The adoption of 3D image-guided
brachytherapy for cervical carcinoma
is gaining momentum in Southeast
Asia and heading north
WHITE PAPER
Chiang Mai University Hospital, Thailand
Ekkasit Tharavichitkul, MD
3D image-guided brachytherapy (3D IGBT) in patients with cervical carcinoma
is associated with very good clinical outcomes. This has been recognized for
many years throughout the world, and is being applied actively in Europe and
the United States.
During 3D IGBT, MRI images are used to contour the tumor and surrounding
organs-at-risk (OAR), enabling highly accurate planning of sufficient radiation
doses to better treat the tumor. At the same time, doses to OARs, such as the
bladder and rectum, are reduced (figures 2-4). Despite these benefits to the
patient, the adoption of 3D IGBT for cervical carcinoma is slow in Southeast Asia,
but is gaining momentum.
Figure 1: Chiang Mai IGBT team – Division of
therapeutic radiology and oncology – faculty
of medicine
Figure 2: MRI axial view - contouring of the tumor and organs-at-risk (OARs)
Figure 4: MRI dose distributions view
Figure 3: MRI sagittal view - contouring of the tumor and organs-at-risk (OARs)
Challenges and opportunities for the
adoption of 3D IGBT in Southeast Asia
Initially, one of the reasons for the slow acceptance of 3D IGBT has been
the lack of clear guidelines for the imaging protocol, contouring, applicator
reconstruction and planning with three-dimensional volumes. In 2005, such
guidelines were published for the first time by the GEC-ESTRO group in Europe1,
and a second detailed guideline on dose constraints for the tumor and OARs
soon followed.2 The third and fourth GEC-ESTRO guidelines were published to
guide the applicator reconstruction and imaging protocol in the years 2010
and 2012, respectively.3-4
Even more important, the clinical outcomes of treating cervical cancer patients
with 3D IGBT were published in Europe in 2007 by Pötter et al.5 Subsequently,
many studies have been published in international journals demonstrating the
benefits of 3D IGBT in cervical carcinoma.6-9 The supporting data of 3D IGBT
has therefore increased around the world.
In Southeast Asia, the implementation of 3D IGBT has relied on these
supportive clinical data and guidelines. Nevertheless, there still are other
obstacles hindering its adoption. These include lack of knowledge, having the
necessary equipment and infrastructure and reimbursement/public health
schemes for the procedure.
Knowledge is one of the easier obstacles to overcome. International, regional
and national training courses by GEC-ESTRO, ASTRO and the IAEA have
supported radiation oncologists and physicists from Southeast Asia in gaining
the necessary knowledge to put the technique of 3D IGBT into practice. In
addition, Elekta has played an important role in overcoming the knowledge
barrier by supporting educational workshops in 3D IGBT. Leading physicians
from Southeast Asia have attended workshops at AKH Vienna, Austria, as well as
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workshops held in India (TATA Memorial Hospital in Mumbai and AIMS hospital
in Kochi), Singapore (National University Hospital) and Thailand (Chulalongkorn
University Hospital in Bangkok and Chiang Mai University Hospital). However, the
participants who have been trained on the theory of 3D IGBT may have issues
with their infrastructures when they plan to implement 3D IGBT at their centers.
The next step of on-site training or practical consultancy may be important as
follow up to improve the progress of 3D IGBT implementation in this region.
The lack of equipment and infrastructure is a more difficult obstacle to address.
Access to CT or MRI for brachytherapy is still one of the factors inhibiting the
implementation of 3D IGBT today in Asia. Although the installation of MRI
simulators has increased, it is difficult for some institutes in Southeast Asia
to acquire MRI for their brachytherapy workflow. A compromise is to use CT
instead of MRI. A CT-based contouring guideline linked to the GEC-GESTRO
recommendations supports CT-based IGBT for cervical carcinoma.10-11
Moreover, the local availability of specialized applicators compatible with the
imaging devices is another obstacle. The conventional (metal) applicator
causes many CT artifacts that affects target/OAR determination, and standard
applicators cannot be used in the MRI magnetic field. The use of CT/MR
applicators solves this problem, but sufficient funds to buy new applicators
are required. This may delay 3D IGBT in some centers.
The impediment of a lack of a reimbursement infrastructure varies in its
severity between countries. Reimbursement depends on each government’s
policy, whereas today, in many countries in Southeast Asia, government health
schemes for brachytherapy are often limited to non-existent, with no additional
reimbursement for using 3D IGBT. As a consequence, in many cases today in
Southeast Asia, the use of 3D IGBT is limited to patients with private insurance.
