Emerging Technologies in Cancer Radiotherapy – Original Research Article

Evaluation of a New Method for CyberKnife
Treatment for Central Lung and Mediastinal
Tumors by Tracheobronchial Tracking

Technology in Cancer Research &Treatment
Volume 23: 1-12
© The Author(s) 2024
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DOI: 10.1177/15330338241232557
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Toshihiro Suzuki, MSc1 , Masahide Saito, PhD2 ,Hiroshi Takahashi, MD, PhD1, Hidekazu Suzuki, MSc2,
Koji Makino, PhD3, Koji Ueda, RTT2, Koji Mochizuki, RTT1,
Zennosuke Mochizuki, MSc1, Hikaru Nemoto, MSc2,
Naoki Sano, PhD2, and Hiroshi Onishi, MD, PhD2

Abstract
Background: CyberKnife treatment for central lung tumors and mediastinal tumors can be difﬁcult to perform with marker less.
Purpose: We aimed to evaluate a novel tracheobronchial-based method (ie, tracheobronchial tracking) for the purpose of minimallyinvasive CyberKnife treatment for central lung and mediastinal tumors. Methods: Five veriﬁcation plans were created using an inhouse phantom. Each plan included ﬁve irradiation sessions. The reference plan irradiated and tracked the simulated tumor (using thetarget tracking volume, TTV). Trachea plans tracked the simulated tracheo-bronchus and irradiated the simulated tumor and included
two types of subplans: correlated plans in which the displacement of the simulated tracheobronchial and the simulated tumor werecorrelated, and non-correlated plans in which these factors were not correlated. Moreover, 15 mm and 25 mm TTVs were evaluatedfor each plan. The sin waveform and the patient’s respiratory waveform were prepared as the respiratory model. Evaluations were
performed by calculating the dose difference between the radiophotoluminescent glass dosimeter (RPLD)-generated mean dose values (generated by the treatment planning system, TPS) and the actual absorbed RPLD dose. Statistical analyses were performed toevaluate ﬁndings for each plan. Correlation and prediction errors were calculated for each axis of each plan using log ﬁles to evaluate
tracking accuracy. Results: Dose differences were statistically signiﬁcant only in comparisons with the non-correlated plan. Whenevaluated using the sin waveform, the mean values for correlation and prediction errors in each axis and for all plans were less than
0.6 mm and 0.1 mm, respectively. In the same manner, they were less than 1.1 mm and 0.2 mm when evaluated using the patient’s
respiratory waveform. Conclusion: Our newly-developed tracheobronchial tracking method would be useful in facilitating minimallyinvasive CyberKnife treatment in certain cases of central lung and mediastinal tumors.
Keywords
CyberKnife, central lung tumor, mediastinal tumor, motion tracking, trachea, bronchi
Received: November 2, 2023; Revised: December 27, 2023; Accepted: January 24, 2024.

Introduction
Stereotactic body radiotherapy (SBRT) is one method foradministering external beam radiotherapy (EBRT). The usefulness of SBRT has been reported in the treatment of various
regions and cancer types.1-5 The CyberKnife system (Accuray,
Sunnyvale, CA) can acquire 2D images every 5 to 150 s byusing orthogonal x-ray devices (ie, via a target locating system,
TLS), allowing for the delivery of SBRT to a moving target.6
The CyberKnife system enables two respiratory tracking
methods: the Synchrony Respiratory Tracking System (SRTS)
and the Xsight Lung Tracking System (XLTS).7,8 The SRTS
requires ﬁducial markers to be placed in or around the target.

However, percutaneous placement sometimes causes complications such as pneumothorax and bleeding.9 In contrast, the
XLTS is a ﬁducial-free non-invasive system that tracks
1

CyberKnife Center, Kasugai General Rehabilitation Hospital, Yamanashi, Japan
Department of Radiology, University of Yamanashi, Yamanashi, Japan3
Department of Mechatronics, Faculty of Engineering, University of Yamanashi,
Yamanashi, Japan
2

Corresponding Author:
Masahide Saito, Department of Radiology, University of Yamanashi, 1110
Shimokato, Chuo-city, Yamanashi, 409-3898, Japan.
Email: masahides@yamanashi.ac.jp

