Introduction
Stereotactic body radiotherapy (SBRT) is a highly effective
treatment for patients with primary or metastatic
liver cancer. The use of the SBRT technique,
with its high dose gradient, allows for the effective
preservation of normal tissues while reducing treatment-
related side effects.[] The success of SBRT
treatment is related to minimizing geometric uncertainties
in the treatment area. One of the most significant
sources of uncertainty affecting the success
of SBRT treatments for liver tumors is tumor motion
due to respiration. By employing respiratory control
techniques, ITV (Internal Target Volume) and
PTV (Planning Target Volume) volumes can be reduced,
thereby minimizing the volume of normal tissue
exposed to high doses.[-] Respiration-related
tumor motion can be reduced using two methods.
One involves treatment during the deep inspiration
phase, which requires the patient to hold their breath
(DIBH), and the other is through treatment with abdominal
compression (AC). However, many patients
cannot tolerate treatment with the DIBH technique;
therefore, free breathing is preferred.[]
Image-guided radiotherapy (IGRT) has the potential
to detect and correct baseline movements in the
liver"s position relative to the bone, respiratory motion,
or pre-treatment deformations. Unlike lung tumors,
imaging of liver tumors is difficult due to the lack of
soft tissue contrast of image-guided radiotherapy modalities
such as computed tomography (CT) and conebeam
tomography (CBCT).[-] For liver SBRT, given
that direct visualization of the tumor is not feasible
using X-ray-based IGRT systems such as two-dimensional
fluoroscopy or 3D-CBCT. But, reference structures
like bony landmarks, the whole liver, and fiducial
markers placed inside or near the tumor can be tracked
to indirectly monitor the tumor"s position.[,]
This study is important in highlighting the impact
of abdominal compression in liver tumors on the geometric
uncertainties and positional errors occurring in
the ITV due to respiratory motion.
Methods
Patient preparation for CT simulation
This study was conducted in accordance with the declaration
of Helsinki and was approved by the by the
Ethics Committee of Memorial Şişli Hospital Ethics
Committee (Ethical Approval No: 004/ 26.12.2024).
Twenty patients treated with hypo-fractionated liver
SBRT between 2016-2018 at our clinic were included in
the study. The clinical features and treatment planning
schemes of the patients are shown in Table 1. In all patients,
an Elekta body frame was used in conjunction
with an abdominal compression plate. This combination
was utilized to reduce tumor motion due to respiration
and ensure reproducible positioning. Patients were set up
in the head-first-supine (HFS) position with their arms
above their heads. The patients were prepared as shown
in Figure 1 and three-phase CT images (at 30, 90, and
180 seconds) with contrast were acquired during free
breathing using a Siemens Somatom Computed Tomography
system (Siemens Medical Systems, Germany) to
assess internal target movement for ITV determination.
Table 1: Clinical characteristics of the patients
Fig. 1: The setup and immobilization method used in patients with liver tumors.
Pre-treatment and post-treatment 3D-CBCT images
of each patient were evaluated with IGRT protocol that
was routinely applied at our clinic. Patients underwent
to treatment after daily position corrections were made
on pre-treatment 3D-CBCT images. After each daily
treatment session, a second set of 3D-CBCT images was
acquired from the same patient and recorded. Planning
CT and 3D-CBCT registrations were done based on
the entire liver. It was calculated the Anterior-Posterior
(AP), Cranial-Caudal (CC), and Medial-Lateral (ML)
shifts of the PTV, as well as the three-dimensional displacement
vector (VT), using 3D-CBCT images taken
before and after treatment for first 3 treatment fractions.
Determination of internal target volume (ITV)
For helical-mode contrast-enhanced scans (rotation
time: 1 sec), CT images of 2.5 mm cross-sectional
thickness were obtained 30, 90 and 180 sec after intravenous
administration of a contrast agent. All CT images
were transferred to the Eclipse treatment planning
system (Version13, Varian, Palo Alto-USA). GTVs in
images obtained at 30, 90 and 180 seconds were named
as GTV30, GTV90 and GTV180, respectively. In addition
to the planning tomography, magnetic resonance (MR)
images for each patient were imported into the system
and co-registered with the tomography images to define
the Gross Target Volume (GTVMR). To obtain the
ITV, the GTV structures defined in each imaging set
were combined using the following formula.
ITV = GTV30+GTV90+GTV180+GTVMR
PTV was created ITV+ 5 mm.
Planning process of Volumetric Modulated Arc
Therapy (VMAT)
For the planning of SBRT treatment, 6 or 10 FFF
(Flattening Filter Free) photon energies were selected according to the depth of the tumor among
the energies available in the Varian Truebeam STX.
