agenda - aapm.org

ASTRO2003:High doseTx for LungCa 2007-8-16

L. Marks/jh 1

Functional imaging for RT Functional imaging for RT planning: planning:

Normal tissue and tumorNormal tissue and tumor

Larry Marks, M.D.Larry Marks, M.D.Shiva Das, Ph.D.Shiva Das, Ph.D.

Duke University Medical CenterDuke University Medical Center

Duke UniversityDuke University

AgendaAgendaFunctionalimagingvs. incorporatingfunctional

info into CT-basedplanningNormal tissueand TumorInterpret functional data= f (anatomy

knowledge)Shortcomingsof nuclearmedicineimagesPET (tumor),SPECT(normal tissues),MRI

(both)Functionalimaging:studyRT-inducedregional

injury3D basedplanningvia functionaldataFunctionalimagingchangesDURING Tx?

Helps plan tx?


AnatomyAnatomy FunctionFunction




L. Marks/jh 2


••CTCT--based planningbased planning••Actually pretty good!Actually pretty good!••PhysiologicunderstandingPhysiologic understanding

••Better!Better!


anatomy/case4/4_2.html

TubulesthatTubulesthatgo deeper intogo deeper intothethe medullarymedullaryportion of theportion of the

kidney dokidney doMORE urineMORE uri neconcentratingconcentrat ing

Duke UniversityDuke UniversityMarks IJROBP 34:1168, 1996 Duke UniversityDuke UniversityMarks IJROBP 34:1168, 1996


L. Marks/jh 3

Duke UniversityDuke UniversityBurgel U, et al. Neuroimage 1999; 489-499.

OR: optic radiation

AR: acousticradiation

MGB: medial geniculate bodyLGB: lateralgeniculatebody

IOF: inferior occifitofrontal fascicleUF: uncinateuncinatefasciclefascicle


a, c, e: optic radiation

b, d, f: lateral geniculate bodyBurgel U, et al. Neuroimage 1999; 489-499.


Incorpor atingIncorporatinganatomic/functionalanatomic/functional

information to improveinfor mation to improveCTCT--basedplanning:based planning:

EsophagusEsophagus


3D dose3D dosedistr ibutiondistribution OutcomeOutcome

(symptom)(symptom)

DVHDVH


L. Marks/jh 4


AnatomyAnatomyPhysiologyPhysiologySpatial informationSpatial information

3D dose3D dosedistributiondistributio n OutcomeOutcome

(symptom)(symptom)

DVHDVH

AnatomicallyAnatomicallyCorrect DVHCorrect DVH


Esophaguscontours:Esophagus contours:variable areavariable area

(volume)(volume)


SuperiorSuperior InferiorInferior


esophagealesophagealcontourscontours 3D metrics3D metrics

OutcomeOutcomeRTOG acuteRTOG acute

& late toxicity& late toxicity

CTCT

““ correctedcorrected””3D metri cs3D metrics

correctioncorrection

Univari ateUnivariate and Multivari ate Analysesand Mul tivariate Analyses


L. Marks/jh 5


AcuteAcute≥≥≥≥≥≥≥≥ grade 2grade 2 0.0080.008 0.0050.005

AcuteAcute≥≥≥≥≥≥≥≥ grade 3grade 3 0.050.05 0.0030.003

LateLate≥≥≥≥≥≥≥≥ grade 1grade 1 0.140.14 0.080.08

Toxicity = f (Toxicity = f (DosimetricDosimetr ic Parameters)Parameters)

V 50V 50CorrectedCorrected

Adapted from KahnAdapted from Kahn et al.et al. 2004 (Duke)2004(Duke)

V 50V 50UncorrectedUncorrected

pp--valuesvalues


CT + Anatomy,CT + Anatomy,physiologyphysiology >> CT aloneCT alone


CT isnCT isn’’ t perfect.t perfect.Functional often better.Functional often better.


Functional ImagingFunctional Imaging

•• Lung: SPECT perfusionLung: SPECT perfusion

•• Li mit dose toLi mit doseto ““ goodgood”” lunglung

•• StudyStudy regionalregional normal tissueinjur ynormal tissueinjury

•• Heart: SPECT; normal tissueinj uryHeart: SPECT; normal tissue inju ry

•• Tumor: PETTumor: PET

•• Functional DVH: DF(function)HFunctional DVH: DF(function)H

•• Plan evaluation/rankingPlan evaluation/ranking


L. Marks/jh 6


APPAAPPA

APPAAPPAObliquesObliques

ObliquesObliques


Local doseLocal dose→→→→→→→→ local perfusion losslocal perfusion lossSPECT perfusionSPECT perfusion

(micro(micro--emboli)emboli)

∑∑∑∑∑∑∑∑ Local effectsLocal effects →→→→→→→→ global functionalglobal functionalchangeschanges

pulmonary functionpulmonary functiontests,symptomstests,symptoms

UsingfunctionalimagingtoUsingfunctionalimaging tostudynormal tissuetoxicitystudy normaltissuetoxicity