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tumors directly10,11 using target tracking volume (TTV). Thissystem matches digitally reconstructed radiograph (DRR)
images with the TTV obtained in the TLS using patternsimilarity matching. Following this, a correlation model is generated from tumor locations in various respiratory phases andLED (light-emitting diode) marker signals (based on sensors
attached to the body surface). The location of the tumor after
115 ms of treatment is identiﬁed using this correlation
model.12 The use of the XLTS is recommended under the following conditions: a tumor diameter of >15 mm in every direction, a tumor location in the peripheral region of the lung, and atumor location that does not overlap with the vertebral bone(within the TLS).8 These conditions are due to the fact that
XLTS is a method of tracking tumors using contrast differences
between the lung and the tumor. First, if the tumor is too small,
it is difﬁcult for the operator and the system to recognize it on
the TLS. Second, tumors in the hilar region of the lungs tend tooverlap with blood vessels and vertebral bone, reducing contrast. Finally, mediastinal tumors cannot be recognizedbecause they are not located in the lungs. These cause the inevitable problem of a difﬁculty utilizing the TLS for central lungand mediastinal tumors.
To address the problems, we focused on the fact that thetracheo-bronchus contains air and thus shows high contrast in
the TLS due to the tracheobronchial wall; hence, we considered
a new tracking system using the tracheo-bronchus as basis forthe tracking volume in the XLTS of nearby central lung or
mediastinal tumors. To the best of our knowledge, no previous
studies have evaluated this technique.
The purpose of this study was to develop and evaluate thisnew method (ie, tracheobronchial tracking) using an in-house
phantom. The outcomes evaluated were dose accuracy(obtained using a radiophotoluminescent glass dosimeter,
RPLD, Asahi Glass CO., Tokyo, Japan) and tracking accuracy(obtained using log ﬁles).

Materials and Methods
Tracheobronchial Tracking
Figure 1 shows a schematic diagram of a typical XLTS at our
institution. First, after the planning CT is acquired, the tumor
is contoured. Second, the tumor is deﬁned as a TTV.
Optimization is then performed, and treatment is performed.
Figure 2 shows a schematic diagram of the tracheobronchial
tracking methodology evaluated herein. First, to conﬁrm thecorrelation between respiratory movement of the tumor andthe tracheo-bronchus, a four-dimensional computed tomography (4D-CT) image was acquired using a body surface monitoring system (an RPM system, Varian Medical Systems, Palo
Alto, CA, USA) under resting respiratory conditions. If there
was a correlation, treatment planning was performed using
XLTS. Second, the tracheo-bronchus nearby the tumor was
contoured as the TTV; the setting depended on the size andlocation of the tumor. Then, the TTV was conﬁrmed by DRR
imaging, and optimization was performed in order to deliver

Technology in Cancer Research & Treatment

Figure 1. Schematic diagram of the XLTS at our institution.

the prescribed dose to the tumor. Finally, treatment was performed using tracheobronchial tracking.

Radiophotoluminescent Glass DosimeterIn this study, point doses were evaluated using the RPLD. RPLDs
are individual dosimeters that can indirectly measure absorbed
doses using radio photo luminescence (RPL), which emits lightin proportion to the amount of radiation energy, and thus has
few fading phenomena. Silver-activated phosphate glass element
containing silver ions with a composition of 31.55% P, 51.16%
O, 6.12% Al, 11.00% Na, 0.17% Ag, effective atomic numberof 12.039 and density of 12.039 g/cm3.13 The small size of
RPLD makes it suitable for measuring small ﬁelds.14,15

Veriﬁcation Plan
This retrospective study was approved by the institutional
review board (IRB) of our hospital (receipt number: 2023-2).
The veriﬁcation plans evaluated herein consisted of a reference
plan (Ptumor, with the simulated tumor as the TTV) and a trachea
plan (Ptra, with the simulated tracheo-bronchus as the TTV).
Moreover, the Ptra consisted of a correlated (Ptra, corr) and a non-Suzuki et al

Figure 2. Schematic diagram of the tracheobronchial tracking. The
tracheo-bronchus nearby to the tumor was contoured as the TTV.
Treatment planning is performed with the Xsight Lung Tracking
System.

