Damian Dupuy, MD

“Image Guided Intervention (IGI) Studies”

10:25 – 11:05 AM

1/4/2011

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Image Guided Intervention Image Guided Intervention (IGI) Studies(IGI) Studies

Damian E. Dupuy, M.D., FACRDamian E. Dupuy, M.D., FACRProfessor of Diagnostic ImagingProfessor of Diagnostic Imaging

The Warren Alpert Medical School of The Warren Alpert Medical School of Brown UniversityBrown University

Director of Tumor AblationDirector of Tumor AblationRhode Island HospitalRhode Island HospitalRhode Island HospitalRhode Island Hospital

ObjectivesObjectives

•• Define IGI and why it is and will be Define IGI and why it is and will be i t ti t timportantimportant

•• Describe various IGI trial Describe various IGI trial considerationsconsiderations

•• Review the trials and tribulations of Review the trials and tribulations of running IGI trials from perspective of running IGI trials from perspective of running IGI trials from perspective of running IGI trials from perspective of PIPI

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What is IGI?What is IGI?1.1. Procedure to treat diseaseProcedure to treat disease2.2. Must use radiological imaging method to guide Must use radiological imaging method to guide 2.2. Must use radiological imaging method to guide Must use radiological imaging method to guide

placement of device(s) and monitor treatmentplacement of device(s) and monitor treatment3.3. May be extracorporeal, endoluminal, May be extracorporeal, endoluminal,

percutaneous or surgicalpercutaneous or surgical4.4. Goal is minimally invasive adjunct or Goal is minimally invasive adjunct or

alternative to more invasive, expensive or alternative to more invasive, expensive or toxic reference standard (e.g. extirpative toxic reference standard (e.g. extirpative

di ti h th ) di ti h th )surgery, radiation, chemotherapy)surgery, radiation, chemotherapy)5.5. Goal is less morbidity and mortality with Goal is less morbidity and mortality with

improved or similar outcomes and improved improved or similar outcomes and improved quality or quantity of life quality or quantity of life

Procedure Example•• Cryoablation of lung cancerCryoablation of lung cancer

•• Local controlLocal control

•• Symptom palliationSymptom palliation

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Ultrasound ACRIN 6673Ultrasound ACRIN 6673RFA of Hepatocellular CarcinomaRFA of Hepatocellular Carcinoma

Imaging FollowImaging Follow--up Criticalup Critical

Solitary HCC in a cirrhoticSolitary HCC in a cirrhotic

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Imaging as a BiomarkerImaging as a BiomarkerWas the target destroyed?Was the target destroyed?

CT 48 hrs after RFACT 48 hrs after RFA

Symptom Control ACRIN 6661Symptom Control ACRIN 6661RFA of Painful Bone MetastasesRFA of Painful Bone Metastases

RFA of Lung Met to RFA of Lung Met to Lumbar spineLumbar spine

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69 y.o. Woman with Lung Cancer 69 y.o. Woman with Lung Cancer Met to FemurMet to Femur

S/P XRT with Persistent Pain S/P XRT with Persistent Pain

RFARFAPre RF CTPre RF CT

Pain Scale One Week after RFA Pain Scale One Week after RFA for Lung Met to Femurfor Lung Met to Femur

Memorial Pain Assessment Card quantifies pain reliefMemorial Pain Assessment Card quantifies pain relief

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Combination Trial with synergistic Combination Trial with synergistic modalitiesmodalities--Trans Arterial Trans Arterial

Chemoembolization and Thermal Ablation Chemoembolization and Thermal Ablation of Hepatocellular Carcinomaof Hepatocellular Carcinoma

CT Pre RX CT Pre RX --7cm HCC7cm HCC TACETACE--7cm HCC7cm HCC

Microwave Ablation of Large HCC Microwave Ablation of Large HCC after TACEafter TACE

POST TACE and MWAPOST TACE and MWA 2 years POST TACE and 2 years POST TACE and MWAMWA

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Why will IGI RX Increase?Why will IGI RX Increase?Oncology!Oncology!

•• Population aging ( e g Baby boomers)Population aging ( e g Baby boomers)•• Population aging ( e.g. Baby boomers)Population aging ( e.g. Baby boomers)•• Cancer detection increasingCancer detection increasing-- more more

blood tests and more imagingblood tests and more imaging•• Technology and treatment monitoring Technology and treatment monitoring

will improvewill improvew mpw mp•• Current reference standards costly Current reference standards costly

so will IGI be more cost effective?so will IGI be more cost effective?•• And will quality of life improved?And will quality of life improved?

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Comparison costs of Lung Cancer RX in Comparison costs of Lung Cancer RX in the elderly from 1983the elderly from 1983--19971997

No change in survival over that time period!No change in survival over that time period!

Cancer 2007;110:2511Cancer 2007;110:2511--88

IGI Trial OpportunitiesIGI Trial OpportunitiesNot just RX studies!Not just RX studies!