Duke UniversityDuke University Duke UniversityDuke University

Prospective Study of RTProspective Study of RT--InducedLung injuryInducedLung injury

•• >300patients enrolled since1992;87%>300 patients enrolled since1992;87%white, 45% male,white, 45% male, 70% lung pri mary70% lung pri mary

•• PrePre-- andand serialserial postpost--RT evaluationsRT evaluations•• Function: Pulmonary function tests(Function: Pulmonary function tests(PFTsPFTs))•• Imaging: SPECT perfusion scan, CT scanImaging: SPECT perfusion scan,CT scan

•• EndpointsEndpoints•• Symptoms,radiographs,Symptoms,radiographs, PFTsPFTs


L. Marks/jh 7

0

20

40

60

80

100

0 20 40 60 80 100

RegionalDose(Regional Dose(GyGy))

0

20

40

60

80

100

0 20 40 60 80 100

%%ReductionReductionRegionalRegionalPerfusionPerfusion -25

0

25

50

75

100

PE

RC

EN

TR

ED

UC

TIO

NIN

PE

RF

USI

ON

0 2000 4000 6000 8000

DOSE(cGy)

12 MONTHS

9 MONTHS

6 MONTHS

3 MONTHS

1.5 MONTHS

Marks 1997Marks 1997

From: Steppenwolde & Lebes que Sem Rad Oncol 11:247, 2001


∑∑∑∑∑∑∑∑VVdd ×××××××× RRdd ==

Sum ofSum ofpredictedpredicted

regional injurie sregional injurie s““ integral injuryintegral injury ””(overall response(overall response

parameter)parameter)

%%reductionreductionperfusionperfusion

regional doseregional doseDD

VVdd

%%lunglung

““ volumevolume””

differentialdifferentialDVHDVH

dosedoseresponseresponse

DDregionaldoseregional dose

RRdd

ddmaxmax

d = 0d = 0


L. Marks/jh 8


0 10 20 30 40 50-60

-40

-20

0

20

40

60

Overall Group

R = 0.30,p = 0.005

Predicted Reduction in PFTs (%)

ActualReduction

DLCO(%)

y = x


SurgerySurgery: %: % PerfusedPerfusedLung RemovedLung Removed vsvs..% Declinein Pulmonary Function% Declinein Pulmonary Function

Julius (9)Julius (9) 0.800.80CordinerCordiner (18)(18) 0.820.82Pierce(45)*Pierce(45)* 0.87 0.560.87 0.56BolligerBolliger (22)(22) 0.81 0.740.81 0.74GiordaioGiordaio (41)*(41)* 0.870.87

Correlation CoefficientCorrelation Coefficient

FEVFEV11DLCODLCO

** some%some% ““ segmentssegments”” removedremovedadapted from Fan 2001adapted from Fan 2001

Author (Number pts)Author (Number pts)

Prospective HEART StudyProspectiveHEART Study•• PatientsPatients

•• 19981998--2005;130pts with left2005; 130pts with left--sided breast casided breast ca•• Agerange 26Age range26--82,median 5482, median 54

•• TreatmentTreatment•• Photon tangents46Photon tangents46--5050 GyGy•• Chemotherapy before RT: 64%Chemotherapy before RT: 64%

•• Study designStudy design•• Single photon emissioncomputed tomographySingle photon emission computed tomography

(SPECT) to assessleft ventricular(SPECT) to assessleft ventricular perfusionperfusion•• Pre & serial postPre & serial post--RT SPECT scans comparedRT SPECT scanscompared•• 90 patients90 patients with normal prewith normal pre--RT scans inRT scansin

present analysispresentanalysis


L. Marks/jh 9


Pre-RT Post-RTPre-RT Post-RT

EvensES,et al. Seminarsin Radiat Oncol 2007;72-79.Duke UniversityDuke University

PrePre--RTRT PostPost--RTRT

New Defect


66 11%(11%(6/556/55)) 39%(39%(12/3112/31)) 0.000.00

1212 7%(7%( 3/443/44)) 25%(25%(6/246/24)) 0.030.03

1818 0%(0%( 0/250/25)) 13%(13%(2/162/16)) 0.070.07

2424 0%(0%( 0/140/14)) 31%(31%(4/134/13)) 0.020.02

M onthsM onthspostpost--RTRT

Perfusion DefectsPerf usion Defects

YesYesNoNo

Ratesof WallRatesof Wall--Motion AbnormalitiesMotion Abnormali tiesWith or Wit hout Perfusion DefectsWith or Wit hout Perfusion Defects

pp--valuevalue22--tailedtailed

M arks ASTRO 2002M arks ASTRO 2002


L. Marks/jh 10


PerfusionPerfusionchangeschanges

cardiac wallcardiac wallmotionmotionabnormaliti esabnormalities

changesinchangesinejection fraction,ejection fract ion,symptomssymptoms

RTRT

Volume Dependence- set-up accuracy


Functional ImagingFunctional Imaging

•• Target delineationTarget delineation


Rate of PETRate of PET--defined changedefined changein grosstarget for lungin grosstarget for lung

cancercancer

MunleyMunley (1996)*(1996)* 34% (12/25)34% (12/25)KifferKiffer (1998)(1998) 27% (4/15)27% (4/15)Nestle(1999)Nestle (1999) 35% (12/34)35% (12/34)