correlated plan (Ptra, non−corr); Ptra, corr correlated the displacement of the simulated tracheo-bronchus and the simulated
tumor, while Ptra, non−corr did not correlate with this displacement. The Ptra, non−corr were evaluated with the aim of excluding
scenarios where they produce the same results as plans with correlations, even in the absence of actual correlation. In standard
XTLS, the tumor itself is deﬁned as the TTV (ie, the size
approximates the tumor). However, our proposed method
used the non-tumor region as the TTV. Therefore, the Ptra
deﬁned two sizes for the TTV (15 mm and 25 mm), centeredon the tracheal bifurcation as well as in various distributed
regions. The 15 mm represents the lower limit under the recommended conditions of the vendor, while 25 mm includes a size
sufﬁcient to encompass the diameter of the simulated tumor. To
verify the above plans, an experiment was conducted using a
dynamic phantom. Figure 3a shows the appearance of thenovel dynamic phantom (APEX Medical Inc., Tokyo, Japan),which has two drive systems operating in three axes and wasdeveloped jointly with the University of Yamanashi. The accuracy of dynamic phantom is shown in the prior literature.16 The
surrogate part that reproduces respiratory amplitude is attachedto the anterior-posterior (AP) axis of Drive-1. Figure 3b shows a
20 mm acrylic simulated tumor and an acrylic box (60 × 70 ×3
50 mm), which was designed in order to consider x-ray
build-up and such that the RPLD could be inserted directly
into the center of the simulated tumor. Figure 3c shows thein-house phantom setup for the Ptra. The in-house phantom consists of a dynamic phantom, a simulated tumor, and a simulated
tracheo-bronchus (total length: 12.5 cm, outer diameter: 2.5 cm,
inner diameter: 1.5 cm, density: 1.14-1.15 g/cm3) created via a
3D printer (Stratasys, Ltd, Eden Prairie, MN, USA) and a thoracic vertebral phantom (Avice Inc., Tokyo, Japan). The simulated tumor was set at the level of the tracheal bifurcation of thesimulated tracheo-bronchus, 75 mm from the tracheal bifurcation to the center of the simulated tumor on the right side; the
RPLD was set at parallel locations to the left and to the rightof the simulated tumor.
Figure 3d shows the in-house phantom setup for the Ptumor. If
the simulated tumor overlaps the vertebrae in the TLS, it may
not be tracked properly, so the placement of the simulated
tumor in this study was designed so that it does not overlap
the vertebrae in the TLS; the direction of the RPLD was thesame in the Ptra.
The simulated displacement of the simulated tracheobronchus and the simulated tumor was expressed using theactual displacement of the tracheo-bronchus as measured inlung cancer patients. More speciﬁcally, the respiratory displacement of the translational axis at the tracheo-bronchus was calculated from 4D-CT images (Optima CT660; GE Medical
Systems, Milwaukee, WI, USA; 120 kV, 200 mA, 1.25 mm
slice thickness, 500 mm ﬁeld of view) in 10 patients who underwent SBRT using XLTS for lung cancer at our institution.
For evaluating the calculation method, CT images of 10
phases were imported into 3D-Slicer ver. 4.11, a free, open
source and multi-platform image analysis software widelyused for medical, biomedical, and related imaging research(https://slicer.org). The coordinates of the tracheal bifurcation
were then obtained for each phase. The minimum values ofeach axis for the in-house phantom were 0; the other phases
were calculated accordingly. The waveforms of one cycle
obtained by 4D-CT were divided by 10% intervals (ie, from
0% to 90%).
In the current study, displacement data for a typical sin function was also prepared, and one typical patient’s displacement
data was simulated from the displacement data of 10 patients.
In addition, one respiration cycle was set to 3 s.17 The
in-house phantom requires a value input every 30 ms.
Therefore, values for 10 phases were interpolated to 100
points using MATLAB software (MathWorks, Natick, MA,
USA). It is necessary to consider whether the volume changes
with respiration, because this method deﬁnes the tracheobronchial as the TTV.
The tracheobronchial air regions were entered into MIM
Maestro Software (Cleveland, OH, USA), including the TTV
range deﬁned in this study and using 30% phase images(WW 1500, WL −550). The contours were propagated toeach phase using deformable image registration in order to calculate the air volume in each phase. Veriﬁcation planning was
performed using CT images (120 kV, 400 mA, 1.25 mm slice

4Technology in Cancer Research & Treatment

Figure 3. (a) Appearance of the dynamic phantom with two drive systems operating in three axes. (b) A 20 mm acrylic simulated tumor and anacrylic box (60 × 70 × 50 mm), which was designed in order to consider x-ray build-up; the RPLD could be inserted directly into the simulated
tumor. (c) Experimental set-up of the Ptra. (d) Experimental set-up of the Ptumor.

thickness, 500 mm ﬁeld of view) with the CyberKnife
MultiPlan TPS (ver. 3.2.0, Accuray Radiotherapy, Sunnyvale,
CA, USA).
The simulated tumor was deﬁned as the target (which also
serves as the TTV in the Ptumor) and the RPLD was deﬁned
as the target RPLD. As shown in Figure 4a and 4b, the TTVof the Ptra was deﬁned for the 15 mm and 25 mm regions centered on the tracheal bifurcation. As shown in Figure 4c, theTTV of the Ptumor was deﬁned as that for the simulated
tumor. All planning was conducted with a collimator of
20 mm, a target-RPLD mean dose of approximately 2 Gy/1fr,
and a Monte Carlo simulation (uncertainty: 1%).
Each plan included irradiation conducted ﬁve times with different RPLDs, and the TLS imaging parameters were performed
at 80 kV, 80 mA, and 80 ms (irradiation interval time, 30 s).
Furthermore, the algorithm parameters were set as follows:
uncertainty threshold of 40%, dxAB threshold of 2.5 mm, andtracking range of x: 4 mm, y: 4 mm. Conﬁrmation of tracking
during irradiation was achieved through the evaluation ofthese parameters and the image recognition by the operator.
The calculated tracheobronchial displacement was used fordesigning the simulated tracheo-bronchus and simulated
tumor in the Ptra, corr. On the other hand, in the Ptra, non−corr,
the superior-inferior (SI) axis displacement of the simulated
tumor was changed to the opposite of positive and negative.

