Stereotactic body radiotherapy for stage I lung cancer and small lung metastasis: evaluation of an immobilization system for suppression of respiratory tumor movement and preliminary results
Stereotactic body radiotherapy for stage I lung cancer and small lung metastasis: evaluation of an immobilization system for suppression of respiratory tumor movement and preliminary results
Fumiya Baba 2
Yuta Shibamoto 2
Natsuo Tomita 1
Chisa Ikeya-Hashizume 0
Kyota Oda 3
Shiho Ayakawa 2
Hiroyuki Ogino 2
Chikao Sugie 2
0 Nagoya Radiosurgery Center, Nagoya Kyoritsu Hospital , Nagoya , Japan
1 Department of Radiation Oncology, Aichi Cancer Center Hospital , Nagoya , Japan
2 Department of Radiology, Nagoya City University Graduate School of Medical Sciences , Nagoya , Japan
3 Department of Radiation Therapy, Aizawa Hospital , Matsumoto , Japan
Background: In stereotactic body radiotherapy (SBRT) for lung tumors, reducing tumor movement is necessary. In this study, we evaluated changes in tumor movement and percutaneous oxygen saturation (SpO2) levels, and preliminary clinical results of SBRT using the BodyFIX immobilization system. Methods: Between 2004 and 2006, 53 consecutive patients were treated for 55 lesions; 42 were stage I non-small cell lung cancer (NSCLC), 10 were metastatic lung cancers, and 3 were local recurrences of NSCLC. Tumor movement was measured with fluoroscopy under breath holding, free breathing on a couch, and free breathing in the BodyFIX system. SpO2 levels were measured with a finger pulseoximeter under each condition. The delivered dose was 44, 48 or 52 Gy, depending on tumor diameter, in 4 fractions over 10 or 11 days. Results: By using the BodyFIX system, respiratory tumor movements were significantly reduced compared with the free-breathing condition in both craniocaudal and lateral directions, although the amplitude of reduction in the craniocaudal direction was 3 mm or more in only 27% of the patients. The average SpO2 did not decrease by using the system. At 3 years, the local control rate was 80% for all lesions. Overall survival was 76%, cause-specific survival was 92%, and local progression-free survival was 76% at 3 years in primary NSCLC patients. Grade 2 radiation pneumonitis developed in 7 patients. Conclusion: Respiratory tumor movement was modestly suppressed by the BodyFIX system, while the SpO2 level did not decrease. It was considered a simple and effective method for SBRT of lung tumors. Preliminary results were encouraging.
Stereotactic body radiotherapy (SBRT) is now spreading
worldwide as a new treatment modality for stage I
nonsmall cell lung cancer (NSCLC). Following the pioneering
work by Uematsu et al. [1,2], promising clinical results
with excellent local control and low complication rates
have been reported. Clinical outcomes on 257 patients
from 14 institutions in Japan were published recently,
which showed a 5-year survival rate of 71% in medically
operable patients receiving sufficient radiation doses .
At present, SBRT is considered a therapeutic option in
stage I NSCLC either for inoperable patients or for
patients refusing surgery. SBRT for lung cancer is under
evaluation in clinical trials. Japan Clinical Oncology
Group (JCOG) conducted a phase II study 0403 of SBRT
in operable and medically inoperable patients with
pathologically proven T1N0M0 NSCLC to evaluate efficacy
and safety. JCOG 0702, a phase I dose escalation study of
SBRT in patients medically inoperable or unfit for surgery
with pathologically proven T2N0M0 NSCLC, has started
to determine the recommended dose. Radiation Therapy
Oncology Group (RTOG) is developing a phase II trial
0236 and 0618 of SBRT. These trials are designed for
patients with pathologically proven, inoperable and
operable T1, T2, T3 (chest wall primary tumors only), N0, M0
NSCLC. The primary endpoint is 2-year local control.
Results of these studies are awaited.
A lung tumor is a movable target so that management of
tumor motion is required for SBRT of lung tumors. The
lung tumor movement can result from respiration, cardiac
motion and aortic pulsation. While it is difficult to
diminish the non-respiratory organ motion, there are some
approaches to reduce the respiratory organ motion [4-6].
