normal tissue imaging · unc 4dct yaremko bp, et al. ijrobp 2007; 562-571. 3d plan imrt plan unc...
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ASTRO 2003: High dose Tx for Lung Ca 2010-5-14
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Normal Tissue ImagingNormal Tissue Imaging
Lawrence B Marks M DLawrence B Marks M DLawrence B. Marks, M.D.Lawrence B. Marks, M.D.
Radiation OncologyRadiation OncologyUniversity of North Carolina at Chapel HillUniversity of North Carolina at Chapel Hill
AgendaAgenda• Pre-treatment
• Normal tissue definition: not always so obvious
• Anatomy vs function• During treatment (not much)
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g ( )• Changes in normal anatomy/function• Secondary changes due to tumor response
• Post-Treatment• Imaging to detect normal tissue injury
Pre-treatment normal tissue imaging
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UNCUNCFrom Tucker &Travis, MDACC, IJROBP 38:1045, 1055 ,97. Mice
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AnatomyAnatomy FunctionFunction
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AnatomyAnatomy FunctionFunction
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AnatomyAnatomy FunctionFunction
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••CTCT--based planning based planning ••Actually pretty good!Actually pretty good!••Physiologic understandingPhysiologic understanding
••Better!Better!
Tubules that Tubules that go deeper into go deeper into the medullary the medullary portion of the portion of the
anatomy/case4/4_2.html
portion of the portion of the kidney do kidney do
MORE urine MORE urine concentratingconcentrating
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UNCUNCMarks IJROBP 34:1168, 1996
UNCUNCMarks IJROBP 34:1168, 1996
AR: acoustic radiation
MGB: medial geniculate body
IOF: inferior occifitofrontal fascicleUF: uncinate fascicleuncinate fascicle
UNCUNCBurgel U, et al. Neuroimage 1999; 489-499.
OR: optic radiation
LGB: lateral geniculate body
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a, c, e: optic radiation
b, d, f: lateral geniculate bodyBurgel U, et al. Neuroimage 1999; 489-499.
Incorporating Incorporating anatomic/functional anatomic/functional
information to improve information to improve
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ppCTCT--based planning: based planning:
EsophagusEsophagus
3D dose 3D dose distributiondistribution OutcomeOutcome
(symptom)(symptom)
DVHDVH
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AnatomyAnatomyPhysiologyPhysiology
3D dose 3D dose distributiondistribution OutcomeOutcome
(symptom)(symptom)
DVHDVH
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y gyy gySpatial informationSpatial information
Anatomically Anatomically Correct DVHCorrect DVH
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Esophagus contours: Esophagus contours: variable area variable area
(volume)(volume)
SuperiorSuperior InferiorInferior
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esophagealesophagealcontourscontours 3D metrics3D metricsCTCT
correctioncorrection
Univariate and Multivariate AnalysesUnivariate and Multivariate Analyses
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OutcomeOutcomeRTOG acute RTOG acute
& late toxicity& late toxicity
““corrected”corrected”3D metrics3D metrics
Acute ≥ grade 2Acute ≥ grade 2 0.0080.008 0.0050.005
Toxicity = f (Dosimetric Parameters)Toxicity = f (Dosimetric Parameters)
V 50 V 50 CorrectedCorrected
V 50 V 50 UncorrectedUncorrected
pp--valuesvalues
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Acute ≥ grade 3Acute ≥ grade 3 0.050.05 0.0030.003
Late ≥ grade 1Late ≥ grade 1 0.14 0.14 0.080.08
Adapted from Kahn Adapted from Kahn et al. et al. 2004 (Duke)2004 (Duke)
CT + Anatomy, CT + Anatomy, physiologyphysiology >> CT aloneCT alone
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Representative Canine Lung Data Representative Canine Lung Data
UNCUNCFrom Osborne et al. J Comput Assist Tomogr 9:73-77, 1985
SPECT Scintillation
Duke
Accuracy Accuracy of SPECT?of SPECT?
