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Applications of Modern Radiotherapy Systems
Thomas Rockwell Mackie
ProfessorUniversity of Wisconsin
Co-Founder and Chairman of the Board
TomoTherapy Inc.
Financial Disclosure
I am a founder and Chairman of TomoTherapy Inc. (Madison, WI) which is participating in the commercial development of helical tomotherapy.
Acknowledgements
John SchreinerJerry BattistaTim HolmesGustavo OliveraWeiguo LuKatja Langen
Paul KeallDavid ShepardCedric YuThomas BortfeldAn LiuChet Ramsey
Outline
• Setup correction for interfraction motion
• Off-line adaptive techniques
• On-line adaptive strategies
• Modern Delivery methods
• Treatment Planning Issues
• Delivery time
• Novel clinical applications
• Clinical impact
Courtesy of John Schreiner, Kingston Regional Cancer Centre, Ontario
Dose Sculpting and Painting
2-D Planning
IMRT
3-D
Conformal
Dose
Painting
Why 3D Image-Guided Radiotherapy (IGRT)?
• Eventually, most curative radiotherapy will be IMRT, even many palliative treatments, e.g., re-treatments.
• All IMRT should be image-guided:– IMRT is justified by sparing critical tissues (conformal avoidance) which produces higher dose gradients.
– IGRT enables higher gradients to be delivered safely and effectively.
– IGRT enables a smaller setup margins to be defined.• In some radiotherapy sites, e.g., prostate, IGRT may be more important than IMRT.
• 2D imaging is inadequate to obtain volume information.
“If you can’t see it , you can’t hit it
If you can’t hit it, you can’t cure it”
From Jerry Battista
1 second 1 minute 1 hour 1 day 1 week
Intra-fractional time scale
Inter-fractional time scale
time
respiratory,
cardiac
motion digestive
system
motion
bowel/
bladder
filling
random/
systematic
setup errors
tumor
growth
and
shrinkage
weight
gain and
loss
Radiotherapy Time Scales
Is Daily Imaging Necessary?Translational Setup Error by Disease Site
0.0
1.0
2.0
3.0
4.0
5.0
6.0
7.0
0 1 2 3 4 5
Disease Site
Error (mm)
Rotational Setup Error by Disease Site
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
0 1 2 3 4 5
Disease Site
Error (degrees)
∆ systematic
● random
lateral
longitudinal
vertical
Brain H&N Lung Prostate Brain H&N Lung Prostate
∆ systematic
● random
roll
• Translational corrections smaller for brain and H&N than for lung and prostate treatments
• Rotational corrections greater for brain and H&N than for lung and prostate
• Shows that when we image, we do make shifts. Does this improve outcomes? Can we use this to image less?
Residual Errors For Imaging Protocols
Error As a Function of % Days Image Guidance Used
0
20
40
60
80
100
0 20 40 60 80 100
% Image Guidance
% Times Error
Occurs
Error > 3 mm
Error > 5 mm
Error > 10 mm
Every second day
Weekly
NeverEvery day
Adapted from Zeidan et al, Int. J. Radiat. Oncol. Biol. Phys. 2007; 67:670-677
Head and Neck
Small residualuncertainty
Off-line Adaptive Techniques
• Dose verification and replanning
• Dose reconstruction
• Deformable registration of contours and dose distributions
• Dose trending
Off-Line Adaptive3-D Imaging
OptimizedPlanning
Pre-DeliveryImaging
RadiotherapyTreatment
DoseReconstruction
Setup Adjustment
DeformableDose
Registration
Quantitative Imaging forAdaptive Therapy
• Quantitative images are required for many
Adaptive Therapy Processes:
– Delivery Verification.
– Dose Reconstruction.
– Deformable Dose Registration.
– Re-optimization.
• All of these can be achieved with
tomotherapy’s CT images.
