Margins in Radiation Therapy
DATE: Tuesday, July 29, 2008
START TIME: 07:30 AM
END TIME: 08:25AM
LOCATION: Auditorium C
Dan Low
Dale Litzenberg
Washington University
University of Michigan
Abstract
Conformal radiation therapy has historically used margins to account for geometrical
uncertainties in the position of a target volume. The margins, in their simplest form,
are simply expansions to the shape of a treatment beam, to ensure that dosimetric
planning criteria are met in the presence of inter- and intra-fraction setup variations.
Historically, the size of the margin in a given treatment site was difficult to determine
due to the available technology and the time and effort required to obtaining
accurate data.
Consequently, margins were estimated to accommodate a
population of patients. As new technologies have emerged, target volume position
errors have become easier to measure, their accuracy has increased, and the
measurements can be made much more frequently. As the quantity and quality of
data has increased for patient populations, and even for individual patients, the
conceptual basis of employing margins has evolved. Strategies for ensuring
dosimetric coverage may now be individualized to a specific patient’s geometric
uncertainty characteristics with customized margins, or they may incorporate
geometric correction based on predefined action levels. Other strategies may
incorporate continuous monitoring to gate or modify the beam. And finally, other
strategies seek to eliminate margins by including the estimated geometrical
uncertainty into the development of the dose distribution.
Educational Objectives
• To motivate the need for margins and review ICRU
definitions
• To provide an educational review of the technologies
and methods of measuring target volume positioning
errors.
• To review methods of determining population margins
from measured data.
• To review corrective and intervention strategies for
patients with individualized margins.
• To briefly review planning strategies which seek to
eliminate margins.
Disclaimer
The content of this presentation is for general
educational purposes only.
The mention of trade names, commercial products
does not imply an endorsement on the part of AAPM
or the presenters.
The views, opinions and comments made in this
refresher course are those of the presenters and not
necessarily those of AAPM.
Conflict of Interest
DA Low:
Tomotherapy
Varian Medical Systems
DW Litzenberg:
Calypso Medical Technologies
Outline
I.
The Need for Margins
II.
Treatment Site Considerations
III. Simulation Imaging Modalities
IV. Examples of Motion
V.
Treatment Planning
VI. In-room Guidance and Correction Strategies
VII. Off-line Adaptive Stratagies
VIII. Planning without margins
Outline
I.
The Need for Margins
II.
Treatment Site Considerations
III. Simulation Imaging Modalities
IV. Examples of Motion
V.
Treatment Planning
VI. In-room Guidance and Correction Strategies
VII. Off-line Adaptive Stratagies
VIII. Planning without margins
I. The Need for Margins
A. Systematic and random errors
B. Inter- and intra-fraction motion
C. Dosimetric criteria
D. Population and individualized margins
Systematic and Random Errors
Σ small
σ small
Σ small
σ large
Σ large
σ small
Σ large
σ large
Inter- and Intra-Fraction Positioning Errors
Inter-Fraction:
Variations caused by uncertainty in
reproducing target volume position at
isocenter each time patient is placed on
treatment table
Intra-Fraction:
Variations in position while patient is on
treatment table
Each may have Systematic and Random Errors
Inter-Fraction Motion and Deformation
Inter-Fraction Motion and Deformation
Systematic shift due to
distention on planning
CT
Importance of Image Guidance
N=127, patients treated to 78 Gy between 1993 and 1998
No daily image guidance
Outcomes analyzed by rectal distention at the time of simulation
MDACC: de Crevoisier et al., IJROBP, 62, 965-973, 2004
What was Missing?
• Method for directly measuring
prostate position
• On-board CT
– CBCT
• Kilovoltage or Megavoltage
– Helical Megavoltage CT
• Markers
–
–
–
–
Imbedded markers
Planar imaging
On-board CT
Radiofrequency
Dosimetric Coverage
Prescribed
Dose Level
(eg. 95%)
m
Dose
“Tumor”
m
Underdose
x
Population-Based Motion
Frequency
1.0
0.5
0.0
-4
-2
0
Position (cm)
2
4
Patient Specific Motion
Frequency
1.0
0.5
0.0
-4
-2
0
Position (cm)
2
4
Patient Specific Margin
Σ=0
Frequency
PTV margin = Setup + Inter + Intra-fraction
Estimate Σ
And correct
Position (cm)
Ten Haken
Ten Haken
Outline
I.
The Need for Margins
II.
Treatment Site Considerations
III. Simulation Imaging Modalities
IV. Examples of Motion
V.