Accurate set-up is required for SBRT, so immobilization
devices are used for diminishing the positioning error, i.e.
repositioning accurately. Some of them also have effect of
diminishing the organ motion errors, i.e. reducing the
tumor movement. Among several devices that have been
developed for immobilization, we have used the BodyFIX
system (Medical Intelligence, Schwabmuenchen,
Germany) . It is one of commercially available
immobilization devices, and is designed to readily fix patients body
and to suppress respiratory movement. In this study, we
measured motion of lung tumors, and examined
suppression of respiratory tumor movement when using the
BodyFIX system. We also monitored the percutaneous oxygen
saturation (SpO2) level with a finger pulseoximeter while
using the BodyFIX system. In addition, we report clinical
outcomes of SBRT for lung tumors performed with this
Between February 2004 and June 2006, 53 patients
underwent stereotactic body radiotherapy (SBRT) for a lung
tumor. Two patients received SBRT twice for different
lesions, so a total of 55 lesions were treated. Accordingly,
lung tumor movement and changes of SpO2 levels were
measured 55 times. There were 39 men and 14 women.
The age at SBRT ranged from 16 to 86 years, with a median
of 74 years. The eligibility criteria for the patients were as
follows: (1) histologically-confirmed primary NSCLC
diagnosed as T1N0M0 or T2N0M0 stage according to the
International Union Against Cancer (UICC) 1997 system
by CT scans, bone scintigraphy and brain magnetic
resonance imaging (MRI), or clinically diagnosed as recurrent
or metastatic lung cancer; (2) tumor diameter 50 mm,
and (3) World Health Organization performance status
2. When 18-fluoro-deoxyglucose-positron emission tom
ography (FDG-PET) was performed, bone scintigraphy
was omitted. FDG-PET was performed in 24 patients with
primary NSCLC, 2 with lung metastasis, and 2 with
postoperative local recurrence of NSCLC. Although the
diagnosis of primary NSCLC could not be confirmed with
CTguided biopsy in 1 patient, this case was included in the
study considering the positive FDG-PET finding and the
increase in tumor size during observation period. Of the
55 lesions, 42 were primary NSCLC, 10 were metastatic
lung cancer, and 3 were postoperative local recurrence of
NSCLC. The tumor diameter ranged from 10 to 50 mm
with an average of 26 mm. Of the 55 lesions, tumor
location was the right upper, middle and lower lobes in 17, 2
and 13 cases, respectively, and the left upper and lower
lobes in 13 and 10 cases, respectively. All of them were
treated using the BodyFIX immobilization device. Patient
characteristics are summarized in Table 1. In all patients,
pulmonary functions were assessed before SBRT.
Respiratory functions were categorized as obstructive dysfunction
when the ratio of forced expiratory volume in 1 second to
forced vital capacity (FEV 1.0%) was less than 70%, as
constrictive dysfunction when the percent vital capacity
(%VC) was less than 80%, and as mixed dysfunction
when both criteria were fulfilled.
The BodyFIX system consists of a vacuum cushion, a clear
plastic sheet covering the patient's torso and lower
extremities, and a vacuum pump. The patient lied in
supine position on a vacuum cushion. Both arms were
raised using a T-shaped holding bar. The vacuum cushion
was filled with small styrofoam balls, and the enclosed air
was evacuated through a vacuum pump, so that the
cushion was molded to the patient's posterior body surface.
The reference marks were drawn on the patient's skin and
the vacuum cushion to locate the patient body in the same
position repeatedly. A clear plastic sheet was attached to
Follow-up period (month)
*for all 55 lesions treated.
**Sq = squamous cell carcinoma; Ad = Adenocarcinoma; NSC = Non-small-cell carcinoma.
the lower sides of the vacuum cushion covering the
patient's lower body up to the abdomen or thorax. The air
among the clear plastic sheet, patient, and vacuum
cushion was evacuated with a pressure of 80 mbar, while the
vacuum cushion retained its mold. Once the vacuum
cushion was molded to the patient's back and sides, the
air among the clear plastic sheet, patient, and the vacuum
cushion was evacuated; then the system became a rigid
immobilization device (Figure 1), and patients underwent
treatment planning CT and SBRT under these conditions.
