Acknowledgements
Methods to manage respiratory motion
in radiation treatment
William Beaumont Hospital , Royal Oak, MI
Remouchamps, Letts, Yan, Kestin, Vicini, Martinez
Memorial Sloan Kettering Cancer Center, NY, NY
G. Mageras, E. Yorke, E. Ford
Oakwood Hospital, Dearborn, MI
O. Salazar
John Wong
William Beaumont Hospital
Royal Oak, USA
Princess Margaret Hospital, Toronto,Canada
D. Jaffray, M. Sharpe
NCI (USA) and Elekta Inc.
Respiratory Trace by Spirometry
Respiratory Motion
7
•
•
•
•
•
Quiet breathing is an involuntary action
Periodic in response to chemo-receptors, mainly CO2
Breathing cycle ~ 14 breathes per min
~ 4 sec and 400 – 500 cc / breath
Diaphragmatic excursion :
– > 1 – 2 cm quiet; > 4 cm voluntary deep breathing
• Clinical Sites: lung ca, liver ca, pancreas ca,
breast, lymphoma
Mechanics of Breathing
Time
6
Maximum
inspiratory
capacity
5
Liters
4
3 Tidal volume
2
1
Vital
capacity
Total lung
capacity
Functional
residual capacity
Residual
volume
0
Mechanics of Breathing
Inspiration :
mostly due to
diaphragmatic contraction
O
O
Expiration:
Passive relaxation
O
O
O
DIAPHRAGM
THORAX
O
1
Respiration motion is non-uniform in 3D
A. Breath-hold 1
B. Breath-hold 2
B-A
Deep inspiration breath-hold
• immobilization
• local cardiac motion
A. End Normal
Expiration
B-A
B. End Normal
Inspiration
Methods to manage breathing motion
• Gating (MSKCC) :
– turn radiation on/off at a specific breathing phase
• Tracking (MCV) :
– synchronize beam motion with breathing motion
• Immobilization :
– voluntary deep inspiration breath-hold (MSKCC)
– active breathing control (WBH)
• Optimize free-breathing PTV (UM, NKI, WBH)
Respiratory Gating System:
Varian Real-time Position Management (RPM)
Components:
Managing Respiratory Motion:
Surrogate and Margin
• Validity of the surrogate signal to breathing motion
– Gating/Tracking : Reflective external body
markers
– Breath-hold : lung volumes with spirometry
• Margin determination:
– Identify the margin achievable with the method
• fluoroscopy, CT
– Match the appropriate method to resource
available, patient acceptance and clinical goal
RPM - Record/Playback
RPM - Record/Playback
• Initial tracking determines min/
max marker position.
• Recorded fluoroscopy is
synchronized with the external
marker position.
CCD
• Reflective external
marker placed on
abdomen or chest
Breathing monitor
• Infrared illuminator/
CCD camera
• Workstation to
process signals &
generate trigger for
CT/simulator/linac
On/off
Control workstation
Treatment machine
Marker position vs time
• User specifies a treatment
point in breathing cycle via
threshold levels (amplitude
based).
• Bottom trace indicates
beam enable intervals.
• More recent: phase-based
gating option
2
Initial clinical experience with gating
Effect of instruction on patient breathing
Example Patient Breathing Signal
• Patients given recorded instruction (“breathe in, breathe out”)
• Instruction affects breathing pattern in 2 ways:
• Changes in patient breathing
can affect gating performance
• At simulation, thresholds set
to gate at end expiration.
• At treatment, irregular
breathing can cause beam
enable at unintended intervals.
