nori D. Measurements of P, Berman M, et al. Outcomes of High-Dose-Rate Interstitial
radiation dose distributions for shielded cervical applicators. Int J Radiat Brachytherapy in the Treatment of Locally Advanced Cervical Cancer:
Oncol Biol Phys 1985;11:861‑8. Long-term Results. Int J Radiat Oncol. 2013;85:714-20.
35. Nath  R, Urdaneta  N, Bolanis  N, Peschel  R. A  dosimetric analysis of 55. Syed AMN, Puthawala AA, Abdelaziz NN, El-Naggar M, Disaia
morris, fletcher, and henschke systems for treatment of uterine cervix P, Berman M, et al. Long-term results of low-dose-rate interstitial-
carcinoma. Int J Radiat Oncol 1991;21:995‑1003. intracavitary brachytherapy in the treatment of carcinoma of the cervix.
36. Joelsson I, Bäckström A. Applicators for remote afterloadjng technique Int J Radiat Oncol. 2002;54:67-78.
for optimum pelvic dose distribution in carcinoma of the uterine cervix. 56. Schoeppel  SL, Fraass  BA, Hopkins  MP, La Vigne  ML, Lichter  AS,
Acta Oncol 1970;9:233‑46. McShan  DL, et al. A  CT‑compatible version of the Fletcher system
37. Nair  MT, Cheng  MC, Barker  A, Rouse  BS. High dose rate  (HDR) intracavitary applicator: Clinical application and 3‑dimensional
brachytherapy technique: For carcinoma of uterine cervix using treatment planning. Int J Radiat Oncol Biol Phys 1989;17:1103‑9.

Journal of Medical Physics  ¦  Volume 46  ¦  Issue 4  ¦  October-December 2021 241

