Download the clinical implementation of respiratory

Medical Dosimetry, Vol. 31, No. 2, pp. 152-162, 2006
Copyright © 2006 American Association of Medical Dosimetrists
Printed in the USA. All rights reserved
0958-3947/06/$–see front matter
doi:10.1016/j.meddos.2005.12.002
THE CLINICAL IMPLEMENTATION OF RESPIRATORY-GATED
INTENSITY-MODULATED RADIOTHERAPY
PAUL KEALL, PH.D., SASTRY VEDAM, PH.D., ROHINI GEORGE, PH.D., CHRIS BARTEE, B.S.,
JEFFREY SIEBERS, PH.D., FRITZ LERMA, PH.D., ELISABETH WEISS, M.D., and
THEODORE CHUNG, M.D., PH.D.
Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA
( Accepted 21 December 2005)
Abstract—The clinical use of respiratory-gated radiotherapy and the application of intensity-modulated radiotherapy (IMRT) are 2 relatively new innovations to the treatment of lung cancer. Respiratory gating can reduce
the deleterious effects of intrafraction motion, and IMRT can concurrently increase tumor dose homogeneity and
reduce dose to critical structures including the lungs, spinal cord, esophagus, and heart. The aim of this work is
to describe the clinical implementation of respiratory-gated IMRT for the treatment of non-small cell lung
cancer. Documented clinical procedures were developed to include a tumor motion study, gated CT imaging,
IMRT treatment planning, and gated IMRT delivery. Treatment planning procedures for respiratory-gated
IMRT including beam arrangements and dose-volume constraints were developed. Quality assurance procedures
were designed to quantify both the dosimetric and positional accuracy of respiratory-gated IMRT, including film
dosimetry dose measurements and Monte Carlo dose calculations for verification and validation of individual
patient treatments. Respiratory-gated IMRT is accepted by both treatment staff and patients. The dosimetric and
positional quality assurance test results indicate that respiratory-gated IMRT can be delivered accurately. If
carefully implemented, respiratory-gated IMRT is a practical alternative to conventional thoracic radiotherapy.
For mobile tumors, respiratory-gated radiotherapy is used as the standard of care at our institution. Due to the
increased workload, the choice of IMRT is taken on a case-by-case basis, with approximately half of the
non-small cell lung cancer patients receiving respiratory-gated IMRT. We are currently evaluating whether
superior tumor coverage and limited normal tissue dosing will lead to improvements in local control and survival
in non-small cell lung cancer. © 2006 American Association of Medical Dosimetrists.
Key Words: IMRT, lung cancer, respiratory-gated IMRT.
variable and unpredictable.26 Thus, respiratory motion
management is one of the key components required to
test the hypothesis of Ling et al. that technologic innovations will improve radiotherapy of non-small cell lung
cancer, and enable radiotherapy to rival post-surgical
outcomes.30 Respiratory gating31– 48 is one commercially
available method to manage respiratory motion. IMRT
for lung cancer also shows significant promise.49 –52 We
describe the clinical implementation of respiratory-gated
intensity modulated radiotherapy at Virginia Commonwealth University (VCU). It reflects our experience, and
is intended as a “how to” guide for institutions developing respiratory-gated IMRT programs. This article is not
a review of respiratory-gated IMRT, and for further
information, readers are urged to consult the references
listed and related works. Although not discussed further
here, positron emission tomography (PET) scanning is an
important part of the treatment planning process for
non-small cell lung cancer.53 Gated and 4D PET/CT
approaches are currently under development.54 –56
At VCU, we treated our first respiratory-gated
IMRT patient, verified with Monte Carlo dose calculation, in 2001. Since 2003, we have followed a policy of
evaluating all lung cancer patients for their suitability for
respiratory gating. In 2005, we have followed the proce-
INTRODUCTION
Lung cancer causes more deaths in the United States than
any other cancer and more than the next 3 cancers
combined.1 Despite significant efforts to improve treatment, 5-year lung cancer survival remains at around
15%.1 A recent RTOG retrospective analysis of 1290
NSCLC patients demonstrates that every 10-Gy increase
in biologically equivalent dose (BED) results in an 18%
decrease in the risk of death,2 clearly demonstrating the
need for dose intensification. Martel et al.3 estimate from
their data that to achieve 50% local progression-free
survival at 30 months, 85 Gy—a dose level considerably
higher than the current standard of care—will be required (in 2-Gy fractions). Stereotactic hypofractionated
early-stage NSCLC regimens also show a dose-response.4,5 The cost of dose intensification is normal
tissue toxicity, which has been shown to have a doseresponse for the lung,6 –11 heart,12 and esophagus.13,14
Lung tumors move with respiration15–29 up to 5 cm
for free breathing16; however, the magnitude of motion is
Reprint requests to: Paul Keall, Ph.D., Medical Physics Division,
Department of Radiation Oncology, Massey Cancer Center, Virginia
Commonwealth University, P.O. Box 980058, Richmond, VA 23298.
E-mail: [email protected]
152
Respiratory-gated IMRT ● P. KEALL et al
153
good correlation (0.99)59 to very poor correlation
(0.39)57 with phase shifts of over 1 second observed.61
Note that respiratory gating as a concept is not
limited to its current implementation of the respiratory
signal being based on the external motion of the patient,
and the confidence and accuracy of respiratory-gated
delivery will increase as the relationship between R and
T improves.
PATIENT SELECTION
Fig. 1. The clinical decision tree for respiratory-gated lung
cancer patient evaluation.
dure shown schematically in Fig. 1. The respiratorygating device is the Real-Time Position Management
(RPM) system (Varian Medical Systems, Palo Alto, CA).
The RPM system is connected to a GE Lightspeed 16slice scanner (GE Medical Systems, Waukesha, WI) for
retrospective 4D CT imaging, a PQ 5000 CT scanner
(Philips Medical Systems, Cleveland, OH) for prospective gated CT imaging, and a 21EX linear accelerator
(Varian Medical Systems). The Pinnacle (Philips Medical Systems, Milpitas, CA) system is used for treatment
planning.