In the Ptumor, the same displacement as that in the Ptra, corr
was used for the simulated tumor.

Evaluation
Dose differences and tracking errors were evaluated using
CyberKnife G4 system (version 10.5), based on the results of
the Ptra using the results obtained within the Ptumor as a reference. Dose evaluation was performed using the mean value of
the RPLD readings (Dw , i ) as well as the mean dose of the
RPLD in the TPS.
RPLD readings were taken on a FGD-1000 (AGC Techno
Glass Co., LD, Shizuoka, Japan) and Dw , i was calculatedusing the following formula.18,19
Dw , i = (Mi · SCFi − M0,i′ · SCFi′ ) · ND,r · fen · fp · flin · fCK
Where Mi is the reading of the i-th RPLD, SCFi is the sensitivity
correction factor of the i-th RPLD, M0,i′ is the background value
the i’-th RPLD, ND,r is the RPLD calibration constant at the reference line quality, fen is the correction factor for the radiation
quality, fp is the correction factor for the phantom material,
flin is the correction factor of nonlinearity, and fCK is the correction factor by ﬂattening-ﬁlter-free (FFF) of CK.

Suzuki et al

5

Figure 4. DRR images of each plan. (a) The TTV deﬁned in the Ptra, corr and Ptra, non−corr (TTV 15 mm). (b) The TTV deﬁned in Ptra, corr andPtra, non−corr (TTV 25 mm). (c) The TTV deﬁned in the Ptumor.

The dose differences were then calculated using the following formula:Dw , i − DRPLD dose  × 100
Dose difference[%] = 
DRPLD dose
where Dw , i is the absorbed dose of the i-th RPLD and
DRPLD dose is the mean dose of the RPLD calculated by the TPS.

Tracking accuracy was evaluated by analyzing correlationand prediction errors.
In building the correlation model, multiple x-ray images are
acquired in the TLS to determine the position of the tracking
target at various positions in the respiratory cycle.20 The correlation error results from the difference between the output of thecorrelation model and the position of the tracking target

6
determined by the TLS. In addition, the prediction errors arise
from differences between the forecasting algorithm and the corresponding correlation model.21 During treatment, CyberKnife generates the following log ﬁles: ModelPoints.log, Modeler.log,
Predictor.log, and ERsiData.log.12,20,22 The correlation error analysis was performed using the ModelPoints.log ﬁle in order tocalculate the values for the AP, left-right (LR), and SI axes. The
prediction error for the AP, LR, and SI axes were calculatedusing Modeler.log, Predictor.log, and ERsiData.log, respectively.
3D coordinates of the target are recorded in patient coordinatesin ModelPoints.log, while the 3D coordinates in Modeler.log,
Predictor.log, and ERsiData.log are recorded in robot coordinates.8
Therefore, all coordinates were transformed from robot coordinates to patient coordinates using the Coord-transfm ﬁle of the
CyberKnife system.
All data were statistically analyzed using Wilcoxon
signed-rank tests, which were conducted using IBM SPSS statistical software (ver. 27, BM, Armonk, NY, USA).

Results
Tracheobronchial Movement and Air Volume
Figure 5 shows the position of the 10 phases of tracheobronchus acquired using 4D-CT.
Moreover, Figure 6 shows the displacements in each axis forthe 10 patients and the displacements used for evaluation, as
well as the sin waveforms used.

Technology in Cancer Research & Treatment
The mean and standard deviation (SD) of the maximum tracheobronchial displacement for 10 patients and the maximum
displacement used in the veriﬁcation are presented herein.
More speciﬁcally, the mean maximum values for the 10 patientswere 2.01 ± 0.84 mm, 1.87 ± 0.54 mm, and 5.88 ± 2.77 mm in
the AP, LR, and SI axes, respectively; the maximum valuesof displacement used in the veriﬁcation were 1.57 mm,
1.24 mm, and 3.75 mm in the AP, LR, and SI axes, respectively. In addition, the standard deviation (SD) of the tracheobronchial air volume for each respiratory phase ranged from± 0.05 cc to ± 0.38 cc.