Osborne et al.Osborne et al. J of Comp Assist Tomography, 9(1):73J of Comp Assist Tomography, 9(1):73--77, 198577, 1985Duke
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Patient #2Patient #2
UNCUNCFrom Marks et al. IJROBP 26:659-668
Functional Imaging PaperFunctional Imaging PaperCT SPECT (DFH)
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of C
T-D
efin
ed
Lung
Vol
ume
From Marks, Spencer, Sherouse et al. IJROBP 33:65-75
of S
PE
CT-
Def
ined
Lu
ng V
olum
e
FunctionFunction--based Lung Treatment Planning based Lung Treatment Planning
•• Duke (Marks 1995, McGuire Duke (Marks 1995, McGuire 2005)2005)
•• NKI (Seppenwoold 2000)NKI (Seppenwoold 2000)•• MDAH (Shouama 2007)MDAH (Shouama 2007)
SPECT SPECT & IMRT& IMRT
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MDAH (Shouama 2007)MDAH (Shouama 2007)•• Marsden (Lavrenkov 2007, Marsden (Lavrenkov 2007,
Christian 2005Christian 2005))•• MRI; Sheffield (Ireland 2007)MRI; Sheffield (Ireland 2007)
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4DCT-derived ventilation image
4DCT4DCT
4DCT
Volume-constrained baseline plan Ventilation-constrained plan
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4DCT4DCT
Yaremko BP, et al. IJROBP 2007; 562-571.
3D Plan IMRT Plan
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From Marsden
Lavrenkov et al. Radiotherapy and Oncology 82:156-162, 2007
Conventional 3D CT Plan
Without functional lung data, beams pass through a large area of the functional
t l t l l
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From Christian et al. Radiotherapy and Oncology 77:271-277, 2005
SPECT Plancontralateral lung
With SPECT
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Pre-RT SPECT 3 field clinical planBeam Set up
Plan optimized for MLD
Optimized for MpLD
Optimized for V20 with
UNCUNCNKI: Seppenwoold et al. Radiotherapy and Oncology 63:165-177, 2000
for MLD MpLD V20 with perfusion
Conventional CT Plan SPECT Plan
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MDAH: Shouama et al. IJROBP 68:1349-1358, 2007
University of Sheffield (UK)University of Sheffield (UK)
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From Ireland et al. IJROBP 68:273-281, 2007
Hyperpolarize 3He MRI 1H MRI
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DukeDuke
MDAHMDAH
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MDAHMDAH
CTCT--based based planplan
Optimize per Optimize per DVH’sDVH’s
Compare Compare SPECTSPECT--based based
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metricsmetrics
SPECTSPECT--based plan based plan
Optimized based Optimized based on SPECTon SPECT
CTCT--based based planplan
Optimize per Optimize per DVH’sDVH’s
Compare Compare SPECTSPECT--based based
Ha Ha: Ha Ha: SPECT is SPECT is
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metricsmetrics
SPECTSPECT--based plan based plan
Optimized based Optimized based on SPECTon SPECT
better!!better!!
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Can’t assume IMRT will “clean it up”. Beam direction selection matters
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Dose Distributions
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UNCUNCDas SK, et al. Med Phys 2004; 1452-1461.
FDG-PETSPECT
Superimposed on the images are CT contoured target and OARs
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Target Si Fl ibilit & Littl
Traditional 3D planningTraditional 3D planning
Not much flexibility
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Size
Pulmonary Function
Flexibility & Need (large gain?
Little need
•More of this space is applicable
•Complex shapes more-readily addressed
Target Si
With IMRTWith IMRT
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y
•Clinically useful??Size
Pulmonary Function
Imaging changes in normal tissue during/after therapy
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Pre-RT SPECT
6 month Post-RT
Pre-RT CT
Patient #1Patient #1
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SPECT 67 Gy
From Marks et al. IJROBP 26:659-668 1993.