THE RELATIONSHIP BETWEEN
RESPIRATORY MOTION AND TUMOR
MOTION
It is important to note upfront that gating, as implemented at our institution, uses an external respiration
signal, determined from optically tracking a marker typically placed between the umbilicus and xyphoid process. Thus, the respiration signal is the abdominal wall
motion, while the quantity of interest is the tumor motion. In general, the respiratory signal, R at time t can be
related to the tumor motion, T, from the following equation
R(t) ! I " M!T"t " #$)# " %(t),
(1)
where I is the interfraction internal motion due to dayto-day anatomic changes,57 M is the motion ratio of the
respiratory signal to the tumor, !$ is the phase difference
(in units of time) between the respiratory signal and the
tumor, and %(t) is an error term, which under ideal
conditions is negligible.
The correlation between R and T has been quantified in several articles,58 – 61 which demonstrate very
There are many factors that may contribute to a
patient’s suitability for respiratory gating, such as lung
function, age, oxygen dependency, tumor position, etc.;
however, we do not exclude any patients a priori before
the clinical evaluation.
The 3 main clinical decisions, as shown in Fig. 1
are:
1. Is there sufficient motion to warrant respiratory gating? A 5-mm threshold is used (based on the AAPM
Task Group draft report).
2. Can clinical goals be fully achieved without respiratory gating?
3. Is the respiratory pattern sufficiently reproducible to
make the use of gating worthwhile?
The first decision is made under fluoroscopy (note
that tumor motion can also be observed with 4D CT;
however, the number of breathing cycles that data is
acquired for at any given location is typically 5–10
seconds for 4D CT and 20 –30 seconds for fluoroscopy).
The answer to the second question is difficult to quantify
and depends on factors such as treatment intent (palliative vs. radical), tumor size, tumor stage, patient comorbidities, etc., and is evaluated on a case-by-case basis.
The answer to the third question is also difficult to
quantify; however, patients with breathing rates above 20
cycles per minute, or traces exhibiting significant baseline shift, are generally not good candidates for gating.
Our approach is to try the gated imaging procedure. If
unsuccessful, the fallback position is to treat without
gating. In our experience, we have not yet had a patient
who was successfully imaged with gating not be able to
be treated with gating due to degraded respiratory reproducibility during treatment.
In our experience, over 80% of lung cancer patients
have more than 5 mm of fluoroscopy-evident motion and
their breathing is sufficiently reproducible to benefit
from gating. We tend to be conservative and use gating,
unless it is perceived that respiratory gating will have
negligible impact on the clinical goals of the treatment
(decision 2 above).
RESPIRATORY TRAINING
Recent studies have shown that visual62 and audiovisual63,64 biofeedback improves the respiratory reproducibility of lung cancer patients over the treatment
154
Medical Dosimetry
Volume 31, Number 2, 2006
Fig. 2. Example images from the tumor motion study at (a) inhale and (b) exhale. The fluoroscopic image and part of
the respiratory trace are shown. The image was acquired at the part of the respiratory cycle that intersects the solid
vertical line. The position of the diaphragm in both images is shown by the arrow.
course. Improved respiratory reproducibility affects both
the accuracy and efficiency of respiratory gating, as well
as improves the images used for treatment planning.
Users are recommended to implement breathing training
where possible.
FLUOROSCOPY PROCEDURE
A fluoroscopic evaluation of the patient serves three
purposes:
1. To determine if the motion is significant enough to
warrant gating (as described).
2. To observe the correlation between the tumor motion
and respiratory surrogate motion and evaluate if
there is a phase shift between the internal anatomic
motion and the synchronously acquired respiratory
signal. A detected phase shift can be corrected for by
altering the gating window settings.
3. To observe respiratory reproducibility.
Example fluoroscopic images at inhale and exhale
are shown in Fig. 2. A step-by-step fluoroscopy procedure guide is given in Appendix I.
RESPIRATORY-GATED CT IMAGING
At VCU, lung cancer patients are positioned supine on a wingboard with their arms raised above their
head.
Accounting for respiratory motion during CT imaging can reduce motion artifacts observed on CT scans. As
an example, images of static, respiratory-gated, and free
breathing CT images for a lung phantom are shown in
Fig. 3 (a comparison of respiratory-gated and freebreathing patient images can be found in Ref. 32). The
motion phantom settings for a sinusoidal motion pattern
were a 1-cm range of motion and 4-second motion period. For patients, the extent of the observed artifacts for
the free-breathing scans will depend on the magnitude
and period of motion as well as the CT scan acquisition
parameters. If unaccounted for, motion artifacts occur in
all imaging modalities, although may manifest them-
Respiratory-gated IMRT ● P. KEALL et al
155
Fig. 5. Respiratory-gated IMRT dose-volume histogram calculated with superposition (solid curves) and Monte Carlo
(dashed curves).
Fig. 3. (a) Lung IMRT phantom with a “tumor” outlined and
implanted markers placed on a prototype motion platform (see
Fig. 9) and coronal CT images acquired under (b) static, (c)
gated, and (d) free-breathing conditions (1-cm range of
motion).
selves differently depending on the acquisition type.
Detailed procedures for CT imaging for retrospective 4D
CT imaging and prospective gated CT imaging are given
in Appendices II and III, respectively.
RESPIRATORY-GATING IMRT TREATMENT
PLANNING
A useful guide for the planning process of thoracic
radiotherapy is given in Ref. 65. The first stage of treat-
ment planning involves contouring, and it should be
noted that this is perhaps the most error-prone step in the
treatment process due to observer variability.65–70 Per
RTOG guidelines,71 the GTV is defined as the tumor and
regional lymph nodes greater than 1 cm in short axis. The
GTV to CTV margin is 6 mm for squamous cell carcinoma and 8 mm for adenocarcinoma for tumors in the
lung,72 and 5 mm in the mediastinum. The GTV-CTV
expansion is edited such that it does not extend in to the
chest wall, mediastinum, or across lobe boundaries unless infiltrated by the tumor.50 The CTV to PTV margin
is 8 mm to account for setup error, residual motion
during the treatment gate, and day-to-day changes in
tumor position with respect to the skeletal anatomy.