*Higher now: Availability, Experience,Comfort level,Availability, Experience,Comfort level,AcceptableAcceptable

Duke UniversityDuke University2/14 (14)12/14 (86)14Gondi et al. 2007

7/21 (33)11/21 (52)18/21(86)21Grills et al. 2006

5/19 (26)5/19 (26)10/19(52)19Ashamalla et al. 2005

3/18 (17)7/18 (39)10/18(55)18M essaet al. 2005

11/21(52)3/21 (14)14/21(67)21Van der Wel, et al. 2005

21/92(23)24/92 (26)45/92(49)101Deniaud-Alexandre, et al.2005

3/24 (12)11/24 (46)14/24(58)26Bradley et al. 2004

4/6 (66)1/6 (17)5/6 (83)6Cienik et al. 2003

5/23 (22)5/23(22)30Mah et al. 2002

4/11 (36)7/11 (64)11/11(100)11Erdi et al. 2002

16/102(16)22/102(21)38/102(37)102Mac Manus et al. 2001

29/63(40)16/63 (22)45/73(62)73Vanuyselet al. 2000

9/34 (26)3/34 (9)12/34(35)34Nestleet al. 1999

12/35 (34)12/35(34)35M unley et al. 1996

4/15(27)4/15(27)15K iffer et al. 1998

GTV decrease(%)

GTV increase(%)

Overall changesinGTV (%)

No. of ptsAuthor/year

Rate of FDG-PET -defined changein GTV for NSCLC


L. Marks/jh 11

88%reductionin GTV

Atelectasis

Gondi V, et al. IJROBP 2007; 187-195.(University of Wisconsin)Duke UniversityDuke University

M agnitude of changesin CT-basedGTV and PET-CT basedGTVamong observersof headand neckcancerpatients

CT GTV changePET-CT GTV change

PET: lessinter -observer variability vs. CT

AshamallaH, et al. IJROBP2007 ; 388-395. (Cornell University)


CT GTV (overallSD: 1.02) FDG/PET-CT GTV (overallSD: 0.42)

subcarinal LN

blood vessels

PET: lessinter -observervariability vs.CT:Lung cancer GTV delineation

SteenbakkersRJ, etal. IJROBP 2006; 435-448.( The NetherlandsCancer Instisute) Duke UniversityDuke University

Definition of GTV based on differ ent thr esholdsof SUV

SUV-normalized FDG-PET Projected onto planning CT

Hybrid FDG-PET/CT

Gondi V, et al. IJROBP 2007;187-195.


L. Marks/jh 12

Duke UniversityDuke UniversitySteering doseby PET via IM RT, Shiva Das2003


Percentile SPECTimages(F50, F90)

Anatomic plan Functional plan

The impact of incorporating functional imaginginto IMRT for NSCLC

ShioyamaY, etal. IJROBP 2007; in press.


4DCT-derivedventilation image

4DCT4DCT

4DCT

Volume-constrainedbaselineplan Ventilation -constrainedplan

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

Shortcomings of Nuclear Medicine Images

• Path-length of the positron• Challenges of registration• assume "inherently registered to CT”• Approximation

• Resolution• Window & Level: magic• Auto-segmentation of images

• They are typically not gated• Need to know anatomy and patterns

spread. (larynx example)


L. Marks/jh 13


Monte Carlo-calculated distribution of annihilation eventsaround a positron point source embedded in different tissuesas seenin the imageplane of a PET camera

SanchezSanchez--CrespoA, et al. Eur J Nucl Med Mol Imaging 2004;44CrespoA, et al. Eur J Nucl MedMol Imaging 2004;44--5151.. Duke UniversityDuke University

Functional Adaptive TherapyFunctional Adaptive Therapy

•• Adaptive vs. Functional PlanningAdaptive vs. Functional Planning•• Functional more conducive for Functional more conducive for

adaptive?? adaptive?? •• Function changes fasterFunction changes faster

•• Animal and human data supporting Animal and human data supporting physiologic changes early during physiologic changes early during therapytherapy•• Physiologic changes Physiologic changes ----> Outcome> Outcome••MRI and PETMRI and PET


Going Well,Going Well,ContinueContinue

Start TherapyStart Therapy

Alter Therapy orAlter Therapy orAbort TherapyAbort Therapy

Not goingNot goingwellwell

AssessResponseAssessResponse

Modifying therapybasedModifying therapybasedon physiologicon physiologic changeschanges

during RTduring RT


L. Marks/jh 14


Even without variation in function

patient

tumor

Align daily perSPECT (or PET)

Gamma detector

Gam

ma

dete

ctor


What maychange?Whatmaychange?

