mackie-advances in radiotherapy · radiotherapy timeline 1895 1950 1965 1980 1995 • 100-400 kev...
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Thomas Rockwell MackieProfessorDepts. Of Medical Physics, Human Oncology,and Engineering PhysicsUniversity of WisconsinMadison WI 53706
Advances in Radiotherapy
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Financial DisclosureI am a founder and Chairman of TomoTherapy Inc. (Madison, WI) which is participating in the commercial development of helical tomotherapy.
www.tomotherapy.comTomoTherapy’s 63,000 sqft. Madison WI Facility
Assembly Floor
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99% of Radiation Therapy Procedures are to Treat Cancer
Diagnostic Planar X-ray of a Crab
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Somatic Mutations and Cancer
• Like wrinkles and other aging symptoms, cancer is usually the result of many somatic mutations.
• Reversing cancer is about as likely as reversing aging.
• There is more money spent on wrinkles than cancer, so it is likely that a cure for wrinkles will happen before a cure for cancer.
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Sell betatron stop Sell Cobalt unit stop The cure for cancer will come from polyoma virus research stop
Telegraph from E.A McCulloch to H. Johns 1962
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“It will take another 15 to 20 years for the new biology to revolutionize our concepts of cancer treatment”
E. Hall 1995
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Imagine if Radiation Were A Drug
• It could target arbitrarily-defined anatomic sites.
• It would cause little damage to normal tissue away from the tumor.
• The site of its action could be verified precisely.
• Its side effects were well known.• It could be non-invasively measured in small
quantities.• It would make other drugs more potent.• Drug tolerance would not develop. • Saving hundreds of thousands of people a
year, it would surely be considered our most important anit-cancer drug.
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100 % - diagnosed with cancer
70 % - have loco-regional disease on presentation
30 % - have metastatic disease
35 % are treated with radiation ± other treatment modality
25 % achieveloco-regionalcontrol
10 % fail withloco-regionalrecurrence ± metastases
5 % fail due to biological causes
50 % Patients who will not survive
25 % achieveloco-regionalcontrol
10 % fail withloco-regionalrecurrence ± metastases
Adapted from Jerry Battista,London Regional Cancer Centre, Ontario
5 % fail due to physical causes
35 % are treated without radiation
Developed World
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Societal Costs
• The direct costs of cancer in the US is about $80B annually.
• Radiotherapy costs about $10B.• Radiotherapy equipment is about $2B.• In addition there is over $150B in
indirect costs due to disability and premature death.
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Radiotherapy Costs in Perspective
PROCEDURE COST ($/yr of life saved)
Bone Marrow Transplant 10,000 to 125,000Treatment of Heart Disease 10,000 to 100,000Kidney Dialysis 20,000 to 50,000Societal Acceptance 25,000 – 100,000Chemotherapy 4,500 to 50,000Radiation Therapy 350* to 1,800**
ASCO 1992
*Ontario Ministry of Health, Canada
**Perez IMRT, assuming 10 years gainedAdapted from Jerry Battista,London Regional Cancer Centre, Ontario
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Radiotherapy Costs in Perspective
PROCEDURE COST ($/yr of life saved)
Bone Marrow Transplant 10,000 to 125,000Treatment of Heart Disease 10,000 to 100,000Kidney Dialysis 20,000 to 50,000Societal Acceptance 25,000 – 100,000Chemotherapy 4,500 to 50,000Radiation Therapy 350* to 1,800**
ASCO 1992
*Ontario Ministry of Health, Canada
**Perez IMRT, assuming 10 years gainedAdapted from Jerry Battista,London Regional Cancer Centre, Ontario
500 to 3,000
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Radiotherapy Timeline
1895 1950 1965
1980 1995
• 100-400 keV X-Rays• Rotation Therapy
• Co-60• Low Energy Linacs• Betatrons
• Computerized 2-D Planning
• High Energy Linacs
• Simulators
• CT Scanners• 3-D Planning• Accurate Dosimetry
• MRI, PET, PET-CT• MLCs, Optimization, and IMRT• Image-Guided Radiotherapy
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Scientific Forces Behind Our Field
1950 1960 1970 1980 1990 2000
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Scientific Forces Behind Our Field