Normal tissues contoured for IMRT planning are the
esophagus, spinal cord (both expanded 5 mm for planning purposes),50 the lungs, heart, and planning normal
tissue volume (entire thorax minus PTV).50
Fig. 4. Respiratory-gated IMRT isodose plans calculated with (a) Superposition and (b) Monte Carlo. The 74-, 40-, and
20-Gy isodose levels are shown. The Monte Carlo calculations are used clinically at our institution as part of the quality
assurance process for each IMRT patient, with the results recorded in the patient’s chart and reviewed by the patient’s
physician.
156
Medical Dosimetry
Volume 31, Number 2, 2006
Table 1. Dose-volume constraints for respiratory gated IMRT treatment planning that produces acceptable plans
over a range of tumor volumes and locations
Structure
Constraint Type
Dose (Gy)
% Volume
Weight
Rationale
PTV
PTV
PTV
PTV
PTV
Heart
Heart
Cord PRV
Esophagus PRV
Esophagus PRV
Lungs minus GTV
Lungs minus GTV
Skin minus PTV
Min DVH
Min Dose
Max Dose
Min Dose
Max Dose
MaxDVH
MaxDVH
Max Dose
MaxDVH
MaxDVH
MaxDVH
MaxDVH
Max Dose
74.0
66.6
88.8
74.0
74.0
40.0
40.0
45.0
55.0
40.0
20.0
20.0
80.0
95
50
25
30
30
30
15
-
100
40
40
10
10
20
1
50
40
1
20
1
100
Prescription dose71
Based on Liu et al.50
Based on Liu et al.50
Soft constraint to obtain uniform PTV dose
Soft constraint to obtain uniform PTV dose
Reduce heart dose
Soft constraint to further reduce heart dose
Upper limit on cord
Reduce esophagus dose
Soft constraint to further reduce esophagus dose
Reduce lung dose
Soft constraint to further reduce lung dose
Reduce high dose areas to uncontoured normal
tissue outside PTV
Generally, 6 coplanar non-opposed predominantly
anterior-posterior beams, e.g., gantry angles of 320°, 0°,
40°, 160°, 200°, 240° (or variants thereof depending on
tumor location) are used. Note that for our linacs, a
gantry angle of 0 means that the beam is pointing toward
the floor.
Table 1 gives a list of dose volume constraints
giving acceptable plans over a wide variety of tumor size
and locations. As an example, 74 Gy in 37 fractions were
prescribed to 95% of the PTV. This fractionation scheme
was determined to be the maximum tolerated dose for
concomitant chemotherapy in the RTOG 0117 study.71
Note that this clinical implementation differs from the
RTOG 0117 trial in that IMRT and gating are utilized, a
superposition convolution dose calculation algorithm
with heterogeneity corrections is used for dose calculations and different GTV-CTV and CTV-PTV margins.
The superposition algorithm used for treatment
planning, although a significant improvement over other
algorithms historically used for planning, does not explicitly transport particles through the complex MLC
geometry or in the patient. Thus, at VCU, we use Monte
Carlo for verification of all IMRT treatments. Representative isodose distributions for a typical respiratory gated
treatment plans calculated with superposition and Monte
Carlo algorithms are given in Fig. 4. Although for this
case there is good general agreement, the Monte Carlo
74-Gy isodose curve is slightly smaller than that of the
superposition curve, and a cold spot is observed near the
bronchiole. The corresponding dose volume histograms
are given in Fig. 5.
PRETREATMENT PORTAL IMAGING
Respiratory motion affects the electronic portal image (EPI) verification for thoracic radiotherapy as the
anatomy typically used for patient alignment (apart from
the vertebral bodies) move with respiration, namely the
chest wall, diaphragm, ribs, aortic knop, and carina. This
motion causes 2 problems: (1) the anatomy imaged is not
representative of its actual position during treatment; and
(2) motion of the anatomy during the image acquisition
process blurs the image, reducing contrast and diminishing the utility of the images. These problems can be
mitigated by utilizing respiratory-gated EPI. Apart from
the improvements made by respiratory gating during CT
simulation (and hence more anatomically representative
DRRs) and the potential for margin reduction during
treatment planning, we can hypothesize that respiratory
gated EPI: (1) reduces motion during imaging; and (2)
Fig. 6. (a) Static and (b) dynamic images of the PIPSpro QC-3 image quality device on a prototype motion platform (see
Fig. 9).
Respiratory-gated IMRT ● P. KEALL et al
157
the tumor image would be blurred, thus reducing contrast
and potentially leading to a geometric error due to misalignment.
RESPIRATORY-GATING IMRT DELIVERY
Respiratory gating changes a continuous delivery to
a periodic delivery, as the beam is off when the patient’s
respiratory pattern is not within the preset gating window. Thus, the treatment time increases and the periodic
nature can affect beam output. With IMRT, the treatment
time increases over conventional delivery. Gating combined with IMRT increases the treatment time by approximately 2 minutes in our experience, although this
will be affected by the duty cycle used, treatment dose
rate, and leaf sequencing algorithms. A treatment sequence for respiratory gated DMLC IMRT is shown in
Fig. 8. Detailed instructions for respiratory-gated delivery are described in Appendix IV.
Fig. 7. An example respiratory-gated electronic portal image
prior to a patient treatment. The tumor is located within the
circle. If the image had been acquired while the tumor was
mobile, the soft tissue contrast would have decreased, increasing the chance of beam-target misalignment.
increases contrast and thus allow better visualization and
use of images. Together these 2 advances result in improved tumor-beam targeting during radiotherapy.
The effect of the 2 hypotheses are demonstrated
using the PIPSpro QC-3 phantom (Standard Imaging)
placed on a motion platform prototype (Standard Imaging) with a 2-cm amplitude of motion and a 3.5-second
period of motion. Examples of images without and with
motion are shown in Fig. 6a and Fig. 6b, respectively.
Clearly, the motion blurring in the right image is evident.
The image quality was too poor for the PIPSpro software
to determine the contrast-to-noise ratio on the moving
image.