•• OxygenationOxygenation

•• Cell cycledistributionCell cycledistribution

•• GrowthfractionGrowth fraction

•• TumorgrowthTumorgrowth


Kin eticsof:Reoxygenation: Days

Experimetal models(Hall pp 106)Humans: RT and Hyperthermia (Brizel)

Resortment: DaysHuman cell LinesCell Cycle- specific drug efficacy

Repopulation: DaysWrither's, Fowler's DataHuman tri als of shortenedtreatment time


Radiobiology for theRadiologist; Eric Hall, Lippincott WilliamsAnd Wilkins, 2004, via Rockwell

Changesin P O2 in transplantedtumors in animals


L. Marks/jh 15


Sample of human data supportingSample of human data supportingphysiologic changesdur ing RTphysiologic changesduring RT

•• P O2P O2

•• MRIMRI

•• PETPET


BrizelBrizel et alet al

•• Soft tissuesarcoma(N=21)Soft tissuesarcoma (N=21)•• Serial P O2 measurements(Serial P O2 measurements(EppendorfEppendorf))

•• PrePre--RTRT•• During first wk of RT; preDuring first wk of RT; pre--heatheat•• After FIRSTheat treatmentAfter FIRSTheat treatment

•• RelatedP O2 changesto pathologicRelatedP O2 changesto pathologicresponseresponse

CancerResearch56: 5347, 1996,DukeUniversity


Resection:Assesspathologicresponse

SarcomaDiagnosis

<--- RT --->

Pre-RT

Post-RT

Post-RT/Heat

P O2Brizel, CancerResearch56: 5347,1996, DukeUniversity

<-- Heat -->

M edian 6 4 12

Duke UniversityDuke UniversityBrizel, CancerResearch 56: 5347,1996,Duke University

P O2 post-first heat/pre-tx

Earlychangesin P O2 predictfor laterpathologicresponse


L. Marks/jh 16


M eisany et al

• Invasive BreastCancer,N = 16• Adria and Cytoxan x 4• T size2-9cm• MRI for sizeand spectroscopy(choline)

-Pre Chemo-24 hrs after dose1-after 4th cycle

Radiology 233:424-31,2004,University of Minnesota


Assessclinicalresponse

BreastCancerDiagnosis

4 cycleschemo

Pre-RT

24hours

Post-chemo

M RI assessments

Meisamy Radiology 2004


<1 8/8

> 1 0/5

p < 0.01

Meisamy, Radiology 233:424-31,2004

Choline Level(24 hrs/Pre-chemo)

Responserateafter 4 Cycles


Before RT After RT

BeforeRT

At week2 of RT

Liang PC,et al. Liver Int 2007; 516-528.

Isodosedistribution ROIs

T1 contrastenhancement MRI

Time Intensity Curve of ROIs

15Gy

tumor

30Gy

spleen


L. Marks/jh 17


OutcomebyOutcomeby ““ early PETearly PET”” response to RT/CTresponseto RT/CT

0/10/11/11/1responseresponseDuri ng RTDuring RTlunglungErdiErdi

1/131/1313/1713/17Path CRPath CR2 wks post RT/CT2 wks post RT/CTlunglungChoiChoi

3/153/155/115/11Path CRPath CR2 wks post RT/CT2 wks post RT/CTlunglungRyuRyu

9%9%11/1311/13NEDNEDVariable 1Variable 1--12 mo12 molunglungPatzPatz

10%10%50%50%NED (40 pts)NED (40 pts)Wk 2Wk 2 preoppreopchemochemo

GEGE JuncJuncWeberWeber

0/60/613/1613/16NEDNED1 mo post chemo1 mo post chemoH/NH/NGrevenGreven

0/50/514/2314/23NEDNEDCycle3 chemoCycle3 chemoNHLNHLJerusalemJerusalem

1/141/1444/4444/44NEDNED6 mo6 molunglungBuryBury

0/20/23/33/3CRCREndEnd txtxlunglungAbeAbe

0/260/2656/6756/67NEDNEDAfter chemoAfter chemolymphlymphSpaepen

0/10/11/11/1NEDNEDCycle1Cycle1--2 chemo2 chemolymphlymphHokestraHokestra

No ResponseNo ResponseResponseResponseEndEnd--pointpointInterval postInterval post--txtxSiteSiteAuthorAuthor


SummarySummary• Physiology/functionwith CT-basedplanning

• Needto understandanatomyto interpretnuclearmedicine/functional images

• Functional imaging:Normal tissueandTumor• PET, SPECT, MRI• RT-inducedregional injury

• Shortcomingsof nuclearmedicine images• e.g. Pathlength, fusion

• Functional imagingchangesDURING Tx?• 3D basedplanning via functionaldata(Shiva)


Radiation Oncology:Radiation Oncology:LawrenceMarks, M.D.LawrenceMarks, M.D.JessicaJessicaHubbsHubbs, B.S., B.S.Jinl iJinli Ma, M.D.Ma, M.D.Patricia M.Patrici a M. HardenberghHardenbergh, M.D., M.D.Christopher Kelsey, M.D.Christopher Kelsey, M.D.Carol Hahn, M.D.Carol Hahn, M.D.JohnJohn KirpatrickK irpat rick , M.D., Ph.D., M.D., Ph.D.

