Assessment of Target Volume Definition for Precise
Radiotherapeutic Management of Locally Recurrent
Biliary Tract Cancers: An Original Research Article Volume 46- Issue 1
Omer Sager*, Selcuk Demiral, Ferrat Dincoglan and Murat Beyzadeoglu
Department of Radiation Oncology, University of Health Sciences, Gulhane Medical Faculty, Turkey
Received: August 2, 2022; Published: September 08, 2022
*Corresponding author: Omer Sager, University of Health Sciences, Gulhane Medical Faculty, Department of Radiation Oncology,
Gn.Tevfik Saglam Cad. 06018, Etlik, Kecioren Ankara / Turkey
Objective: Biliary tract cancer (BTC) refers to a heterogeneous group of tumors
including intrahepatic, perihilar, and extrahepatic cholangiocarcinomas, along with
gallbladder cancers. BTC originates from the biliary epithelium of small ducts in the
periphery of the liver (intrahepatic) and from main ducts of the hilum (extrahepatic).
Although comprising a small proportion of all cancers, BTC accounts for the second
most frequent hepatic malignancy after hepatocellular carcinomas. Patients with BTC
may be diagnosed at relatively advanced stages, and symptoms may deteriorate quality
of life significantly. Currently, multidisciplinary management may be utilized for
achieving optimal therapeutic outcomes. Radiation therapy (RT) may play a role in definitive,
adjuvant, or palliative setting and also for management of recurrent disease.
Target volume definition comprises a critical aspect of radiotherapeutic management
for BTC. In this original research article, we shed light on this critical issue by assessment
of multimodality imaging with incorporation of Magnetic Resonance Imaging
(MRI) for RT target volume definition of locally recurrent BTC.
Materials and Methods: In this original research article, we undertook a comparative
analysis of target definition for radiotherapeutic management of locally recurrent
BTC based on Computed Tomography (CT) simulation images only or by incorporation
of fused CT-MRI. Main outcome measure of the study was to investigate the
utility of multimodality imaging for target definition.
Results: Ground truth target volume has been found to be identical with fused
CT-MRI based target definition for patients with locally BTC as the primary endpoint
of this original research article.
Conclusion: Consideration of multimodality imaging with incorporation of MRI
in the RT planning procedure should be prioritized for optimal radiotherapeutic management
of patients with locally recurrent BTC.
Biliary tract cancer (BTC) refers to a heterogeneous group
of tumors including intrahepatic, perihilar, and extrahepatic
cholangiocarcinomas, along with gallbladder cancers. BTC
originates from the biliary epithelium of small ducts in the
periphery of the liver (intrahepatic) and from main ducts of the
hilum (extrahepatic). Extrahepatic BTC includes the gallbladder
cancers, ampullary cancers, and cancers of pancreatic biliary ducts.
While extrahepatic cancers originate from similar epithelia, the
etiology may differ due to their anatomy. Although comprising a
small proportion of all cancers, BTC accounts for the second most
frequent hepatic malignancy after hepatocellular carcinomas [1-5].
The subclassification includes intrahepatic cholangiocarcinomas
arising from the biliary tree within the liver, and extrahepatic
cholangiocarcinomas arising from the biliary tree outside the liver,
and gallbladder carcinoma. Extrahepatic cholangiocarcinomas may
be subcategorized into perihilar and distal cholangiocarcinomas.
Gallbladder is a small and pear-shaped organ which lies underneath
the liver with the main function of storing bile. Although the
gallbladder is a small organ, it may be associated with cancer.
There may be preponderance for early spread with resultant
poor prognosis partly due to the lack of serosa layer and close
proximity to critical surrounding structures along with extension
to lymphatics [1-5].
Patients with BTC may be diagnosed at relatively advanced
stages, and symptoms may deteriorate quality of life significantly.
Currently, multidisciplinary management may be utilized for
achieving optimal therapeutic outcomes [2-10]. Radiation therapy
(RT) may play a role in definitive, adjuvant, or palliative setting and
also for management of recurrent disease. Target volume definition
comprises a critical aspect of radiotherapeutic management
for BTC. Advances in surgery, RT, and systemic treatment offer
improved life expectancies for patients suffering from BTC. Within
this context, treatment induced toxicity has become an endpoint
of increasing importance recently. With excellent integration of
contemporary approaches in cancer management, radiotherapeutic
strategies have demonstrated critical progress in the millenium era.