Patient courtesy of Tim Holmes, St. Agnes Cancer Center Baltimore, MD
Re-calculated plan with shifted target
Dose Verification – Recomputing Dose
Planed Dose to the PTV
Delivered Dose to the PTV
Planned Max Cord Dose
Max Cord Dose with Existing Plan
Per-fraction DVH
Re-calculated plan with shifted target
Clinical Adaptive Planning
Patient courtesy of Tim Holmes St. Agnes Cancer Center Baltimore, MD
Patient courtesy of Tim Holmes, St. Agnes Cancer Center Baltimore, MD
Planed Dose to the PTV
Delivered Dose to the PTV
Planned Max Cord Dose
Max Cord Dose with Existing Plan
PerPer--fraction fraction DVHDVH
Revised Plan Revised Plan DVH for DVH for remaining remaining fractionsfractions
Replanning
Revised plan for remaining Revised plan for remaining
fractionsfractions
Max Cord Dose with Revised Plan
Original Planning CT
Original planning CT
Reference CT
Daily CT Daily CT mapped
to Reference CT
Original planning CT
Reference CT
Daily CT Daily CT mapped
to Reference CT
Original planning CT
Reference CT
Daily CT Daily CT mapped
to Reference CT
Accuracy of Automatic H+N MVCT contours
kVCT contours: MVCT contours:
Parotids: Visual inspection of automatic
contours
MVCT to kVCTDeformable Image Registration
kVCT:
PTV
Cord
MVCT:
PTV
Cord
Accuracy of Automatic H+N MVCT Contours
Spinal Cord: Automatic vs. manual contours
Compare dose-based end points: Dmax, Dmean
3 patients:
Dmax %difference: 1.1 + 3.5%
Dmean %difference: 0.1 + 2.5 %
Langen et al., AAPM, 2006
Dmean
0.6
0.8
1.0
0 5 10 15 20 25 30 35Treatment fraction
Dose (Gy)
Automatic Manual
Dmax
1.0
1.2
1.4
0 5 10 15 20 25 30 35Treatment fraction
Dose (Gy)
Automatic Manual
Trending
1st fraction
Cont. to 35 fractions
Trending
Re-plan at 20 fractions
Trending
On-line Adaptive Techniques
• Detection of intrafraction motion
• Methods of motion management• Gating
• Tracking
• Delivery modification
Lung Motion Dynamics
The motion can be complex
Motion close
to diaphragm
Motion mid
lung
Motion tumor
at center
Motion lower
chest
Lung Motion Dynamics
Navotek RealTrack System• Fine radioactive wire is implanted in the patient.• Can see the wire on IGRT systems.• Can track wire position in real time.
Calypso System• Electromagnetic transponders are implanted in the patient.• Can see the transponder on IGRT systems.• Can track transponder position in real time.
Degradation of Alignment Quality after Initial Setup for Prostate Cancer
0
10
20
30
40
50
60
0 5 10 15Time (minutes)
Precentageof observations
Percentage of displacements
observed
over time after initial alignment
>3 mm
>5 mm
>7 mm
>10 mm
17 patients
551 Calypso
sessions
Mean: 32
tracks
per patient
Courtesy of Katja Langen, M.D. Anderson Cancer Center, Orlando, FL
MRI-Guided Systems for Real Time Imaging
View Ray
AlbertaUtrecht
Motion Management
• Margin: Put an ITV on a CTV
• Breath holding: Either active or passive
• Gating: Not very efficient
• Tracking: Move the patient or move the beam
• Delivery Modification: Can also handle non-rigid motion
The Breathing Cycle
Inhalation Inhalation
Exhalation
Gating Paradigm
Assumes no motion
in gated portion
Loss of Efficiency
Motion Management (4D Planning and Delivery)
Treating while the patient breathes is more accurate as compared to tracking, and saves time as compared to gating.
Works in Progress
Nemo Demo
Motion SurrogateNemo
Static Tank
Fish Represents a Moving Tumor
How Necessary is Motion Management?Magnitude of Motion
Tumor Size
< 5 mm > 5mm < 1cm > 1 cm
SmallFraction, Including Margin, of OAR Volume
Not Needed Not Needed
Not Needed Not Needed PerhapsNeeded
LikelyNeeded
PerhapsNeeded
MediumFraction of OAR Volume
LargeFraction of OAR Volume
Not Needed
Not Needed
Why IMRT Is Needed
• 5 IMRT beams is more conformal than 5 conformally-shaped beams.
– If uniform fields were sufficient, the pencil beam weights for each beam would be identical.
