ACRIN 6660 – Protocol Review Whole-Body MRI in the Evaluation of Pediatric Malignancies Marilyn J Siegel, M.D Frederic Hoffer, M.D Brad Wyly, M.D Alicia Y Toledano, ScD Aims ♦ Primary Aim • Establish non-inferior diagnostic accuracy of whole body MRI compared with conventional imaging studies for detecting metastatic disease for use in staging common pediatric tumors ♦ Secondary Aims • Determine the incremental benefit in accuracy of adding out-of-phase imaging to turbo STIR for detecting distant disease • Obtain preliminary data concerning the relative accuracies of FDG PET and whole body MRI in detecting distant disease American College of Radiology Imaging Network ACRIN: 6660 Pediatric MRI Clinical Significance ♦ Accurate staging is critical to treatment planning ♦ Conventional techniques have long imaging times and often use sedation and ionizing radiation ♦ If one imaging study can replace established imaging patterns this will have an impact on the care of young cancer patients American College of Radiology Imaging Network ACRIN: 6660 Pediatric MRI Imaging Background ♦ Studies in adult women with breast cancer show that whole body MRI with turbo STIR can serve as a single examination for staging ♦ Sensitivity • MRI>>95% • Conventional imaging=80% ♦ Neuroblastoma Staging: RDOG (Radiology Diagnostic Oncology Group) Results • MRI effective in detecting marrow metastases • Conventional MRI equivalent to combination of CT and bone scintigraphy for staging • Limitations: Whole body images not obtained; newer, faster sequences not used Siegel MJ et al Radiol 2002; 223-168 American College of Radiology Imaging Network ACRIN: 6660 Pediatric MRI Imaging Background: PET vs MRI ♦ 21 patients (51 bone metastases) ♦ Small cell tumors ♦ Sensitivity • 90% FDG PET • 82% whole body MRI (T1- weighted) – No STIR or other marrow sensitive image • 71% scintigraphy ♦ MRI and PET may improve detection of bone metastases Daldrup-Link AJR 2001; 177:229 American College of Radiology Imaging Network ACRIN: 6660 Pediatric MRI Study Overview ♦ Required Conventional Studies • Scintigraphy (Bone or MIBG or gallium) • Abdominal/Pelvic CT or MRI ♦ Experimental Studies • Whole-Body Fast MRI • FDG-PET (optional) ♦ Expected Accrual - 250 Patients in 12 Months • 50 Neuroblastomas • 60 Rhabdomyosarcomas • 30 Other sarcomas • 110 Lymphomas ♦ Expected Stage IV Disease • Neuroblastomas - 50% (25/100) • Rhabdomyosarcomas - 16% (10/60) • Other sarcomas - 20% (6/30) • Lymphomas - 30% (33/110) American College of Radiology Imaging Network ACRIN: 6660 Pediatric MRI Eligibility Criteria ♦ Age 21 years or younger ♦ Proven rhabdomyosarcoma, Ewing’s sarcoma family of tumors, neuroblastoma, Hodgkin’s disease, and non-Hodgkin’s lymphoma, or newly diagnosed mass strongly suspected to represent any of these tumors ♦ All examinations (CT, MRI, scintigraphy, and PET) must be done prior to treatment and within 14 days of each other and within 14 days of any diagnostic or operative procedure ♦ Participants with CT studies, conventional MR, or scintigraphy, performed at outside institutions are eligible if these studies were performed with the same technical standards specified in the protocol (see Appendix V) ♦ Signed informed consent by parent or child if older than 18 American College of Radiology Imaging Network ACRIN: 6660 Pediatric MRI Ineligibility Criteria ♦ Contraindications for MRI or CT • Includes active cardiac pacemakers or intracranial vascular clips ♦ Lack of parental permission or participant assent ♦ Patient has had a previous malignancy ♦ Patient has a CNS primary tumor ♦ Patient is pregnant or nursing ♦ Patient has uncontrolled diabetes mellitus or has controlled diabetes but with a fasting blood glucose value > 200 mg/dL, immediately before the injection of FDG American College of Radiology Imaging Network ACRIN: 