Treatment Planning
VI. In-room Guidance and Correction Strategies
VII. Off-line Adaptive Strategies
VIII. Planning without margins
II. Treatment Site Considerations
A. Treatment Position
B. Immobilization & Localization
Accuracy of Localization
Patient Position
Motion
Management
Immobilization
Measurement
Correction
Localization
Simulation &
Planning
Treatment Position
1997: No in-room soft tissue guidance available,
Little to no evidence of respiratory motion.
Zelefsky, IJROBP, 1997;37:13-19.
Treatment Position
Intrafraction Motion: Fluoroscopy
Position (cm)
Supine Positioning Results
4
2
2
0
-2
-2
-4
Initial Position
7
8
9
10
Patient #
Maximum
+/- 1σ
Average
Minimum
Ave
LR
AP
IS
Position (cm)
Supine Positioning Results
4
LR
AP
IS
2
0
-2
-4
Initial Position
Position (cm)
7
8
9
10
Ave
10
Ave
Patient #
4
2
0
-2
-4
Final Position
7
8
9
Patient #
Supine vs Prone Treatment Position
• Respiratory motion reduced when supine
Dawson, IJROBP, 2000
Kitamura, IJROBP, 2002
• Significantly less dose to small bowel,
bladder and rectum when supine
Bayley, Radiother & Oncol, 2004
• ~ 95% treated supine
ASTRO IGRT Symposium, 2006
Treatment Position
• Steenbakkers RJHM, Duppen JC, Betgen A, et al. Impact of knee support and shape of tabletop on
rectum and prostate position. International Journal of Radiation Oncology*Biology*Physics
2004;60:1364-1372.
• Adli M, Mayr NA, Kaiser HS, et al. Does prone positioning reduce small bowel dose in pelvic
radiation with intensity-modulated radiotherapy for gynecologic cancer? International Journal of
Radiation Oncology*Biology*Physics 2003;57:230-238.
• Algan Ö, Fowble B, McNeeley S, et al. Use of the Prone Position in Radiation Treatment for Women
With Early Stage Breast Cancer. International Journal of Radiation Oncology*Biology*Physics
1998;40:1137-1140.
• Liu B, Lerma FA, Patel S, et al. Dosimetric effects of the prone and supine positions on image
guided localized prostate cancer radiotherapy. Radiotherapy and Oncology, 2008; 88(1):67-76.
• Stroom JC, Koper PCM, Korevaaar GA, et al. Internal organ motion in prostate cancer patients
treated in prone and supine treatment position. Radiotherapy and Oncology 1999;51:237-248.
• Verhey LJ. Immobilizing and positioning patients for radiotherapy. Seminars in Radiation Oncology
1995;5:100-114.
• Dawson LA, Litzenberg DW, Brock KK, et al. A comparison of ventilatory prostate movement in four
treatment positions. International Journal of Radiation Oncology*Biology*Physics 2000;48:319-323.
• Zelefsky MJ, Happersett L, Leibel SA, et al. The effect of treatment positioning on normal tissue
dose in patients with prostate cancer treated with three-dimensional conformal radiotherapy.
International Journal of Radiation Oncology*Biology*Physics 1997;37:13-19.
Immobilization
• Fiorino C, Reni M, Bolognesi A, et al. Set-up error in supine-positioned patients immobilized with two
different modalities during conformal radiotherapy of prostate cancer. Radiotherapy and Oncology
1998;49:133-141.
• Halperin R, Roa W, Field M, et al. Setup reproducibility in radiation therapy for lung cancer: a
comparison between T-bar and expanded foam immobilization devices. International Journal of
Radiation Oncology*Biology*Physics 1999;43:211-216.
• Hanley J, Debois MM, Mah D, et al. Deep inspiration breath-hold technique for lung tumors: the
potential value of target immobilization and reduced lung density in dose escalation. International
Journal of Radiation Oncology*Biology*Physics 1999;45:603-611.
• Wong JW, Sharpe MB, Jaffray DA, et al. The use of active breathing control (ABC) to reduce margin
for breathing motion. International Journal of Radiation Oncology*Biology*Physics 1999;44:911-919.
• Barnes EA, Murray BR, Robinson DM, et al. Dosimetric evaluation of lung tumor immobilization using
breath hold at deep inspiration. International Journal of Radiation Oncology*Biology*Physics
2001;50:1091-1098.
• D'Amico AV, Manola J, Loffredo M, et al. A practical method to achieve prostate gland immobilization
and target verification for daily treatment. International Journal of Radiation Oncology*Biology*Physics
2001;51:1431-1436.
• Gilbeau L, Octave-Prignot M, Loncol T, et al. Comparison of setup accuracy of three different
thermoplastic masks for the treatment of brain and head and neck tumors. Radiotherapy and Oncology
2001;58:155-162.
