Feasibility study on image guided patient positioning for stereotactic body radiation therapy of liver malignancies guided by liver motion
Heinz et al. Radiation Oncology
Feasibility study on image guided patient positioning for stereotactic body radiation therapy of liver malignancies guided by liver motion
Christian Heinz 0
Sabine Gerum 0
0 Equal contributors Department of Radiation Oncology, LMU Munich , 81377 Munich , Germany
Background: Fiducial markers are the superior method to compensate for interfractional motion in liver SBRT. However this method is invasive and thereby limits its application range. In this retrospective study, the compensation method for the interfractional motion using fiducial markers (gold standard) was compared to a new non-invasive approach, which does rely on the organ motion of the liver and the relative tumor position within this volume. Methods: We analyzed six patients (3 m, 3f) treated with SBRT in 2014. After fiducial marker implantation, all patients received a treatment CT (free breathing, without abdominal compression) and a 4D-CT (consisting of 10 respiratory phases). For all patients the gross tumor volumes (GTVs), internal target volume (ITV), planning target volume (PTV), internal marker target volumes (IMTVs) and the internal liver target volume (ILTV) were delineated based on the CT and 4D-CT images. CBCT imaging was used for the standard treatment setup based on the fiducial markers. According to the patient coordinates the 3 translational compensation values (tx, ty, tz) for the interfractional motion were calculated by matching the blurred fiducial markers with the corresponding IMTV structures. 4 observers were requested to recalculate the translational compensation values for each CBCT (31) based on the ILTV structures. The differences of the translational compensation values between the IMTV and ILTV approach were analyzed. Results: The magnitude of the mean absolute 3D registration error with regard to the gold standard overall patients and observers was 0.50 cm ± 0.28 cm. Individual registration errors up to 1.3 cm were observed. There was no significant overall linear correlation between the respiratory motion and the registration error of the ILTV approach. Conclusions: Two different methods to calculate the translational compensation values for interfractional motion in stereotactic liver therapy were evaluated. The registration accuracy of the ILTV approach is mainly limited by the non-rigid behavior of the liver and the individual registration experience of the observer. The ILTV approach lacks the accuracy that would be desired for stereotactic radiotherapy of the liver.
Stereotactic body radiation therapy; Liver; Patient positioning; Fiducial marker; CBCT
Stereotactic body radiation therapy (SBRT) has emerged
as an alternative in treatment of hepatocellular
carcinoma (HCC) [
] and oligometastatic liver disease [
over the past decade. Nevertheless, SBRT of liver
malignancies is challenging due to the high biologically
effective doses and the uncertainty of the tumor position
resulting from a combination of a) intrafractional
quasiperiodic motion resulting from the patient’s respiration,
b) intrafractional motion (e.g., baseline shifts due to
relaxation) and c) interfractional motion resulting from
e.g., different fillings of the gastrointestinal tract and
In general, uncertainties resulting from intrafractional
motion are minimized (e.g., abdominal compression,
breath hold, gating) and compensated by specific margin
concepts (e.g., ITV). Interfractional motion, which leads
to a systematic shift of the tumor position, is usually
managed by image guidance modalities (e.g., CBCT,
ultrasound). However, imaging of liver malignancies and
hereby the compensation of interfractional motion is
Regularly, the skeletal anatomy is inadequate for SBRT
] and the target itself may not be
detectable in CT or CBCT. Hence only a surrogate of the
exact tumor position can be visualized (e.g., fiducial
]). On the one hand, it has been shown that
the implantation of fiducial markers next to the tumor
allows a high-precision tumor radiation setup [
on the other hand the implantation of fiducial markers
is naturally an invasive procedure that is not applicable
for all patients and thereby limits the application range
of SBRT. Furthermore, fiducial markers compromise
the image quality of the planning CT [
] and make
the tumor delineation more difficult. It is obvious
that a different surrogate of the exact tumor position
In this retrospective study, the compensation method
for the interfractional motion using fiducial markers
(gold standard) was compared to a new approach which
does not rely on fiducial markers but on the organ
motion of the liver and the relative tumor position within
the liver volume.
Preparation and treatment workflow
All patients received a magnetic resonance imaging
(MRI) scan and fiducial markers were implanted prior to
the planning CT acquisition. Patient positioning for
CT imaging and treatment was realized by the use of a
vacuum cushion in combination with the WingSTEP
(Elekta AB, Sweden). The patients were instructed to
breathe freely, and respiration was not restricted by
any device. Afterwards, a treatment planning CT and a
4D-CT were acquired. The spatial resolution of the
treatment CT (1.074 mm × 1.074 mm × 3.0 mm) was
equal to the resolution of the 4D-CT, which consisted
of 10 respiratory phases. For each patient an internal
target volume (ITV) was delineated containing the
gross tumor volume (GTV) outlines of the 10
respiratory phases enlarged by an isotropic margin of 6 mm.