An example of a pretreatment gated patient EPI
image acquired at exhale is shown in Fig. 7. Note that the
tumor is visible in this image; however, if the image had
been acquired during mid-inhalation or mid-exhalation,
PROCEDURAL ISSUES
Not all record-and-verify (R/V) systems integrate
with respiratory gating devices. Treating without gating
as part of the R/V system can result in multiple error
scenarios including (1) ignoring gating when gating was
prescribed; (2) applying gating when not prescribed; and
(3) treating a patient with another patient’s gating treatment settings. Instruction of, and communication between, the simulation, planning, and treatment teams is
an important part of reducing delivery errors.
POSITIONAL QUALITY ASSURANCE
As respiratory gating is by nature accounting for
positional change, positional quality assurance is important. Performing a system positional check is recommended. This involves gated CT imaging of a motion
phantom, from which digitally-reconstructed radiographs
(DRRs) are created. The phantom is then setup on the
treatment unit, from which gated portal images are acquired. The comparison of the DRRs with the gated
treatment images yields an estimate of the geometric
uncertainty under ideal conditions. For patient cases,
Fig. 8. A treatment sequence for respiratory gated DMLC IMRT.
158
Medical Dosimetry
Volume 31, Number 2, 2006
Table 2. Ion chamber dosimetric machine output and motion
measurements
Phantom
Moving?
Beam
Gated?
Relative
Dose
% Reproducibility
(1&)
Machine output dose measurements
No
No
1.0
No
Yes
0.99
1.0
0.4
Moving phantom dose measurements
No
No
1.0
Yes
Yes
1.01
Yes
No
1.03
0.2
0.4
1.2
Fig. 9. The lung IMRT phantom and motion platform used for
the positional and dosimetric quality assurance. The ionization
chamber and film positions are shown.
Dose values are relative to dose measured for a static beam to a static
phantom.
margins for microscopic spread, set-up error, and internal motion should be added.
shows that the output of a respiratory-gated IMRT beam
is similar to that of an ungated IMRT beam, and also that
if the beam is not gated and there is motion, the results
start to significantly deviate from the planned delivery.
Film dosimetry for a gated IMRT patient is shown
in Fig. 10 for static, gated, and free breathing cases. The
magnitude of the dosimetric difference between the static
delivery are smaller for the gated delivery than for the
free breathing delivery. We perform film dosimetry for
all of our IMRT patients (gated or otherwise), but not for
gated non-IMRT patients.
DOSIMETRIC QUALITY ASSURANCE
Several publications have described dosimetric
quality assurance methods that can be used for respiratory gating.31,40,46 – 48,73 To ensure that the linear accelerator output is stable when the beam is turned on and off
during gated delivery, experiments should be performed
to ensure, that in the absence of detector motion, the
machine output with and without gating are similar.
Measurements with the detector in motion for gated and
free breathing situations give estimates of the benefits of
gating over not accounting for motion.
Using the phantom on the motion platform shown in
Fig. 9, ionization measurements were performed using
the IMRT fields. The results are given in Table 2, which
SUMMARY
Respiratory-gated IMRT is a complex procedure
requiring understanding of the process, intradepartmental
communication during the planning and delivery processes and quality assurance measures at several steps of
Fig. 10. An isodose comparison of static delivery (dashed lines in all figures) with (a) respiratory-gated delivery and (b)
free-breathing delivery. The standard deviation of the dosimetric difference from the static delivery was 2.2% for the
gated delivery and 4.3% for the free-breathing delivery.
Respiratory-gated IMRT ● P. KEALL et al
the radiotherapy procedure. If carefully implemented, the
potential benefits of both of these modalities can be
combined to lead to an anticipated improvement of therapeutic outcome.
17.
18.
Acknowledgments—The authors acknowledge the input of Drs. Vijay
Kini and Radhe Mohan to the early development of the respiratory
gated IMRT program at Virginia Commonwealth University. PJK also
acknowledges the conversations and email correspondence with Dr.
Suresh Senan from the VU University Medical Center in Amsterdam.
The authors thank Devon Murphy for reviewing and improving the
clarity of the manuscript. This work was partially supported by NIH
grant R01 93626.
REFERENCES
1. Cancer Facts and Figures 2005, American Cnacer Society. Available at: http://www.cancer.org/downloads/STT/CAFF2005f4PW
Secured.pdf. Accessed February 6, 2006.
2. Machtay, M. Higher BED is associated with improved localregional control and survival for NSCLC treated with chemoradiotherapy: An RTOG analysis. Int. J. Radiat. Oncol. Biol. Phys.
63:S66; 2005.
3. Martel, M.K.; Ten Haken, R.K.; Hazuka, M.B.; et al. Estimation of
tumor control probability model parameters from 3-D dose distributions of non-small cell lung cancer patients. Lung Cancer 24(1):
31–7; 1999.
4. Wulf, J.; Baier, K.; Flentje, M.P. Dose escalation in radiotherapy
of lung tumors by stereotactic irradiation: Is there a dose-response
relationship for local tumor control? Int. J. Radiat. Oncol. Biol.
Phys. 63:S52; 2005.
5. McGarry, R.C.; Papiez, L.; Williams, M.; et al. Stereotactic body
radiation therapy of early-stage non-small-cell lung carcinoma:
Phase I study. Int. J. Radiat. Oncol. Biol. Phys. 63:1010 –5; 2005.
6. Graham, M.V.; Purdy, J.A.; Emami, B.; et al. Clinical dosevolume histogram analysis for pneumonitis after 3D treatment for
non-small cell lung cancer (NSCLC). Int. J. Radiat. Oncol. Biol.
Phys. 45:323–9; 1999.
7. Hernando, M.L.; Marks, L.B.; Bentel, G.C.; et al. Radiationinduced pulmonary toxicity: a dose-volume histogram analysis in
201 patients with lung cancer. Int. J. Radiat. Oncol. Biol. Phys.
51:650 –9; 2001.
8. Kwa, S.L.; Lebesque, J.V.; Theuws, J.C.; et al. Radiation pneumonitis as a function of mean lung dose: An analysis of pooled
data of 540 patients. Int. J. Radiat. Oncol. Biol. Phys. 42:1–9;
1998.