Introduction of contemporary therapeutic concepts and techniques
such as Intensity Modulated RT (IMRT), Image Guided RT (IGRT),
molecular imaging methods, automatic segmentation techniques,
stereotactic RT, and adaptive RT (ART) have clearly contributed to
optimal radiotherapeutic management [11-50].
Integration of these relatively newer radiotherapeutic
approaches led to more precise and accurate targeting of tumors by
virtue of steeper dose gradients around the target volumes resulting
in decreased normal tissue exposure. Reduced critical organ doses
may allow for decreased adverse effects and treatment dose
escalation which could pave the way for an improved therapeutic
ratio. Admittedly, vigilance is warranted for clinical implementation
of these state-of-the-art radiotherapeutic concepts in daily routine.
Optimization of target volume determination has become an
indispensable component of recent RT protocols for BTC. Currently,
Computed Tomography (CT) simulation plays a significant role in
RT planning at majority of treatment centers globally. CT serves
as a plausible imaging modality for dose calculation purposes,
nevertheless, inclusion of other imaging modalities for RT planning
may clearly add to the accuracy and precision in target definition.
In the literature, there have been many studies addressing the use
of multimodality imaging for optimal target definition for RT [51-
87]. Herein, we assess target definition for locally recurrent BTC by
use of multimodality imaging and provide an extensive review of
relevant literature.
Patients referred to Department of Radiation Oncology
at Gulhane Medical Faculty, University of Health Sciences for
radiotherapeutic management of BTC have been assessed for target
definition by use of multimodality imaging in this original research
article. A comparative analysis has been performed to evaluate
target determination based on CT simulation images only or by
incorporation of Magnetic Resonance Imaging (MRI). Ultimate goal
of this study was to evaluate the utility of multimodality imaging
for target definition, however, other factors such as contouring
of critical organs, interobserver and intra observer variations
have also been investigated. A ground target volume has been
used for comparative analysis and for comparison purposes, and
the ground truth target volume has been defined by our expert
group of radiation oncologists following thorough consideration
of all imaging and relevant data with meticulous colleague peer
review and consensus. Decision making for RT was based on
multidisciplinary assessment of patients by experts from surgical
oncology, radiation oncology, and medical oncology. Patient, disease,
and treatment related characteristics were considered individually
by taking into account age, symptomatology, performance status,
previously administered therapies, lesion size, localization and
association with surrounding critical structures, expected results
of suggested treatments, patient preferences and logistical issues.
Synergy (Elekta, UK) linear accelerator (LINAC) has been used
in delivery of irradiation with integration of IGRT techniques. After
robust immobilization of the patients, CT simulation images have
been acquired at the CT simulator (GE Lightspeed RT, GE Healthcare,
Chalfont St. Giles, UK) for RT planning. Thereafter, these acquired RT
planning images were sent to the contouring workstation (SimMD,
GE, UK) through the network for generation of individualized
structure sets including target volumes and critical structures.
For the purpose of this study, we have performed a comparative analysis to evaluate target and critical organ determination based
on either CT simulation images only or fused CT-MR images.
Multimodality imaging by integration of MRI for target
volume determination has been evaluated for patients referred
for radiotherapeutic management of locally recurrent BTC in
this original research article. All treatments were administered
at Department of Radiation Oncology, Gulhane Medical Faculty,
University of Health Sciences and included patients underwent
thorough multidisciplinary assessment by experts from surgical
oncology, radiation oncology, and medical oncology. We undertook
a comparative analysis for assessment of target and critical organ
definition by use of either CT only imaging or by fused CT-MRI in
an attempt to reveal the role of multimodality imaging. Tumor
related parameters which were taken into account in management
were lesion size, localization and association with surrounding
critical structures. Also, individual characteristics such as patient
symptomatology, age, performance status have been evaluated
along with logistical factors. RT planning has been performed
by expert radiation physicists by consideration of reports by
American Association of Physicists in Medicine (AAPM) and
International Commission on Radiation Units and Measurements
(ICRU). Electron density, tissue heterogeneity, CT number and
HU values in CT images were considered in precise RT planning.