PostPost--RTRT
33G 33G
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PrePre--RTRT
33Gy 33Gy
33Gy 33Gy
100100
0
20
40
60
80
100
0 20 40 60 80 100
Regional Dose (Gy)Regional Dose (Gy)
0
20
40
60
80
100
0 20 40 60 80 100
% % ReductionReductionRegionalRegionalPerfusionPerfusion
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6-month Population DRC
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Junan Zhang and Sumin Zhou 2006Junan Zhang and Sumin Zhou 2006
40
60
80
100
3mo (37)6mo (43)9mo (13)12mo (30)15mo (7)18-21mo (11)24mo (9)55-85mo (6)
PercentReductionin RegionalP f i
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0
20
40
0 20 40 60 80 100
gPerfusion
Regional Dose (Gy)Woel et al 2002Woel et al 2002
4040
12121818
66
>55>55
tion
Per
fusi
onti
on P
erfu
sion
p=0.0001R2 > 0.93
Linear Fit
60
80
100
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00
Regional Dose Regional Dose (Gy) (Gy)
% R
educ
t%
Red
uct
20 40 600 80
20
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Slope of Dose Response CurveSlope of Dose Response CurveJunan Zhang 2006Junan Zhang 2006
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0
25
50
75
100
PercentPatientsWith
CT DensityIncreases
0 10 20 30 40 50 60
Normalized Total Dose (Gy)
Data from Mah, PMH, IJROBP 28:563, 94
0
10
20
30
40
NormalizedIncreasein CT
Density
0 10 20 30 40 50 60
Regional Dose (Gy)
From Boersma, NKI, R & O 32:201, 1994
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-250
0
250
500
750
1000
Increasein
CTNumber
0 20 40 60 80 100
Dose (Gy)Levinson (Duke), Rad Onc Levinson (Duke), Rad Onc 48:53, 1998
••Different endpointsDifferent endpoints••Steeper than SPECT dose Steeper than SPECT dose response curvesresponse curves
New Defect
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PrePre--RTRT PostPost--RTRT
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Co-registration of MRI and 11C-methionine PET
Received 3 Gy Received 57 Gy
Adapted from Buus et al. Radiother Oncol 2004 73:289-296.
Dose Dose dependent dependent reductions reductions in function in function in in partsparts of of
parotid parotid
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Registration of CT and 11C-methionine PET
Adapted from Buus et al. Radiother Oncol 2004 73:289-296.
parotid parotid glandgland
AcknowledgementsAcknowledgementsRadiation Oncology/PhysicsRadiation Oncology/Physics
•• Janet BaileyJanet Bailey•• David FriedDavid Fried•• Liyi XieLiyi Xie•• Jessica HubbsJessica Hubbs•• Junan ZhangJunan Zhang•• Micheal Lawrence Micheal Lawrence
PulmonaryPulmonary: : •• Patricia Rivera, MDPatricia Rivera, MD•• Rod Folz, MDRod Folz, MD
Nuclear MedicineNuclear Medicine•• William McCartney, MDWilliam McCartney, MD
•• Arif Sheik, MDArif Sheik, MD
•• Terrence Wong, MD, PhDTerrence Wong, MD, PhD
UNCUNC
•• Micheal Lawrence Micheal Lawrence •• Sumin Zhou, Ph.DSumin Zhou, Ph.D•• Shiva Das, PhDShiva Das, PhD•• Junan Zhang, PhDJunan Zhang, PhD•• Daniel Kahn, PhDDaniel Kahn, PhD
g, ,g, ,
•• Salvador BorgesSalvador Borges--Neto, MDNeto, MD
Data Management/StatisticsData Management/Statistics
•• Donna Hollis, MSDonna Hollis, MS
•• Robert Clough, BARobert Clough, BA
NIH and DOD Grants
UNC for PLUNC Tx Planning Software
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AcknowledgmentsAcknowledgments•• Physics teams at Duke and UNCPhysics teams at Duke and UNC•• Charles Curle, Shiva Das (integral dose)Charles Curle, Shiva Das (integral dose)•• Su Min Zhou (normal tissue data)Su Min Zhou (normal tissue data)•• Mark Kostich, photographer/dosimetristMark Kostich, photographer/dosimetrist•• PostPost--docs: Micheal Lawrence, Janet Bailey, David Fried, Liyi docs: Micheal Lawrence, Janet Bailey, David Fried, Liyi
Xie, Jessica Hubbs, Jiho Nam, Mert Saynack, Jinli Ma, Xie, Jessica Hubbs, Jiho Nam, Mert Saynack, Jinli Ma, Senem Demirci, Junan Zhang Senem Demirci, Junan Zhang
UNCUNC
, J g, J g•• QA data: QA data: Ellen L. Jones, Melanie Wright, Christopher G. Ellen L. Jones, Melanie Wright, Christopher G.
Willett, Fang Fang Yin, Kim L. Light, Jessica L. Hubbs, Willett, Fang Fang Yin, Kim L. Light, Jessica L. Hubbs, Debra L. Georgas, Robert Clough, Mingwei LeiDebra L. Georgas, Robert Clough, Mingwei Lei
•• Therapists, DosimetristsTherapists, Dosimetrists•• Varian, Lance Armstrong Foundation, DOD, NIHVarian, Lance Armstrong Foundation, DOD, NIH•• PLUNC (University North Carolina at Chapel Hill)PLUNC (University North Carolina at Chapel Hill)