Dose Accuracy
Figure 7 shows information on the generated veriﬁcation plans.
All plans comprised 85 beams and 85 nodes, and the mean
RPLD dose was 2.00 Gy for all plans. Prescribed isodose lineof test plan was 94.9%, 95.2%, 95.1%, 94.8%, and 95.1% for
the Ptra, corr (TTV 15 mm), Ptra, corr (TTV 25 mm), the Ptumor,
the Ptra, non−corr (TTV 15 mm), and the Ptra, non−corr (TTV
25 mm), respectively. Table 1 shows the results for theabsorbed dose in the Ptumor and Ptra using the sin waveform.
The means and SDs of the dose differences were as follows:
1.22 ± 0.80%, 0.98 ± 0.75%, 1.37 ± 0.91%, 4.75 ± 0.80%, and4.51 ± 0.43% for the Ptumor, Ptra, corr (TTV 15 mm), Ptra, corr
(TTV 25 mm), Ptra, non−corr (TTV 15 mm), and Ptra, non−corr(TTV 25 mm), respectively.

Figure 5. The position of tracheo-bronchus in each phase acquired using 4D-CT. The position of the tracheal bifurcation at 0% is indicated by a
red line, and the position of the tracheal bifurcation in each phase is indicated by a white arrow.

Suzuki et al

7

Figure 6. The displacements in each axis for the 10 patients and the displacements used for evaluation, and the sin waveforms used (red line).
The maximum displacement patient waveforms used in the veriﬁcation were 1.57 mm, 1.24 mm, and 3.75 mm in the AP, LR, and SI axes,
respectively.

Figure 7. Information on the generated veriﬁcation plans. The upper row is the schematic diagram for incident beam directions and the lower row
is the dose distribution. The white arrow indicates the beam while the red arrow indicates the simulated tumor.

The results of the statistical analysis for each veriﬁcation
plan are likewise presented herein. There were no statisticallysigniﬁcant differences between the Ptumor and the Ptra, corr
(TTV: 15 mm, 25 mm) (P = .893). By contrast, between
Ptumor and Ptra, non−corr (TTV 15 mm, 25 mm), respectively(P = .043). In addition, a statistical analysis was performed
with regard to the TTV size in the Ptra; there were no statisticallysigniﬁcant differences found between the TTV of 15 mm andthe TTV of 25 mm for the Ptra, corr and Ptra, non−corr, respectively(P = .345, .500).

8Technology in Cancer Research & Treatment

Table 1. The Results of the Absorbed Dose for the Ptumor and the Ptra in sin Waveform.
Ptra

PtumorTPS RPLD mean dose (Gy)
RPLD Dw , i mean ± SD (Gy)Dose difference Mean ± SD (%)

XLTS

Ptra, corr
(TTV 15 mm)

Ptra, corr
(TTV 25 mm)

Ptra, non−corr (TTV 15 mm)

Ptra, non−corr (TTV 25 mm)

2.00
1.98 ± 0.02
1.22 ± 0.80

2.00
1.98 ± 0.02
0.98 ± 0.75

2.00
1.98 ± 0.03
1.37 ± 0.91

2.00
1.91 ± 0.02
4.75 ± 0.80

2.00
1.91 ± 0.01
4.51 ± 0.43

Table 2. The Results of Absorbed Dose for the Ptumor and the Ptra in the Patient’s Respiratory Waveform.
PtumorTPS RPLD mean dose (Gy)
RPLD Dw , i mean ± SD (Gy)Dose difference Mean ± SD (%)

Ptra

XLTS

Ptra, corr
(TTV 15 mm)

Ptra, corr
(TTV 25 mm)

Ptra, non−corr(TTV 15 mm)

Ptra, non−corr(TTV 25 mm)

2.00
2.01 ± 0.02
1.07 ± 0.67

2.00
2.02 ± 0.02
0.72 ± 0.62

2.00
1.99 ± 0.02
1.16 ± 0.60

2.00
1.98 ± 0.05
3.03 ± 1.23

2.00
1.92 ± 0.03
4.05 ± 1.43

Table 2 shows the results for the absorbed dose in the Ptumor
and Ptra using the patient’s respiratory waveform. The means andSDs of the dose differences were 1.07 ± 0.67%, 0.72 ± 0.62%,
1.16 ± 0.60%, 3.03 ± 1.23%, and 4.05 ± 1.43% for the Ptumor,
Ptra, corr (TTV 15 mm), Ptra, corr (TTV 25 mm), Ptra, non−corr(TTV 15 mm), and Ptra, non−corr (TTV 25 mm), respectively.
The results of the statistical analysis for each veriﬁcation
plan are likewise presented herein. There were no statisticallysigniﬁcant differences between the Ptumor and the Ptra, corr
(TTV: 15 mm, 25 mm) (P = .345, .893). By contrast, between
Ptumor and Ptra, non−corr (TTV 15 mm, 25 mm), respectively(P = .043). In addition, a statistical analysis was performed
with regard to the TTV size in the Ptra; there were no statisticallysigniﬁcant differences found between the TTV of 15 mm andthe TTV of 25 mm for the Ptra, corr and Ptra, non−corr, respectively(P = .080, .345).

