mohan - swaapm - treatment planning and protons...
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Treatment Planning and ProtonsTreatment Planning and Protons
Radhe Mohan PhDRadhe Mohan, PhD
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SWAAPM Meeting, Houston, TXOctober 9 - 10, 2009
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The more you learn, the more you realizeThe more you learn, the more you realize how little you know …
Attributed to Socrates by Platoy
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OutlineOutline
Characteristics of protonsCharacteristics of protonsDose calculationsUncertaintiesPassively scattered protons strategiesy p gScanning beam and IMPT strategiesLimitation of the concept of PTVLimitation of the concept of PTVPlan robustnessSome clinical resultsProton therapy research at MDACC
4
py
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Characteristics of ProtonsCharacteristics of Protons
Loose energyPristine Bragg peak due Loose energy continuouslyDeposit less energy
Pristine Bragg peak due to a pencil beam of
protons in homogeneous Deposit less energy per unit pathlength in plateau and more
p gphantom
p ateau a d o enear the end of the range
Dos
e
Have a finite range –they stop
D
5Depth
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To Make Protons Useful for Radiotherapy …
Thin pencil beams must be spread laterally and longitudinally
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The Passive Scattering Mode of Proton Beam DeliveryBeam Delivery
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Dose Calculations for Passively Scattered Proton Therapy
SOBP is decomposed into pencils and
Proton Therapy
SOBP is decomposed into pencils and layers of energyIntegral of each pencil across a planeIntegral of each pencil across a plane for each energy is its depth doseLateral dose distribution approximated by multiple Gaussians to account for MCS, nuclear i i
Xinteractions, etc.Ray tracing used to approximately account for inhomogeneities
2400
2600
2800
2400
2600
2800
account for inhomogeneitiesEmpirical corrections and fitting of parameters leads to acceptable 1600
1800
2000
2200
1600
1800
2000
2200
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parameters leads to acceptable accuracy in most situations
50 100 150 200 250 300
1200
1400
Y distance [pixels]50 100 150 200 250 300
1200
1400
Y distance [pixels]
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Uncertainties in Proton TherapyUncertainties in Proton Therapy
Inter-and intra-fractional variationsInter-and intra-fractional variationsDosimetric : CT numbers, high-Z artifacts,
i t t i dconversion to stopping powers, dose computation approximationsAssumption of Radiobiological Effectiveness (RBE) to be 1.1…
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Proton Therapy of Moving Lung TumorsProton Therapy of Moving Lung Tumors
Prescription Dose Line
Treatment planned based on single free-breathing CT
The same treatment plan calculated on 10 phases of
10
image (perceived dose distribution)
pthe 4D CT image
Dong
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Inter-Fractional Variations
IMRT: 7 beams plan
Original Plan After Two weeks of Radiotherapy
p
Proton: 3 beams planProton: 3 beams plan
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Vulnerability of Protons to UncertaintiesVulnerability of Protons to Uncertainties
Protons more sensitive to uncertainties thanProtons more sensitive to uncertainties than photonsI t i d l (i th 1980 )Importance recognized early (in the 1980s)
Limited by tools by today’s standard (repeat CTs, 4D CT) t bt i tit ti i f ti b t4D CT) to obtain quantitative information about the consequences and find solutions
Rudimentary early solutions were developedRudimentary early solutions were developed …
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Accounting for UncertaintiesAccounting for Uncertainties
Margins, Apertures and g , pCompensators
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Beam Specific Margins for UncertaintiesBeam-Specific Margins for Uncertainties -
Proximal Margin
Protons
Proximal Margin
CTV Lateral Margin =Lateral Margin PTV Margin
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Distal Margin
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Compensator “Smearing” to Account for Lateral P iti Ch i I h itiPosition Changes in Inhomogeneities