• Negoro Y, Nagata Y, Aoki T, et al. The effectiveness of an immobilization device in conformal
radiotherapy for lung tumor: reduction of respiratory tumor movement and evaluation of the daily setup
accuracy. International Journal of Radiation Oncology*Biology*Physics 2001;50:889-898.
• Bayley AJ, Giovinazzo J, Rakaric P, et al. Med-Tek type-S immobilization system: calculating the setup margin for radiotherapy of head and neck cancer patients. International Journal of Radiation
Oncology*Biology*Physics 2002;54:289-289.
• Fuss M, Salter BJ, Cheek D, et al. Repositioning accuracy of a commercially available thermoplastic
mask system. Radiotherapy and Oncology 2004;71:339-345.
Outline
I.
The Need for Margins
II.
Treatment Site Considerations
III. Simulation Imaging Modalities
IV. Examples of Motion
V.
Treatment Planning
VI. In-room Guidance and Correction Strategies
VII. Off-line Adaptive Strategies
VIII. Planning without margins
Simulation Imaging Modality
A. What you see
1. Computed Tomography
2. Magnetic Resonance
3. Positron-Emission Tomography
B. What you contour
K Langen
PROSTATE DELINEATION:
DIAGNOSTIC KV CT vs ABSOLUTE TRUTH
Radiotherapy and Oncology, 85(2), 239-246, 2007
Visible Human Project - Male
6 radiation oncologists, 120 delineations on KV CTs
PROSTATE DELINEATION:
DIAGNOSTIC KV CT vs ABSOLUTE TRUTH
Radiotherapy and Oncology, 85(2), 239-246, 2007
Visible Human Project - Male
6 radiation oncologists, 120 delineations on KV CTs
CT volumes on average 30% larger than true
volume
CT volumes encompassed, on average, 84% of the
true volume.
Extended too anteriorly
Missed posteriorly
Simulation Imaging Modality
• 15 brain cases
• 1 neuro-radiologist
• 1 radiation oncologist
• Contours on CT, MR, registered CT-MR
Ten Haken, Radiotherapy and Oncology, 25, 121-133, 1992.
Simulation Imaging Modality
GTV
CTV = GTV + 2 cm
14% CT only
56% Both
30% MR only
Adding margin reduces impact
“… the degree of inter-observer variation in volume definition is on the order of the
magnitude of differences in volume definition seen between the modalities, …”
“Given that tumor volumes independently apparent on CT and MRI have equal
validity, composite CT-MRI input should be considered for planning …”
Ten Haken, Radiotherapy and Oncology, 25, 121-133, 1992.
Simulation Imaging Modality
12 patients
Inflammation used to
ID lumpectomy cavity
Cavity volume ratio
(PET CT)/CT = 1.68
Range = 1.24 – 2.45
PTV volume ratio
(PET CT)/CT = 1.16
Range = 1.08 – 1.64
PET CT largely
encompassed CT
Ford, IJROBP, 71, 595-602, 2008.
Outline
I.
The Need for Margins
II.
Treatment Site Considerations
III. Simulation Imaging Modalities
IV. Examples of Motion
V.
Treatment Planning
VI. In-room Guidance and Correction Strategies
VII. Off-line Adaptive Strategies
VIII. Planning without margins
III. Examples of Motion
A. Head and Neck
B. Lung
C. Liver
D. Pancreas
E. Prostate
Inter-Fraction Motion:
Head and Neck: Implanted Markers
Fraction
Markers
Zeidan, ASTRO 2007
Marker
Stability
Intrafraction Motion and Deformation: 4D CT
Low, Wash U.
Liver – Inter-Fraction Motion
•
•
•
Implanted Markers (clips okay)
Localized using OBI (orthogonal X-Rays at Exhale)
3 mm threshold for adjustment
Intrafraction Motion and Deformation: MRI
Balter, UM
Intrafraction Motion and Deformation: cineMRI
Courtesy Larry Kestin and Michel Ghilezan, WBH
Outline
I.
The Need for Margins
II.
Treatment Site Considerations
III. Simulation Imaging Modalities
IV. Examples of Motion
V.
Treatment Planning
VI. In-room Guidance and Correction Strategies
VII. Off-line Adaptive Strategies
VIII. Planning without margins
IV. Treatment Planning
A. Margins
1. ICRU-29, 50, 62 – Definitions
2. Margin Recipes
•
Margin Compromises
Margins
ICRU 29 (1978)
2 years after whole-body CT scanners introduced
Target volume:
• contains those tissues that are to be irradiated to a
specified absorbed dose according to a specified timedose pattern.
• Includes expected movements, expected variation in
shape and size, variations in treatment setup
Treated volume:
• The volume enclosed by the isodose surface
representing the minimal target dose.