Tracking Accuracy
Figure 8a shows the means and SDs of the correlation error ineach axis for each plan using the sin waveform. The number oflive images acquired was 260, 288, 284, 284, and 288 images
for the Ptumor, the Ptra, corr (TTV 15 mm), the Ptra, corr (TTV
25 mm), the Ptra, non−corr (TTV 15 mm), and the Ptra, non−corr(TTV 25 mm), respectively; no value was larger than 1.1 mm.
Moreover, the mean values were less than 0.6 mm for eachaxis in all veriﬁcation plans. Among the three axes, the SI
axis, which had the largest average value, showed a proportion(0.46%) where only Ptra, non−corr (TTV25 mm) exceeded 1 mm,
but there were no plans exceeding 2 mm. No statistically significant differences were observed between the Ptumor and thePtra, corr (TTV 15 mm, 25 mm) in the LR axis, or between the
Ptumor and the Ptra, non−corr (TTV 15, 25 mm) in the AP, LR
and SI axes, respectively (P = 1.00). Next, the Ptra were compared by differences in TTV size, and statistically signiﬁcantdifferences were observed on the Radial axis (P < .001).

Next, Figure 8b shows the means and SDs for the prediction
error in each axis and for each plan using the sin waveform. The
number of prediction error data in each axis was 12,252,
10,216, 10,227, 10,406, and 10,341 data for the Ptumor,
the Ptra, corr (TTV 15 mm), the Ptra, corr (TTV 25 mm), thePtra, non−corr (TTV 15 mm), and the Ptra, non−corr (TTV
25 mm), respectively. The values were less than 0.2 mm in allaxes for all veriﬁcation plans. Moreover, the mean values
were less than 0.1 mm for each axis in all veriﬁcation plans.
No statistically signiﬁcant differences were observed between
the Ptra, corr (TTV 25 mm) and the Ptra, non−corr (TTV 25 mm)in the SI axis (P = .556). The Ptra were also compared by differences in TTV size, and statistically signiﬁcant differences wereobserved for all axes (P < .001).
In addition, Figure 8c shows the means and SDs of the correlation error in each axis for each plan using the patient’s respiratory waveform. The number of live images acquired were 196,
204, 204, 220, and 224 images for the Ptumor, the Ptra, corr
(TTV 15 mm), the Ptra, corr (TTV 25 mm), the Ptra, non−corr(TTV 15 mm), and the Ptra, non−corr (TTV 25 mm), respectively;
no value was larger than 3 mm. Moreover, the mean values wereless than 1.1 mm for each axis in all veriﬁcation plans. Amongthe three axes, the SI axis, which had the largest average value,
showed the following proportions exceeding 1 mm for therespective parameters:21.73%, 24.02%, 12.76%, 48.19%, and38.69% for the Ptra, corr (TTV 15 mm), the Ptra, corr (TTV
25 mm), the Ptumor, the Ptra, non−corr (TTV 15 mm), and thePtra, non−corr (TTV 25 mm), respectively. Furthermore, the proportions exceeding 2 mm were as follows: 0%, 0.16%, 0.51%,
7.38%, and 6.85%, respectively. No statistically signiﬁcant differences were observed between the Ptumor and the Ptra, corr
(TTV 25 mm), or between the Ptumor and the Ptra, non−corr (TTV
15 mm) in the LR axis, respectively (P = .070, .271). In contrast,
statistically signiﬁcant differences were observed between thePtra, corr (TTV 15 mm, 25 mm) and the Ptra, non−corr (TTV
15 mm, 25 mm) in the LR and SI axes (P < .001). Next, theSuzuki et al

9Figure 8. (a) The means and sds of the correlation error in each axis for each plan in the sin waveform. No value was larger than 1.1 mm. Moreover, themean values were less than 0.6 mm for each axis in all veriﬁcation plans. (b) The means and SDs of the prediction error in each axis for each plan in the sin
waveform. No value was larger than 0.2 mm. Moreover, the mean values were less than 0.1 mm for each axis in all veriﬁcation plans. (c) The means andSDs of the correlation error in each axis for each plan in the patient’s respiratory waveform. No value was larger than 3.0 mm. Moreover, the mean values
were less than 1.1 mm for each axis in all veriﬁcation plans. (d) The means and SDs of the prediction error in each axis for each plan in the patient’s
respiratory waveform. No value was larger than 1.0 mm. Moreover, the mean values were less than 0.2 mm for each axis in all veriﬁcation plans.

