Treatment Margins

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 patients 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.
II.

V.
Treatment Planning

VII. Off-line Adaptive Stratagies
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

small
small
small
large
large
small
large
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%)
Dose
Tumor
Underdose
Population-Based Motion
Frequency
1.0
0.5
0.0
-4
-2
Position (cm)
Patient Specific Motion
Frequency
1.0
0.5
0.0
-4
-2
Position (cm)
Patient Specific Margin

=0
Frequency
PTV margin = Setup + Inter + Intra-fraction
Estimate
And correct
Position (cm)
Ten Haken
Ten Haken
Outline
I.
II.

V.
Treatment Planning

VII. Off-line Adaptive Strategies
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
0
-2
-2
-4
Initial Position
7
10
Patient #
Maximum
+/- 1
Average
Minimum
Ave
LR
AP
IS
Position (cm)
Supine Positioning Results

4
LR
AP
IS
2
0
-2
-4
Initial Position
Position (cm)
10
Ave
10
Ave
Patient #
4
2
0
-2
-4
Final Position
7
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 , 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.
II.

V.
Treatment Planning

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
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.

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.

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.
II.

V.
Treatment Planning

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.
II.

V.
Treatment Planning

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 patients 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 organs 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.
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
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
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.
Grills IS, Fitch DL, Goldstein NS, et al. Clinicopathologic Analysis of Microscopic
Extension in Lung Adenocarcinoma: Defining Clinical Target Volume for Radiotherapy.
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,
treatment preparation errors
influence all fractions
Random errors,
treatment execution errors
influence each fraction individually
ICRU 62 Combining Errors
Add systematic and random errors quadratically,

with equal weighting
SDTot = 2 + 2
Combining Errors
Systematic errors are much more important

in determining margins than random errors
PTV Margin Recipe

mPTV = +
~ 2 2.5
~ 0.7
- combined standard deviation of
systematic errors (2 = 2m + 2s + 2d)
- combined standard deviation of

random errors ( 2 = 2m + 2s)
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.
Dan Low
takes
over!
Outline
I.
II.

V.
Treatment Planning

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, 561569, 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 Varian
Sample CBCT Respiratory Synchronized CBCT

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
-15
-25
VERTICAL (mm)
LONGITUDINAL (mm)
6
ROLL (mm)
20
-20
-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
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
CM < 1 mm
Pouliot, IJROBP, 2003
99.6% visualization of 3 markers
18 MV (1x3 mm)
Herman, IJROBP, 2003
Automated marker extraction

93% per marker, 85% for 3 markers
Aubin, MedPhys, 2003
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)
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), 942953, 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

Cone Beam KV CT Alignment techniques

Fiducials vs Soft Tissues
Agreement within 3 mm
LR
AP
SI
91%
64%
64%
Pearsons
correlations R2
LR 0.90
AP 0.55
SI
0.41
MOTION
INTRA FRACTION
Real-Time Marker Tracking
IRIS
Dual Fluoroscopy
and Flat Panels
Courtesy George Chen, Harvard and Mass General Hospital
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
(meas2 + pos2)1/2
0.2
Lam, AAPM, 2006
0.0
0.5
0.0
0.1
6 8
6 8
1
10
Action Level (mm)
6 8
100
Adjustment Frequency
Corrected Uncertainty, (mm)
4.0
Patient Specific Margin
Frequency
=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
Intra
-2
-0.2
Assume s = 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:
Patient 1
80%
Patient 2
5%
Patient 3
93%
Plan Evaluation
for a 8mm PTV margin:
Patient 1
<1%
Patient 2
0%
Patient 3
3.3%
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.
II.

V.
Treatment Planning

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
De Boer, et al, IJROBP, 2001
Shrinking Action Level protocol SAL

Nmax ~ 5 portal images to estimate N
If N < N = / 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.
II.

V.
Treatment Planning

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

Treatment Margins

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Treatment Margins

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Margins in Radiation Therapy

DATE: Tuesday, July 29, 2008

The Need for Margins

Treatment Site Considerations

III. Simulation Imaging Modalities

VI. In-room Guidance and Correction Strategies

The Need for Margins

Treatment Site Considerations

III. Simulation Imaging Modalities

VI. In-room Guidance and Correction Strategies

I. The Need for Margins

Systematic and Random Errors

Inter- and Intra-Fraction Positioning Errors

Inter-Fraction Motion and Deformation

Inter-Fraction Motion and Deformation

Systematic shift due to

Importance of Image Guidance

MDACC: de Crevoisier et al., IJROBP, 62, 965-973, 2004

What was Missing?

Patient Specific Motion

Patient Specific Margin

PTV margin = Setup + Inter + Intra-fraction

The Need for Margins

Treatment Site Considerations

III. Simulation Imaging Modalities

VI. In-room Guidance and Correction Strategies

II. Treatment Site Considerations

1997: No in-room soft tissue guidance available,

Intrafraction Motion: Fluoroscopy

Supine Positioning Results

Supine Positioning Results

Supine vs Prone Treatment Position

Significantly less dose to small bowel,

~ 95% treated supine

The Need for Margins

Treatment Site Considerations

III. Simulation Imaging Modalities

VI. In-room Guidance and Correction Strategies

Simulation Imaging Modality

Radiotherapy and Oncology, 85(2), 239-246, 2007

Visible Human Project - Male

Radiotherapy and Oncology, 85(2), 239-246, 2007

Visible Human Project - Male

Extended too anteriorly

Simulation Imaging Modality

Ten Haken, Radiotherapy and Oncology, 25, 121-133, 1992.

Simulation Imaging Modality

the degree of inter-observer variation in volume definition is on the order of the

Simulation Imaging Modality

The Need for Margins

Treatment Site Considerations

III. Simulation Imaging Modalities

VI. In-room Guidance and Correction Strategies

III. Examples of Motion

Zeidan, ASTRO 2007

Intrafraction Motion and Deformation: 4D CT

Liver Inter-Fraction Motion

Implanted Markers (clips okay)

Intrafraction Motion and Deformation: MRI

Intrafraction Motion and Deformation: cineMRI

Courtesy Larry Kestin and Michel Ghilezan, WBH

The Need for Margins

Treatment Site Considerations

III. Simulation Imaging Modalities