9. Oetzel, D.; Schraube, P.; Hensley, F.; et al. Estimation of pneumonitis risk in three-dimensional treatment planning using dosevolume histogram analysis. Int. J. Radiat. Oncol. Biol. Phys.
33:455– 60; 1995.
10. Seppenwoolde, Y.; Lebesque, J.V.; de Jaeger K.; et al. Comparing
different NTCP models that predict the incidence of radiation
pneumonitis. Int. J. Radiat. Oncol. Biol. Phys. 55:724 –35; 2003.
11. Yorke, E.D.; Jackson, A.; Rosenzweig, K.E.; et al. Dose-volume
factors contributing to the incidence of radiation pneumonitis in
non-small-cell lung cancer patients treated with three-dimensional
conformal radiation therapy. Int. J. Radiat. Oncol. Biol. Phys.
54:329 –39; 2002.
12. Prosnitz, R.G.; Chen, Y.H.; Marks, L.B. Cardiac toxicity following
thoracic radiation. Semin. Oncol. 32:S71– 80; 2005.
13. Bradley, J.; Deasy, J.O.; Bentzen, S.; et al. Dosimetric correlates
for acute esophagitis in patients treated with radiotherapy for lung
carcinoma. Int. J. Radiat. Oncol. Biol. Phys. 58:1106 –13; 2004.
14. Ahn, S.J.; Kahn, D.; Zhou, S.; et al. Dosimetric and clinical
predictors for radiation-induced esophageal injury. Int. J. Radiat.
Oncol. Biol. Phys. 61:335– 47; 2005.
15. Barnes, E.A.; Murray, B.R.; Robinson, D.M.; et al. Dosimetric
evaluation of lung tumor immobilization using breath hold at deep
inspiration. Int. J. Radiat. Oncol. Biol. Phys. 50:1091– 8; 2001.
16. Chen, Q.S.; Weinhous, M.S.; Deibel, F.C.; et al. Fluoroscopic
study of tumor motion due to breathing: Facilitating precise radi-
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
159
ation therapy for lung cancer patients. Med.Phys. 28:1850 – 6;
2001.
Ekberg, L.; Holmberg, O.; Wittgren, L.; et al. What margins
should be added to the clinical target volume in radiotherapy
treatment planning for lung cancer? Radiother. Oncol. 48:71–7;
1998.
Erridge, S.C.; Seppenwoolde, Y.; Muller, S.H.; et al. Portal imaging to assess set-up errors, tumor motion and tumor shrinkage
during conformal radiotherapy of non-small cell lung cancer. Radiother. Oncol. 66:75– 85; 2003.
Grills, I.S.; Yan, D.; Martinez, A.A.; et al. Potential for reduced
toxicity and dose escalation in the treatment of inoperable nonsmall-cell lung cancer: A comparison of intensity-modulated radiation therapy (IMRT), 3D conformal radiation, and elective nodal
irradiation. Int. J. Radiat. Oncol. Biol. Phys. 57:875–90, 2003.
Hanley, J.; Debois, M.M.; Mah, D.; et al. Deep inspiration breathhold technique for lung tumors: The potential value of target
immobilization and reduced lung density in dose escalation. Int. J.
Radiat. Oncol. Biol. Phys. 45:603–11; 1999.
Murphy, M.J.; Martin, D.; Whyte, R.; et al. The effectiveness of
breath-holding to stabilize lung and pancreas tumors during radiosurgery. Int. J. Radiat. Oncol. Biol. Phys. 53:475– 82; 2002.
Plathow, C.; Ley, S.; Fink, C.; et al. Analysis of intrathoracic
tumor mobility during whole breathing cycle by dynamic MRI. Int.
J. Radiat. Oncol. Biol. Phys. 59:952–9; 2004.
Ross, C.S.; Hussey, D.H.; Pennington, E.C.; et al. Analysis of
movement of intrathoracic neoplasms using ultrafast computerized
tomography. Int. J. Radiat. Oncol. Biol. Phys. 18:671–7;1990.
Seppenwoolde, Y.; Shirato, H.; Kitamura, K.; et al. Precise and
real-time measurement of 3D tumor motion in lung due to breathing and heartbeat, measured during radiotherapy. Int. J. Radiat.
Oncol. Biol. Phys. 53:822–34; 2002.
Shimizu, S.; Shirato, H.; Ogura, S.; et al. Detection of lung tumor
movement in real-time tumor-tracking radiotherapy. Int. J. Radiat.
Oncol. Biol. Phys. 51:304 –10; 2001.
Stevens, C.W.; Munden, R.F.; Forster, K.M.; et al. Respiratorydriven lung tumor motion is independent of tumor size, tumor
location, and pulmonary function. Int. J. Radiat. Oncol. Biol. Phys.
51:62– 8; 2001.
Engelsman, M.; Damen, E.M.; De Jaeger K.; et al. The effect of
breathing and set-up errors on the cumulative dose to a lung tumor.
Radiother. Oncol. 60:95–105; 2001.
Sixel, K.E.; Ruschin, M.; Tirona, R.; et al. Digital fluoroscopy to
quantify lung tumor motion: Potential for patient-specific planning
target volumes. Int. J. Radiat. Oncol. Biol. Phys. 57:717–23; 2003.
Liu, H.H.; Choi, B.; Zhang, J.; et al. Assessing respiration-induced
tumor motion and margin of internal target volume for imageguided radiotherapy of lung cancers. Int. J. Radiat. Oncol. Biol.
Phys. 63:S52; 2005.
Ling, C.C.; Yorke, E.; Amols, H.; et al. High-tech will improve
radiotherapy of NSCLC: A hypothesis waiting to be validated. Int.
J. Radiat. Oncol. Biol. Phys. 60:3–7; 2004.
Ramsey, C.R.; Scaperoth, D.; Arwood, D. Clinical efficacy of
respiratory gated conformal radiation therapy. Med. Dosim. 24:
115–9; 1999.
Keall, P.J.; Kini, V.R.; Vedam, S.S.; et al. Potential radiotherapy
improvements with respiratory gating. Australas. Phys. Eng. Sci.