 Mourya, et al.: Gynecological brachytherapy applicators

57. Weeks  KJ, Montana  GS. Three‑dimensional applicator system Vienna/Venezia hybrid high‑dose rate brachytherapy applicators
for carcinoma of the uterine cervix. Int J Radiat Oncol Biol Phys for cervical cancer: A  single‑institution experience. Brachytherapy
1997;37:455‑63. 2021;20:104‑11.
58. Ling  CC, Schell  MC, Working  KR, Jentzsch  K, Harisiadis  L, 75. Gonzalez  Y, Giap  F, Klages  P, Owrangi  A, Jia  X, Albuquerque  K.
Carabell S, et al. CT‑assisted assessment of bladder and rectum Predicting which patients may benefit from the hybrid
dose in gynecological implants. Int J Radiat Oncol Biol Phys intracavitary+interstitial needle  (IC/IS) applicator for advanced
1987;13:1577‑82. cervical cancer: A dosimetric comparison and toxicity benefit analysis.
59. Roeske  JC, Lund  C, Pelizzari  CA, Pan  X, Mundt  AJ. Reduction Brachytherapy 2021;20:136‑45.
of computed tomography metal artifacts due to the Fletcher‑Suit 76. Schnell E, Thompson S, Ahmad S, Herman TS, De La Fuente Herman T.
applicator in gynecology patients receiving intracavitary brachytherapy. Dosimetric considerations when utilizing Venezia, Capri, Rotte double
Brachytherapy 2003;2:207‑14. tandem, and tandem and ring with interstitial needles for the treatment
60. Xia  D, Roeske  JC, Yu  L, Pelizzari  CA, Mundt AJ, Pan  X. A  hybrid of gynecological cancers with high dose rate brachytherapy. Med Dosim
approach to reducing computed tomography metal artifacts in 2020;45:21‑7.
intracavitary brachytherapy. Brachytherapy 2005;4:18‑23. 77. Han DY, Webster MJ, Scanderbeg DJ, Yashar C, Choi D, Song B, et al.
61. Simpson DR, Scanderbeg DJ, Carmona R, McMurtrie RM, Einck J, Direction-Modulated Brachytherapy for High-Dose-Rate Treatment of
Mell LK, et al. Clinical Outcomes of Computed TomographyBased Cervical Cancer. I: Theoretical Design. Int J Radiat Oncol. 2014;89:666-
Volumetric Brachytherapy Planning for Cervical Cancer. Int J Radiat 73.
Oncol. 2015 Sep;93(1):150-7.. 78. Han  DY, Safigholi  H, Soliman A, Ravi A, Leung  E, Scanderbeg  DJ,
62. Pötter R, Dimopoulos  J, Georg  P, Lang  S, Waldhäusl C, et al. Direction modulated brachytherapy for treatment of cervical
Wachter‑Gerstner N, et al. Clinical impact of MRI assisted dose volume cancer. II: Comparative planning study with intracavitary and
adaptation and dose escalation in brachytherapy of locally advanced intracavitary‑interstitial techniques. Int J Radiat Oncol Biol Phys
cervix cancer. Radiother Oncol 2007;83:148‑55. 2016;96:440‑8.
63. Kim Y, Modrick JM, Pennington EC, Kim Y. Commissioning of a 3D 79. Safigholi H, Han DY, Soliman A, Song WY. Direction modulated
image‑based treatment planning system for high‑dose‑rate brachytherapy brachytherapy (DMBT) tandem applicator for cervical cancer treatment:
of cervical cancer. J Appl Clin Med Phys 2016;17:405‑26. Choosing the optimal shielding material. Med Phys. 2018;45:3524-33.
64. Kim Y, Muruganandham M, Modrick JM, Bayouth JE. Evaluation 80. Elzibak AH, Kager PM, Soliman A, Paudel MR, Safigholi H, Han DY,
of artifacts and distortions of titanium applicators on 3.0‑Tesla et al. Quantitative CT assessment of a novel direction‑modulated
MRI: Feasibility of titanium applicators in MRI‑guided brachytherapy tandem applicator. Brachytherapy 2018;17:465‑75.
brachytherapy for gynecological cancer. Int J Radiat Oncol Biol 81. Safigholi  H, van Veelen  B, Niatsetski  Y, Song  WY. Modeling of
Phys 2011;80:947‑55. the direction modulated brachytherapy tandem applicator using the
65. Rao YJ, Zoberi JE, Kadbi M, Grigsby PW, Cammin J, Mackey SL, et al. Oncentra Brachy advanced collapsed cone engine. Brachytherapy
Metal artifact reduction in MRI‑based cervical cancer intracavitary 2018;17:1030‑6.
brachytherapy. Phys Med Biol 2017;62:3011‑24. 82. Yang W, Kim Y, Wu X, Song Q, Liu Y, Bhatia SK, et al. Rotating‑shield
66. Haack  S, Nielsen  SK, Lindegaard  JC, Gelineck  J, Tanderup  K. brachytherapy for cervical cancer. Phys Med Biol 2013;58:3931‑41.
Applicator reconstruction in MRI 3D image‑based dose planning of 83. Liu  Y, Flynn  RT, Kim  Y, Yang  W, Wu  X. Dynamic rotating‑shield