Irradiated volume:
• The volume that receives a dose considered significant
in relation to normal tissue tolerance.
Hot spot:
• Area that received a dose higher than 100% of the
specified target dose, at least 2cm in a section.
J Purdy, 2004
ICRU 50 (1993)
Gross Target Volume
Demonstrable extent of malignant growth
Clinical Target Volume
Microscopic extension, full dose to achieve aim
Planning Target Volume
CTV + uncertainty margins, “dose cloud”
Organs at Risk
Normal tissues that may influence plan
ICRU Reference Point
J Purdy, 2004
ICRU 62 Supplement (1999)
ICRU 50
+
Setup Margin
Uncertainties in machine-patient positioning
Internal Margin
Uncertainties in patient-CTV positioning
Internal Target Volume
CTV + internal margin
Planning Organ at Risk Volume
OAR + uncertainty margins
J Purdy, 2004
ICRU Definitions Evolve
Skip over ICRU definitions!
J Purdy, 2004
ICRU Definitions
Irradiated volume:
• Tissue volume that receives a dose
that is considered significant in relation
to normal tissue tolerance.
ICRU Definitions
Treated volume:
• Tissue volume that is planned to receive at
least a dose selected and specified by
radiation oncology team as being
appropriate to achieve the purpose of the
treatment.
ICRU Definitions
GTV - Gross Tumor Volume
• Complete actual or visible/demonstrable extent and
location of the malignant growth.
CTV - Clinical Target Volume
• A tissue volume that contains a GTV and/or subclinical
microscopic malignant disease, which has to be
eliminated.
• This volume has to be treated sufficiently in order to
achieve the aim of the therapy: cure or palliation.
ICRU Definitions
PTV - Planning Target Volume
• Defined by specifying the margins that must be
added around the CTV to compensate for the
variations of organ, tumor and patient movements,
inaccuracies in beam and patient setup, and any
other uncertainties.
• A static geometrical concept, can be considered a 3D
envelope in which the tumor and any microscopic
extensions reside and move (Dose cloud)
ICRU Definitions
Organs at risk:
• Normal tissues (eg, spinal cord) whose
radiation sensitivity may significantly
influence treatment planning and/or
prescribed dose.
ICRU Definitions
ICRU Reference point:
•
The system for reporting doses is based on the selection of a
point within the PTV, which is referred to as the ICRU Reference
point
– The dose at the point should be clinically relevant.
– The point should be easy to define in clear and unambiguous way.
– The point should be selected so that the dose can be accurately
determined.
– The point should in a region where there is no steep dose gradient.
ICRU Definitions
Setup margin (SM):
• Uncertainties in patient-beam positioning in
reference to the treatment machine coordinate
system.
• Related to technical factors.
• Can be reduced by
– Accurate setup and immobilization of the patient
– Improved mechanical stability of the machine.
ICRU Definitions
Internal margin (IM):
•
Variations in size, shape, and position of the CTV in reference
to the patient’s coordinate system using anatomic reference
points.
•
Caused by physiologic variations
•
Difficult to control from a practical viewpoint.
•
The volume formed by the CTV and the IM called Internal
target volume (ITV)
ICRU Definitions
Planning organ at risk volume (PRV):
• A margin is added around the organ at risk to
compensate for that organ’s geometric uncertainties.
• Analogous to the PTV margin around the CTV.
Margins Around Organs at Risk
Considerations
– Systematic errors
• Sensitive to shifts in a particular direction
– Random errors
• Impact of dose blurring
– Serial organs at risk
• Sensitive to hot spots
– Parallel organs at risk
• Some tolerance to limited hot spots
Challenges of Implementing ICRU 50 & 62
A. Delineating Volumes
B. New Technologies
C. Adding Errors
Delineating the GTV
• Based mostly on clinical judgment
• Depends significantly on the imaging modality
(CT, MRI, PET, Registration)
• CT is still the principal source of imaging data
used for defining the GTV for 3DCRT and IMRT
• Window and level settings are critical
J Purdy, 2004
Delineating the CTV
• More of an art than a science because
current imaging techniques are not
capable of detecting subclinical tumor
involvement directly.
J Purdy, 2004
GTV to CTV Margins
• Giraud P, Antoine M, Larrouy A, et al. Evaluation of microscopic tumor extension in
non-small-cell lung cancer for three-dimensional conformal radiotherapy planning.
International Journal of Radiation Oncology*Biology*Physics 2000;48:1015-1024.
• Choo R, Woo T, Assaad D, et al. What is the microscopic tumor extent beyond clinically
delineated gross tumor boundary in nonmelanoma skin cancers? International Journal
of Radiation Oncology*Biology*Physics 2005;62:1096-1099.