Med. 25:1– 6; 2002.
Minohara, S.; Kanai, T.; Endo, M.; et al. Respiratory gated irradiation system for heavy-ion radiotherapy. Int. J. Radiat. Oncol.
Biol. Phys. 47:1097–103; 2000.
Ford, E.C.; Mageras, G.S.; Yorke, E.; et al. Evaluation of respiratory movement during gated radiotherapy using film and electronic portal imaging. Int. J. Radiat. Oncol. Biol. Phys. 52:522–31;
2002.
Ohara, K.; Okumura, T.; Akisada, M.; et al. Irradiation synchronized with respiration gate. Int. J. Radiat. Oncol. Biol. Phys.
17:853–7; 1989.
Vedam, S.S.; Keall, P.J.; Kini, V.R.; et al. Determining parameters
for respiration-gated radiotherapy. Med. Phys. 28:2139 – 46; 2001.
Hara, R.; Itami, J.; Kondo, T.; et al. Stereotactic single high dose
irradiation of lung tumors under respiratory gating. Radiother.
Oncol. 63:159 –163; 2002.
160
Medical Dosimetry
38. Wagman, R.; Yorke, E.; Giraud, P.; et al. Reproducibility of organ
position with respiratory gating for liver tumors: Use in doseescalation. Int. J. Radiat. Oncol. Biol. Phys. 55:659 – 68; 2003.
39. Shen, S.; Duan, J.; Fiveash, J.B.; et al. Validation of target volume
and position in respiratory gated CT planning and treatment. Med.
Phys. 30:3196 –205; 2003.
40. Duan, J.; Shen, S.; Fiveash, J.B.; et al. Dosimetric effect of
respiration-gated beam on IMRT delivery. Med. Phys. 30:2241–
52; 2003.
41. Starkschall, G.; Forster, K.M.; Kitamura, K.; et al. Correlation of
gross tumor volume excursion with potential benefits of respiratory
gating. Int. J. Radiat. Oncol. Biol. Phys. 60:1291–7; 2004.
42. Liu, H.H.; Koch, N.; Starkschall, G.; et al. Evaluation of internal
lung motion for respiratory-gated radiotherapy using MRI: Part
II-margin reduction of internal target volume. Int. J. Radiat. Oncol.
Biol. Phys. 60:1473– 83; 2004.
43. Ramsey, C.R. Implementation of a Video Based Respiratory Gating System For Radiation Therapy. Knoxville: University of Tennessee; 2000.
44. Berson, A.M.; Emery, R.; Rodriguez, L.; et al. Clinical experience
using respiratory gated radiation therapy: Comparison of freebreathing and breath-hold techniques. Int. J. Radiat. Oncol. Biol.
Phys. 60:419 –26; 2004.
45. Yorke, E.; Rosenzweig, K.E.; Wagman, R.; et al. Interfractional
anatomic variation in patients treated with respiration-gated radiotherapy. J. Appl. Clin. Med. Phys. 6:19 –32; 2005.
46. Hugo, G.D.; Agazaryan, N.; Solberg, T.D. The effects of tumor
motion on planning and delivery of respiratory-gated IMRT. Med.
Phys. 30:1052– 66; 2003.
47. Hugo, G.D.; Agazaryan, N.; Solberg, T.D. An evaluation of gating
window size, delivery method, and composite field dosimetry of
respiratory-gated IMRT. Med. Phys. 29:2517–25; 2002.
48. Dietrich, L.; Tucking, T.; Nill, S.; et al. Compensation for respiratory motion by gated radiotherapy: An experimental study. Phys.
Med. Biol. 50:2405–14; 2005.
49. Chapet, O.; Thomas, E.; Kessler, M.L.; et al. Esophagus sparing
with IMRT in lung tumor irradiation: An EUD-based optimization
technique. Int. J. Radiat. Oncol. Biol. Phys. 63:179 – 87; 2005.
50. Liu, H.H.; Wang, X.; Dong, L.; et al. Feasibility of sparing lung
and other thoracic structures with intensity-modulated radiotherapy for non-small-cell lung cancer. Int. J. Radiat. Oncol. Biol.
Phys. 58:1268 –79; 2004.
51. Mehta, M.; Scrimger, R.; Mackie, R.; et al. A new approach to
dose escalation in non-small-cell lung cancer. Int. J. Radiat. Oncol.
Biol. Phys. 49:23–33; 2001.
52. Murshed, H.; Liu, H.H.; Liao, Z.; et al. Dose and volume reduction
for normal lung using intensity-modulated radiotherapy for advanced-stage non-small-cell lung cancer. Int. J. Radiat. Oncol.
Biol. Phys. 58:1258 – 67; 2004.
53. Gambhir, S.S.; Czernin, J.; Schwimmer, J.; et al. A tabulated
summary of the FDG PET literature. J. Nucl. Med. 42:1S–93S;
2001.
54. Nehmeh, S.A.; Erdi, Y.E.; Ling, C.C.; et al. Effect of respiratory
gating on quantifying PET images of lung cancer. J. Nucl. Med.
43:876 – 81; 2002.
55. Nehmeh, S.A.; Erdi, Y.E.; Ling, C.C.; et al. Effect of respiratory
gating on reducing lung motion artifacts in PET imaging of lung
cancer. Med. Phys. 29:366 –71; 2002.
56. Nehmeh, S.A.; Erdi, Y.E.; Pan, T.; Four-dimensional (4D) PET/CT
imaging of the thorax. Med. Phys. 31:3179 – 86; 2004.
57. ICRU. ICRU Report 62. Prescribing, Recording and Reporting
Photon Beam Therapy (Supplement to ICRU Report 50). Bethesda,
MD: International Commission on Radiation Units and Measurements; 1999.
58. Ahn, S.; Yi, B.; Suh, Y.; et al. A feasibility study on the prediction
of tumour location in the lung from skin motion. Br. J. Radiol.
77:588 –96; 2004.
59. Hoisak, J.D.; Sixel, K.E.; Tirona, R.; et al. Correlation of lung
tumor motion with external surrogate indicators of respiration. Int.