54
12
3
54
12
3
Multileaf Collimators (MLC’s)
Siemens Varian NOMOS
• Conventional MLC’s were designed for field shaping
and have limitations when used for IMRT.
BinaryConventional
• Binary (off-on) MLC’s are designed for IMRT and are
the easiest to model and provide high modulation.
Segmental MLC IMRT
• “Step and shoot”.
• Deliver multiple MLC apertures within a field to apply the intensity in a paint-by-number fashion.
• May be a straightforward technique for “forward” optimization.
• Little change in paradigm involved in field boundary verification using portal imaging.
• May be relatively time consuming if field delivery is verified in exactly the same way.
• Only discrete intensity levels can be delivered.
Segmental MLC IMRT
A set of leaf sequences to deliver
an intensity modulated field.Conventional MLC’s have been designed
for field shaping not IMRT.
Dynamic MLC IMRT
• Pairs of MLC leaves are in continuous movement across the field with the intensity at a point equal to the total exposure time of the leaf pair above it.
• Most efficient delivery for modest modulation of intensities.
• High spatial variation of intensities are difficult.
• Continuous intensity levels.
• Difficult to verify with conventional techniques as anatomic details blend into the continuous intensity levels.
Dynamic MLC Leaf Motion
From Paul Keall, Stanford University
Intensity Modulated Arc Therapy (IMAT)
• Collimator leaves move dynamically as the gantry rotates.
• Beams delivered from all coplanar directions. • Requires multiple arc deliveries to achieve intensity modulation.
• Provided field length is not too long, no couch translations are necessary.
• Proposed by Cedric Yu and implemented by Wilfried DeNeve (Ghent, Belgium).
• Single arc IMAT is branded “VMAT” or “RapidArc” and also changes the dose rate during the rotation to achieve some limited modulation.
IMAT
Field shape changes dynamically during rotation.Needs multiple rotations.
IMAT Intensity Levels
i is the number of non-zero intensity levels.n is the number of rotations.
3
n = 2
Two Rotation IMAT
71i
n = 3 n = 1
Three Rotation IMAT
One Rotation
IMAT
2 1ni = −
Following Equation is from Cedric Yu:
3 SeparateRotations with
Different IntensitiesPer Rotation
1 2 3 4 5 6 7
Example of 3 IMAT Rotations
Yields 7 Unique Non-Zero Intensity Levels
From David ShepardAnd Cedric Yu
Tomotherapy
• Tomotherapy is intensity modulated rotational therapy with a fan beam of radiation and is analogous to a CT scanner.
• It utilizes a binary collimator to provide the modulation.
• Serial tomotherapy was first form of IMRT
• In helical tomotherapy, the gantry and couch move simultaneously.
TomoTherapy HI-ART Unit
Linac ShownWithout Shielding
Pulse FormingNetwork andModulator
DetectorBeam StopHigh VoltagePower Supply
ControlComputer
Magnetron
Data Acquisition System
Circulator
Gun Board
How the Intensity is Modulated with Tomotherapy
Open
Closed
For Low Intensity ALeaf Is Open for a Short Time DuringThe Projection
For High Intensity ALeaf Is Open for a Long Time During The Projection
One Rotation is Divided into Angular SegmentsCalled a Projection
Binary leaves were specifically designed for IMRT.
Sample Sinogram
Collimator Position
Angle
A delivery sinogramis a representationof the energy fluence delivered to thepatient. The energyfluence distributionis the realization ofthe sinogram andtakes into accountphoton attenuation.
A Sinogram Specifies the Relation Between Collimators and Voxels
Collimator Index
GantryAngle
Helical Delivery Sinogram
Example with 13 Rotations
GantryAngle
Collimator Index
Darker Is HigherIntensity or LongerOpening Time
AvoidanceOf NormalTissue
The delivery sinogramspecifies the intensity(or leaf opening time) as a function ofgantry angle.
IMRT Requires Optimization
Hard Constraints• cannot be violated
• may not lead to a feasible solution
Soft Constraints• constraints may be violated
• find optimal intensity profile
• may lead to a local minimum
Beamlet-Based Optimized Planning
• Two-step approach to treatment planning:
1. Fluence map optimization – Delivery constraints ignored
2. Leaf sequencing – Accounts for delivery constraints
• Employed by nearly all vendors.