Methods for Suppression of Respiratory Tumor Movement
To investigate the optimal methods for suppression of
respiratory tumor movement using the BodyFIX system,
TFihgeuBroed1yFix immobilization system
The BodyFix immobilization system. Patient lied in the
molded vacuum cushion with a T-shaped holding bar, the
marks on the patient's skin and the vacuum pillow being
matched. The air among the clear plastic sheet, patient, and
the vacuum cushion was evacuated covering the patient's
lower body up to the abdomen with the clear plastic sheet.
motion of tumor was measured with fluoroscopy under
the following conditions; A: breath holding, B: free
breathing on a couch, C: free breathing in the BodyFIX
system with a patient's lower body covered up to the
upper abdomen with a clear plastic sheet, D: free
breathing in the BodyFIX with a patient's lower body covered up
to the upper thorax with a clear plastic sheet. Fluoroscopy
measurements were performed prior to CT scan for
treatment planning. Patients were positioned in the molded
vacuum cushion on the couch of an X-ray simulator to
estimate tumor movement. A cross-line scale was
superimposed on the screen of fluoroscopy to measure the
amplitude of tumor movement. The amplitude was
measured visually by at least 3 staff members in the
anteroposterior (AP) and lateral directions for 30 seconds each after
respiration became stable. Measurements were possible
for all tumors in both directions.
Percutaneous Oxygen Saturation
To evaluate whether or not the immobilization methods
affected the oxygenation status, SpO2 levels were
measured with a finger pulseoximeter every 15 seconds for 2
minutes under conditions B, C and D. For control, SpO2
was also measured under breath holding (condition A)
every 5 seconds for up to 40 seconds.
CT images for treatment planning were acquired using a
CT simulator (Mx8000, Philips Medical Systems, Best, the
Netherlands) after patients were positioned in the
BodyFIX system in the supine position. First CT scan was
performed under normal breathing. Then 2 additional scans
were performed with breath holding at the expiratory and
inspiratory phases. The table pitch was 0.75 mm/second,
and the rotation time was 2 seconds under the
free-breathing conditions and 1 second under the expiratory and
inspiratory breath-holding conditions. All CT scans were
reconstructed at 2.5 mm thickness.
The outlines of the target were delineated on a
3-dimensional radiation treatment planning system (3D RTPS)
(Eclipse Version 220.127.116.11, Varian Medical Systems, Palo
Alto, California, USA) using lung CT window setting
(window width: 1300 Hounsfield units (HU); and
window level: -350 HU, typically). The clinical target volume
(CTV) was defined by the visible gross tumor volume
(GTV). The CTV on CT at the 3 phases were superimposed
on the 3D RTPS to represent the internal target volume
CT was taken just before the first and third fractions of
SBRT to evaluate the accuracy of reproducibility of patient
and tumor position, and any positioning error was
corrected; patients were then transferred to the treatment
couch together with the BodyFix system. In addition, AP
and lateral portal images were obtained for verification
before every treatment. They were compared visually with
digitally reconstructed radiograph (DRR) derived from
the planning CT scan by at least 3 staff members in
relation to bony structures. We measured setup errors for 40
times in the first 10 patients. Absolute setup errors were
5 mm in 93%, 90% and 78%, and 10 mm in 100%,
100% and 98% in lateral (right-to-left, RL), AP and
craniocaudal (CC) directions, respectively. So we defined the
planning target volume (PTV) margin for the ITV to be 5
mm in the RL and AP directions, and 10 mm in the CC
direction. The patient was repositioned if the setup error
was greater than 3 mm in any direction.
Three coplanar and 4 noncoplanar static ports were used.
The beam arrangement was selected for the gantry not to
collide with the patient and the BodyFix system. We
avoided the interference of the thick carbon bars that lie
on the right and left sides of the couch. Dry run was
performed to choose appropriate beam arrangement before
SBRT was performed.
SBRT was delivered by a linear accelerator (CLINAC 23EX,
Varian Medical Systems, Palo Alto, California, USA) with
6-MV photons. The planned dose was 44 Gy in 4 fractions
for tumors with a maximum diameter of less than 1.5 cm,
48 Gy in 4 fractions for tumors with a maximum diameter
of 1.53 cm, and 52 Gy in 4 fractions for those larger than
3 cm. A total dose of 34 or 36 Gy in 2 fractions was
delivered for metastatic lung cancers with a maximum
diameter of less than 1.5 cm. Pencil beam convolution with
Batho power law correction of the Eclipse system was used
for dose calculation algorithm. The dose was prescribed at
the isocenter; 95% of the PTV was ensured to be covered
with at least 80% of the prescribed isocenter dose. Since
the total irradiation time was less than 30 minutes per
fraction, intrafractional tumor movement was not
Paired t-test was used to examine differences in tumor
movement between different patient conditions. A
correlation coefficient was calculated to assess the relationship
between the respiratory function and tumor movement.