183157 lung ap 1
Treatment session
Marker vs Time
3
No Instruct
2
Marker Position (cm)
Fluoroscopy session
183157 lung ap 10
Larger
amplitude
1
0
3
0
5
10
15
20
25
30
Less
variation
in peak
position
With Instruct
2
1
0
0
5
10
15
20
25
30
Time (s)
External monitor vs internal anatomic motion:
Automatic tracking of lung anatomy in fluoroscopy
Example Diaphragm / External Marker Correlation
Fluoroscopy
No Instruction
2.0
Diaphragm
Marker
6.5
1.5
1.0
Diaphragm Position (cm)
Diaphragm Position (cm)
1.5
0.5
0.0
0.0
2.5
0.5
1.0
1.5
With Instruction
2.0
6.0
1.0
5.52.0
0.5
5.0
1.5
0.0
4.5
100
1.0
Marker Position (cm)
2.5
200
0.5
300
400
Time (seconds x10)
0.0
0.0
0.5
1.0
1.5
2.0
Marker Position (cm)
Example phase delay in diaphragm motion
Diaphragm
0.5
0.0
0.7s
0.0
0
10
20
30
0.7s delay applied
to marker waveform
40
Diaphragm Position (cm)
Time (s)
1.0
1.0
0.5
0.5
0.0
0.0
0.5
Marker Position (cm)
1.0
0.0
0.0
0.5
Marker Position (cm)
1.0
Variability, SD (mm)
1.0
0.5
Marker Position (cm)
Diaphragm Position (cm)
Diaphragm Variability (SD) :
Fluoro vs Treatment
1.5
Marker
1.0
Fluoro: No Gate
Fluoro: Gate
Tx Localization Film
10
8
6.9±2.1 mm
6
4
2.8±1.0 mm
2.6±1.7 mm
2
0
1
2
3
4
5
6
7
8
Patient
3
Comparison unsynchronized vs RTCT
RPM – Respiratory Triggered CT (RTCT)
• RTCT:
– Acquisition in axial
mode
– Each gate triggers 1
CT slice
Inspiration
Free Breathing
Expiration #2
Expiration #1
CT Reproducibility – other organs
• Average S-I shifts for all organs:
– E-I shift: 12.8 mm (range: 3.0 - 29.2 mm)
– E-E shift: 2.0 mm (range: 0.0 - 6.4 mm)
Diaphragm Reproducibility
• 10 liver patients simulated, 8 treated (177 treatments)
with gating at end-expiration
20
18
Displacement (mm)
16
Fluoro data
14
12
10
8
6
CT data
Avg. △S-I
(mm)
Gated
Ungated
Avg. △S-I
(mm)
E-E
E-I
R Diaphragm
3.9
14.7
R Diaphragm
2.2
11.5
L Diaphragm
3.8
21.4
4
2
0
Liver
R Kidney
L Kidney
Sup-inf, E-I
Spleen
GTV
Sup-inf, E-E
Film-based verification of lung position/inflation during gating
Gated film / EPI: respiration motion variation
Diaphragm-vertebral displacement relative to DRR
Patient #1
4
2
0
0
Number
2
4
insp
2
0
#3
4
#6
0
#7
4
2
2
0
0
#4
mean
4
insp
2
#8
4
2
0
0
Gated Localization Film
Number
#2
4
DRR from Exhale CT
Patient #5
4
2
-10
Superior
-5
0
5
10
Displacement (mm) Inferior
Lung Treatment
-10
Superior
-5
0
5
10
Displacement (mm)
Inferior
Liver Treatment
4
Managing Respiration Motion:
Respiration Correlated CT (RCCT)
Respiratory gated treatment summary
Gated RT:
•
•
•
•
•
•
10 patients treated to date (2 lung, 8 liver)
8 patients gated at end exhale, 2 at end inhale
Preserve patient’s comfort at free breathing
Regular breathing important, instruction helps
Setup needs to be characterized for systematic correction
Breathing motion reduced to 5mm (exhale); PTV ~ 10mm
or unchanged
• Treatment session times increased ~5min, mostly due to
decreased beam duty cycle
Standard
Free
breathing
• Respiration-triggered CT Î images at
only 1 phase, acquisition times 4-5x longer
• Cannot determine free-breathing PTV for
ungated treatment
Respiration correlated CT:
• Adapted from Kachelriess & Kalender
1998
• “4D” imaging – 3D images at 8-10 phases
Î treatment volume better approximates
target
RCCT – Acquisition
Resp.