Furthermore each fiducial marker was delineated in all
respiratory phases and a covering volume (hull)
without any additional margin was generated, hereafter
referred to as “internal marker target volume” (IMTV).
In analogy to the IMTV a second structure set has
been created for this study, including only an “internal
liver target volume” (ILTV). For the daily treatment, all
patients were setup by using CBCT imaging. Due to
the slow temporal resolution of the CBCT, fiducial
markers were blurred over several respiration cycles
similar to the contoured IMTVs generated from the
patient’s 4D-CT. According to the patient coordinates
defined in the DICOM standard, the 3 translational
compensation values (tx, ty, tz) for the interfractional
motion were calculated by matching the blurred
fiducial markers with the corresponding IMTV structures.
Afterwards the compensation values were sent to a
robotic couch to correct the daily patient position.
Recalculation of the compensation values using different approaches
In this retrospective study, 4 observers were requested
to recalculate the translational compensation values. The
virtual patient setup was done in MOSAIQ (Elekta AB,
Sweden), using the image registration module. Table 1
gives an overview of the patient data.
Starting in 2014 this retrospective study includes 6 patients
(3f, 3 m), that suffered from HCC (5/6) and
oligometastatic disease (1/6). Prescribed doses and fractionation
depended on localization, size of the lesion, mobility and
liver function. One patient was not able to complete the
radiotherapy course due to an accident resulting in a
Patient setup using fiducial markers
The first method to recalculate the translational
compensation values followed a workflow similar to the
method used for the daily treatment setup. For each
available CBCT a coarse rigid preregistration has been
calculated, based on the gray values in CBCT and the
initial planning CT. Due to the differences in the daily
patient anatomy a second registration step was required.
For that reason a manual rigid registration was applied
Seg. I + VIII
with a strong focus to optimize the correlation between
the blurred fiducial markers in the CBCT and the
corresponding IMTV structures (see Fig 1a). For each CBCT
the resulting translational compensation values were
calculated once and served as a gold standard for the
Patient setup using organ motion of the liver
The second method also makes use of a coarse rigid
preregistration based on the image intensities. But the final
manual registration step relies on the ILTV structure that
was generated for each patient. Not only the fiducial
markers but also the whole liver volume appears to be
blurred in the daily CBCT. Therefore the 4 observers were
requested to optimize the correlation between the blurred
liver volume and the ILTV structure generated from the
patient’s 4D-CT (see Fig 1b). Again, the resulting translational
compensation components were recorded for each CBCT.
In total, 31 different CBCT data sets from 6 different
patients were registered by 4 observers using the second
approach. As a result of each registration the difference
(registration error) of the translational compensation
values between the actual registration and the gold
standard has been calculated. All values were recorded in cm.
Thereby the dx component denotes the left-right, the dy
component denotes the anterior-posterior and the dz
component denotes the superior-inferior deviation
between the actual registration and the registration based on
the fiducial markers. Besides, an overall deviation
magnitude from all three components was calculated (see Fig 2).
The smallest standard deviation of the registration
error over all patients and observers can be observed in
the dx component (0.24 cm), followed by standard
deviation of the dy (0.33 cm) and the dz component
(0.41 cm). The magnitude of the mean absolute 3D
registration error over all patients and observers was
0.50 cm ± 0.28 cm. Although the standard deviations of
a single component imply a small registration error,
individual registration errors of up to 1.3 cm were
observed. The evaluation of the data by the individual
observers is shown in Table 2.
The dx, dy and dz components of the registration
errors increase in the named order. Hence a relation
between the magnitude of respiratory induced motion
and the components of the registration error was
assumed. From [
] it is known that the organ motion
of the liver in the superior-inferior direction is bigger
than in the other directions. As a consequence the
uncertainty of registration in that direction should
also be higher than in the other directions. To check
for a correlation between the respiratory motion and
the registration errors for each fiducial marker the
trajectory of its center of mass (COM) was calculated
from the 4D-CT data (Table 3). If there is a correlation
between respiratory induced motion and the registration
error, it will be reasonable to reduce the respiratory
motion by additional actions (e.g., abdominal compression).