Ptra were compared by differences in TTV size, and statisticallysigniﬁcant differences were observed on the LR axis (P < .001).
Finally, Figure 8d shows the means and SDs for the prediction
error in each axis and for each plan using the patient’s respiratory
waveform. The number of prediction error data in each axis was
11,255, 10,538, 10,477, 11,511, and 11,435 data for the Ptumor,
the Ptra, corr (TTV 15 mm), the Ptra, corr (TTV 25 mm), thePtra, non−corr (TTV 15 mm), and the Ptra, non−corr (TTV 25 mm),
respectively. The values were less than 1.0 mm in all axes for
all veriﬁcation plans. Moreover, the mean values were lessthan 0.2 mm for each axis in all veriﬁcation plans. Statisticallysigniﬁcant differences were observed between the Ptumor andPtra in all axes (P < .001). The Ptra were also compared by differences in TTV size, and statistically signiﬁcant differences wereobserved for all axes (P < .001).

Discussion
Higher biological doses can be delivered with stereotactic radiotherapy as compared with more standard therapeutic modalities.

However, it can be difﬁcult to prescribe high-dose SBRT forcentral lung tumors because of the proximity of the tumor to critical organs and organ system components such as the esophagus,
heart, blood vessels (ie, the cardiovascular system), and thetrachea.23 Nuyttens et al performed SBRT for 58 central lungtumors (in tumors located < 2 cm from the tracheobronchialregion or esophagus, tumors located < 6 mm from the heart, andtumors located in the mediastinum) in 56 patients and reported a
local control rate of 76% over the course of 2 years.24
The placement of ﬁducial markers in this study was performed using several methods, including previously reported
intravascular and percutaneous methods as well as abronchoscopy-based method.24,25 The complications ofmarker placement were not considered, although ﬁducial
markers were placed in all patients. Fiducial marker placement
using the intravascular method or bronchoscopy reduces therisk of pneumothorax; however, these methods are quite invasive. Therefore, developing a safer method of tumor tracking
is important. However, the existing XLTS cannot be applied
to central lung and mediastinal tumors.