triggered
End expiration
RCCT – Retrospective correlation
Slow table: Pitch 0.5; 0.5mm spacing (0.5s)
5mm
Time or z
3mm thick
time
0
5 0
1 0 0
1 5 0
Spiral CT trajectory
X
A x is
T it le
CT slices
2 0 0
5 0
0
1s
5 0
1 0 0
X
Varian RPM
system
A x is
1 5 0
2 0 0
5 0
T it le
Slices at end exhale
Slices at end inhale
Slices at intermediate phase
Respiration trace Î
Time stamp each CT slice with phase
RCTC : Phantom Study
RTTC: Phantom study
Static
RTCT
0.0
0.6
1.3
1.9
2.5
3.1
3.8
4.4
5.0
5.7
Moving
RCCT
Number of unique phases is a function of:
respiratory period, CT rotation period, fraction of rotation information
5
RCCT - Treatment planning:
RCCT – Summary
Internal target volume definition
Intra-fractional motion
GTV SI
0
A
P
Position (cm)
-1
GTV AP
0
ITV ungated
-1
0
Diaphragm
-1
Gate
1
RPM Trace
• Potential benefits to RT planning:
– Intra-fx motion info Î improve PTV defintion for
breathing motion
– Deformable registration models Î dose to moving
organs
– Simulate errors for standard CT & RT Î what is effect
on dose to organs for std RT, how much will RCCT
benefit RT?
• RTTC :
– PQ5000: 8-10 phases, 5mm spacing, 1s/slice, 9 cm scan
0
0
1
2
3
4
5
Time (s)
ITV gated
Cine CT – Patient 1
10 phases @ 0.5s
Clinac 23EX mounted with dual X-ray sources and flat panel
X-ray sensors
Fig １
• 4-slice CT: 30cm scan, 2.5mm
spacing, 0.5s/slice
• Allow validation of surrogate
signal for gating or tracking
Y. Takai, 1 et al, 1Department of Radiation Oncology, School of Medicine,
Tohoku University, Sendai, Japan, 2Varian Medical Systems, CA, USA
Image processing courtesy Tinsu Pan
Fig 4
Real-time tracking of a gold seed
in lung cancer with DFFP system
Fig 6
Tracking virtual
respiratory motion
(one cycle)
End-exhale
End-inhale
6
Management of respiratory motion:
Breath-hold techniques
DIBH - Patient Setup at MSKCC
• Breath-hold is immobilization; and reproducible if the
breathing pattern does not deviate significantly
• End inspiration or deep inspiration to increase separation
of thoracic contents
• Voluntary Breath-hold Techniques
– MSKCC : instruction based on spirometry
– Cross Cancer Center : instruction without monitoring
signal
• Active Breathing Control/Coordinator
– Beaumont : digital spirometry linked to a computer
controlled valve
(a) Normal
breathing
(b) ABC
(c) ABC
30 min. later
DIBH Summary
• Over 20 patients treated since 2/98 at MSKCC;
breath-hold duration of 10 sec
• No margin reduction at present
• Dose increase from 69.4 to 87.9 Gy (ave.) possible
with NTCP <25%
• 3-5 mm margin seems possible (MSKCC, Beaumont)
• Simulation and treatment times ~ 1.5X longer
• Compliance hurdle at MSKCC:
– ~1/2 of patients unable to perform procedure
– patient fatigue
(Rosenzweig ‘00)
Active Breathing Control (ABC)
• ABC is a technique to immobilize respiratory motion
repeatedly and reproducibly for a period of time that can be
comfortably tolerated by the patient
• Moderate deep inspiration breath-hold (mDIBH) at 75% to
80% of maximum inspiration capacity to
– displace of thoracic contents
– avoid tiring the patient
• Patient selection; long breath-hold (>15 sec) is desirable
• Therapists involve in verbal coaching
ABC Apparatus
Valve
Flow
Meter
Mouthpiece
7
ABC at Beaumont
Visual display of breathing motion
ABC Margin Determination : CT Study Protocol
• CT protocol to set PTV for
breathing motion
– 2 scans at mDIBH
– 1 end inspiration (NI), 1
end expiration (NE)
– repeat 1 mDIBH 1 to 2
weeks later
• Left sided breast patients as
surrogate for evaluation of
lung immobilization
• Breath-hold duration based
on individual patient
Segmental - Regional analysis of left and right lung separately
• Repeat (intra and inter-fraction) CT scans registered using the
bony landmark.