Radiation Physics:Radiation Physics:ShivaShiva DasDas, Ph.D., Ph.D.SuSu--Min Zhou, Ph.D.Min Zhou, Ph.D.JunanJunan Zhang,Zhang, Ph.D.Ph.D.FangFang--Fang Yin, Ph.D.Fang Yin, Ph.D.MichaelMichael MunleyMunley, Ph.D., Ph.D.Daniel Kahn, Ph.D.Daniel Kahn, Ph.D.MoyedMifte nMoyedMiften , Ph.D., Ph.D.Kim Light, R.T.T., C.M.D.Kim Light, R.T.T., C.M.D.Phil AntoinePhil AntoineJaneJaneHoppenworthHoppenworth

Data/Statistics:Data/Statistics:Robert CloughRobert Clough

Donna Hollis, M.S.Donna Hollis,M.S.

AndreaAndrea TischTisch, R.T.T., R.T.T.

UNC: JulianUNC: Julian RosenmanRosenman

Nuclear Medicine:Nuclear Medicine:Terry Wong, M.D.Terry Wong, M.D.R. Edward Coleman, M.D.R. Edward Coleman,M.D.RonaldRonald JaszczakJaszczak, Ph.D., Ph.D.SalvadorBorgesSalvador Borges--NetoNeto

Varian Medical Systems,NIH CAVarian Medical Systems,NIH CA--69579 and69579andR01R01--CA33541,and DODCA33541, and DOD DAMDDAMD 1717--9898--11--8071 and8071and 1717--0202--11--0374,Lance Arm strong0374,Lance Armstrong

Pulmonary: Rodney Folz

Cardiology: MichaelBlazingMichaelBlazing

AcknowledgmentsAcknowledgments

Functional Image-Guidance to ReduceTox icity: Treatm ent Plann ing and

Technical Details

Shiva Das & Lawren ce Marks

Dept of Radiation Oncol ogy

Duke Univer sity


L. Marks/jh 18

Duke University

Asum ption: all areas of normal lung have equal funct ion.

Reality: lung funct ion is spatially heter ogeneo us.

Reduce lung toxicity: reduce dose to higher funct ioningnor mal lung ⇒⇒⇒⇒ better quality of life!

Duke University

Single Photon Emission Comp uted Tomogr aphy

SPECT provides a map of perfusion .

In animal studies : perf usion ∝∝∝∝ function

Duke University

Objectiv es

� Develop a manu al algo rit hmic methodo logy forintegrating SPECT-gui dance into the ECLIPSE treatmen tplanning optimizatio n process.

� Automate the method olog y.

� Apply in clinic!

Duke University

This is all well and good, except that ECLIPSE doesnot accept SPECT imag es …………….

Create a CT look -alike cont ainin g SPECT data

� Register SPECT to plannin g CT outside ECLIPSE� Resample SPECT to match CT slices and resolution� Make a copy of DICOM CT which will be used to

house SPECT data (“ fake” CT)� Modify DICOM header in fake CT; strip out CT Data

and replace with SPECT data� Import fake CT (SPECT data) into ECLIPSE.


L. Marks/jh 19

Duke University Duke University

� Initial IMRT plan generated without SPECT-guidance.Dose-volumes obtained in this plan are used in SPECT-guided plan.

� SPECT image is segmented into 4 areas from low to highintensity.

Methodolog y

Duke University

Methodology (cont ’d.)

� Set current SPECT structure under consideration to thelowest intensity structure.

� For all SPECT structures with higher intensity, volumesabove constraint doses are constrained to zero (maximumimportance).

� Optimize PTV dose while keeping all normal structuresother than lung within dose-volume limits.

� If PTV coverage is unsatisfactory, or normal structuresother than lung have exceeded limits, set the SPECTstructure under consideration to the next higher intensitystructure, and repeat.

Duke University

Functional Metrics

VD = volume above D Gy.

FD = function above D Gy (function = volume× SPECTintensity)

DVH: Dose volume histogram.

DFH: Dose function histogram.


L. Marks/jh 20

Duke University

Manually implemented this methodology in 5 lung cancerpatients.

� 9 beams oriented at 30° spacing on predominant tumorside.

� Primary tumor to 40 Gy, boost to 66 Gy.