J. Radiat. Oncol. Biol. Phys. 60:1298 –306; 2004.
60. Mageras, G.S.; Pevsner, A.; Yorke, E.D.; et al. Measurement of
lung tumor motion using respiration-correlated CT. Int. J. Radiat.
Oncol. Biol. Phys. 60:933– 41; 2004.
61. Tsunashima, Y.; Sakae, T.; Shioyama, Y.; et al. Correlation between the respiratory waveform measured using a respiratory sen-
Volume 31, Number 2, 2006
62.
63.
64.
65.
66.
67.
68.
69.
70.
71.
72.
73.
sor and 3D tumor motion in gated radiotherapy. Int. J. Radiat.
Oncol. Biol. Phys. 60:951– 8 ; 2004.
Kini, V.R.; Vedam, S.S.; Keall, P.J.; et al. Patient training in
respiratory-gated radiotherapy. Med Dosim. 28:7–11; 2003.
George, R.; Keall, P.J.; Chung, T.; et al. Does breathing training
reduce residual motion for respiratory-gated radiotherapy? In: Yi,
B.Y.; Ahn, S.D.; Choi, E.K.; et al. editors. The Use of Computers
in Radiation Therapy. Seoul, Korea: Jeong Publishing; 2004: 437–
441.
George, R.; Vedam, S.S.; Chung, T.D.; et al. The application of the
sinusoidal model to lung cancer patient respiratory motion. Med.
Phys. In press.
Senan, S.; De Ruysscher D.; Giraud, P.; et al., on behalf Of The
Radiotherapy Group Of The European Organization For R, Treatment Of C. Literature-based recommendations for treatment planning and execution in high-dose radiotherapy for lung cancer.
Radiother. Oncol. 71:139 – 46; 2004.
Bowden, P.; Fisher, R.; Mac Manus M.; et al. Measurement of lung
tumor volumes using three-dimensional computer planning software. Int. J. Radiat. Oncol. Biol. Phys. 53:566 –73; 2002.
Giraud, P.; Elles, S.; Helfre, S.; et al. Conformal radiotherapy for
lung cancer: Different delineation of the gross tumor volume
(GTV) by radiologists and radiation oncologists. Radiother. Oncol.
62:27–36; 2002.
Senan, S.; van Sornsen de Koste J.; Samson, M.; et al. Evaluation
of a target contouring protocol for 3D conformal radiotherapy in
non-small cell lung cancer. Radiother. Oncol. 53:247–55; 1999.
Van de Steene J.; Linthout, N.; de Mey J.; et al. Definition of gross
tumor volume in lung cancer: inter-observer variability. Radiother.
Oncol. 62:37– 49; 2002.
Steenbakkers R.J.; Duppen, J.C.; Fitton I.; et al. Observer variation
in target volume delineation of lung cancer related to radiation
oncologist-computer interaction: a ‘Big Brother’ evaluation. Radiother. Oncol. 77(2):182–90; 2005.
Bradley, J.; Byhardt, R.; Govindan, R.; et al. RTOG 0117: A phase
I/II dose intensification study using three-dimensional conformal
radiation therapy and concurrent chemotherapy for patients with
inoperable, non-small cell lung cancer. Available at: http://
www.rtog.org/members/protocols/L0117/0117.pdf. Accessed February 6, 2006.
Giraud, P.; Antoine, M.; Larrouy, A.; et al. Evaluation of microscopic tumor extension in non-small-cell lung cancer for threedimensional conformal radiotherapy planning. Int. J. Radiat. Oncol. Biol. Phys. 48:1015–24; 2000.
Kubo, H.D.; Wang, L. Compatibility of Varian 2100C gated operations with enhanced dynamic wedge and IMRT dose delivery.
Med. Phys. 27:1732– 8; 2000.
APPENDIX I. FLUOROSCOPIC TUMOR MOTION
EVALUATION PROCEDURES
Before procedure
1. Examine patient chart for information about tumor location.
Before imaging: At fluoroscope
1. Swing C-Arm into position using the controls provided to appropriately image the anatomy of interest.
2. Wear lead apron before initiating fluoro acquisition if operator is
in-room.
3. Instruct patient to be relaxed and breathe normally throughout the
entire procedure and especially during gated procedures.
4. Place Mag. Ring on the patient so that it is in the field of view of
the fluoroscopy C-Arm unit but is outside of the actual tumor
volume.
5. Fluoroscopy acquisition can be initiated by pressing and holding on
the foot pedal.
Before imaging: At RPM Respiratory gating system console
1. Connect the RPM Respiratory gating system for the FLUORO
mode
● Cables to be connected are appropriately labeled as FLUORO
and CT for fluoro and CT simulation, respectively.
2. Start RPM Respiratory Gating system by clicking on the icon on
the RPM workstation desktop.
Respiratory-gated IMRT ● P. KEALL et al
3. Click on Add Treatment Field (Name it as Fluoro NOT for Treatment)
4. By default, the system starts tracking. Verify grayed out “Track”
button.
5. After learning motion extents, the RPM system should start recording motion. If recording does not start automatically:
● Check to see if a marker block has been placed on patient’s
abdomen.
● Check to see that both markers are visible on RPM image
window and are within the field of view for entire breathing
cycle.
● Click on Stop and Track again and if necessary, click on the
Record button.
During imaging: At fluoroscope
1. Adjust CT C-Arm position until tumor is approximately in the
center of the display.
2. Press and Hold Fluoro Foot Pedal for 30 seconds.
3. Release Foot Pedal to Stop acquisition.
During imaging: At RPM Respiratory gating system console
1. Click Save on the RPM system menu bar.
2. Evaluate motion of anatomy of interest using the playback tools
provided in the RPM system
Use anatomic landmarks to estimate motion magnitude.
Evaluate correlation between external respiratory motion and
internal motion.
APPENDIX II. RETROSPECTIVE 4D CT IMAGING
PROCEDURE DOCUMENTATION
Equipment
1. Plastic infra-red reflective marker block.
2. Patient immobilization devices.
3. Ball bearings (BBs).
Before start of imaging study
1. Remove camera assembly from the wall and mount RPM camera
assembly onto the CT couch. Note that the camera only attaches to
the flat couch, which is required for radiotherapy.