Figure 3 shows the error magnitude of each
component plotted against the movement of the fiducial
markers (COM) in the same direction. The plot does
not show a significant overall linear correlation between
the respiratory motion and the registration error. The
coefficients of determination (R2) are low and vary
between different observers (0.0003–0.4929).
Liver SBRT is a highly effective locally ablative technique
and may be applied non-invasively. Due to quasiperiodic
motion of the liver and its partially non-rigid behavior,
fiducial markers are regarded as gold standard when
delivering high radiation dose to malignant liver lesions.
Within this study, we examined whether fiducial marker
implantation was really necessary to account for all
different modes of motion. A soft-tissue approach was
chosen employing a liver ITV concept (ILTV) being
coregistered to a CBCT blurred liver anatomy; if the
liver was comparable to a rigid body, this should result
in comparable results to the implanted fiducial markers.
We included 31 different datasets from 6 patients in
this study and found that the accuracy of the motion
based patient setup is limited to 3D registration errors
of 0.23 ± 0.05 cm up to 0.98 ± 0.08 cm depending on a
specific patient and observer. The largest registration
errors were observed in the cranio-caudal direction which
is the major direction of liver motion. A componentwise
comparison of the registration errors and the
corresponding motion extents led to the assumption of a
correlation between the motion extent and the
registration error. However, this assumption could not be
proved since only poor coefficients of determination
were found for a linear regression. Therefore it is
questionable whether abdominal compression is able
to improve the registration results in an organ motion
based patient setup significantly.
In addition to the respiratory motion, the low image
contrast of soft-tissues in CBCT makes it difficult to
correct the patient’s position using the organ motion based
patient setup. Hence, the experience of the individual
observer has been identified as a main parameter of the
In a similar study [
], it has been shown, that the
soft-tissue-based image guidance with consideration of
the 4D breathing motion (organ motion based patient
setup) is able to increase the accuracy of treatment
compared with stereotactic positioning or image guided
radiotherapy without 4D imaging. However, in
comparison to the fiducial marker based setup (IMTV), which is
supposed to be the superior technique to predict the
tumor position compared to other surrogates [
the registration errors observed in this study imply that
the organ motion based patient setup (ILTV) requires
adapted safety margins larger than the ones used in a
fiducial marker setup.
In general the accuracy of the organ motion based
patient setup is limited by the fact that the liver itself does
not behave like a rigid object, but is deformed under the
influence of respiration. At least three different types of
motion were identified in [
], for singular points in the
liver volume. For this reason a singular rigid registration
of the whole liver will result in different, unknown
registration errors depending on the location inside the liver.
Above all we found a good agreement of the motion
extents of different spots inside the liver compared to [
A new method to compensate for interfractional motion,
based on the organ motion of the liver, was compared to
the patient setup using fiducial markers. The latter
method served as gold standard. It has been shown that
a rigid registration based on the organ motion of the
liver lacks the accuracy that would be desired for
stereotactic radiotherapy of the liver. The registration
accuracy is mainly limited by the non-rigid behavior of
the liver and the individual registration experience of the
observer. Whenever possible, the preferred method to
setup the patient and correct for interfractional changes
or motion is to place fiducial markers next to the target
location and coregister the estimated IMTV to the daily
Ethics approval and consent to participate
This retrospective study was exempt from requiring ethics
approval. Bavarian state law (Bayrisches Krankenhausgesetz/
Bavarian Hospital Law §27 paragraph 4) allows the use
of patient data for research, provided that any person’s
related data are kept anonymous.
Consent for publication
Availability of data and materials
The presented data is summarized in this paper. The
complete datasets can be retrieved from the authors
upon formal request from interested readers.
4D-CT, 4-dimensional computed tomography; CBCT, cone beam computed
tomography; COM, centre of mass; CT, computed tomography; GTV, gross
tumor volume; HCC, hepatocellular carcinoma; ILTV, internal liver target volume;
IMTV, internal marker target volume; ITV, internal target volume; PTV, planning
target volume; SBRT, stereotactic body radiation therapy.
The authors declare that they have no competing interests.
CH, SG contributed equally to this work, participated in the design of the
study, carried out the study, analyzed the data and drafted the manuscript.
Data collection was conducted by CH, SG, PF and MN, who conceived and
coordinated the study, and edited the manuscript. UG, FR, SC, CB helped to
implement the clinical standard workflow, made the clinical data available and
reviewed the manuscript. All authors read and approved the final manuscript.
Our department receives research grants from Elekta AB, Sweden. Elekta had
no involvement in study design, data collection and analysis.
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