1950 1960 1970 1980 1990 2000
Nucle
ar a
nd P
artic
le P
hysi
cs
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Scientific Forces Behind Our Field
1950 1960 1970 1980 1990 2000
Nucle
ar a
nd P
artic
le P
hysi
csComputer S
cience
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Scientific Forces Behind Our Field
1950 1960 1970 1980 1990 2000
Nucle
ar a
nd P
artic
le P
hysi
csComputer S
cience
Imaging
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Scientific Forces Behind Our Field
1950 1960 1970 1980 1990 2000
Nucle
ar a
nd P
artic
le P
hysi
csComputer S
cience
Imaging
Biot
echn
olog
y
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Scientific Forces Behind Our Field
1950 1960 1970 1980 1990 2000
Nucle
ar a
nd P
artic
le P
hysi
csComputer S
cience
Imaging
Biot
echn
olog
y
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2D Treatment Planning
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2D Treatment Planning
2D simulation films or computer-generated “DRRs”
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2D Treatment Planning
2D simulation films or computer-generated “DRRs”
Treatment machine port films
Tumors are hard to see in 2D images, especially port films, and you must rely on “landmarks.”
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3-D Treatment Planning
Planning workstations use 3D imaging and accurate dose calculations to allow highly “conformal” treatment planning.
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CT Slices Forming a Patient Representation is the Modern Basis for
Radiotherapy
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The Tumor and Sensitive Structures are Outlined
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The Beam Directions are Chosen
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Preconditions for 3D Conformal Radiotherapy
• Early detection of cancer.– Blood testing (e.g., PSA test).– Mammography.– Imaging screening of selected patients.
• CT to produce accurate representations of the patient.
• Well trained radiation oncologist and physicists.• Much of the developing world does not have
the preconditions for modern radiotherapy.
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The Gamma Knife
201 Co-60 Sources Collimated by a “Helmet”
Gamma Knife Model C (Elekta)
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Traditional Linac Stereotactic Radiosurgery Equipment
Collimator setTypically ~10-40mm diameter
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Cranial Stereotactic Localizer
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Stereotactic Arc Plans
Localizer Rods on 3D image
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Optimization and Intensity-Modulated Radiotherapy
(IMRT)• Let the computer do the work…
Let the computer optimize the plan, varying the intensity within each beam, to “conform” and “spare” even more.
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Optimization and Intensity-Modulated Radiotherapy
(IMRT)• Let the computer do the work…
Let the computer optimize the plan, varying the intensity within each beam, to “conform” and “spare” even more.
3D Conformal
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Optimization and Intensity-Modulated Radiotherapy
(IMRT)• Let the computer do the work…
Let the computer optimize the plan, varying the intensity within each beam, to “conform” and “spare” even more.
3D Conformal IMRT
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Prostate IMRT (Tomotherapy)
Dose Rate Cumulative Dose
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Courtesy of J. Schreiner Kingston Regional Cancer Centre, Ontario
Dose Sculpting2-D Planning
IMRT
3-D
Conformal
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Zelefsky et al, J Urol, 2001
3DConformal
IMRT
IMRT Significantly Reduces Rectal Complications
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Head and neck plan with avoidance of the spine and parotids.
Tomotherapy IMRT PlanSpine
Parotids
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Re-treatments, using tomotherapy for patients not eligible for conventional photon radiation therapy due to cord tolerance.
Patients courtesy of UAB
Re-Treatments
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PSI Switzerland
Protons and Heavy (“Light”) Ions
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Will the Long Term Future Be Protons?
Protons stop sointegral doseis less.
Not so greatlateral penumbra.