• Lungs and main bronchi are contoured as surrogates for
internal thoracic contents.
Intra- and Inter-fraction Lung Reproducibility:
Distance-to-agreement (cm)
0.7
0.6
0.35
0.3
0.0
0.0
• Surrogates for 3D distance-to-agreement (DTA) measurements
– Lung surface for chest wall motion (~ 300,000 points)
– trachea and main bronchus alignments show results similar
with lung surface data
8
Lung surface distance to agreement : mean (SD) in cm
Lung surface distance to agreement : mean (SD) in cm
between 2 registered mDIBH intra-fraction ABC Scans
between 2 registered mDIBH intra-fraction ABC Scans
INTRA-FRACTION
(Same day)
Full
Lung
Region I
II
III
IV
V
Region VI
(Bottom
(20%) (20%) (20%) (20%) (Top 10%)
10%)
Left
0.19
Lung (0.32)
0.43
(0.56)
0.25
0.15 0.14 0.14
(0.38) (0.20) (0.17) (0.17)
0.14
(0.17)
Right 0.22
Lung (0.33)
0.44
(0.54)
0.35
0.17 0.14 0.13
(0.46) (0.20) (0.16) (0.15)
0.15
(0.20)
Alpha
Cradle
Left
0.11
Lung (0.12)
0.17
(0.15)
0.15
0.10 0.09 0.08
(0.14) (0.09) (0.08) (0.08)
0.09
(0.07)
14 patients
Right 0.10
Lung (0.11)
0.10
(0.10)
0.12
0.09 0.09 0.08
(0.13) (0.08) (0.08) (0.08)
0.13
(0.09)
No Cradle
7 patients
ABC Margin Studies : Summary
• The lung surface is well immobilized with ABC at mDIBH
– 3 mm margin for superior 7/10th of lung
– 6 mm margin for inferior 3/10th of lung, (diaphragmatic
regions)
• Similar results observed with the trachea/carina and main
bronchi; maybe applicable for internals of the lung
• Setup compromises breathing immoblization with ABC
• mDIBH is highly reproducible:
– minimizes the variation in breathing pattern
– expanded lung volume less sensitive to positional variation
Free Breathing
Alpha
Cradle
Immobilization
INTRAFRACTION
(Same day)
14 patients
INTERFRACTION
(2-3 weeks
later)
8 patients
Full
Lung
Region I
II
(Bottom
(20% )
10%)
III
(20%)
IV
V
Region VI
(20%) (20%) (Top 10%)
Left
0.11
Lung (0.12)
0.17
(0.15)
0.15
(0.14)
0.10
0.09 0.08
(0.09) (0.08) (0.08)
0.09
(0.07)
Right 0.10
Lung (0.11)
0.10
(0.10)
0.12
(0.13)
0.09
0.09 0.08
(0.08) (0.08) (0.08)
0.13
(0.09)
Left
0.13
Lung (0.15)
0.17
(0.15)
0.17
(0.20)
0.11
0.09 0.10
(0.12) (0.09) (0.09)
0.15
(0.10)
Right 0.14
Lung (0.16)
0.19
(0.18)
0.17
(0.20)
0.12
0.11 0.12
(0.09) (0.10) (0.11)
0.16
(0.12)
ABC : Clinical Implementation
• IMRT for left sided breast --- mDIBH to reduce heart dose
– >50 patients CT planning and margin studies at
Beaumont, Royal Marsden
– 20 treated with IMRT at Beaumont
• Lung --- tumor immobilization
– Royal Marsden (UK), Mount Vernon (UK), Oakwood
Hospital, University of Colorado, Beaumont …..
