TG113: Improving Treatment
Consistency and Data Quality
for Clinical Trials
Educational Objectives
1.
2.
Jean M. Moran, Ph.D.
To describe the goals of TG#113:
Physics Practice Standards for
Clinical Trials
To highlight some factors that directly
impact clinical trials that involve IMRT
and IGRT
The University of Michigan
Department of Radiation Oncology
AAPM 2007
Moran AAPM 2008 2
Task Group 113
Members
Robert Dryzmala
Jon Kruse
Jean Moran (Chair)
Art Olch
Mark Oldham
Robert Jeraj
Outline
Liaisons
James Galvin – RTOG
Andrea Molineu – RPC
Jatinder Palta – RCET,
TG100
James Purdy – ITC
Marcia Urie – QARC
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Motivation
Challenges for multi-institutional
trials
Factors impacting clinical trials
Examples for imaging, localization
Role of benchmarks
Summary
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1
Motivation
Expected Users of TG113
Physics QA for clinical trials
Physicists & Others
Assure consistency in each part of the
treatment planning and delivery process
Advanced Technology Consortium
ITC, QARC, RCET, RTOG, and RPC
Organizations provide QA services and
some trial and benchmark design
However, there are no standard
guidelines for the physics aspects of
clinical trials
Implement trials at department
level
Involved in all parts of the
treatment planning and
delivery process
Can significantly improve data
consistency if guidelines
are available
QA Organizations
Credentialing
Benchmarks - Dry run,
phantom
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Cooperative Groups
Trial Design
Make trials more specific
with respect to physics
aspects
Vendors
Data export: Dosimetric,
imaging, localization
Dose calculation quality –
heterogeneity corrections
Plan assessment tools
Delivery software and devices
Equipment
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Factors Impacting Data for Clinical Trials
Factors Impacting Data for Clinical Trials
Patient
immobilization
Patient
immobilization
Imaging for
Volume definition
Imaging for
Volume definition
Patient localization:
Setup accuracy
Patient localization:
Setup accuracy
Treatment planning
Treatment planning
Treatment guidance
Treatment guidance
Treatment
delivery
Treatment
delivery
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What is the clinical trial
designed to study?
What are the clinical
endpoints?
What data are collected?
What level of accuracy is
required for the treatment
planning and delivery chain?
Will we want to know more
later? e.g. NTCP modeling of
lung
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2
Challenges
TG113
Challenges to clinical trials
Can changes be made to improve the
consistency of clinical trials (better data)
without overwhelming:
Accrual
Time
Expense
Physics issues are not always explicitly
included in the design of clinical trials
These exclusions may dilute the quality of
data from a clinical trial
Imaging
Homogeneous vs. heterogeneous dose
calculations
Patient setup details
Physicians and physicists designing clinical
trials?
The treatment team participating in trials?
The QA centers supporting clinical trials?
Our work focuses on external beam radiation
therapy
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Contouring Targets:
Effect of Window on Target Volume
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Contouring Targets:
Effect of Window on Target Volume
Bowden et al. IJROBP 53: 566-573, 2002.
To improve consistency in trials
Protocols can provide guidance for
window/gray levels in the trial design
Bowden et al. IJROBP 53: 566-573, 2002.
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3
SBRT Dry Run Study:
11 institutions
Effect of Delivery Technique
Minimum PTV: 35-46 Gy
Homogeneity index: 1.05-1.4
Breath hold CT
2 mm slices - lung
Matsuo et al. IJROBP 68: 416-425, 2007.
Matsuo et al. IJROBP 68: 416-425, 2007.
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Bowden et al. compared mean tumor volume values for
volumes drawn with a lung window compared to a
mediastinal window for 6 physicians on 6 datasets.
Dry Run: SBRT (continued)
Inter-institutional variations in planning for
SBRT for lung cancer, Matsuo et al. IJROBP,
2007, 416-425
16.6% variation in target volumes
Significant differences
Treatment delivery technique
Dose calculation algorithms
The average ratio of the lung window to mediastinal
window (LW/MW) was:
25%
1.
25%
2.
25%
3.
25%
4.
100% (no difference)
120%
150%
180%
Chose to use 1-D methods rather than mix; recalc with
CVSP when available
ATC supporting digital data submission
10
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4
Patient Immobilization
and Localization
To improve consistency in clinical trials:
Contouring instructions must be
explicit
A range of acceptable values can be given
Treatment planning guidelines must be
explicit
(1) Intra-fraction reproducibility
(2) Inter-fraction variations over the course of
treatment
(3) Inter-institutional variations
Frequency of assessment
Surrogates for tumor position
One size fits all may not be appropriate
target and OAR margins
Some trials specify dose-volume
constraints and minor and major
variations
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Initial Position: Prostate setup
assessed from imaging 3 gold BBs
What is the true delivered dose? Do we know?
How can we interpret the data?
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Prone
4
LR
AP
IS
2
0
-2
-4
1
2
3
4
5
6
Ave
Patient #
Supine
Position (cm)
Should a single margin be specified for all
trials?
What about immobilization?
What about imaging protocol? Is it off-line or
adaptive? Is it daily or weekly?
Should clinics use the same margin because
the patient is on a multi-institutional trial
even if their methods are different?
Position (cm)
What margin should be used in the
clinical trial?
Litzenberg et al.