Patients

Duke University

SPECT distribution can bevery spatially heterogeneous

Duke University

Dose Function Histo grams: SPECT Structur es(one patient)

Hig hest inten sity SPECT region DFH 2nd Highest intensity SPECT regionDFH

3rd Hig hest intensity SPECT regionDFH

Lowe st intensity SPECT region DFH

0 20 40 60 800

2

4

6

8

10

Dose (Gy)

%F

unct

ion

Base PlanSPECT Plan

Highest SPECTintensity structure

0 20 40 60 800

5

10

15

20

25

Dose (Gy)

%F

unct

ion

Base PlanSPECT Plan

2nd Highest SPECTintensity structure

0 20 40 60 800

5

10

15

20

25

30

Dose (Gy)

%F

unct

ion

Base PlanSPECT Plan

3rd Highest SPECTintensity structure

0 20 40 60 800

10

20

30

40

Dose (Gy)

%F

unct

ion

Base PlanSPECT Plan

Lowest SPECTintensity structure

Base

SPECT

Duke University

0 20 40 60 800

20

40

60

80

100

Dose (Gy)

%F

unct

ion

Base PlanSPECT Plan

Lung DFH

Lung Dose-Function Histog rams (5 patients)

Base

SPECT

0 20 40 60 800

20

40

60

80

100

Dose (Gy)

%F

unct

ion

Base PlanSPECT Plan

Lung DFH

0 20 40 60 800

20

40

60

80

100

Dose (Gy)

%F

unct

ion

Base PlanSPECT Plan

Lung DFH

0 20 40 60 800

20

40

60

80

100

Dose (Gy)

%F

unct

ion

Base PlanSPECT Plan

Lung DFH

0 20 40 60 800

20

40

60

80

100

Dose (Gy)

%F

unct

ion

Base PlanSPECT Plan

Lung DFH


L. Marks/jh 21

Duke University

Dose distr ibution

Non SPECT-guided plan SPECT-guided plan

Duke University

Lung function sparing above 20 Gy, 30 Gy

10.5±5.8

Average13.6± 5.2Average

7.524.526.58.042.446.1E

18.07.38.920.913.617.2D

5.927.329.014.244.652.0C

5.635.137.29.251.156.3B

15.632.037.915.851.060.6A

%Reduction

SPECT(%)

Base(%)

% ReductionSPECT(%)

Base(%)

F30F20Patient

Duke University

Clinical Applicati on

Clinician

Lawrenc e Marks, MD

(SPECT – NIH funded)

Physics

Shiva Das, PhD

Sarah McGuire, PhD

Sumin Zhou, PhD

SPECT/PET facility

Tim Turkin gton, PhD

Terry Wong, MD

Duke University

Clinical Case

� 58 yo male

� poor pulmonary fun ctio n: FEV1 0.7 liter s 20% predicted

� soli tary nodule (non -small cell)

�2.5 cm in medial rt cent ral lung

� hypermetaboli c on PET

� Patient imaged in CT-SPECT (GE Hawkeye system)


L. Marks/jh 22

Duke University

Clinical Case

� Patient imaged with 4D CT

� ITV created from union of 4DCT GTVs

� Expanded to create PTV: 1 cm margin; 1.5 cm in sup -inf

� Patient imaged in CT-SPECT (GE Hawkeye system)

� Prescription: SBRT 12 Gy ×××× 4 frac tions

Duke University

GE HAWKEYE SYSTEMPlanning CT CT from SPECT

CT from SPECT – poor qual ity (maybe notsuitabl e for dose computa tion?)

Nevert heless, very useful for registrat ion

Planning CT

CT from SPECT

SPECT

Duke University

GE HAWK EYE SYSTEM

Integrate s GE Millennium VG SPECT with low pow er X-ray tub e anddetec tor array.

X-ray generator: 2.5 mA, 140 kVp

CT: 10 mm thick slices , 256 x 256,∼∼∼∼ 1.5 mm inp lane resolutio n.

40 slices, acquired at 3 slices /minute.

SPECT: continu ous rotat ion or step-and-shoot mode.

SPECT and CT can not be acquire dsimultaneously.

Duke University

Converting SPECT to TPS readable DICOM

CT: 40 cm(1cm spacing)

SPECT: 57 cm(0.44 cm spacin g)

CT: 256 ×××× 256 ×××× 40

0.22 cm pi xel size

SPECT: 128 ×××× 128 ×××× 128

0.44 cm pi xel size


L. Marks/jh 23

Duke University


SPECT: obtai ned as interfi le form at (nucle ar medici ne form at) fromGE Hawkeye system

CT: dicom format

Interfile Format

� 2 fil es: .img and .hdr

� Can be read usin g MATLAB interfi lei nfo(), inte rfil eread()

� Info

� TotalNum berOfI mages (number of slic es)

� Centr eCentreSl iceSep arationPixels (sl ice separa tion in pi xels)

� MatrixSize (resolution )

� ScalingFactorMmPix el (pixel size) Duke University


Resample SPECT into sp ace of CT image

128 ×××× 128 ×××× 128 →→→→ 256 ×××× 256 ×××× 40 (unsigned int*16)

SPECT dicom: replac e CT dico m data with resampled SPECT data.

