Normal Tissue Imaging · UNC 4DCT Yaremko BP, et al. IJROBP 2007; 562-571. 3D Plan IMRT Plan UNC From Marsden Lavrenkov et al. Radiotherapy and Oncology 82:156-162, 2007 Conventional

ASTRO 2003: High dose Tx for Lung Ca 2010-5-14

L. Marks/jh 1

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)

UNCUNC

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

UNCUNC


L. Marks/jh 2

UNCUNCFrom Tucker &Travis, MDACC, IJROBP 38:1045, 1055 ,97. Mice

UNCUNC

AnatomyAnatomy FunctionFunction

UNCUNC


L. Marks/jh 3


UNCUNC


UNCUNC

••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


L. Marks/jh 4

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


L. Marks/jh 5

UNCUNC

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

UNCUNC

ppCTCT--based planning: based planning:

EsophagusEsophagus

3D dose 3D dose distributiondistribution OutcomeOutcome

(symptom)(symptom)

DVHDVH

UNCUNC


L. Marks/jh 6

AnatomyAnatomyPhysiologyPhysiology

3D dose 3D dose distributiondistribution OutcomeOutcome

(symptom)(symptom)

DVHDVH

UNCUNC

y gyy gySpatial informationSpatial information

Anatomically Anatomically Correct DVHCorrect DVH

UNCUNC

Esophagus contours: Esophagus contours: variable area variable area

(volume)(volume)

SuperiorSuperior InferiorInferior

UNCUNC


L. Marks/jh 7

esophagealesophagealcontourscontours 3D metrics3D metricsCTCT

correctioncorrection

Univariate and Multivariate AnalysesUnivariate and Multivariate Analyses

UNCUNC

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

UNCUNC

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

UNCUNC


L. Marks/jh 8

UNCUNC

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


L. Marks/jh 9

Patient #2Patient #2

UNCUNCFrom Marks et al. IJROBP 26:659-668

Functional Imaging PaperFunctional Imaging PaperCT SPECT (DFH)

UNCUNC

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

UNCUNC

MDAH (Shouama 2007)MDAH (Shouama 2007)•• Marsden (Lavrenkov 2007, Marsden (Lavrenkov 2007,

Christian 2005Christian 2005))•• MRI; Sheffield (Ireland 2007)MRI; Sheffield (Ireland 2007)


L. Marks/jh 10

4DCT-derived ventilation image

4DCT4DCT

4DCT

Volume-constrained baseline plan Ventilation-constrained plan

UNCUNC

4DCT4DCT

Yaremko BP, et al. IJROBP 2007; 562-571.

3D Plan IMRT Plan

UNCUNC

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

UNCUNC

From Christian et al. Radiotherapy and Oncology 77:271-277, 2005

SPECT Plancontralateral lung

With SPECT


L. Marks/jh 11

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

UNCUNC

MDAH: Shouama et al. IJROBP 68:1349-1358, 2007

University of Sheffield (UK)University of Sheffield (UK)

UNCUNC

From Ireland et al. IJROBP 68:273-281, 2007

Hyperpolarize 3He MRI 1H MRI


L. Marks/jh 12

DukeDuke

MDAHMDAH

UNCUNC

MDAHMDAH

CTCT--based based planplan

Optimize per Optimize per DVH’sDVH’s

Compare Compare SPECTSPECT--based based

UNCUNC

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

UNCUNC

metricsmetrics

SPECTSPECT--based plan based plan

Optimized based Optimized based on SPECTon SPECT

better!!better!!


L. Marks/jh 13

Can’t assume IMRT will “clean it up”. Beam direction selection matters

UNC

Dose Distributions

UNC

UNCUNCDas SK, et al. Med Phys 2004; 1452-1461.

FDG-PETSPECT

Superimposed on the images are CT contoured target and OARs


L. Marks/jh 14

Target Si Fl ibilit & Littl

Traditional 3D planningTraditional 3D planning

Not much flexibility

UNCUNC

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

UNCUNC

y

•Clinically useful??Size

Pulmonary Function

Imaging changes in normal tissue during/after therapy

UNCUNC


L. Marks/jh 15

Pre-RT SPECT

6 month Post-RT

Pre-RT CT

Patient #1Patient #1

UNCUNC

SPECT 67 Gy

From Marks et al. IJROBP 26:659-668 1993.

PostPost--RTRT

33G 33G

UNCUNC

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


L. Marks/jh 16

6-month Population DRC

UNCUNC

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

UNCUNC

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

UNCUNC

00

Regional Dose Regional Dose (Gy) (Gy)

% R

educ

t%

Red

uct

20 40 600 80

20


L. Marks/jh 17

Slope of Dose Response CurveSlope of Dose Response CurveJunan Zhang 2006Junan Zhang 2006

UNCUNC

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

UNCUNC

-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

UNCUNC

PrePre--RTRT PostPost--RTRT


L. Marks/jh 18

UNCUNC

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

UNCUNC

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


L. Marks/jh 19

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)

Documents

Normal Tissue Imaging · UNC 4DCT Yaremko BP, et al. IJROBP 2007; 562-571. 3D Plan IMRT Plan UNC From Marsden Lavrenkov et al. Radiotherapy and Oncology 82:156-162, 2007 Conventional