15 Urie, et al, Phys. Med. Biol., 1983.
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Scanning Beams and Intensity Modulated Proton TherapyIntensity Modulated Proton Therapy
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Scanning Beams and IMPTScanning Beams and IMPTBeam 174 MeV
3.2mBeam Profile Monitor
Beamlet
Scanning Magnets
Helium Chamber
S t P iti M itSpot Position MonitorDose Monitor 1, 2 20 cm
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Isocenterσ = 0.8 cm
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Scanning Beams and IMPTScanning Beams and IMPT
Range of energies (72 – 221 MeV for Hitachi)Range of energies (72 – 221 MeV for Hitachi)Spots positioned by magnetic steeringDiscrete spot scanning or raster scanning Spots from placed in layers in the target for p p y geach of multiple fieldsSpot intensities determined usingSpot intensities determined using optimization techniques
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Layer-by-Layer Scanning of Proton Beamlets for IMPTProton Beamlets for IMPT
19 Spot positionMovie.10Movie.10 Cumulative dosedoseMovie.9Movie.9
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Dose Calculations for Intensity Modulated Proton TherapyProton Therapy
Beamlets are assumed to be GaussianBeamlets are assumed to be GaussianApproximations related to
Scattering from beam line componentsNuclear interactions
Contributions from thousands of “spots” of specified energies and intensities constituting the scanned beam are summedMinor inaccuracies can add up to significant p gdiscrepancies
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Intensity Modulated Proton TherapyIntensity Modulated Proton Therapy
Three possible IMPT optimization strategiesThree possible IMPT optimization strategiesSingle field uniform dose (SFUD)
Robustness similar to PSPTRobustness similar to PSPT
3D IMPTIn-between robustnessIn between robustness
Distal edge trackingMost vulnerable to uncertaintiesost u e ab e to u ce ta t es
No need for compensatorNormally no apertureNormally, no aperture
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Accounting for Uncertainties in IMPTAccounting for Uncertainties in IMPT
No such thing as smearing - consequences ofNo such thing as smearing - consequences of lateral variations in inhomogeneities ignoredF SFUD di t l d i l iFor SFUD, distal and proximal margins = those for PSPTFor 3D IMPT and DET, no current solutionFuture solution- Robust optimizationp
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Evaluation of Proton Plans
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The PTV Concept is Not Valid for ProtonsThe PTV Concept is Not Valid for Protons
Main reason: Planning margins to CTV areMain reason: Planning margins to CTV are different in different directions and for different beamsdifferent beamsThen how do we
Evaluate plans using DVHsCompare proton plans with photon plansAdd proton dose distributions to photon dose distributions
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PTV Concept is Not Adequate Even for PhotonsEven for Photons
PTV
CTVCTV
DVH for PTV represents the “worst” case scenarioDVH for CTV represents the “best” case scenariao
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p
Levegrun et al, IJROPB 2000: No prostate dose response
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One Solution
“Uncertainty” (or “Worst Case”) Analysis
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Parallel Opposed Prostate – TransversePrescription (75 6 CGE) Isodose
5 mm Post.Prescription (75.6 CGE) Isodose
Range –3.5%g
Range +3.5%
Nominal
275 mm Ant.
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Some Clinical ResultsSome Clinical Results
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Planning Study (23 patients) to Design Randomized PSPT vs IMRT NSCLC TrialRandomized PSPT vs. IMRT NSCLC Trial
0 001
(%)
Aut oPl an Dosi mpl an Pr ot onpl an
0 820. 00
0. 0790. 015
0. 0010. 001
0. 230. 4010. 0010. 0
0. 00030. 005
60708090
100
ativ
e Vo
lume
0. 9
0. 820. 450. 079
0. 0
0. 4010. 069
01020304050
[Gy]
or
Rela
0
PTVD
at95
%V
PTVD
2cc
Lung
Vat 5
Gy
Lung
Vat 2
0Gy
MLD
Cor d
Dose
at1%
V
EsoD
1/3G
y
Hear
t D1/
3Dose
Dose-volume indices are averaged over 23 patient
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D-V Indices of the First 5 Patients Enrolled on R d i d PSPT IMRT NSCLC T i lRandomized PSPT vs. IMRT NSCLC Trial
8000
Aut oPl an Cl i ni cal Phot on Cl i ni cal Pr ot on
6000
7000
3000
4000
5000
Dose
[cG
y]
1000
2000
3000Do
0
1000
PTVD95 LungV20 MLD Cor dD1% EsoD1/ 3 Hear t D1/ 3
30Dose-volume indices are averaged over 5 patient
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Proton Therapy vs. 3D CRT & IMRT of Locally Advanced NSCLCLocally Advanced NSCLC
Median Total DoseMedian Total Dose3D CRT & IMRT: 63 GyProton therapy: 74 CGEProton therapy: 74 CGE