To prevent conf usion , chang e StudyInstan ceUID andSeriesInstanceUID in SPECT dicom. e.g., change list digi ts of both:StudyInstanceUI D =1.2.124.113532.152.16.194.14.20070430.84447.6023314,SeriesInstanceUID =1.2.840.113619.2.170.1.2.0.152007.152731390.30842

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Optimization Strateg y (orig inal)

Title: A methodology for using SPECT to reduce intensity-modulated radiation therapy (IMRT)dose to functioning lungAuthor(s): McGuire SM (McGuire, Sarah M.), Zhou SM (Zhou, Sumin), Marks LB (Marks,Lawrence B.), Dewhirst M (Dewhirst, Mark), Yin FF (Yin, Fang-Fang), Das SK (Das, Shiva K.)Source: INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS 66 (5):1543-1552 DEC 1 2006

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Optimization Strategy (simpl er)


L. Marks/jh 24

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BEAM DIRECTION SELECTION IS IMPORTANT FOR SPECT AVOIDANCE

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Highest SPECT activ it y region

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2 Highes t SPECT activity regions

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3 Highest SPECT activ ity regions


L. Marks/jh 25

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4 Highes t SPECT activity regions

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Dose Distrib ution

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PTV and Highe st SPECT region DVHs

“conven tional ” plan

SPECT-guided plan

PTV “ conventional ” plan

PTV SPECT-guided plan

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2nd Highes t SPECT region DVH

“conven tional ” plan

SPECT-guide d plan


L. Marks/jh 26

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3rd Highest SPECT region DVH

“ conventi onal ” plan

SPECT-guided plan

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4th Highest SPECT region DVH

“ convention al” plan

SPECT-guide d plan

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DVH of remaining minim ally perf used lung

“c onventional ” plan

SPECT-guided plan

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DVH of all lung

“co nventiona l” plan

SPECT-guide d plan


L. Marks/jh 27

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SPECT-guided vs. Convent ion al Plan: mean dose inSPECT regions

Overall mean lung dose redu ct ion: 3.2 vs. 3.7 Gy (13% ↓↓↓↓ )

1st Highest SPECT region: 1.2 Gy vs. 2.4 Gy (49%↓↓↓↓ )

2nd Highest SPECT regio n: 4.6 Gy vs. 6.7 Gy (32% ↓↓↓↓)

3rd Highest SPECT regio n: 3.4 Gy vs. 4.1 Gy (17% ↓↓↓↓)

4th Highest SPECT region : 2.1 Gy vs. 2.4 Gy (13% ↓↓↓↓)

Remaining “non -perfu sed”: 3.45 vs. 3.42 Gy (1%↑↑↑↑ )

Patient was treate d with Amplit ude Gating and CBCT-guided setup

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SPECT-guided vs. Convent ional Plan: mean dose inSPECT regions (Patient #2)

Dose: 33 fxs ×××× 200 cGy

Overall mean lung dose redu ctio n: 7.9 vs. 8.3 Gy (6% ↓↓↓↓ )

1st Highest SPECT region: 6.4 Gy vs. 7.2 Gy (12%↓↓↓↓ )

2nd Highest SPECT regio n: 8.0 Gy vs. 8.8 Gy (8% ↓↓↓↓)

3rd Highest SPECT regio n: 8.5 Gy vs. 8.8 Gy (4% ↓↓↓↓)

4th Highest SPECT region : 7.1 Gy vs. 7.3 Gy (3% ↓↓↓↓)

Remaining “ non -perfu sed”: 9.1 vs. 9.0 Gy (1%↑↑↑↑ )

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CONCLUSION

Incorporating SPECT-guid ance into IMRT planningfor thoracic tumors redu ces irradiat ed funct ioninglung volumes ⇒⇒⇒⇒ (hopefully) reduced toxicit y.

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ONE THOUGHT TO LEAVE YOU WITH ….

In addition to using SPECT avoid ance,

Put high er tumor dose in FDG-PET avid areas, or,dump “ collateral ” hig h dose int o FDG-PET avid areas.

Controversial, but ….

Several studies have shown that hig her FDG-uptake iscorrelated to higher grade and poo rer respo nse post -therapy.

Perhaps more appro priate for proliferatio n (18F-FLT)or hypox ia (18F-MISO).


L. Marks/jh 28

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axial sagittal

corona l

Title: Feasibil ity of opti mizi ng the dose distribution in lung tumors using fluorine -18-fluoro deoxyg luc ose positron emission tomography and single photo n emission

computed tomography guide d dose prescrip tionsAuthor(s): Das SK, Miften MM, Zhou S, Bell M, Munley MT, Whiddon CS, Craciunescu O,

Baydush AH, Wong T, Rosenman JG, Dewhirst MW, Marks LBSource: MEDICAL PHYSICS 31 (6): 1452-1461 JUN 2004


Local doseLocal dose Local effectLocal effect

3D RT dose3D RT doseSum local effectsSum local effects ∆∆∆∆∆∆∆∆ PFTPFT

FunctionalFunctionalimaging SPECTimaging SPECT SymptomsSymptoms

Patients donPatients don’’ t usually care aboutt usually care aboutimaging!imaging!