brachytherapy for cervical cancer. Radiother Oncol 2009;91:187‑93. brachytherapy. Med Phys 2013;40:121703.
67. Mahantshetty U, Sturdza A, Naga CP, Berger D, Fortin I, Motisi L, 84. Liu  Y, Flynn  RT, Kim  Y, Dadkhah  H, Bhatia  SK, Buatti  JM,
et al. Vienna‑II ring applicator for distal parametrial/pelvic wall et al. Paddle‑based rotating‑shield brachytherapy. Med Phys
disease in cervical cancer brachytherapy: An experience from two 2015;42:5992‑6003.
institutions: Clinical feasibility and outcome. Radiother Oncol 85. Dadkhah  H, Kim  Y, Wu  X, Flynn  RT. Multihelix rotating shield
2019;141:123‑9. brachytherapy for cervical cancer. Med Phys 2015;42:6579‑88.
68. Kirisits C, Lang S, Dimopoulos J, Berger D, Georg D, Pötter R. The Vienna 86. Lozares‑Cordero  S, Font‑Gómez JA, Gandía‑Martínez A,
applicator for combined intracavitary and interstitial brachytherapy of Miranda‑Burgos  A, Méndez‑Villamón A, Villa‑Gazulla  D, et al.
cervical cancer: Design, application, treatment planning, and dosimetric Treatment of cervical cancer with electronic brachytherapy. J Appl Clin
results. Int J Radiat Oncol Biol Phys 2006;65:624‑30. Med Phys 2019;20:78‑86.
69. Serban M, Kirisits C, de Leeuw A, Pötter R, Jürgenliemk-Schulz 87. Morcos M, Enger SA. Monte Carlo dosimetry study of novel rotating
I, Nesvacil N, et al. Ring Versus Ovoids and Intracavitary Versus MRI‑compatible shielded tandems for intensity modulated cervix
Intracavitary-Interstitial Applicators in Cervical Cancer Brachytherapy: brachytherapy. Phys Med 2020;71:178‑84.
Results From the EMBRACE I Study. Int J Radiat Oncol. 2020;106:105- 88. Morcos M, Antaki M, Viswanathan AN, Enger SA. A novel minimally
62. invasive dynamic‑shield, intensity‑modulated brachytherapy system for
70. Keller  A, Kim  H, Houser  CJ, Beriwal  S. Feasibility and early the treatment of cervical cancer. Med Phys 2021;48:71‑9.
outcomes for cervical and endometrial cancer patients treated with 89. Safigholi H, Han DY, Mashouf S, Soliman A, Meigooni AS, Owrangi A,
HDR brachytherapy boost utilizing venezia applicator. Brachytherapy et al. Direction modulated brachytherapy  (DMBT) for treatment of
2019;18:S55. cervical cancer: A planning study with 192 Ir, 60 Co, and 169 Yb HDR
71. Smolic  M, Sombroek  C, Bloemers  MC, van Triest  B, Nowee  ME, sources. Med Phys 2017;44:6538‑47.
Mans  A. Needle use and dosimetric evaluation in cervical cancer 90. Lindegaard  JC, Madsen  ML, Traberg  A, Meisner  B, Nielsen  SK,
brachytherapy using the Utrecht applicator. Radiother Oncol Tanderup K, et al. Individualised 3D printed vaginal template for MRI
2018;126:411‑6. guided brachytherapy in locally advanced cervical cancer. Radiother
72. Fredman  E, Traughber  B, Podder  T, Colussi  V, Zheng  Y, Russo  S, Oncol 2016;118:173‑5.
et al. 3T multiparametric MRI‑guided high‑dose‑rate combined 91. Fokdal L, Tanderup K, Hokland SB, Røhl L, Pedersen EM, Nielsen SK,
intracavitary and interstitial adaptive brachytherapy for the treatment et al. Clinical feasibility of combined intracavitary/interstitial
of cervical cancer with a novel split‑ring applicator. Brachytherapy brachytherapy in locally advanced cervical cancer employing MRI with
2018;17:334‑44. a tandem/ring applicator in situ and virtual preplanning of the interstitial
73. Walter F, Maihöfer C, Schüttrumpf L, Well J, Burges A, Ertl‑Wagner B, component. Radiother Oncol 2013;107:63‑8.
et al. Combined intracavitary and interstitial brachytherapy of cervical 92. Logar  HBZ, Hudej  R, Šegedin B. Development and assessment
cancer using the novel hybrid applicator Venezia: Clinical feasibility of 3D‑printed individual applicators in gynecological MRI‑guided
and initial results. Brachytherapy 2018;17:775‑81. brachytherapy. J Contemp Brachytherapy 2019;11:128‑36.
74. Keller A, Rodríguez‑López JL, Patel AK, Vargo JA, Kim H, Houser CJ, 93. Laan RC, Nout RA, Dankelman J, van de Berg NJ. MRI‑driven design
et al. Early outcomes after definitive chemoradiation therapy with of customised 3D printed gynaecological brachytherapy applicators