Esophagitis Gr ≥ 3 Tx Related Pneumonitis Gr ≥ 3
40.00%45.00%
Esophagitis Gr ≥ 3
30 00%
35.00%
Tx Related Pneumonitis Gr ≥ 3
3D CRTIMRTP t
25.00%30.00%35.00%
20.00%25.00%30.00%
Protons
10.00%15.00%20.00%
5 00%
10.00%15.00%
310.00%5.00%
0.00%5.00%
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Reduction of Bone Marrow Toxicity inReduction of Bone Marrow Toxicity inReduction of Bone Marrow Toxicity in Reduction of Bone Marrow Toxicity in Patients with LA NSCLC treated with Patients with LA NSCLC treated with Concurrent ChT/ PBT compared to IMRTConcurrent ChT/ PBT compared to IMRTConcurrent ChT/ PBT compared to IMRTConcurrent ChT/ PBT compared to IMRT
Ritsuko Komaki,M.D,
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Tumor Volume and BM toxicityTumor Volume and BM toxicity
GTV (cc)GTV (cc) NN % of % of >>2 Grade 2 Grade Hemoglobin Hemoglobin
EventsEvents
P valueP value % of % of >>2 Grade 2 Grade PlateletsPlateletsEventsEvents
P valueP value
(%)(%) (%)(%)
>>100100 PBT = 19PBT = 19IMRT= 64IMRT= 64
1 (5%) 1 (5%) 24 (38%)24 (38%)
<0.001<0.001 1 (5%)1 (5%)3 (5%)3 (5%)
0.0290.029IMRT= 64 IMRT= 64 24 (38%) 24 (38%) 3 (5%)3 (5%)
>>200200 PBT = 7PBT = 7IMR 43IMR 43
0 (0%)0 (0%)19 (44)19 (44)
0.0010.001 1 (14%)1 (14%)2 (5%)2 (5%)
0.0560.056IMR= 43IMR= 43 19 (44)19 (44) 2 (5%)2 (5%)
>>300300 PBT = 5PBT = 5 0 (0%)0 (0%) 0.720.72 0 (0%)0 (0%) 0.3070.307IMR= 30IMR= 30 14 (47)14 (47) 2 (7%)2 (7%)
>>400400 PBT = 3PBT = 3 0 (0%)0 (0%) 0.1980.198 0 (0%)0 (0%) 0.7540.754IMR= 26IMR= 26
( )( )7 (27%)7 (27%)
( )( )2 (8%)2 (8%)
>>500500 PBT = 2PBT = 2 0 (0%)0 (0%) 0.3960.396 0 (0%)0 (0%) 0.3660.366
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>>500500 PBT 2PBT 2IMR = 19IMR = 19
0 (0%)0 (0%)7 (37%)7 (37%)
0.3960.396 0 (0%)0 (0%)1 (5%)1 (5%)
0.3660.366
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Tumor Volume and BM toxicityTumor Volume and BM toxicity
GTV GTV (cc)(cc)
NN % of % of >>2 2 Grade Grade
NeutrophilNeutrophil
P P valuevalue
% of % of >>2 2 Grade Grade WBCWBC
P P valuevalue
% of % of >>2 2 Grade Abs. Grade Abs.
LymphocyteLymphocyte
P valueP value
Neutrophil Neutrophil EventsEvents
(%)(%)
WBCWBCEvents Events
(%)(%)
Lymphocyte Lymphocyte EventsEvents
(%)(%)
>>100100 PBT = 19PBT = 19IMRT=62 IMRT=62
554444
0.0280.028 26266767
0.0140.014 1001009797
<0.001<0.001
>>200200 PBT = 7PBT = 7IMRT= 42IMRT= 42
004343
0.270.27 14146363
0.1820.182 1001009898
0.0010.001
>>300300 PBT = 5PBT = 5IMRT = 29IMRT = 29
004848
0.3280.328 20206363
0.2740.274 1001009696
<0.006<0.006
>>400400 PBT = 3PBT = 3IMRT= 25IMRT= 25
004040
0.7040.704 33335757
0.4280.428 1001009696
0.6120.612
34>>500500 PBT = 2PBT = 2
IMRT = 18IMRT = 1800
33330.8130.813 5050
44440.5790.579 100100
1001000.8810.881
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Current Research at MDACC (In Collaboration with MGH)(In Collaboration with MGH)
Reduction in uncertainties andReduction in uncertainties and accounting of residual uncertainties
Stopping powers improvementStopping powers improvementGating and breath-holdAdaptive replanningp p gDose calculation accuracy
IMPT developmentpRobust optimizationEvaluation of robustness of treatmentEvaluation of robustness of treatment plansDose accumulation
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Dose accumulationTrials and studies
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SummarySummary
Abundant room for improvement ofAbundant room for improvement of efficiency, cost-effectiveness, accuracy and quality of treatmentsand quality of treatmentsA boon and a bain for physicistsEven in the current state of the art PT has the potential to be significantly superior for certain sites
LungPediatrics…
36Future potential is great
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However, Be Mindful of Irrational Exuberance LestExuberance Lest …
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Parachute use to prevent death and major trauma l t d t it ti l h ll t ti i frelated to gravitational challenge: systematic review of
randomised controlled trials – Smith et al, BMJ 2003;327:1459-14612003;327:1459-1461
Conclusion:As with many interventions intended to prevent ill health, the effectiveness of parachutes has not been subjected to rigorous evaluation by usingbeen subjected to rigorous evaluation by using randomised controlled trials. Advocates of evidence based medicine have criticised the adoption of interventions evaluated by using only observational data. We think that everyone might benefit if the mostWe think that everyone might benefit if the most radical protagonists of evidence based medicine organised and participated in a double blind,
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randomised, placebo controlled, crossover trial of the parachute.
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Thank YouThank You
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