• Corvus (NOMOS)• Eclipse (Varian) • XiO (CMS)• Pinnacle (Philips)• Oncentra (Nucletron)• Hi-Art (TomoTherapy)
Field Divided into a Grid of Beamlets
From Cedric Yu, U. of Maryland
2
1
1
1
1
1
2
2
2
1
1
1
2
1
1
2
1
1
2
2
1
3
21 1 32
3 12
3
2 1
3 1 11
11 11
21111
1
2
1
1
2
2
21111 2
Optimized Fluence Map
From Cedric Yu, U. of Maryland
Leaf Sequencing
2
1
1
1
1
1
2
2
2
1
1
1
2
1
1
2
1
1
2
2
1
3
21 1 32
3 12
3
2 1
3 1 11
11 11
21111
1
2
1
1
2
2
21111 2
Optimized Fluence Map
Deliverable Apertures
From Cedric Yu, U. of Maryland
Beamlet IMRT Approach for Conventional MLC IMRT
Clinical Objectives, Constraints
Intensity Maps
MLC Segments1
654
32
From Cedric Yu, U. of Maryland
Aperture-Based IMRT
Clinical Objectives, Constraints
MLC Segments1
654
32
Shepard, Earl, Li, Naqvi, Yu
“Direct aperture optimization”
Med. Phys. 29(6):1007-1018, 2002
From Cedric Yu, U. of Maryland
Delivery Type Dictates IdealOptimization Type
√
X
IMAT
XX√Aperture
√√XBeamlet
Tomotherapy
(Binary MLC)
DMLC (Dynamic MLC)
SMLC
(Step and Shoot)
Delivery Type
Ideal Optimization Type
Inadequateangularsampling
Inadequateintensitysampling.
Inadequatespatial (pixel)resolution.
Spatial and Angular ResolutionAngular sampling interval, ∆Φdominates image resolution at the peripheryof an axial image.
Pixel size, ∆ldominates imageresolution at thecenter. ∆l
∆Φ
FOV
Angular Sampling Required for CT
FOV is the field of view.
∆l is the spatial resolution.
1260 views
FOV = 40 cm
∆l = 0.1 cm
Large FOV
630 viewsRequirement
FOV = 20 cm
∆l = 0.1 cm
Small FOV
# / oFOV
Viewsl
ππππ
∆∆∆∆====360
Angular Sampling Required for Radiotherapy
FOV is the field of view (max field width)
∆l is the spatial resolution (collimator
resolution)
51 views
FOV = 40 cm
∆l = 0.6 cm
Tomotherapy
25 viewsRequirement
FOV = 15 cm
∆l = 0.5 cm
Conv. IMRT
# / o FOVViews
l
ππππ
∆∆∆∆====360
Brahme‘s Classic 1982 Paper on Rotational IMRT
Phantom
Target OAR
Dose
Rotating
Source
From Tomas Bortfeld
Fluence
Sufficient Modulation and Beam Numbers Are Needed to “Construct Dose”
1 Beam 5 Beams 11 Beams
17 Beams 25 Beams 51 Beams
mm mm mm
mmmmmm
Notice the High Degree of ModulationRequired Even if Rotation is Used
Discretization Error
i is the number of non-zero intensity levels.N is the number of beam directions.
2.2%
i = 1
N = 180
Single Arc
VMAT
0.04%2.2%1 S.D. Error
i = 100
N = 51
i = 5
N = 7
Helical Tomotherapy
Step and Shoot
IMRT
σσσσ ====1
12 i N
Following Equation is from Imaging Theory:
Conventional IMRT Delivery Time Analysis
From Sha Chang, UNC
Average Tomo
Tomo’s Time In Room and Treatment Time
Ave = 5 min
Treatment Time = Beam on Time = Time for Treatment Irradiation
Ave = 17 min
• Other studies have put the average beam on time at 7 minutes for tomotherapy
• Depends on the amount of modulation
• Shorter tumors like prostate have shorter beam on time
• Longer tumors like cranial spinal have longer beam on times
Re-treatments, using tomotherapy for patients not eligible for conventional photon radiation therapy due to cord tolerance.