To compare the change of SpO2 levels under conditions C
and D, repeated measure analysis of variance was used.
Survival rates and cumulative incidences of complications
were calculated by the Kaplan-Meier method.
Respiratory Tumor Movement
Patient compliance with the BodyFIX system was 100%.
Amplitude of tumor movement is shown in Table 2 and
Figure 2. Under breath-holding conditions, the average
tumor movement was less than 2 mm in both CC and RL
directions, whereas it was 710 mm in the CC direction
and 23 mm in the RL direction under the other three
conditions. Statistical differences in tumor movement
among conditions B, C and D are shown in Table 3. By
covering the patient's lower body up to the upper
abdomen or upper thorax with the sheet (condition C or D),
respiratory tumor movements were slightly but
significantly reduced in both CC and RL directions, compared
with free-breathing condition B. There were no differences
in tumor movement between conditions C and D.
The tumor movement was defined as increased and
decreased when the amplitude in condition B minus the
amplitude in condition C or D exceeded - 2 and 2 mm,
respectively; otherwise, the tumor movement was
regarded as no change. Under both conditions C and D,
the tumor movement increased in 2 cases, did not change
A: Breath holding.
B: Free breathing on a couch.
C: Free breathing covering the patient's lower body up to the abdomen with a clear plastic sheet.
D: Free breathing covering the patient's lower body up to the thorax with a clear plastic sheet.
p*: Paired t-test for mean values of tumor movement.
X Y: Amplitude of tumor movement in condition X minus that in condition Y.
in 38 cases, and decreased in 15 (27%) cases, compared
with the free-breathing condition B in the CC direction. In
the RL direction, the tumor movement did not change in
51 (93%) and 49 (89%) cases and decreased in 4 (7%)
and 6 (11%) cases under conditions C and D, respectively.
Thus, respiratory tumor movement in the CC direction
was reduced by 3 mm or more in about one-quarter of the
patients by covering the patient's lower body up to the
upper abdomen or upper thorax with the sheet.
We defined the upper lobe in the right lung and the
segment 1+2 and 3 in the left lung as the upper lung field,
and the rest of the lung as the lower lung field. The tumor
movement in the lower lung field was much greater than
in the upper lung field in the CC direction (Table 4 and
Figure 3). In both lung fields, respiratory tumor
movements were significantly reduced under conditions C and
D compared with the free-breathing condition B in both
CC and RL directions (Table 5). Again, however, there was
no difference between conditions C and D in both fields.
Under conditions C and D, decrease of tumor movement
3 mm in the CC direction was observed in 38% of the
patients in the lower lung field, whereas it was seen in
17% in the upper lung field.
Relationship between pulmonary function and tumor
movement was analyzed. Thirteen and 10 tumors in the
upper and lower lung fields, respectively, were in patients
with normal pulmonary function. Ten, 2 and 4 tumors
each in the upper and lower lung fields were in patients
with obstructive dysfunction, those with constrictive
dysfunction and those with mixed dysfunction, respectively.
FAimguplriteud2e of tumor movement under conditions A, B, C and D in the craniocaudal and right-to-left directions
Amplitude of tumor movement under conditions A, B, C and D in the craniocaudal and right-to-left directions.
A: breath holding; B: free breathing; C: free breathing covering the patient's lower body up to the abdomen with a clear plastic
sheet; D: free breathing covering the patient's lower body up to the thorax with a clear plastic sheet. Bars represent SD.
The correlation coefficients between %VC and FEV 1.0%
and amplitudes of tumor movement in the CC and RL
directions were calculated, but there was no significant
correlation between respiratory function and the
amplitude of tumor movement in both directions (data not
Percutaneous Oxygen Saturation Level
Changes in SpO2 levels are shown in Figure 4. There were
10 cases in which SpO2 decreased by 3% or more; in 1
case, the decrease was as large as 10%. There was 1 case in
which SpO2 increased by 3% or more under the
breathholding condition A. On average, the SpO2 level did not
decrease under condition A. There were 5 cases in which
SpO2 decreased by 3% or more and 4 cases in which SpO2
increased by 3% or more under both conditions C and D.