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Dose Distribution ComparisonProtons
Photons(Tomotherapy)
90% line
50% line
Low integralDose.
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Why 3D Image-Guided Radiotherapy (IGRT)?
• Eventually most 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.
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Setup Alignment with Ultrasound
When contour alignment to ultrasound is satisfactory, shift the patient to the new position.
Using Varian’s Ultrasound Localization System
From Dr. Wolfgang Tomé
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Pitfall: Pubic Arch Interference
Probe placed over treatment isocenter.
Probe displaced by 1cm superiorly from treatment isocenter.
From Dr. Wolfgang Tomé, UW-Madison
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CT in the Treatment Room
From Minoru Uematsu et al.IJROBP 48, 432 (2000)
First CT
Then Treat
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CT in Treatment Room
GE CT + Varian LinacSiemens Primatom“CT on Rails”
From Tim Holmes, St. Agnes Hospital
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Cone Beam Imaging
Elekta Synergy Varian Trilogy
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Helical Tomotherapy Unit
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Helical Tomotherapy UnitLinac
Pulse FormingNetwork andModulator
DetectorBeam StopHigh VoltagePower Supply
ControlComputer
Magnetron
Data Acquisition System
Circulator
Gun Board
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Tomotherapy Verification Scanning With the Treatment Beam
Gold Seeds
Hip Prostheses
Orange
Parallel Plate Chamber
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Register Verification CT to Planning CT
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Register Verification CT to Planning CT
Auto
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Register Verification CT to Planning CT
Auto Man
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Register Verification CT to Planning CT
Auto Man
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Tomotherapy Registration of Lung Case
From Chet Ramsey , Thompson Cancer Survival Center
VerificationCT
Planning CT
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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.
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In June 2005, the world’sfirst TMI patient was treated at City of Hope in Los Angeles.
From Dr. An Liu
Total MarrowIrradiation UsingTomotherapy
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• TMI • TBI
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Total Marrow Irradiation (TMI) vs. Total Body Irradiation (TBI)
From Dr. An Liu
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With Better Avoidance of Normal Tissue Can We Shorten Courses of
Therapy?
• 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.
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CT PET CT+PET
PET/CT will Become the Main Instrument for Radiotherapy Planning
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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.
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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.
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Oligometastases or “Weeding the Garden”
• Following definitive radiotherapy with local control we often have metastatic progression.
• Chemotherapy (analogous to pre-emergent herbicides) may 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.
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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
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Irradiation of Metastases with One Setup
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100 % - diagnosed with cancer
70 % - have loco-regional disease on presentation
30 % - have metastatic disease
35 % are treated with radiation ± other treatment modality
25 % achieveloco-regionalcontrol
10 % fail withloco-regionalrecurrence ± metastases
5 % fail due to biological causes
50 % Patients who will not survive
25 % achieveloco-regionalcontrol
10 % fail withloco-regionalrecurrence ± metastases
Adapted from Jerry Battista,London Regional Cancer Centre, Ontario
5 % fail due to physical causes
35 % are treated without radiation
Developed World
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100 % - diagnosed with cancer
70 % - have loco-regional disease on presentation
30 % - have metastatic disease
35 % are treated with radiation ± other treatment modality
25 % achieveloco-regionalcontrol
10 % fail withloco-regionalrecurrence ± metastases
5 % fail due to biological causes
50 % Patients who will not survive
25 % achieveloco-regionalcontrol
10 % fail withloco-regionalrecurrence ± metastases
Adapted from Jerry Battista,London Regional Cancer Centre, Ontario
5 % fail due to physical causes
35 % are treated without radiation
Developed World
5 % fail due to biological causes
?