4
2
0
-2
-4
7
8
9
Patient #
10
Ave
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5
Position (cm)
Final Position: Patient setup
assessed based on imaging 3 gold BBs
Prone
Treatment Guidance
4
2
LR
AP
IS
0
-2
-4
2
1
3
4
5
6
Ave
Supine
Position (cm)
Patient #
Image guidance methods
Cameras
RF beacons
kV fluoroscopic imaging
MV cine loops
Type of intervention depends on the
frequency of the event
4
2
Real-time evaluation is needed to
address intra-fraction motion
Fiducials
0
-2
-4
7
8
9
10
Ave
Patient #
Litzenberg et al.
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Example: Image Guidance – HN
MVCT: Bony anatomy registration
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Example: Treatment Guidance
Error As a Function of % Image Guidance
• 3 transponders
100
Error > 3 mm
Error > 5 mm
Error > 10 mm
% of Times Error Occurs
90
80
• Implanted transrectally
under ultrasound guidance
70
60
50
• 10 minute procedure
40
30
• Consistent with gold marker
implant effects
20
10
• Good positional stability over
8 weeks (σave = 0.8 mm)
0
0
10
20
30
40
50
60
70
80
90
100
% Image Guidance
Slide courtesy of Zeidan
MDACC-Orlando, (IJROBP, 2007)
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Slide courtesy of Litzenberg
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6
Prostate: Necessary PTV margin
PTV Margin (mm)
12
IS
AP
LR
10
8
To improve consistency in trials:
Margins should be based on each
institution’s image guidance protocols
Or
The trial should specify the acceptable
methods and frequency of interventions
6
4
2
0
Skin Marks Skin Marks
+ Motion
Initial
Setup
Pre-Beam Intra-fraction
Correction Correction
Litzenberg Int J Radiat Oncol Biol Phys 2006
Patient enrollment information should
include immobilization method and
localization information
Frequency
Action level
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Treatment Delivery
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Credentialing for Clinical Trials
Does it matter if the treatment is:
Facility questionnaire
Delivered with a conventional Linac or
something else (Tomotherapy,
Cyberknife)?
Static, IMRT, or arc delivery?
Is motion management needed?
Some part of the credentialing process
may be dependent on delivery
technique
Process appropriate margins can be used
incorporating other factors
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Information about department, equipment and
software used for patient care
Dry run
Hard copy or electronic submission of a treatment
plan that intends to meet the guidelines of the
protocol
Additional testing depends on the trial and
QA organization
Benchmarks, e.g. phantom irradiation
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7
Importance of Credentialing
RPC: IMRT H&N Phantom Results
RPC: IMRT H&N Phantom
•Primary PTV
4 cm diameter
4 TLD
•Secondary PTV
2 cm diameter
2 TLD
•Organ at risk
1 cm diameter
2 TLD
•Axial and sagittal
radiochromic films
• 163 irradiations were analyzed
• 115 irradiations passed the criteria
• 28 institutions irradiated multiple times
Primary
PTV
Secondary
PTV
Organ at
Risk
•1º PTV treated to 6.6 Gy
•2º PTV treated to 5.4 Gy
•OAR limited to < 4.5 Gy
• 48 irradiations did not pass the criteria
• 128 institutions are represented
~30% of institutions fail the criteria
on the first irradiation.
Designed in collaboration with RTOG;
Molineu et al, IJROBP, October 2005
Courtesy of Molineu, RPC
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RPC: Explanations for Failures
Explanation
Min # of occurrences
Incorrect output factors in TPS
1
Incorrect PDD in TPS
1
Inadequacies in beam modeling at leaf
ends (Cadman, et al; PMB 2002)
14
Not adjusting MU to account for dose
differences measured with ion chamber
3
Errors in couch indexing with Peacock
system
2
2 mm tolerance on MLC leaf position
1
Setup errors
7
Target malfunction
1
Courtesy of Molineu, RPC
Courtesy of Molineu, RPC
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Effect of Leaf Position Offset on IMRT
Cadman et al PMB: 3001-3010 (2002).
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The number institutions who pass the
benchmark irradiation of the RPC head
and neck phantom is:
Effect of Leaf Position Offset on IMRT
Uncorrected leaf offset
-3-12% errors
25%
1.
25%
2.
25%
3.
25%
4.
Leaf offset corrected
+/- 5%
5%
10%
30%
45%
10
Cadman et al PMB: 3001-3010 (2002).
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Inaccuracy in the modeling of curved
multileaf collimator leaves was shown to
result in dosimetric errors up to:
25%
1.
25%
2.
25%
3.
25%
4.
2%
12%
25%
30%
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To improve consistency in clinical trials
There is a clear role for dosimetric
verification when complex technologies
are being introduced
RPC phantom found dosimetric errors
that would have adversely affected trial
results
Request immobilization and setup
information as part of patient
enrollment on a clinical trial
10
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How should new technologies be
incorporated into clinical trials?
We do not want to limit participation in
clinical trials, but we do want delivery to be
as accurate as possible
Results should also represent how patients will
be treated in a variety of hospital settings
Focus is on physics issues that affect the
consistency of data acquired during clinical
trials
Expect improved confidence in the data submitted
as part of a clinical trial
Should improve interpretation of studies looking
at tissue response
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TG 113 Summary
Emphasis on process improvements to
decrease the variability in clinical trials (and
improve our knowledge of differences)
Design of trials: Allow for variable margins based
on immobilization and localization methods
Continue to require credentialing as new
technologies are implemented at different centers
and as benchmarks continue to show significant
failures
Looking forward: Trials on treatment assessment
We are in the process of completing our
written report for submission to Therapy
Physics Committee and then submission for
publication.
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