242 Journal of Medical Physics  ¦  Volume 46  ¦  Issue 4  ¦  October-December 2021

 Mourya, et al.: Gynecological brachytherapy applicators

with curved needle channels. 3D Print Med 2019;5:8. 2018;10:470‑7.

94. Sethi  R, Cunha A, Mellis  K, Siauw  T, Diederich  C, Pouliot  J, et al. 96. Ricotti  R, Vavassori  A, Bazani  A, Ciardo  D, Pansini  F, Spoto  R,
Clinical applications of custom‑made vaginal cylinders constructed et al. 3D‑printed applicators for high dose rate brachytherapy:
using three‑dimensional printing technology. J Contemp Brachytherapy Dosimetric assessment at different infill percentage. Phys Med
2016;8:208‑14. 2016;32:1698‑706.
95. Sekii S, Tsujino K, Kosaka K, Yamaguchi S, Kubota H, Matsumoto Y, 97. Adam J, Cunha M. Bio-compatibility and sterilization for 3D printing
et al. Inversely designed, 3D‑printed personalized template‑guided materials. Available at: https://amos3.aapm.org/abstracts/pdf/99-30943-
interstitial brachytherapy for vaginal tumors. J Contemp Brachytherapy 360478-110230-598827223.pdf. [Last accessed on 2021 Oct 28].

Journal of Medical Physics  ¦  Volume 46  ¦  Issue 4  ¦  October-December 2021 243

a b c d
Supplementary Figure 1: Early radium radioactive source based
gynecological applicator design. (a) Danlos initial intracavitary
brachytherapy applicator[8]. (b‑d) Wickham applicator design[9]

a b c d
Supplementary Figure 2: Stockholm intracavitary brachytherapy
applicator. (a and b) Flat Box with preloaded radium sources for vagina
placement.[13] (c) Intrauterine tube capsules of radium with variable
length.[10] (d) Sagittal view of applicator preloaded with radium sources
in the intrauterine and vaginal box[10]

a b c d e f
Supplementary Figure 3: Paris system intracavitary applicator. (a) Radium‑226 source tubes. (b) Blind ended rubber tandem having three radium
sources (1:1:0.5) i.e. 13.33 mg, 13.33 mg, 6.66 mg of radium‑226 sources. (c) Metal sheath of vaginal colpostat. (d) Radium tube inside rubber
tandem. (e) Two Colpostat joined contain one 13.33 mg radium‑226 source in each.[18] (f) Coronal view of whole applicator assembly inside the patient[20]
a b c
Supplementary Figure 4: Represents the Manchester applicator. (a) Small,
medium, large sizes of tandems and ovoids. [23] (b) Washer and
spacer. (c) Manchester whole applicator assembly

Supplementary Figure 5: List of Fletcher family applicators design development[24‑27,29‑32]

Applicator Material Ovoids/colpostat Schematic diagram of Ovoids
Preloaded 1950
Fletcher Double (a) Stainless Steel
Fletcher Single (b) Stainless Steel

Afterloading 1960
Fletcher-Suit (a) Stainless Steel-Rectangle Handle
Fletcher-Green (b) Stainless Steel-Round Handle

Afterloading Mini 1970

Delclos-Mini Stainless Steel and No Shields

Fletcher-Suit- Stainless Steel

Delclos

FSD mini ovoid (a)