2. Add BBs to patient on skin marks.
3. Check patient entry into bore and mark maximum extent of wingboard into PET bore- collision a potential issue.
Before imaging: at RPM respiratory gating system console
1. Add patient name.
2. Click on Add Treatment Field (Name it as CT Use for Treatment).
3. Click Select.
4. Click “Yes” when prompted to set this field as a reference field.
5. Adjust gating thresholds by moving the semi-circular bar on the left
hand side of the chart window. Typically, we use 30 –70% phase
range to image at exhale.
6. Just before x-ray on (Start) then hit record on RPM— only gives 6
minutes of recording time; therefore, restart before imaging.
Imaging: at Discovery LS console
1. Insert patient name- format LastName^FirstName.
2. Select Resp Gating protocol.
3. Acquire AP and Lateral scouts.
4. Ensure patient is aligned.
5. Ensure BBs are marked.
6. Insert cine duration " Breathing period from RPM # 1.0 seconds
(round up).
7. From tab Thickness/Speed update Cine time between images "
Breathing period/10 (round down).
After imaging: at RPM respiratory gating system console
1. Click on Stop.
2. Add exam number and series number from CT scanner.
3. Click on Save.
4. Click on “Yes” when prompted to save data as new session.
5. Close RPM interface.
161
After imaging: at advantage 4D CT workstation
1. Select patient, and axial series.
2. Start advantage 4D.
3. Check that default selected RPM file by id numbers (default
should be correct but always check).
4. In 4D review add series number “300”.
5. Align X to tumor Centroid.
6. Right click to assess motion in movie.
7. Cursor on phase % — step through phases with left/right arrow
keys.
8. Choose phases to use for treatment plan.
9. IMPT: Phase(s) sent to Pinnacle should match those from RPM
session.
10. In export, click on MIP and Average-label MIP series 200.
11. If desired, can contour in Fusion.
12. If desired, need to convert contours to DICOM in Advantage sim,
output¡ save plan.
13. In series, select images to send to treatment planning system.
APPENDIX III. PROSPECTIVE GATED CT IMAGING
PROCEDURE DOCUMENTATION
Before imaging: at RPM respiratory gating system console
1. Switch cable connections to enable CT Simulation.
2. Select current patient name.
3. Click on Add Treatment Field (Name it as CT Use for Treatment)
4. Click Select.
5. Click “Yes” when prompted to set this field as a reference field.
6. By default, the system starts tracking. Verify grayed out “Track”
button.
7. After learning motion extents, the RPM system should start recording motion. If recording does not start automatically:
● Check to see if a marker block has been placed on patient’s
abdomen.
● Check to see that both markers are visible on RPM image
window and are within the field of view for entire breathing
cycle.
8. Click on Stop and Track again and if necessary, click on the
Record button.
9. Click on Enable Gating.
10. Adjust gating thresholds by moving the semi-circular bar on the
left hand side of the chart window (green shade should fall around
exhale portion of the respiratory motion trace).
11. Confirm with therapist that RPM system is setup for gated CT
scan acquisition.
12. Perform gated CT scan.
During Imaging: at PQ 5000 CT console
1. Select protocol and take pilot. The appropriate protocol should be
selected from the axial protocols, which are displayed when Spiral
Onc is not highlighted.
2. Ensure slice thickness and index are set to 3 mm.
3. Select scan limits and save.
4. Under Select Scanning Mode, check that Axial, Multi,
Load’N’Go, and ADS are highlighted.
5. In System Setup, turn Injector to On.
6. Check that ELTP displays Injector On above Help.
7. Press Move Couch and ready for scan.
8. In Varian RPM Gating software, select Enable Gating.
9. Before starting scan wait and ask patient to relax, and breathe
normally. Explain that there will be intermittent noise (this noise
is the beam on/off and has been observed to disturb patient
breathing patterns), and that the couch will also periodically move
then stop.
10. Push CT scanner START button.
11. Note that the first scan is not necessarily synchronized with the
respiratory signal. Furthermore, should the scanner time out for
any reason, the injector port will need to be turned on again, and
the first scan after restarting will not necessarily be synchronized
with the respiratory signal.
12. Observe that the triggering of the CT scanner occurs at the “CT
delay value” before the breathing trace enters the gating limits,
and that the CT scanner slice acquisition begins as the breathing
trace enters the gating limits. Allow some tolerance if the patient
cycle-to-cycle breathing reproducibility is poor.
162
Medical Dosimetry
Volume 31, Number 2, 2006
13. When the scan is complete, put the CT scanner back in spiral
mode for the next CT simulation.
7.
APPENDIX IV. GATED TREATMENT DELIVERY
PROCEDURE DOCUMENTATION—TREATMENT SESSION
In treatment room
1. Check that Marker Block has correct patient name.
2. Place Marker Block on patient’s chest with silver dots facing
camera. The sagittal laser should not cover the silver dots.
In console room
1. On Gating Board, turn key to Gating Enabled.
2. Start Gating program (Gating).
3. Select Patient.
4. Select Session.
5. Hit Stop.
6. Hit Track and wait until the periodicity indicator falls to half or
less of the meter (this may occur automatically). If tracking does
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
not occur, either obscure reflective surfaces seen on the camera
(e.g., belt, watch, etc.) and/or dim the treatment room lights.
Hit Record. Ensure that part on breathing trace is within gating
window.
Hit Enable Gating on Gating Computer.
On Linac console, set treatment field.
Increase treatment time by $4.
Increase dose rate to 600.
Turn key ON (Linac console) and hit the Beam ON button. Note:
for EPID images, the Beam On button should be depressed when
the patient’s breathing trace starts to enter the gating window,
otherwise, an interlock will occur.
Treat next beams.
Hit STOP.
Exit. (Do not save data as a new session.)
Log out of Gating Computer.
Turn key on Gating Board to Gating Disable.
In treatment room
1. Place Marker Block in bag for subsequent sessions.