Some or all of these difficulties have meant that the shift from 2D to 3D
brachytherapy for cervical carcinoma in Southeast Asia has been quite slow.
With increased awareness and more available data supporting 3D IGBT for
cervical carcinoma, the reimbursement for this procedure may change at
the policy level.
Regarding clinical studies of 3D IGBT in Asia, centers - for example TATA
Memorial Hospital in India - have actively participated in the multi-center
international EMBRACE study, which is investigating clinical outcomes with
MRI-based 3D IGBT. After the training in 3D IGBT for cervical carcinoma at the
Medical University of Vienna, the Chiang Mai IGBT team started its own 3D IGBT
research project in 2008. The experience of the radiation oncologists and the
physicists at Chiang Mai is that 3D IGBT improves the quality of treatment in
cervical carcinoma. Their experience showed that better dosing was achieved
for treating the tumor in combination with a lower dose to the OARs, such as
bladder and rectum.12-14
3D IGBT also has the advantage of allowing the performance of more
sophisticated applications, such as the use of interstitial needles with the
Interstitial CT/MR Ring applicator or the Utrecht CT/MR applicator. Even
better coverage of the tumor can be achieved using these techniques, while
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still sparing OARs (i.e., bladder, rectum). The clinical results at Chiang Mai
University Hospital have revealed good clinical control and a low toxicity
profile.15 With all these positive results, it is the belief of many radiation
oncologists that 3D IGBT for cervical carcinoma should become standard of
care for cervical carcinoma in Southeast Asia in the near future.
Pamela Youde Nethersole Eastern Hospital
(PYNEH) - Hong Kong
Implementation of 3D IGBT in Hong Kong
Pamela Youde Nethersole Eastern Hospital (PYNEH) was among the first
hospitals in Hong Kong to treat a patient with cervical carcinoma following the
new GEC-ESTRO Guidelines, using MRI- and CT-based planning and advanced
imaging and target definition techniques.
PYNEH physicists and radiation oncologists overcame some of the
aforementioned obstacles by using the available educational and support
opportunities at renowned centers in the UK and USA, as well as the AKH
Vienna in Austria. Collaboration within the department with nursing support,
as well as other disciplines including gynecologists, radiologists, and
anesthesiologists is essential for the development of this new technique.
Patients were treated according to the AKH Vienna protocol. As it has been
common practice to use tandem & ovoid applicators in the department,
Utrecht CT/MR applicators were used for the insertion in the first few patients.
Figure 5: IGBT team members - Pamela Youde
Subsequently, the Vienna ring applicator was introduced into the practice and
Nethersole Eastern Hospital (PYNEH) - Hong
used in suitable patients. Following the insertion of the applicator in the theater,
Kong. The team include members from different
a MR scan was obtained and the radiation oncologist began contouring the
departments, Clinical Oncology, Medical
tumor and OARs. Brachytherapy planning was carried out by a physicist and
Physics, Diagnostic Radiology , Obstetrics and
the radiation oncologist. Applicator reconstruction and dose optimization
Gynecology and Anesthesiology
were performed and the plan was counter-checked by another physicist and
radiation oncologist before the patient began treatment (see figure 6).
In line with the Vienna protocol, brachytherapy was delivered in two consecutive
Figure 6: MRI based brachytherapy plan
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weeks and each week the patient underwent two fractions of treatment with
one applicator insertion. This meant that the applicator was in place in the
patient overnight. For the second fraction on day 2, a CT scan was obtained and
fused with the MR images of day 1. Target volumes and OARs were contoured
on the CT images for treatment planning on day 2.
Figure 7a: physicists perform a planning
Figure 7b: a 3D CT/MR applicator is used for the
accuracy check
3D IGBT treatment
It has been a very steep learning curve to move from conventional 2D planning
with radiographs to complete 3D planning and optimization. So much additional
anatomical and dosimetric information, as well as a new level of flexibility in
plan optimization is available compared to 2D planning. Linking our previous
experience with the new technique was not trivial. It is especially challenging
to bridge the conventional dose point requirements and 3D dose constraints.
Even our prescription method has evolved accordingly following our increasing
experience in 3D planning.
The clinical and physics team were very proud to be one of the first hospitals
in Hong Kong to start this advanced brachytherapy technique. Many hospitals
throughout Asia are currently or will soon be following suit with 3D IGBT
treatments in patients with cervical carcinoma, to optimize clinical outcomes
for their patients.