The average SpO2 level did not decrease under both
conditions C and D. The change of SpO2 was not different
between conditions C and D (p = 0.56).
In actual treatment, we used the patient condition C, i.e.,
free breathing covering the patient's lower body up to the
abdomen with a clear plastic sheet. The mean SD of PTV
volumes was 53 30 cm3, with a range of 8.1 to 146 cm3.
The median follow-up period was 32 months (range, 24
to 52 months). For follow-up after the SBRT, CT
examination was performed at 2-month intervals until the 6th
months, and every 2 to 4 months thereafter. FDG-PET was
performed whenever necessary. Local recurrence was
suspected by enlargement of a fibrotic mass on CT images
without sign of inflammation, and diagnosed by high
uptake on FDG-PET and/or biopsy.
The local control rate was 80% for all lesions at 3 years. In
42 primary NSCLC treated, 30 lesions were stage IA and
12 were stage IB. We had no patient treated with 44 Gy in
4 fractions. All stage IA lesions were treated with 48 Gy in
4 fractions, and stage IB lesions were treated with 52 Gy in
4 fractions. Local recurrence developed in 8 (5 among
stage IA patients and 3 among stage IB). Regional lymph
p*: Paired t-test for mean values of tumor movement.
X Y: Amplitude of tumor movement in condition X minus that in condition Y.
lFAoimwgupelriteluud3neg ofifetldusmor movement under conditions A, B, C and D in the craniocaudal and right-to-left directions in the upper and
Amplitude of tumor movement under conditions A, B, C and D in the craniocaudal and right-to-left directions
in the upper and lower lung fields. Black diamond: tumors in the upper lung field; open square: tumors in the lower lung
field. A: breath holding; B: free breathing; C: free breathing covering the patient's lower body up to the abdomen with a clear
plastic sheet; D: free breathing covering the patient's lower body up to the thorax with a clear plastic sheet. Bars represent SD.
nodes recurrence occurred in 6 (3 among stage IA and 3
among stage IB). Distant metastasis appeared in 13
patients (8 among stage IA and 5 among stage IB). There
was no difference in regional and systemic progression
between patients with and without FDG-PET staging. At 3
years, overall survival was 76%, cause-specific survival was
92%, progression-free survival was 54%, and local
progression-free survival was 76%. For stage IA, they were
83%, 96%, 55% and 79%, respectively. For stage IB, they
were 58%, 82%, 55% and 74%, respectively.
Toxicity was evaluated using the Common Terminology
Criteria for Adverse Events Version 3. Grade 2 radiation
pneumonitis (symptomatic but not interfering with
activity of daily life) was observed in 7 patients. At 3 years, the
cumulative incidence was 17%. The rate for stage IA and
IB was 17% and 19%, respectively. Other adverse events
were grade 1 atelectasis seen in 3 patients, pleural effusion
of grade 1 and 2 in 5 and 1, respectively, grade 2
esophagitis in 2, grade 1 dermatitis in 2, grade 2 rib fracture in 1,
and soft-tissue swelling in 2.
There are many reports on the respiratory tumor
movement using fluoroscopy, portal image, CT, and MRI
[5,6,8-15]. The correlation between tumor location and
amplitude of movement was analyzed in several studies
[8,9,11-13,15]. Onimaru et al.  evaluated the
amplitude of the tumor motion and the difference in the
amplitude according to the marker sites on a plain chest X-ray
film. Our results were comparable to theirs. A limitation
of our study was that motion in the AP direction was not
measured. Movement in the AP direction often could not
be seen well with fluoroscopy because tumor overlapped
mediastinal structures . Tumor movement in the AP
direction is much less than that in the CC direction, but
on CT images taken at 3 phases, it was well recognized and
the range of movement was included in the PTV. In future
studies, 4-dimensional management of tumor movement
should be warranted.