FSD Ovoid (b)
a b c d
Supplementary Figure 6: Henschke afterloading applicator. (a) Initial
Design of Henschke afterloading applicator with the shield.[28] (b and c)
Modified design of Henschke applicator without the shield in ovoids
and with shielding material in ovoids.[34] (d) Ovoid caps with a slot for
shielding materials

a b c
Supplementary Figure 7: Ring applicator. (a and b) Schematic
diagram of early ring applicator for cervitron II and remote afterloading
machine.[36,38] (c) Applicator with rectal retractor for nucletron machine[39]

a b c
Supplementary Figure 8: Institut gustave roussy applicator. (a) Creiteil
method (or Chassagne and Pierquin) applicator. (b and c) Schematic
diagram of source distribution in vaginal por tion catheter and
radiograph[42]
Supplementary Table 1: Brief details of various gynecological applicators
Era Applicator name Loading type Application Clinical usage Design
type
Manual Remote
1900-1952 Wickham applicator Yes No IC Cervix, endometrium T‑R
Stockholm applicator Yes No IC Cervix, endometrium T‑B
Paris applicator Yes No IC Cervix, endometrium T‑O
Manchester applicator Yes Yes* IC Cervix, endometrium T‑O
1953-2004 Fletcher Yes Yes* IC Cervix, endometrium T‑O with shield
Fletcher‑Suit Yes Yes* IC Cervix, endometrium T‑O with shield
Fletcher Suit delclos Yes Yes* IC Cervix, endometrium T‑O with shield
Henschke applicator No Yes IC Cervix, endometrium T‑O
Tandem‑ring applicator No Yes IC Cervix, endometrium T‑R
Mold applicator No Yes IC Cervix, endometrium, vagina T‑M
Amersham applicator No Yes IC Cervix, endometrium T‑O
MUPIT No Yes IC + IS Cervix, endometrium, vagina, distal parametrium T‑C + TE with needle
Syed‑Neblett applicator No Yes IC + IS Cervix, endometrium, vagina, distal parametrium T‑C + TE with needle
Fletcher-shielded applicator No Yes IC Cervix, endometrium T‑O + S
2005 Vienna applicator No Yes IC + IS Cervix, endometrium T‑R + straight needles
onwards Vienna II applicator No Yes IC + IS Cervix, endometrium, distal parametrium T‑R + oblique needles
(hybrid Utrecht applicator No Yes IC + IS Cervix, endometrium T‑O + needle
applicators)
Split ring applicator No Yes IC + IS Cervix, endometrium T‑R + needle
MAC applicator No Yes IC + IS Cervix, endometrium, vagina, distal parametrium T‑C + TE with needle
Venezia applicator No Yes IC + IS Cervix, endometrium, vagina, distal parametrium T‑R + TE with needle
Geneva applicator No Yes IC + IS Cervix, endometrium, distal parametrium T‑O + TE with needle
Tulip applicator No Yes IC + IS Cervix, endometrium, distal parametrium T + 3D print TE with needle
*Indicate modern design of applicator. IC: Intracavitary, IS: Interstitial, T‑O: Tandem and ovoid, T‑B: Tandem and box, T‑R: Tandem and ring, T‑M: Tandem
and mold, T‑C: Tandem and cylinder, TE: Template for needle insertion, T‑O+S: Tandem and shielded ovoid, MUPIT: Martinez Universal Perineal Interstitial
Template

a b c d

Supplementary Figure 9: Amersham gynecology applicator parts and

Schematic diagram of the whole assembly of it[44,45] e
Supplementary Figure 10: MUPIT and Syed‑Neblett interstitial
applicator. (a) MUPIT Needle template toward patient (b) Cover plate
of MUPIT template* (c) Vaginal obturator* (d) Rectum obturator* (e)
Syed‑Neblett template applicator different parts #. MUPIT: Martinez
Universal Perineal Template, *: MUPIT, Elekta AB, Stockholm, Sweden,
#: Syed‑Neblett Gyn Template, Best Medical International, Virginia,
USA. Permission was obtained from Elekta to reproduce the figure for
publication