C i tC i t•• Comparison outcomesComparison outcomes•• Quality of life studiesQuality of life studies•• Cost efficacy studiesCost efficacy studies

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IGI RXIGI RXWho will benefit?Who will benefit?

•• Localized disease or symptomsLocalized disease or symptoms•• Localized disease or symptomsLocalized disease or symptoms•• Poor surgical candidatesPoor surgical candidates

--advanced ageadvanced age--medical comorbiditiesmedical comorbidities

•• Poor drug and radiation candidatesPoor drug and radiation candidatesPoor drug and radiation candidatesPoor drug and radiation candidates--high tumor volume high tumor volume --known tumor resistanceknown tumor resistance

IGI TherapyIGI TherapyPalliationPalliation

•• Majority of oncology is palliationMajority of oncology is palliation•• IGI can provide meaningful palliationIGI can provide meaningful palliation•• Synergy with conventional therapySynergy with conventional therapy

Few limitations of repeat therapyFew limitations of repeat therapy•• Few limitations of repeat therapyFew limitations of repeat therapy

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IGI ApplicationsIGI Applications

•• Liver TumorsLiver Tumorsii--primaryprimary

--metsmets•• Lung TumorsLung Tumors

--primary primary --metsmetsmetsmets

•• Renal/adrenal tumorsRenal/adrenal tumors--small RCC, VHLsmall RCC, VHL--mets, functioning tumorsmets, functioning tumors

•• MSK Tumors MSK Tumors --Osteoid osteomas Osteoid osteomas metsmets

ApplicationsApplications

--metsmets--sarcomassarcomas

•• Head and Neck malignanciesHead and Neck malignancies--papillary thyroid CA recurrencepapillary thyroid CA recurrence--recurrent squamous cell CArecurrent squamous cell CA

•• Pelvic recurrencesPelvic recurrences--GYN CRCGYN CRCGYN, CRCGYN, CRC

•• Breast tumorsBreast tumors--benignbenign--malignantmalignant

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ImageImage--guided Interventionguided InterventionTechnicalTechnical Problems and SolutionsProblems and Solutions•• Obtaining a negative marginObtaining a negative margin•• Obtaining a negative marginObtaining a negative margin

-- monitoring with imagingmonitoring with imaging--adjunctive RXadjunctive RX

•• Avoiding injury to adjacent structuresAvoiding injury to adjacent structures--advanced image monitoringadvanced image monitoring--separation techniquesseparation techniques-- hydrodissectionhydrodissection

•• Treating larger tumorsTreating larger tumors--multiple applicators and more powerful multiple applicators and more powerful devicesdevices

IGI TrialsIGI TrialsOncologyOncology

•• Local control Local control b id t ( b id t ( --cure or bridge to cure (e.g cure or bridge to cure (e.g

transplant)transplant)--improvement in disease free survival improvement in disease free survival or time to tumor progressionor time to tumor progression

•• Palliation ( e.g. symptom control)Palliation ( e.g. symptom control)Pall at on ( e.g. symptom control)Pall at on ( e.g. symptom control)--primary palliation (e.g bone met primary palliation (e.g bone met ablation)ablation)--secondary palliation ( e.g biliary secondary palliation ( e.g biliary drainage)drainage)

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IGI TrialsIGI TrialsTechnologyTechnology

•• ImagingImaging-- pre, intraproc, postpre, intraproc, post•• Navigation and image fusionNavigation and image fusion-- improve targeting for improve targeting for

g gg g p g gp g g

treatment treatment --opticaloptical--electromagneticelectromagnetic

•• DevicesDevices--stentsstents--ablation applicatorsablation applicators--brachytherapybrachytherapy--extracorporeal (e g HIFU) extracorporeal (e g HIFU) --extracorporeal (e.g HIFU) extracorporeal (e.g HIFU)

•• Targeted agentsTargeted agents--embolicsembolics--nanoparticlesnanoparticles

IGI TrialsIGI TrialsTrial DesignTrial Design

•• Phase A: Single center safety, QA, effect, Phase A: Single center safety, QA, effect, optimize imaging and intervention lesion optimize imaging and intervention lesion optimize imaging and intervention, lesion, optimize imaging and intervention, lesion, organ, patient dataorgan, patient data

•• Phase B: single or multicenterPhase B: single or multicenter-- effect, effect, standardize, translate. standardize, translate. ––lesion, organ, patientlesion, organ, patient

•• Phase C : MultiPhase C : Multi--center center --organ/lesion, patient organ/lesion, patient t m ith m b st d tt m ith m b st d toutcome with more robust dataoutcome with more robust data

•• Phase D: Multicenter patient level data, Phase D: Multicenter patient level data, comparative, RCT preferredcomparative, RCT preferred

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Defining Clinical Trial CohortsDefining Clinical Trial Cohorts