��


Predicting ChangesinPredicting Changesin PFTPFT’’ ss

∑∑∑∑∑∑∑∑ [(fracti on lung at dose[(fract ion lung at doseii)) ××××××××(effect at dose(effect at doseii)] = total loss)] = total loss

96 patientswith follow96 patientswith follow--upupPFTPFT’’ ss≥≥≥≥≥≥≥≥ 6 months6 months

FanFan et al. JCO and IJROBP 2001et al. JCO and IJROBP 2001

DDmaxmax

ii = 0= 0


Corr elation Coefficient (R): PredictedCorrelation Coefficient (R): Predictedvsvs. Measured Decline in DLCO. Measured Declinein DLCO

≥≥≥≥≥≥≥≥ 11 0.41 (59)0.41(59) 0.40 (28)0.40 (28)

≥≥≥≥≥≥≥≥ 22 0.40 (43)0.40(43) 0.56 (17)0.56 (17)

≥≥≥≥≥≥≥≥ 33 0.60 (22)0.60(22) 0.91 (8)0.91 (8)

AllAllPatientsPatients

NoNo ““ CentralCentralTumor WithTumor With

AdjacentAdjacentHypoperfusionHypoperfusion””

# FU# FUPFTPFT’’ ss

Fan 2001Fan 2001


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TreatmentTreatmentPlanningPlanning

Physiologic Imaging in OncologyPhysiologic Imaging in Oncology

NormalNormalTissueTissueEffectsEffects

AssessAssessTumorTumorResponseResponse

TumorTumorImagingImaging

ExtentExtente.g. Hypoxiae.g. Hypoxia

•• optimize therapeutic ratio in each patientoptimize therapeutic ratio in each patient

•• ChemoChemo--, radio, radio--, and heat therapy, and heat therapy••M RI, M RS,PET, etcMRI, MRS, PET, etc

adjust

Duke UniversityDuke UniversityPlanUNCPlanUNC software, Cour tesy UNCsoftware, Cour tesy UNC

Esophagus

PET-based GTVSubcarinal area


L. Marks/jh 30

Duke UniversityDuke UniversityPlanUNCPlanUNC soft ware, Courtesy UNCsoftwa re, Courtesy UNC

PET-based GTVSubca rinal area

Automaticimagesegmentationof targets


Lymph node

GrecoC, et al. Lung Cancer 2007 ; in press.(University of Magna Graecia, Italy)


Esophagealcancer

CT-GTV (blue)

PET-CT GTV (purple)

CT-GTV (blue)

GTV

Leong T, et al. Radiother Oncol 2006; 254-261.(University of Melbourne, Australia)


Oropharyngealcancer Base-of–tonguecancer Floor-of-mouth cancer

Floor-of-mouth cancer Nasopharyngealcancer

CT-GTV (red)

PET-CT (blue) PET-CT (blue)

CT-GTV (red)

CT-GTV (yellow)

PET-CT (green) PET-CT (green)

AshamallaH, et al. IJROBP2007 ; 388-395. (Cornell University)


L. Marks/jh 31

Duke UniversityDuke UniversityDasSK, et al. Med Phys 2004; 1452-1461.

DasSK, et al. Med Phys 2004; 1452-1461.

(a): transverseslice(b): sagittalslice(c): coronal slice

Isodoselines(Gy) superimposed on sliceplanesthroughFDG-PET

CT vs PET-weightedEUD

Dosepainting- IMRT


Responders

Non-responders

Radiology; Meisamyet al., Nov, 2004Duke UniversityDuke University

Percent change lesiondiameterend of therapy

MRI-basedchangeearlyduringTx

Radiology; Meisamyet al., Nov, 2004


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Fusion of 4DCT with FDG-PET

Development of Motion Envelope

Proj ection of 4DCT GTVs onto PET

motion-inducedsmear

Gondi V, et al. IJROBP 2007; 187-195.Duke UniversityDuke University

(a) Non-gatedacquisition (b) 4DCT/PET gatedacquisition

Nehmeh SA, et al. Med Phys 2004; 3179-3186.


Distrib ution ofpercentile functional

Lung volume(4DCT ventilation images)

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

Monitoring response to Monitoring response to TxTx with functional with functional imaging during RTimaging during RT

T1 weightedsignal intensity changes→→→→ predictive of overall survival

During weeks1 and 3 ofRT

MRIGliomaRT20Tsien2007

↑↑↑↑Initial first -passenhancementslopes (slope) and peakenhancementratios (peak)→↑→↑→↑→↑local response

At 2 weeks ofTx

DCE-MRI

HCCRT19Liang2007

↓↓↓↓SUV→↑→↑→↑→↑tumor responseandsurvival

early identification of non-respondersand early modifications of Txprotocol

2 weeks afterinitiati onof Tx

PETEsophagusChemRT

38Wieder2004

↑↑↑↑blood flow during Tx1-2 weeks,6-12 weeks

CTProstateRT22Harvey2001

↑↑↑↑ FDG uptake→↓→↓→↓→↓ tumor size4 h after SRSPETBrainSRS19Maruyama1999

FindingsFollow-upTestTumorTxnStudy


L. Marks/jh 33


IMRT Case:Target OutlinesIM RT Case:Target Outli nes

BEV

PET-GTV

CT-GTV

High Perfusion

Low Perfusion

SPECT

PET-GTV

CT-GTV

CT

PET AvidRegions

FDG-PET

agenda - aapm.org

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