10
Our method is minimally invasive, as it can be performed
without the use of ﬁducial markers if there is a correlation
between the tracheobronchial region and the tumor due to respiration. In this method, the tracheo-bronchus is used as the
TTV, therefore, we calculated changes in tracheobronchialdisplacement and air volume during the respiratory cycle.
We found that displacement of the SI axis was larger thanthat of the other axes. This ﬁnding may be mediated by theeffects of lung expansion due to breathing. Next, changes intracheobronchial air volume were calculated in 10 patients.
The change per respiration was less than 1.0 cc, and the tracheobronchus was considered to be poorly stretched due to the presence of tracheal cartilage. This suggests that deﬁning thetracheo-bronchus as the TTV may not affect volume differences
associated with respiration. In our study, the average motion of
the tracheo-bronchus was 2.01 ± 0.84 mm, 1.87 ± 0.54 mm,
and 5.88 ± 2.77 mm in the AP, LR, and SI axes, respectively.
To our best knowledge, there are no literature reports speciﬁcally measuring the motion of the tracheo-bronchus and thevolume of air in the tracheo-bronchus. Furthermore, the respiratory motion of the tracheo-bronchus should be evaluated infuture studies with more cases. According to AAPM TG 76,
respiratory motion of lung cancer is reported to have a signiﬁcant average range of 3 to 22 mm predominantly in the cranialcaudal direction.26 However, this report also includes motion of
the lower lobes. Therefore, we consider this technique primarily
applicable to cases involving lymph node metastases near the
bronchi or relatively immobile lung tumors. Additionally, we
believe that even in cases where the correlation is weak, there
are instances where increasing the margin size provides more
beneﬁts compared to the risks of bleeding or pneumothorax.
Future studies should include evaluation of respiratory motion
by tumor location.
The evaluated outcomes for the reported method wereabsorbed dose and tracking accuracy. Dose evaluation was
performed using the RPLD placed on the simulated tumor.
As mentioned above, a total of ﬁve veriﬁcation plans werecreated. Although the RPLD is angle-dependent,13,27 CyberKnifeis multi-beam and follows respiration. Hence, it is difﬁcult to compensate for each beam. Therefore, in this study, ﬁve plans werecreated using the same nodes and beams as much as possible.
Evaluation of this method was conducted based on the results of
the Ptumor; speciﬁcally, dose evaluations and tracking evaluations
were performed. With regard to dose evaluations, the results for
the Ptra, corr were not signiﬁcantly different from those of the
Ptumor. The standard uncertainty of the measured RPLD dose isreported to be 1.4%.28 Even considering this, the results of thePtra, corr were lower than the ± 5% dose accuracy required
for radiation therapy as reported in the ICRP (International
Commission on Radiological Protection) report.29 The
results for the Ptra, non−corr were signiﬁcantly different fromall of the other simulated plans and there were no statisticallysigniﬁcant differences in the TTV size between the Ptra.
We analyzed correlation and prediction errors based on
the generated log ﬁles in order to track accuracy. There were
statistically signiﬁcant differences in both correlation andTechnology in Cancer Research & Treatment
prediction errors between the Ptumor and Ptra on almost allaxes. The reason for the observed signiﬁcance is that the correlation error was analyzed for both waveforms, with mean andstandard deviation calculated from approximately 200 data
points each. Similarly, prediction error was analyzed for both
waveforms, with mean and standard deviation calculated
from approximately 10,000 data points each. The large
amount of data and low variability likely contributed to thesigniﬁcance. Moreover, Nakayama et al reported an analysis
of correlation and prediction errors in the XLTS.22 Although
this report was based on clinical data, the results of our study
are similar to that of prior published research and any real differences in plans are to be considered small. These results suggestthat it is possible to treat the tracheo-bronchus deﬁned according
to the TTV using the XLTS. On the other hand, this methodshould be used only after adequate prior correlation of tumor
and bronchial motion has been conﬁrmed, otherwise its use
should be avoided.
The limitations of this study are as follows. First, since thetracheo-bronchus is located close to the heart, it is suggested
that displacement may be affected. However, this was not evaluated in our study. Furthermore, although this study focused ontumors at the level of the tracheal bifurcation, it should also be
performed in other situations, such as when the tumor is at a different location. Second, displacement of the surrogate section
was performed in the same way as the displacement of the
AP axis of the tracheo-bronchus due to the structure of the
in-house phantom. In the lungs, respiratory forces are converted
into airﬂow, which is converted into diaphragmatic contraction.
These dynamics cause the lungs to expand and the tumor to
move.30 In actual patients, the respiratory width and lung morphology are irregular, and tumors especially closer to the lower
lobes migrate more signiﬁcantly, which may affect tracking andirradiation results.17 In this study, the respiratory cycle was
evaluated as 3 s. However, it has been reported that the tracking
error increases when the respiratory cycle is short or whenbreathing is erratic.31,32 Therefore, it is necessary to conﬁrm
our ﬁndings using various waveforms, including real respiratory waveforms. Third, in cases where there is a correlation
between tumor and tracheo-bronchus motion, the results of correlation error and prediction error suggest the potential for
reducing margins. However, in cases where the correlation
between tumor and tracheo-bronchus motion is weak, there isa possibility of increased margins. The evaluation of margins
remains a subject for future study. Fourth, this study used 85
beams and a dose of approximately 2 Gy. However, in clinicalpractice, approximately 150 beams and doses of approximately
10 Gy/fr are used, which may affect the applicability of ourresults. Fifth, the RPLD was used for the evaluation of point
dose in this study due to the structure of the in-house
phantom, but evaluation with detectors such as ionizationchamber dosimeters will also be considered for comparison.
Sixth, this study only focuses on whether tracheobronchialtubes can be used as the TTVs, therefore a quality assurance(QA) is not discussed. Although we perform QA on images
and equipment on a daily basis, it is more important whenSuzuki et al
applying this method for patients in real life. Hence, we consider the use of QA and the improvement of the phantom tobe an issue for future studies. Finally, our dose evaluation
was performed using RPLD-generated mean doses. On the
structure of the in-house phantom used in this study, insteadof the commonly used ionization chambers and ﬁlms, RPLDs
were used, which can be placed within the simulated tumor.
However, the evaluation using ionization chambers and ﬁlms
should be performed using a different device than thephantom used in this study.

Conclusion
Our research group developed a new tracking system using tracheobronchial opacity in a TLS for the XLTS, as reported
herein. Based on the ﬁndings of our research, we believe thattracheobronchial tracking will be useful within the implementation of a TLS in the CyberKnife-based treatment of central lungor mediastinal tumors if the proper constraints can be met. Ourﬁndings, which should be veriﬁed within larger-scale research
efforts, can guide future research directions, medical guidelines,
and clinical decision-making.
Declaration of Conﬂicting Interests
The authors declared no potential conﬂicts of interest with respect tothe research, authorship, and/or publication of this article.

Ethics Statement
This study was approved by the institutional review board (IRB) of
Kasugai General Rehabilitation Hospital (receipt number: 2023-2).

Funding
The authors received no ﬁnancial support for the research, authorship,
and/or publication of this article.

ORCID iDs
Toshihiro Suzuki
https://orcid.org/0000-0003-0414-5218
https://orcid.org/0000-0002-8636-4045
Masahide Saito
Hiroshi Onishi
https://orcid.org/0000-0002-3512-1166

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