Dose rate was selected as 1400 cGy / min. and 2400 cGy / min. for 6 MV FFF and 10 MV FFF photon
beams respectively. All VMAT plans were used at
30-330 degrees" collimator angles to reduce the effects of leakage caused by tongue and grove effect
and allow transverse planar modulation during gantry
rotation. The collimator aperture was adjusted
to encompass the PTV throughout the entire gantry
rotation, with an additional margin of approximately
10 mm. The primary goal during planning was to
ensure adequate PTV coverage for all patients, and
the secondary objective was to reduce individual
critical organ doses as much as possible. All plans
were made to give 95% of the prescribed total dose,
which ranged from 45 Gy to 60 Gy delivered in 3 to
5 fractions, to the PTV.
Determination of the total displacement vector
within the fraction
The displacement vectors were measured in the
anterior-posterior (AP), cranial-caudal (CC), and
Medial-Lateral (ML) directions based on pre- and
post-treatment CBCT images. The total displacement
vector (VT) was calculated using the following
formula:
Results
Table 2 and Figure 2 shows the intra-fractional PTV
displacement data for the patients. The largest shift was
observed during the first fraction of Patient 3. This patient
exhibited a displacement of 8.14 mm in the AP
direction, 0.94 mm in the CC direction, -0.35 mm in
the ML direction, resulting in a total displacement vector
(VT) of 8.2 mm. This disposition in the patient"s intact
tissues and PTV was shown in Figure 3. The impact
of the tumor movement on Dose-Volume Histogram
(DVH) of PTV was shown in Figure 4. In Figure 3 and
Figure 4, PTV1 refers to the initial planned target volume
based on the 3D-CBCT image acquired at the start
of the patient"s first treatment, while PTV2 represents
the planned target volume based on the 3D-CBCT obtained
at the end of the patient"s first treatment. To show
the effect of intra-fractional movements on patient
PTV dose, the DVH of patient number 3, which has the
highest intra-fractional change, is given as an example
in Figure 4. As shown in Figure 4, The DVH evaluation
of the patient revealed a 25% decrease in PTV coverage.
Table 2: 3D-CBCT-guided intra-fractionated PTV volume displacement in patients with liver tumor
Fig. 2: 3D-CBCT- guided intra-fractionated PTV volume displacement in patients with liver tumor; AP: Anterior-posterior
(a), CC: Cranial-caudal (b), ML: Medial-lateral (c) and VT: Total displacement vector (d).
CBCT: Cone-beam tomography; PTV: Planning target volume.
Fig. 3. The coronal image depicts a patient (No:3) with the maximum PTV displacement
observed during the first treatment fraction.
PTV: Planning target volume.
Fig. 4. Dose-volume histogram shows the coverage difference between PTV1 and PTV2.
PTV: Planning target volume.
Discussion
Success in the treatment of liver SBRT depends on the
correct definition of ITV. Displacement of the liver by
free breathing causes a change in the GTV volume;
therefore this effect should be reduced by appropriate
immobilization techniques. Abdominal compression is
a quite effective equipment to prevent intra-fractional
and inter-fractional position errors by limiting the
movement of intra-abdominal organs.
Park et al.[] reported that the IGRT method with
reference marks by 4D-CBCT by using fiducial marker
movements during liver SBRT yielded more accurate
results compared to IGRT procedure performed by
liver contour or diaphragm position.
4D-CBCT was demonstrated to decrease the
blurring of fiducial markers and liver anatomy in a
considerable extent and be beneficial for liver SBRT
performed by IGRT.[-] Case et al.[] reported
change in intra fractional liver movement using 4DCBCT
and demonstrated that it was <3mm in 80% of
fractions in 29 patients.
Dreher et al.,[] reported that use of abdominal
compression (AC) limited tumour movements in their
study that they performed to demonstrate the difference
between the two types of immobilization in 54
patients with liver cancer. Vertical, lateral and cranialcaudal
movements were examined in that study and
the maximum displacement was reported to be in the
cranial-caudal direction.
Studies have been published in the literature reporting
that intra-fractional setup errors can be monitored
and corrected by online imaging. Although it is possible
to correct intra-fractional position errors with
on-line adaptive radiotherapy methods, it is impossible
currently to reflect the change in these position errors
to the treatment plan of the patient.[-]
Twenty patients with liver tumors who underwent
SBRT using the VMAT technique with the application
of an abdominal compression plate were retrospectively
included in the study. The SBRT technique
has enabled application of high-dose radiotherapy for
liver tumors. However, precise positioning and reduction
of liver movement is very important to preserve
the normal tissue and apply the required dose to the
target. To accommodate potential uncertainties, such
as the clinical margin, daily position errors, and intarget
variations in fractionated conformal radiotherapy,
a safety margin of approximately 1.5 cm in
the horizontal plane and 2.5 cm in the cranio-caudal
direction is commonly added to the GTV. This causes
a quite extensive treatment area. Limiting patient and
organ movements has been one of the important steps
in SBRT treatments. Lax et al.[] demonstrated that
target malpositions could be limited to median 3 mm
and maximal 7 mm by developing a frame including a
vacuum pillow and an abdominal compression device
for the SBRT treatment of liver tumors.