•• Phase APhase A-- DoseDose--ranging, safety, Imaging ranging, safety, Imaging d i t ti l ti i ti d i t ti l ti i ti and interventional optimization and interventional optimization --Multiple diseases/ stages/ lesionsMultiple diseases/ stages/ lesions

•• Phase BPhase B-- Standardization, QA, efficacyStandardization, QA, efficacy--Defined disease, lesion +/Defined disease, lesion +/-- stagestage

•• Phases C&DPhases C&D-- RX outcomeRX outcome•• Phases C&DPhases C&D-- RX outcomeRX outcome--Defined disease, lesion, stageDefined disease, lesion, stage

•• Disease, lesion, stageDisease, lesion, stage•• Alternative to reference standard (e.g Alternative to reference standard (e.g

))

Defining Clinical Trial CohortsDefining Clinical Trial Cohorts

surgery)surgery)--patient choicepatient choice--strict inclusion/exclusion criteriastrict inclusion/exclusion criteria

•• Need for improvement given current Need for improvement given current managementmanagement

--costcost--quality of lifequality of lifequality of lifequality of life--existing treatment failuresexisting treatment failures

•• Cohort controlCohort control--none, historical, nonrandomized, none, historical, nonrandomized, randomizedrandomized

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IGI TrialsIGI TrialsStandardization and QAStandardization and QA

•• RX protocol variationRX protocol variation--single vs multiple devicessingle vs multiple devicessingle vs multiple devicessingle vs multiple devices--defined algorithm for treatmentdefined algorithm for treatment

•• RX QARX QA--investigator qualificationinvestigator qualification--technical and eligibility reviewtechnical and eligibility review--imaging documentation of treatmentimaging documentation of treatment

I i QAI i QA•• Imaging QAImaging QA--was imaging protocol followedwas imaging protocol followed--was image quality satisfactorywas image quality satisfactory

IGI Clinical EndpointsIGI Clinical Endpoints

•• IGI RX often repeatable so may want to IGI RX often repeatable so may want to id l t t t d lid l t t t d lconsider vascular treatment modelconsider vascular treatment model

--primary success rateprimary success rate-- target target lesion(s)lesion(s)--secondary success assist ratesecondary success assist rate-- reRXreRX--failurefailure-- residual, recurrent, new residual, recurrent, new fa lurefa lure res dual, recurrent, new res dual, recurrent, new diseasedisease

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3 month FU

Mar ‘07

Pre: 10 HU 90 sec: 70HU 300 sec: 63HU

Possible recurrence

45 sec: 75 HU 180 sec: 67HU

6 month FU

Jun ‘07

Pre: 10 HU 90 sec: 70HU 300 sec: 63HU

45 sec: 75 HU 180 sec: 67HU

Enhancement

0

10

20

30

40

50

60

70

80

0 45 90 180 300

Recurrence

Repeat RFA “Touch-up” for Residual NSCLC

FollowFollow--up CT and PET/CTup CT and PET/CT

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IGI Design IssuesIGI Design IssuesRandomized Controlled TrialsRandomized Controlled Trials

•• Accrual can be problematic if comparing to Accrual can be problematic if comparing to reference standard ( e g turf issues)reference standard ( e g turf issues)reference standard ( e.g turf issues)reference standard ( e.g turf issues)

--Cryo vs XRT for bone metsCryo vs XRT for bone mets•• Ethically difficult to withEthically difficult to with--hold RX if hold RX if

conventional RX is not working ( Chemo vs conventional RX is not working ( Chemo vs chemo plus ablation leads to crossover)chemo plus ablation leads to crossover)

--clock trialclock trial•• Test treatment already widely adopted in Test treatment already widely adopted in

community so patients unwilling to be community so patients unwilling to be randomizedrandomized

IGI TrialsIGI TrialsOther Design IssuesOther Design Issues

•• Reference standard controversial or Reference standard controversial or moving target ( e g CRC chemoRX)moving target ( e g CRC chemoRX)moving target ( e.g CRC chemoRX)moving target ( e.g CRC chemoRX)

•• Placebo arm not applicable/ethical in Placebo arm not applicable/ethical in many instances ? HIFU for palliationmany instances ? HIFU for palliation

•• Comparison of two IGI RXs neither of Comparison of two IGI RXs neither of which is provenwhich is proven

•• Will data be robust enough to lead to Will data be robust enough to lead to specific indication (FDA) or policy specific indication (FDA) or policy support ( ICDsupport ( ICD--9 code)9 code)

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IGI Trials and TribulationsIGI Trials and Tribulations•• Protocol complexityProtocol complexity•• Imaging followImaging follow upup•• Imaging followImaging follow--upup•• Central image archiveCentral image archive•• Site interest and enrollmentSite interest and enrollment•• Site support infrastructureSite support infrastructure•• Site PI involvementSite PI involvement

Sit tu f issu sSit tu f issu s•• Site turf issuesSite turf issues•• Protocol deviationsProtocol deviations•• Data submission errorsData submission errors