To irradiate the tumor precisely and to decrease the
irradiated volume of the normal lung, various methods have
been developed. They can be classified into 5 major
categories; motion-encompassing method, respiratory-gating
method, breath-hold method, forced shallow-breathing
with abdominal compression method, and real-time
tumor-tracking method . In any method, accurate
setup is necessary. Repositioning accuracy of some
commercially available immobilization devices was reported
to be acceptable [6,7,18,19]. They also have an instrument
for reducing the tumor movement. Negoro et al. 
Seconds after start of measurement
SFpigOu2rceha4nge under conditions A (black diamond), B (open square), C (open triangle) and D (X)
SpO2 change under conditions A (black diamond), B (open square), C (open triangle) and D (X). A: breath
holding; B: free breathing; C: free breathing covering the patient's lower body up to the abdomen with a clear plastic sheet; D: free
breathing covering the patient's lower body up to the thorax with a clear plastic sheet. Bars represent SD.
reported the effectiveness of the stereotactic body frame.
The average tumor movement in the CC direction during
free respiration was 7.7 mm, with a range of 0 to 20 mm.
In the patients in whom tumor movement was greater
than 5 mm, the abdominal press reduced the tumor
movement significantly from a range of 8 to 20 mm to a
range of 2 to 11 mm (p = 0.0002). Our method is a
combination of a motion-encompassing method and a forced
shallow-breathing method with abdominal compression.
Using the BodyFIX system, the tumor movements were
modestly but significantly reduced compared with
freebreathing status. However, reduction of tumor movement
by 3 mm or more in the CC direction was obtained in
only 27% of the patients, and in the rest of the patients,
suppression of tumor movement was not considered to be
satisfactory. Therefore, the use of the BodyFix system
appeared to have limited influence on the ITV size.
Covering the patient's lower body up to the abdomen and up to
the thorax with a clear plastic sheet showed no
differences. So, in practical SBRT, we covered the body up to the
upper abdomen. From these considerations, the major
purpose of using this system appeared to be to position
the patient accurately and the second one was to suppress
tumor movement modestly without influencing
oxygenation status of tumors. Other strategies may be necessary in
cases with large tumor movement.
Regarding other uncertainties associated with SBRT,
patient positioning and especially base-line shifts of the
target position have been reported to be the most relevant
uncertainties [20,21]. To decrease these uncertainties, we
used verification CT before the first and third fractions of
SBRT and AP and lateral portal images every time. These
verification methods may be less accurate than the
currently available image-guidance techniques like cone
beam CT. Such newer image guidance systems are
desirable in future SBRT. Regarding intrafractional motions, we
did not measure them, but the BodtFix system should be
useful in reducing this uncertainty.
We monitored the change of SpO2 under conditions A, C
and D, because we had a concern that SpO2 might
decrease by suppression of respiration especially in
patients with low pulmonary function. If SpO2 decreases
significantly, tumor response might become poorer due to
the increase in hypoxia . There was 1 case in which
SpO2 decreased by 10% under breath-holding condition
A. It did not decrease under conditions C and D in the
same patient. In a few patients, SpO2 decreased by 3% or
4% at maximum under conditions C and D, but in the
other patients, SpO2 did not decrease at all while using the
BodyFIX system. Therefore, it was concluded that the
BodyFIX system does not significantly influence SpO2 levels in
the majority of patients.
Clinical outcome of our patients in terms of antitumor
effect and toxicity compares favorably with that published
recently [3,23], suggesting that our fractionation
schedules are, at least, not inferior to those used by other
investigators. The relatively low toxicity may not mainly result
from the use of the BodyFix system. Follow-up periods are
still short in a considerable proportion of patients, and we
will continue further follow-up.
Respiratory tumor movement was modestly suppressed
by using the BodyFIX system, while the SpO2 level did not
decrease. Although the system did not seem to be very
useful to decrease the ITV, it appeared to be a simple and
effective method for SBRT of lung tumors. Our method of
SBRT was safe and the preliminary result was favorable.
The authors declare that they have no competing interests.
FB carried out the study and drafted the manuscript. YS
indicated the design of the study and gave final approval
of the version to be published. NT participated in analysis
and interpretation of data. CIH, KO and SA participated in
acquisition and analysis of data. HO participated in the
design of the study and helped to perform the statistical
analysis. CS participated in analysis and interpretation of
data and helped to draft the manuscript. All authors read
and approved the final manuscript.
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