• Apisarnthanarax S, Elliott DD, El-Naggar AK, et al. Determining optimal clinical target
volume margins in head-and-neck cancer based on microscopic extracapsular
extension of metastatic neck nodes. International Journal of Radiation
Oncology*Biology*Physics 2006;64:678-683.
• Chao KK, Goldstein NS, Yan D, et al. Clinicopathologic analysis of extracapsular
extension in prostate cancer: Should the clinical target volume be expanded
posterolaterally to account for microscopic extension? International Journal of Radiation
Oncology*Biology*Physics 2006;65:999-1007.
• Gao X-s, Qiao X, Wu F, et al. Pathological analysis of clinical target volume margin for
radiotherapy in patients with esophageal and gastroesophageal junction carcinoma.
International Journal of Radiation Oncology*Biology*Physics 2007;67:389-396.
• Grills IS, Fitch DL, Goldstein NS, et al. Clinicopathologic Analysis of Microscopic
Extension in Lung Adenocarcinoma: Defining Clinical Target Volume for Radiotherapy.
International Journal of Radiation Oncology*Biology*Physics 2007;69:334-341.
Delineating the PTV
The following should be taken into account:
– Data from published literature
– Any uncertainty studies performed in the clinic
– the presence of nearby organs at risk.
– The asymmetrical nature of the GTV/CTV
geometric uncertainties.
J Purdy, 2004
Compromises Between Volumes
• PTV and PRV may overlap
• Conflict in optimization criteria
• Judgment required in resolving volume conflicts
J Purdy, 2004
Challenges with New Technologies
IMRT
– Sharp beam gradients
– More conformal
– More sensitive to geometric uncertainties
– Time-dependant delivery
– Motion interplay may lead to hot/cold spots
J Purdy, 2004
Challenges with New Technologies
4D CT and Cone Beam CT
– Protocols for defining volumes
– Variations in motion after simulation
– Changes in volumes during therapy
J Purdy, 2004
Systematic and random errors
Systematic errors, Σ
– treatment preparation errors
– influence all fractions
Random errors, σ
– treatment execution errors
– influence each fraction individually
ICRU 62 – Combining Errors
Add systematic and random errors quadratically,
with equal weighting
SDTot = Σ 2 + σ 2
Combining Errors
Systematic errors are much more important
in determining margins than random errors
PTV Margin Recipe
mPTV = α Σ + γ σ’
α ~ 2 – 2.5
γ ~ 0.7
Σ - combined standard deviation of
systematic errors (Σ2 = Σ2m + Σ2s + Σ2d)
σ’ - combined standard deviation of
random errors (σ’ 2 = σ2m + σ2s)
Margins Around Organs at Risk
The DVH of the Planning Risk Volume should not
underestimate the contribution of the high-dose
components to the Organ at Risk, in 90% of the cases.
Margins Around Organs at Risk
Dan Low
takes
over!
Outline
I.
The Need for Margins
II.
Treatment Site Considerations
III. Simulation Imaging Modalities
IV. Examples of Motion
V.
Treatment Planning
VI. In-room Guidance and Correction Strategies
VII. Off-line Adaptive Strategies
VIII. Planning without margins
Target Volume Localization
A. Skin marks
B. Anatomical Landmarks and Surrogates
Bones
Implanted markers
Soft tissues
C. MV Portal Imaging
D. kV Imaging
E. Ultrasound
F. CBCT
G. MVCT
H. Electromagnetic
I.
Surface mapping
Image Guidance: Positional Variations
Early days
OLD UM STUFF
Chamfer matching of bony anatomy on digitized port films
Balter, IJROBP, 31, 113, 1995
N=10
Weekly Images
4-8 films per
patient
Balter, IJROBP, 31, 113, 1995
TRANSABDOMINAL ULTRASOUND
First widely used targeting technique
Started era of image guidance for routine clinical use
(1998)
Introduced DAILY imaging
Transabdominal Ultrasound: Comparison with Implanted Markers
US (BAT) vs Markers (EPID)
Ant / Post
Sup / Inf
Lateral
Difference: Average ± SD (mm)
-0.7 ± 5.2
2.7 ± 4.5
1.8 ± 3.9
Langen et al., IJROBP, 2003
US (Sonarray) vs Markers (Exactrac)
Frequency of misalignements
0-5 mm
26%
5-10 mm
48%
10-15 mm
17%
15-20 mm
5%
>20 mm
4%
Scarborough et al., IJROBP, 2006
Transabdominal US: Comparison with CT
Dong et al. (MDACC), ASTRO 2004: BAT vs In-Room CT
N=15 patients, 3 CTs per week.