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References
[1]
Haie-Meder C, Pötter R, Van Limbergen E, et al. Recommendations from Gynaecological (GYN) GECESTRO Working Group (I): concepts and terms in 3D image based 3D treatment planning in cervix cancer
brachytherapy with emphasis on MRI assessment of GTV and CTV. Radiother Oncol. 2005; 74(3):
235-45.
[2]
Pötter R, Haie-Meder C, Van Limbergen E, et al. Recommendations from gynaecological (GYN) GEC ESTRO
working group (II): concepts and terms in 3D image-based treatment planning in cervix cancer brachytherapy3D dose volume parameters and aspects of 3D image-based anatomy, radiation physics, and radiobiology.
Radiother Oncol. 2006; 78(1):67-77.
[3]
Hellebust TP, Kirisits C, Berger D, Pérez-Calatayud J, De Brabandere M, De Leeuw A, Dumas I, Hudej R,
Lowe G, Wills R, Tanderup K; Gynaecological (GYN) GEC-ESTRO Working Group. Recommendations from
Gynaecological (GYN) GEC-ESTRO Working Group: considerations and pitfalls in commissioning and
applicator reconstruction in 3D image-based treatment planning of cervix cancer brachytherapy. Radiother
Oncol. 2010; 96(2):153-60.
[4]
Dimopoulos JC, Petrow P, Tanderup K, Petric P, Berger D, Kirisits C, Pedersen EM, van Limbergen E, Haie-Meder
C, Pötter R.Recommendations from Gynaecological (GYN) GEC-ESTRO Working Group (IV): Basic principles
and parameters for MR imaging within the frame of image based adaptive cervix cancer brachytherapy.
Radiother Oncol. 2012; 103(1):113-22.
[5]
Pötter R, Dimopoulos J, Georg P, et al. Clinical impact of MRI assisted dose volume adaptation and dose
escalation in brachytherapy of locally advanced cervix cancer. Radiother Oncol. 2007; 83(2):148-55.
[6]
Pötter R, Georg P, Dimopoulos JC, et al. 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(1): 116-23.
[7]
Charra-Brunaud C, Harter V, Delannes M, et al. Impact of 3D image-based PDR brachytherapy on outcome of
patients treated for cervix carcinoma in France: results of the French STIC prospective study. Radiother Oncol.
2012; 103(3):305-13.
[8]
Lindegaard JC, Fokdal LU, Nielsen SK, et al. MRI-guided adaptive radiotherapy in locally advanced cervical
cancer from a Nordic perspective. Acta Oncol. 2013; 52(7):1510-9.
[9]
Mazeron R, Gilmore J, Dumas I, et al .Adaptive 3D image-guided brachytherapy: a strong argument in the
debate on systematic radical hysterectomy for locally advanced cervical cancer. Oncologist. 2013; 18(4):415-22.
[10]
Viswanathan AN, Dimopoulos J, Kirisits C, et al. Computed tomography versus magnetic resonance imagingbased contouring in cervical cancer brachytherapy: results of a prospective trial and preliminary guidelines for
standardized contours. Int J Radiat Oncol Biol Phys. 2007; 68(2):491-8.
[11]
Viswanathan AN, Erickson B, Gaffney DK, et al. Comparison and consensus guidelines for delineation of clinical
target volume for CT- and MR-based brachytherapy in locally advanced cervical cancer. Int J Radiat Oncol Biol
Phys. 2014; 90(2):320-8.
[12]
Tharavichitkul E, Mayurasakorn S, Lorvidhaya V, et al. Preliminary results of conformal computed tomography
(CT)-based intracavitary brachytherapy (ICBT) for locally advanced cervical cancer: a single institution’s
experience. J Radiat Res. 2011; 52(5):634-40.
[13]
Tharavichitkul E, Sivasomboon C, Wanwilairat S, et al. Preliminary results of MRI-guided brachytherapy in
cervical carcinoma: the Chiangmai University experience. J Radiat Res. 2012; 53(2): 313-8.
[14]
Tharavichitkul E, Wanwilairat S, Chakrabandhu S,et al. Image-guided brachytherapy (IGBT) combined with
whole pelvic intensity-modulated radiotherapy (WP-IMRT) for locally advanced cervical cancer: a prospective
study from Chiang Mai University Hospital, Thailand. J Contemp Brachytherapy. 2013; 5(1): 10-6.
[15]
Tharavichitkul E, Chakrabandhu S, Wanwilairat S, et al. Intermediate-term results of image-guided
brachytherapy and high-technology external beam radiotherapy in cervical cancer: Chiang Mai University
experience. Gynecol Oncol. 2013; 130(1):81-5.
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