Patients courtesy of UAB
Re-Treatments
Complex Abdominal/Pelvic
Heidelberg University Clinic
CraniospinalTomotherapyTomotherapy TraditionalTraditional
Craniospinal
TomotherapyTomotherapy
TraditionalTraditional
Total Marrow
Irradiation
(TMI)
From Dr. An Liu,City of Hope, Duarte CA
Conformal Avoidance of:BrainThyroidLungsLiverKidneysSmall Bowel
Strategy for Conformal Avoidance Radiotherapy
• Use generous treatment volumes.• Outline normal sensitive tissues and concentrate on avoiding them.
• Use image-guidance to assure that the normal tissues are being avoided.
• Conformal avoidance radiotherapy is the complement of conformal radiotherapy.
• If you can’t see it you can’t avoid it.• If you can’t avoid it you can’t spare it.
With Better Avoidance of Normal Tissue is Hypofraction Possible?
• In prostate CA, the tumor may repair even better than the normal tissues.
• In lung CA, rapid proliferation reduces the treatment control probability as the treatment is extended in duration.
• Provided better avoidance of sensitive tissues is maintained, fewer fractions of higher dose/fraction will provide both better tumor control and be less expense to deliver.
• Carefulness can be cost effective.
Image-Guided Radiotherapy of the Future
• Image-based staging of the primary and regional field.
– Determine hypoxic and highly proliferative regions using bioimaging and paint in higher dose.
– Conformally avoid sensitive structures in the regional field.
• IMRT with 3-D image verification.
– Less fraction quantity – greater fraction quality.
– Adaptive radiotherapy to provide patient-specific QA of the whole course of therapy.
Image-Guided Radiotherapy of the Future (Cont.)
• Image-based monitoring of outcome.
– e.g., PET scans for regional or metastatic development using a priori information.
• Aggressive treatment of recurrences or distant metastases using conformal avoidance to spare critical structures.
– Better QA of first treatment will allow safer retreatments.
– “Weeding the garden” with image-guided radiotherapy and prevent spread with chemotherapy and immunotherapy.
Oligometastases or “Weeding the Garden”
• Following definitive radiotherapy with local control we often have metastatic progression.
• Chemotherapy (analogous to pre-emergent herbicides) is known to be effective against 100 to 1000 cell tumorlets.
• With PET it is possible to infer the presence of tumorletswith 100,000 to 1,000,000 labeled cells.
• Perform PET scan followups to catch the emergent tumorlets.
• Weed with conformal avoidance hypofractionatedradiotherapy before they can seed more metastases.
• Keep careful track of the cumulative dose delivered so the process can be repeated several times if necessary.
Courtesy of Chet Ramsey, Thompson Cancer Survival Center
Planned Using PET-CT
PET-CT Scans
Treating Multiple Metastases Determined From PET Scans
Tomotherapy Treatment Plan
Visualization Gap
102 103 104 105 106 107 108 109
External Beam
Radiotherapy
Effective
MR/CT Tumor
Visualization
PET Tumor VisualizationChemotherapy
Effective
Tumor Cell Density
(cells/cm3)
1010
Targeted Agents
Effective
101
Visualization Gap
Implications of the Visualization Gap
• Systemic agents are effective for tiny tumorlets.
• Larger tumorlets may shrink so that they are not visible but they are likely to return.
• Systemic agents are more effective when no tumorletsare visible, i.e., used as a prophylaxis agent.
• Radiation therapy is effective for much larger tumors
• If imaging systems were sensitive for smaller tumors, radiation therapy could be used systemically.
• Systemic agents should aim for higher cell kill.
• If the tumor size range of systemic agents and radiation therapy could overlap, cancer could be made a chronic disease.
Conclusions• Setup corrections can correct for translations and
rotations.
• Adaptive therapy accounts for changes in the patient.
• Motion management can accommodate for breathing
and organ filling.
• IMRT and rotational therapy will dominate curative
treatments
• The type of optimization depends on the type of
delivery.
• IMRT takes more time than conventional radiotherapy
• Treatments not possible with conventional
radiotherapy are being done.
• Conformal avoidance enables hypofractionated
treatments.