N=342 CT/US pairs Average 23 scans/patient
Physician contours on each CT
Prostate center of volume
BAT vs CT differences (Mean + SD):
Lateral
0.5 + 3.6 mm
Ant / Post
0.7 + 4.5 mm
Sup / Inf
0.4 + 3.9 mm
“…the overall performance … seems unsatisfactory.”
Dong et al., IJROBP, 60S, p. S332, 2004
KV CT on Rails
PRIMATOM (SIEMENS)
Diagnostic CT
quality images
Full body field of
view
Limitations:
Room size
Integration
Separate imaging
and treatment
isocenters
Wong et al, IJROBP 61, 561–569, 2005
Cone Beam KV CT
Elekta Synergy
Same Gantry
Coupled to delivery device
Volume acquisition
Varian Trilogy
Sample CBCT Images: Good for H&N
Courtesy of Duke Univ Hosp, Durham
Courtesy Varian
Sample CBCT Images: Worse for Pelvis
CT scan acquisition & reconstruction time ≈ 2 minutes
Elekta Synergy®
Images Courtesy of Floris Pos – Netherlands Cancer Institute
Sample CBCT Images – Motion Artifacts
TP CT
CBCT - 1
Week 6
Week 2
Week 4
Sample CBCT – Breathing Motion Artifacts
Courtesy of Duke Univ Hosp, Durham
Courtesy Varian
Sample CBCT– Respiratory Synchronized CBCT
Courtesy of Duke Univ Hosp, Durham
Courtesy Varian
Liu et al, IJROBP, 2007
-152 cases, 7 anatomic sites
-Daily MVCT prior to each treatment; 3788 scans
-Offsets determined for each case
Li et al, IJROBP, 68; 581-91, 2007
15
LATERAL (mm)
25
0
0
-15
-25
VERTICAL (mm)
LONGITUDINAL (mm)
6
ROLL (mm)
20
0
-20
0
-6
Li et al, IJROBP, 68; 581-91, 2007
Data to help PTV margin determination
Institutional variations in patient position, immobilization, localization
technique, inter- and intra-fraction motion measurements should also
be taken into account when developing margins.
Li et al, IJROBP, 68; 581-91, 2007
LATERAL
Legend
Prostate D95
LONGITUDINAL
Plan
Mean
SD
Max
Min
2.3
2.2
D95 (Gy)
VERTICAL
2.1
2.0
1.9
1.8
1.7
1
2
3
4
5
6
7
8
9
10
Patient
Li et al, IJROBP, 68; 581-91, 2007
GEOGRAPHIC MISSES
Kupelian, IJROBP, 66, 876-82, 2006
VERSUS
DOSIMETRIC MISSES
Impact of real time motion on dosimetry:
Prostate (Calypso tracks)
Li et al: Dosimetric Consequences of Intrafraction Prostate
Motion. IJROBP, 71( 3),801-812, 2008.
Langen et al: Intra-fraction Prostate Motion: Dosimetric Impact
on Delivered Doses. IJROBP, 69, S336-S337. ASTRO 2007
Pierburg et al: Dosimetric Consequences of Intrafraction
Prostate Motion on Patients Enrolled on Multi-Institutional
Hypofractionation Study. IJROBP, 69, S23-S24. ASTRO 2007
WHY NOT IMAGE EVERYDAY?
IMAGING DOSE: MVCT vs KV CBCT
MVCT:
1 - 2 cGy per image*
Relatively uniform dose
40 - 80 cGy per entire course
Can limit length of scan
* Meeks et al., Med Phys. 2005;32(8):2673-81
* Shah et al., IJROBP, 2007; 69(3), S193-194.
ASTRO 07; ABSTRACT 1100
KV CBCT:
1 - 5 cGy per image**, depending on site
Heterogeneous throughout scan volume
40 - 200 cGy per entire course
Cannot limit length of scan
** Amer et al., Br J Radiol. 2007;80(954):476-82.
** Wen et al.,Phys Med Biol. 2007;52(8):2267-76.
** Islam et al., Med Phys. 2006;33(6):1573-82.
Inter-Fraction
Motion Management Example
Implanted Markers
Advantages of Markers
•
•
•
•
•
•
•
Accuracy
Measured in treatment position
Semi- to fully automated
User independent
No contouring
Real-time position possible
Beam gating
Marker Visualization & Extraction
• 3 – 4 markers
• Centroid of visible markers
σCM < 1 mm
Pouliot, IJROBP, 2003
• 99.6% visualization of 3 markers
18 MV (1x3 mm)
Herman, IJROBP, 2003
• Automated marker extraction
¾ 93% per marker, 85% for 3 markers
Aubin, MedPhys, 2003
¾ 90% - 100% based on ROI (MVCT)
Chen, AAPM, 2005
Marker Migration & Stability
• 1.3 (0.44 – 3.04) mm (Pouliot, IJROBP, 2003)
• 1.2 +/- 0.2 mm (Kitamura, Radiother Oncol, 2002)
• 0.7 – 1.7 mm (Litzenberg, IJROBP, 2002)
• 1.01 +/- 1.03 mm (Kupelian, IJROBP, 2005)
• 0.8 mm with Beacons (Willoughby, IJROBP, 2006)
¾ Area of marker triangle proportional to CT
volume of prostate (Moseley, AAPM, 2005)
Frequency & Time for Adjustment
• 5 mm action threshold with skin mark setup
53% of fractions realigned pre-treatment
1.5 minute mean increase in treatment time
Herman, IJROBP, 2003
• 2 mm action threshold
74% of fractions realigned
< 5 minute increase in treatment time
Beaulieu, Radiother & Oncol, 2004
Need for implanted fiducials
with CT scans
kV cone beam CT
MV cone beam CT
Helical MV CT
Sagittal
MV CT
Sagittal
CB CT
Prostate alignment study
MVCT scans
Radiation Therapist vs Physician
Alignment methods:
Marker
Anatomy
Contours
3 patients, 112 scans
Langen et al., IJROBP, 62, pp 1517
Therapist vs Physician registration
Difference ≥ 5 mm
Marker
Anatomy
Contour
A/P: 1 %
S/I: 2 %
Lat: 1 %
A/P: 5 %
S/I: 10 %
Lat: 0 %
A/P: 17 %
S/I: 31 %
Lat: 3 %
Langen et al., IJROBP, 62, 1517, 2005
Cone Beam KV CT Alignment techniques
Fiducials vs Soft Tissues
Moseley et al., IJROBP, 67(3), 942–953, 2007
Princess Margaret Hospital: 15 patients, 256 CT sets
Fiducial vs Soft tissues on cone-beam CT
PTV margins: 10 mm except 7 mm posteriorly
kV Cone Beam CT: Soft Tissues vs Markers
Inter-observer Variability (mm)
Lateral (LR)
Vertical (AP)
Long (SI)
Markers
Systematic Error (SD)
Random Error
0.03
0.26
0.15
0.95
0.01
0.47
Soft tissues
on CBCT
Systematic Error (SD)
Random Error
0.61
1.50
1.61
2.86
2.21
2.85
Less inter-observer variability with markers
Moseley et al., IJROBP, 67(3), 942–953, 2007
Cone Beam KV CT Alignment techniques
Fiducials vs Soft Tissues
Agreement within 3 mm
LR
AP
SI
91%
64%
64%
Pearson’s
correlations R2
LR 0.90
AP 0.55
SI
0.41
Moseley et al., IJROBP, 67(3), 942–953, 2007
MOTION
INTRA FRACTION
Real-Time Marker Tracking
IRIS
Dual Fluoroscopy
and Flat Panels
Courtesy George Chen, Harvard and Mass General Hospital
Real-Time Marker Tracking
Real-Time Marker Tracking
Marker Implantation Feasibility
AC Wireless Magnetic Tracking
Calypso System
Measurements at 10 Hz
Sub-mm resolution
Real-time tracking
Potential for fast correction
Real Time Motion Data – Patient 1
Position (mm)
IS
AP
LR
Real Time Motion Data – Patient 2
Position (mm)
IS
AP
LR
Percentile: Regular Breather
v85
v95
Regular Breather
vx = Volume at
which patient
had v or less
volume x% of
the time
v90
v98
v5
Percentile Analysis
v85
v90
v95
Irregular Breather
v5
v98
Example V98 (93%
) vs V85 (80%
of time
Amount of Motion We Want to Know
)
of time
Available 3D Image Datasets
Ratio 1.38 ± 0.19
Images that cover 80% of breathing cycle show only 72% of the
motion at 93% of the breathing cycle!