– patients selected to maintain breath-hold >15s
– > 30 patients CT studied; > 20 treated with SRS
• Liver --- > 50 patients treated at Oakwood, U of Michigan
mDIBH
Treatment Procedure
CT
DRR
• Treatment slot of 20 min
• Patient positioned during
free breathing
• Field matches tattoo during
FB
• ~ 5s mDIBH to set anterior
SSD
• Shift / gantry rotation
during FB
• IMRT/ABC complete in 15
min
9
Breathing Trace - Daily Treatment
Coaching (Karaoke) by the Therapists
2.5
Medial
Set up
Lateral
2
1.5
1
0.5
0
EPI
-0.5
0
100
200
EPI
300
EPI
400
EPI
500
600
Time (seconds)
Left Sided Breast Treatment
with ABC at mDIBH
Electronic Portal Image
Prescription DRR/Sim film
• 20 patients treated to date
• Average breath-hold duration :
– 20 sec at 1.8 liters, 2 per tangents
• Heart V(30) :
– free-breathing 3.5% (1% - 10%); ABC 0.1% (0% - 0.6%)
• Lung V(20):
– free-breathing 11.6% (8% - 18%); ABC 10.4% (8% - 14%)
Intra-fraction reproducibility:
Difference in positioning errors between 2 BH’s (mm)
MEDIAL
N
Transverse
Radiation Ablation Treatment with ABC and Body Frame
LATERAL
Cranio-caudal
Transverse
Cranio-caudal
Mean
SD
Mean
SD
Mean
SD
Mean
SD
1.3
1.0
2.0
2.5
1.3
1.0
1.8
1.5
11
Combined Set up and Breath-hold errors (in mm) –
(11 patients, 255 to 268 EPIs per beam, 1054 EPIs)
Medial BH1
Medial BH2
Lateral BH1
Lateral BH2
Mean
SD
Mean
SD
Mean
SD
Mean
SD
Transverse
1.3
2.5
1.4
2.3
1.9
2.3
2.3
2.4
Cranio-caudal
2.6
3.0
2.3
2.9
2.5
3.1
3.1
3.2
Rotation
1.1
1.1
1.2
1.0
1.3
1.0
1.0
1.0
Courtesy of Dr. Omar Salazar
10
Radio-ablation of Lung Tumors
PTV dose 70%: 10 Gy/fraction /week
Ave.
Equiv.
Irradiaed Sphere
Vol (cc)
(cc)
Vol
Range
(cc)
Mean
Dose in
PTV (Gy)
3.5
2 – 182
51
37
140
3.3
5.2
4 – 490
55
36
146
5.3
Category
n
ABC-Lung
14
42
primary
Non-ABC
Lung
primary
9
17
4
46
Courtesy of Dr. Omar Salazar
• ABC procedures well accepted by selected patients
and staff
• Accurate treatment reproducibility
• Reductions in the heart dose for left sided breast RT
• Dose escalation for radio-ablation of lung tumors
A Word of Caution - Dosimetric Margin
• Penumbra causes
collateral normal tissue
irradiation.
• Typical distance between
95-50% isodose:
– ~10mm in water
– ~21mm in lung
1.0
18MV
water
0.8
Relative Dose
ABC Summary
lung
0.6
10x10cm2
100cm SSD
5cm depth
0.4
0.2
0.0
-10
-5
0
5
10
Distance from Central Axis [cm]
No inhomogenity correction
1 cm PTV, 8 mm aperture offset
110
105
95
50
20
Superposition calculation
1 cm PTV, 8 mm aperture offset
110
105
95
50
20
11
Superposition calculation; 4 mm aperture offset;
Sharp beam: 15% fluence increase to 15 mm internal rind
110
105
95
50
20
Conclusions
• RCCT facilitates organ motion evaluation
• Gating and ABC are both viable options to reducing margin for
respiratory motion
• ABC:
– pro : active immobilization, highly reproducible
– con : not tolerated by all patient
• Gating:
– pro : patient comfort
– con : larger margin, reduced duty cycle (tracking solution)
• Long term studies required – change of motion
• A combination approach seems most appropriate
12