Main objective of RT planning has been to achieve optimal target
volume coverage with minimal exposure of nearby critical organs.
Ground truth target volume was individually determined for every
patient by board certified radiation oncologists following detailed
assessment, rigorous colleague peer review procedure, and
consensus to be utilized for actual treatment and for comparison
purposes. In addition, IGRT techniques have been used for accurate
setup verification. Synergy (Elekta, UK) LINAC was used for
treatment delivery. The ground truth target volume has been found
to be identical with fused CT-MRI based target determination for
patients with locally recurrent BTC as the endpoint of the study.
BTC may be considered as a heterogeneous group of tumors.
BTC originates from the biliary epithelium of small ducts in the
periphery of the liver (intrahepatic) and from main ducts of the
hilum (extrahepatic). Extrahepatic BTC includes the gallbladder
cancers, ampullary cancers, and cancers of pancreatic biliary ducts.
While extrahepatic cancers originate from similar epithelia, the
etiology may differ owing to their anatomy. Although comprising a
small proportion of all cancers, BTC accounts for the second most
frequent hepatic malignancy after hepatocellular carcinomas [1-5].
The subclassification includes intrahepatic cholangiocarcinomas
arising from the biliary tree within the liver, and extrahepatic
cholangiocarcinomas arising from the biliary tree outside the liver,
and gallbladder carcinoma. Extrahepatic cholangiocarcinomas may
be subcategorized into perihilar and distal cholangiocarcinomas.
The gallbladder is a small and pear-shaped organ which lies
underneath the liver with the main function of storing bile.
Although the gallbladder is a small organ, it may be associated with
cancer. There may be predilection for early spread with resultant
grim prognosis partly due to the lack of serosa layer and close
proximity to critical surrounding structures along with extension
to lymphatics [1-5].
Patients with BTC may be diagnosed at relatively advanced
disease stages, and symptoms may profoundly deteriorate quality
of life. In the meantime, multidisciplinary management may be
used to achieve improved treatment results [2-10]. RT may play a
critical role in definitive, adjuvant, or palliative setting and also for
management of recurrent BTC. Target determination comprises a
considerable aspect of precise RT for BTC. Improvements in surgery,
RT, and systemic treatment offer improved life expectancies for
patients suffering from BTC. Within this context, adverse radiation
effects became an endpoint of increasing importance in recent years.
By virtue of excellent integration of contemporary strategies in
cancer management, RT concepts have shown dramatical progress
in the millenium era. Incorporation of sophisticated technologies
and techniques including IGRT, IMRT, automatic segmentation
techniques, stereotactic RT, ART, and molecular imaging methods
have obviously contributed to optimal RT strategies [11-50].
Integration of these relatively newer RT approaches resulted in
more precise and accurate targeting of tumors by virtue of steeper
dose gradients around the target volumes which led to decreased
exposure of normal tissues. Reduced critical organ doses may
allow for decreased adverse radiation effects and also treatment
dose escalation could be achieved which might pave the way for an
improved therapeutic ratio. Clearly, vigilance is required for clinical
implementation of these excellent radiotherapeutic approaches in
daily routine. Optimization of target definition has recently become
an indispensable component of contemporary RT protocols for BTC.
In the meantime, CT simulation plays a critical role in RT planning
at majority of treatment centers on a global scale. While CT may
be considered as a plausible imaging modality for dose calculation
purposes, integration of other imaging modalities for RT planning
may add to the accuracy and precision of target definition. There
are several studies addressing the use of multimodality imaging for
optimal target definition for RT [51-87]. In this context, we consider
that our study may have implications for routine implementation of
multimodality imaging-based target definition for radiotherapeutic
management of BTC.
We conclude that multimodality imaging through integration of
MRI in the RT planning process may be considered for improving
the accuracy and precision of target definition for radiotherapeutic
management of locally recurrent BTC.