In-Room Correction Strategies
A. Action Levels
B. Gating
Variation vs Action Level
1.0
3.5
0.8
3.0
2.5
0.6
2.0
0.4
1.5
1.0
(σmeas2 + σpos2)1/2
0.2
Lam, AAPM, 2006
0.0
0.5
0.0
2
0.1
4
6 8
2
4
6 8
1
10
Action Level (mm)
2
4
6 8
100
Adjustment Frequency
Corrected Uncertainty, σ (mm)
4.0
Patient Specific Margin
Frequency
Σ=0
0
0
PTV margin = Setup + Inter + Intra-fraction
+ Measurement
+ Correction
Position (cm)
Initial Setup Variations
1
0.1
Position
Position(mm)
(cm)
0
0.0
-1
-0.1
AP
Systematic
σIntra
-2
-0.2
Assume σs = 1 mm
-3
-0.3
-4
-0.4
-5
-0.5
0
60
120
180
240
300 360
Time (s)
420
480
540
600
Intra-Fraction Correction
10
1.0
Position
(cm)
Position
(mm)
8
0.8
6
0.6
4
0.4
2
0.2
0
0.0
-2
-0.2
-4
-0.4
0
60
120
180
240
300 360
Time (s)
420
480
540
600
Margins vs Management Strategy
Radiofrequency transponders: Prostate rotation
• Apply real rotations from tracked data to assess
plan efficacy
• Real-tracking data (sampled at 10Hz) from a
research version of the Calypso System
• Rotational and translational corrections were
applied to the prostate contours for each patient
and the amount of time the prostate was outside
the PTV was determined
C. Noel, Washington University
Plan Evaluation
For 3 patients, over 122 total fractions, the percentage of time
any portion of the prostate is outside of a 5mm PTV: ***
% Time out of 5mm PTV
Patient 1
25%
Patient 2
<1%
Patient 3
51%
***Full results to be presented at ASTRO 2008
Plan Evaluation
…for a 3mm PTV margin:
% Time out of 3mm PTV
Patient 1
80%
Patient 2
5%
Patient 3
93%
***Full results to be presented at ASTRO 2008
Plan Evaluation
…for a 8mm PTV margin:
% Time out of 8mm PTV
Patient 1
<1%
Patient 2
0%
Patient 3
3.3%
***Full results to be presented at ASTRO 2008
Visualize Rotations
Contoured prostate and PTV from plan
Day 1 Prostate Position at Set-up: 9˚
Day 2 Prostate Position at Set-up: 30˚
Visualize Rotations
Tracked motion data
Visualize Rotations
Change PTV from 5mm to 3mm
Outline
I.
The Need for Margins
II.
Treatment Site Considerations
III. Simulation Imaging Modalities
IV. Examples of Motion
V.
Treatment Planning
VI. In-room Guidance and Correction Strategies
VII. Off-line Adaptive Strategies
VIII. Planning without margins
Offline Adaptive Protocols
• Adaptive Radiation Therapy – ART
– N ~ 5 CT scans with contours
– Union of volumes to form patient-specific PTV
Yan, et al, IJROBP, 2000.
• No Action Level protocol – NAL
– N ~ 5 portal images to estimate Σ
De Boer, et al, IJROBP, 2001
• Shrinking Action Level protocol – SAL
– Nmax ~ 5 portal images to estimate ΣN
– If ΣN < αN = α / N1/2, apply offset to all fractions
– Else apply and restart at N = 1
Bel, et al, Radiother Oncol, 1993.
Confidence-Limited PTV (cl-PTV)
transverse
sagittal
coronal
Initial CTV + 4 CTVs = ITV
ITV + Random Setup Error of Bones = cl-PTV
Kestin, RTOG, 2006
Adaptive Radiation Therapy - ART
Adaptive RT Trial
Conventional
PTV
cl-PTV
Margin Reduction (N=600)
• Margins stringently designed to allow <3%
dose reduction within CTV with an 80%
confidence
• PTV volume reduced by mean of 34% (N=600 patients)
– > 30% of conventional PTV unnecessary in 75% of patients
• Equivalent uniform margin: mean = 5.6 mm
• If planning based on single CT scan:
– ~ 14 mm margin (AP) required to meet similar dosimetric
criteria
• Average IMRT dose escalation of 7.5% (86.7 Gy)
Kestin, RTOG, 2006
Meldolesi et al. Int J Radiat Oncol Biol Phys 63:S90-S91; 2005
Outline
I.
The Need for Margins
II.
Treatment Site Considerations
III. Simulation Imaging Modalities
IV. Examples of Motion
V.
Treatment Planning
VI. In-room Guidance and Correction Strategies
VII. Off-line Adaptive Strategies
VIII. Planning without margins
Treatment without Margins
• Multiple Instance Geometry Approximation (MIGA)
• Approximate positional uncertainties by a modeled
sequence of positions (e.g. independent CT scans)
• Dose calculation is for weighted sum of different patient
geometries
• Assuming that model is correct, dose calculation
accounts for geometric uncertainty
MIGA
MIGA
•
•
•
•
Fluence is NOT just a blurring of the PTV-based plan!
No PTV margin
Simultaneous optimization of multiple instances of geometry
Solutions maybe worse than the static geometry solution,
but are much better than the static geometry solution when
compromised by motion
The End!
Thanks for attending!
Up Next:
Deformable Image Registration
Marc Kessler