Damian Dupuy, MD. Image Guided Intervention (IGI) Studies 10:25 11:05 AM

Transcription

1 Damian Dupuy, MD Image Guided Intervention (IGI) Studies 10:25 11:05 AM

2 Image Guided Intervention (IGI) Studies Damian E. Dupuy, M.D., FACR Professor of Diagnostic Imaging The Warren Alpert Medical School of Brown University Director of Tumor Ablation Rhode Island Hospital Objectives Define IGI and why it is and will be important t Describe various IGI trial considerations Review the trials and tribulations of running IGI trials from perspective of PI 1

3 What is IGI? 1. Procedure to treat disease 2. Must use radiological imaging method to guide placement of device(s) and monitor treatment 3. May be extracorporeal, endoluminal, percutaneous or surgical 4. Goal is minimally invasive adjunct or alternative to more invasive, expensive or toxic reference standard (e.g. extirpative surgery, radiation, chemotherapy) 5. Goal is less morbidity and mortality with improved or similar outcomes and improved quality or quantity of life Procedure Example Cryoablation of lung cancer Local control Symptom palliation 2

4 Ultrasound ACRIN 6673 RFA of Hepatocellular Carcinoma Imaging Follow-up Critical Solitary HCC in a cirrhotic 3

5 Imaging as a Biomarker Was the target destroyed? CT 48 hrs after RFA Symptom Control ACRIN 6661 RFA of Painful Bone Metastases RFA of Lung Met to Lumbar spine 4

6 69 y.o. Woman with Lung Cancer Met to Femur S/P XRT with Persistent Pain Pre RF CT RFA Pain Scale One Week after RFA for Lung Met to Femur Memorial Pain Assessment Card quantifies pain relief 5

7 Combination Trial with synergistic modalities-trans Arterial Chemoembolization and Thermal Ablation of Hepatocellular Carcinoma CT Pre RX -7cm HCC TACE-7cm HCC Microwave Ablation of Large HCC after TACE POST TACE and MWA 2 years POST TACE and MWA 6

8 Why will IGI RX Increase? Oncology! Population aging ( e.g. Baby boomers) Cancer detection increasing- more blood tests and more imaging Technology and treatment monitoring will improve Current reference standards costly so will IGI be more cost effective? And will quality of life improved? 7

9 Comparison costs of Lung Cancer RX in the elderly from No change in survival over that time period! Cancer 2007;110: IGI Trial Opportunities Not just RX studies! Comparison outcomes Quality of life studies Cost efficacy studies 8

10 IGI RX Who will benefit? Localized disease or symptoms Poor surgical candidates -advanced age -medical comorbidities Poor drug and radiation candidates -high tumor volume -known tumor resistance IGI Therapy Palliation Majority of oncology is palliation IGI can provide meaningful palliation Synergy with conventional therapy Few limitations of repeat therapy 9

11 Liver Tumors -primary -mets Lung Tumors -primary -mets IGI Applications Renal/adrenal tumors -small RCC, VHL -mets, functioning tumors Applications MSK Tumors -Osteoid osteomas -mets -sarcomas Head and Neck malignancies -papillary thyroid CA recurrence -recurrent squamous cell CA Pelvic recurrences -GYN GYN, CRC Breast tumors -benign -malignant 10

12 Image-guided guided Intervention Technical Problems and Solutions Obtaining a negative margin - monitoring with imaging -adjunctive RX Avoiding injury to adjacent structures -advanced image monitoring -separation techniques- hydrodissection Treating larger tumors -multiple applicators and more powerful devices IGI Trials Oncology Local control -cure or bridge bid to cure (e.g transplant) -improvement in disease free survival or time to tumor progression Palliation at ( e.g. symptom control) -primary palliation (e.g bone met ablation) -secondary palliation ( e.g biliary drainage) 11

13 IGI Trials Technology Imaging- pre, intraproc, post Navigation and image fusion- improve targeting g for treatment -optical -electromagnetic Devices -stents -ablation applicators -brachytherapy -extracorporeal (e.g HIFU) Targeted agents -embolics -nanoparticles IGI Trials Trial Design Phase A: Single center safety, QA, effect, optimize imaging and intervention, lesion, organ, patient data Phase B: single or multicenter- effect, standardize, translate. lesion, organ, patient Phase C : Multi-center -organ/lesion, patient outcome with more robust data Phase D: Multicenter patient level data, comparative, RCT preferred 12

14 Defining Clinical Trial Cohorts Phase A- Dose-ranging, safety, Imaging and interventional ti optimization i -Multiple diseases/ stages/ lesions Phase B- Standardization, QA, efficacy -Defined disease, lesion +/- stage Phases C&D- RX outcome -Defined disease, lesion, stage Defining Clinical Trial Cohorts Disease, lesion, stage Alternative to reference standard (e.g surgery) -patient choice -strict inclusion/exclusion criteria Need for improvement given current management -cost -quality of life -existing treatment failures Cohort control -none, historical, nonrandomized, randomized 13

15 IGI Trials Standardization and QA RX protocol variation -single vs multiple devices -defined algorithm for treatment RX QA -investigator qualification -technical and eligibility review -imaging documentation of treatment Imaging QA -was imaging protocol followed -was image quality satisfactory IGI Clinical Endpoints IGI RX often repeatable so may want to consider vascular treatment t t model -primary success rate- target lesion(s) -secondary success assist rate- rerx -failure- residual, recurrent, new disease 14

16 3 month FU Mar 07 Possible recurrence Pre: 10 HU 90 sec: 70HU 300 sec: 63HU 6 month FU Jun sec: 75 HU 180 sec: 67HU Enhancement Recurrence Repeat RFA Touch-up for Residual NSCLC Follow-up CT and PET/CT 15

17 IGI Design Issues Randomized Controlled Trials Accrual can be problematic if comparing to reference standard ( e.g turf issues) -Cryo vs XRT for bone mets Ethically difficult to with-hold hold RX if conventional RX is not working ( Chemo vs chemo plus ablation leads to crossover) -clock trial Test treatment already widely adopted in community so patients unwilling to be randomized IGI Trials Other Design Issues Reference standard controversial or moving target ( e.g CRC chemorx) Placebo arm not applicable/ethical in many instances? HIFU for palliation Comparison of two IGI RXs neither of which is proven Will data be robust enough to lead to specific indication (FDA) or policy support ( ICD-9 code) 16

18 IGI Trials and Tribulations Protocol complexity Imaging follow-up Central image archive Site interest and enrollment Site support infrastructure Site PI involvement Site turf issues s Protocol deviations Data submission errors 17