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100 % - diagnosed with cancer
70 % - have loco-regional disease on presentation
30 % - have metastatic disease
35 % are treated with radiation ± other treatment modality
25 % achieveloco-regionalcontrol
10 % fail withloco-regionalrecurrence ± metastases
5 % fail due to biological causes
50 % Patients who will not survive
25 % achieveloco-regionalcontrol
10 % fail withloco-regionalrecurrence ± metastases
Adapted from Jerry Battista,London Regional Cancer Centre, Ontario
5 % fail due to physical causes
35 % are treated without radiation
Developed World
5 % fail due to biological causes
?
?10 % fail withloco-regionalrecurrence ± metastases
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100 % - diagnosed with cancer
70 % - have loco-regional disease on presentation
30 % - have metastatic disease
35 % are treated with radiation ± other treatment modality
25 % achieveloco-regionalcontrol
10 % fail withloco-regionalrecurrence ± metastases
5 % fail due to biological causes
50 % Patients who will not survive
25 % achieveloco-regionalcontrol
10 % fail withloco-regionalrecurrence ± metastases
Adapted from Jerry Battista,London Regional Cancer Centre, Ontario
5 % fail due to physical causes
35 % are treated without radiation
Developed World
5 % fail due to biological causes
?
?10 % fail withloco-regionalrecurrence ± metastases
35 % are treated without radiation
?
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100 % - diagnosed with cancer
70 % - have loco-regional disease on presentation
30 % - have metastatic disease
35 % are treated with radiation ± other treatment modality
25 % achieveloco-regionalcontrol
10 % fail withloco-regionalrecurrence ± metastases
5 % fail due to biological causes
50 % Patients who will not survive
25 % achieveloco-regionalcontrol
10 % fail withloco-regionalrecurrence ± metastases
Adapted from Jerry Battista,London Regional Cancer Centre, Ontario
5 % fail due to physical causes
35 % are treated without radiation
Developed World
5 % fail due to biological causes
?
?10 % fail withloco-regionalrecurrence ± metastases
35 % are treated without radiation
?
?30 % - have metastatic disease
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100 % - diagnosed with cancer
70 % - have loco-regional disease on presentation
30 % - have metastatic disease
35 % are treated with radiation ± other treatment modality
25 % achieveloco-regionalcontrol
10 % fail withloco-regionalrecurrence ± metastases
5 % fail due to biological causes
50 % Patients who will not survive
25 % achieveloco-regionalcontrol
10 % fail withloco-regionalrecurrence ± metastases
Adapted from Jerry Battista,London Regional Cancer Centre, Ontario
5 % fail due to physical causes
35 % are treated without radiation
Developed World
5 % fail due to biological causes
?
?10 % fail withloco-regionalrecurrence ± metastases
35 % are treated without radiation
?
?30 % - have metastatic disease
?50 % Patients who will not survive
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Physics is Key to Radiation Therapy
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Economic Forces Driving Our Field
• Cost containment.• Demand for higher quality done more easily.• In the developed world, radiotherapy is about 40
times more medical physics intensive than radiology.
• Expect that radiotherapy will be economically driven to be more like radiology where medical physicists are mainly quality assurance experts and radiation oncologists ultra-specialized.
• Much of that QA will be imaging related.• Like medicine as a whole, radiotherapy will
specialize around disease sites.
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Change from Individual QA to QA of Automated Processes
• Machine QA processes will be built in to the machines.
• QA processes for individual patients will be generated automatically.
• Physicists will be responsible for checking that the automated processes are performing correctly.
• Role will become more like that of a physicist working in radiology.
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Future of RadiotherapyPhysics
• For the next 20 years, in the developed world, there will be a steady increase in therapy medical physicists employed.
• The end of the baby boom and increased automation will end the rapid growth in the developed world.
• Radiotherapy physicists will require more training in imaging.
• Like radiology physicists, radiotherapy physicists will become QA experts.
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Conclusions
• Imaging and computer science is increasing the capability but also the complexity of radiotherapy.
• Radiotherapy is achieving better sparing of normal tissues.
• Radiotherapy will be used for more indications.
• More therapy physicists are needed with increased knowledge of imaging and QA.