Kitamura et al.[] conducted real-time tumor
tracking in 20 patients with liver cancer, utilizing a gold
marker. In their study, they observed tumor displacements of 4±4 mm (ranging from 1 mm to 12 mm) in
the ML direction, 9±5 mm (ranging from 2 mm to 19
mm) in the CC direction, and 5±3 mm (ranging from
2 mm to 12 mm) in the AP direction using real-time
tumor tracking. In that study, the tumour was not affected
by the movement in CC direction, although it
was very much larger than the movements in other
directions. Also in that study, tumour displacement
in ML (2±1 mm) and AP (3±2 mm) in patients with
left lobe tumours were lesser compared to the tumour
displacement in ML (5±4mm) and AP (6±3 mm) in
patients with right lobe tumours.
Wunderink et al.[] found that tumour excursion
had been reduced in CC and AP directions in all patients
by abdominal compression but in majority of
patients ML movement increased with compression. In
our study was not correlate with those finding, it can be
related with tumour location or intra-patient variations.
In this present study in which we had applied abdominal
compression, mean position errors were
found as; for 1st fractions: 0.60±0.64 mm in the AP direction,
0.82±1.00 mm in the CC direction, 0.35±0.28
mm in the ML direction and VT=1.29±0.98 mm; for 2nd
fractions 0.21±0.24 mm in the AP direction, 0.47±0.62
mm in the CC direction, 0.26±0.32 mm in the ML direction
and VT=0.68±0.64 mm; and for 3rd fractions:
0.15±0.23 mm in the AP direction, 0.37±0.48 mm in
the CC direction, 0.74±1.91 mm in the ML direction
and VT=1.04±1.89 mm. This comparison of the AP,
CC, ML position errors and total displacement vectors
(VT) are shown in Figure 2.
We demonstrated that this displacement decreased
the dose in PTV coverage by 25 % by performing two
different planning before and after the treatment in the
patient No:3 with of 1591 cm3 and with the largest position
a liver volume error. Romero et al.[] demonstrated
that daily position corrections with IGRT were sufficient
for the treatment volume but insufficient for critical organs
in the treatment of liver SBRT in 23 patients. Romeo
et al. performed two different planning for each patient
in their study and demonstrated that setup errors
caused 21% dose decrease in PTV coverage. Lovelock et
al.[] studied with larger numerous sample and found
that the mean CC motion was reduced to average 4.4
mm with a range 1-8 mm. In our study we found that
motion could be change with fraction number.
Zeng et al.[] evaluated the amplitude changes
and baseline shifts of respiratory motion in 24 liver patients
using four-dimensional (4D) CT, interfraction,
and intrafraction CBCT. To obtain the respiratory motion
signal, the patients were immobilized with a thermoplastic full-body mask placed between the xiphoid
process and the navel. The 4D CT scan was performed
with free breathing using a 3 mm slice thickness. According
to the baseline shifts, they recalculated the
ITV-PTV margin and redesigned the plans to compare
the dosimetric variation. Significant amplitude changes
occurred during dose delivery compared to that in 4DCT.
They emphasized that using 4.0 mm left-right (LR),
7.0 mm superior-inferior (SI), and 4.0 mm anteriorposterior
(AP) ITV-PTV margins could ensure target
dose coverage and keep the dose limitation of normal
tissues at an acceptable level. Sharma et al.[] identified
9 studies with abdominal compression (AC) in
a systematic review and meta-analysis to recommend
PTV margins with different motion management strategies
for liver SBRT. This study reported that an asymmetric
margin for AC (4 mm in the AP, 6 mm in the SI
and LR directions) may be appropriate.We can say that
the results of our study investigating the intra-fractional
movement of liver tumors during SBRT when AC
was used are consistent with the literature.
Conclusion
Respiratory-related liver motion can lead to the creation
of a large ITV for liver tumors, and therefore
this effect should be reduced by appropriate immobilization
techniques. Abdominal compression is a
quite effective equipment to prevent intra-fractional
position errors by limiting the movement of intra-abdominal
organs. This study demonstrated that when
the abdominal compression method is used, the intra
fractional motion of liver tumors remains within the
5 mm PTV margin.
Ethics Committee Approval: The study was approved by
the Memorial Şişli Hospital Ethics Committee (no: 004, date:
26/12/2024).
Conflict of Interest: All authors declared no conflict of interest.
Financial Support: None declared.
Use of AI for Writing Assistance: No AI technologies utilized.
Authorship Contributions: Concept - A.Ç., E.O.G., Z.A.,
E.K.S.; Design - A.Ç., M.O., B.D.; Supervision - E.K.S., B.D.,
M.O.; Data collection and/or processing - A.Ç., E.O.G., Z.A.;
Data analysis and/or interpretation - A.Ç., E.O.G., M.O.; Literature
search - A.Ç., E.K.S., Z.A.; Writing - A.Ç., E.O.G.,
B.D.; Critical review - E.K.S., Z.A.
Peer-review: Externally peer-reviewed.
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