6660 Pediatric MRI Image Interpretation ♦ Local Interpretation • Images interpreted following practice of each site • Information may be used for treatment planning as determined on an individual basis by each site ♦ Central Reader Interpretation • 10 readers for CT/MRI • 10 readers for scintigraphy – PET, bone scans, gallium • Readers blinded to results of other tests • All studies assessed for distant tumor extent American College of Radiology Imaging Network ACRIN: 6660 Pediatric MRI Positive Findings ♦ Positive whole-body MRI or PET at initial staging • Additional confirmatory imaging – Liver: US, CT or MRI – Bone: Plain X-rays, CT, MRI or scintigraphy (if not done initially) – Brain: CT or MRI – Lung: Thinly collimated CT scans • Biopsy also will be suggested if practical ♦ Positive whole-body MRI or PET at initial staging but no biopsy or imaging confirmation of disease • Repeat imaging with conventional studies recommended at - mos ♦ When abnormality is considered highly suspicious for metastasis or when biopsy proof of that lesion is obtained, patient will receive treatment at discretion of the treating physician American College of Radiology Imaging Network ACRIN: 6660 Pediatric MRI Gallium Protocol ♦ IV dose of 140 µCi/kg, with a minimum dose of 0.25 mCi ♦ Imaging should be performed 3-5 days following injection ♦ SPECT suggested for localization of disease and for distinguishing between normal bowel activity and pathology ♦ Large-field-of-view multidetector gamma camera with medium-energy collimator recommended American College of Radiology Imaging Network ACRIN: 6660 Pediatric MRI MIBG Protocol ♦ Saturated potassium iodide solution (SSKI) or other sources of free iodide the day before and days after study ♦ I-123 MIBG preferred ã Dose is 70-140 àCi/kg, with a minimum dose of 1.0 mCi • Images at 24 hours following tracer administration with a large-fieldof-view gamma camera equipped with a high-resolution low-or medium energy collimator • Additional images at 48 hours if possible ♦ If I-123 MIBG is unavailable, I-131 MIBG can be used ã Dose is 14 àCi/kg, with a maximum dose of 1.0 mCi • Images at 48 hours after tracer administration with a large-field-of- view gamma camera equipped with a high-energy collimator • Additional images can be obtained at 72 hours, if necessary to clarify findings at 48 hours American College of Radiology Imaging Network ACRIN: 6660 Pediatric MRI Fast MRI Techniques ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ ♦ Whole Body Imaging Vertex to toes Coronal plane images Body Coil; phased array coils allowed unless lengthened time of exam Breath hold on scans under 30Sec only Scans performed on a 1.5 T Localizer scan Turbo STIR (water sensitive image) Out-of-phase (OOPS) better than in phase (IPS) for detecting metastases Images acquired in 3-4 stations Total Imaging time ~ 10-15 minutes American College of Radiology Imaging Network ACRIN: 6660 Pediatric MRI OOPS ♦ Why OOPS? • STIR may be overly sensitive and not specific for bone marrow disease • Need a T1 weighted sequence for specificity • Spin echo T1 too long • In phase (IPS) GRE T1 not sensitive for bone marrow mets ♦ OOPS Interruption • On OOPS T1 if both fat and water then dark signal – If fat only (epiphyses) then bright – If water only (bone metastases) then bright • If bright on STIR and OOPS T1 more likely metastatic bone marrow • If dark on STIR and bright on OOPS then more likely fat only American College of Radiology Imaging Network ACRIN: 6660 Pediatric MRI Whole Body MRI Technical Factors Patient Position Supine, arms down at sides Imaging Plane Coronal, sagittal or multiplane Scout Coronal STIR Coronal T1 OOPS Coil(s) Body coil* Body coil* Body coil* Contrast None None None Anatomic coverage Whole body (cranial vertex to feet) TE (msec) 1.9-3.05 30-77 2.2-2.4 TR (msec) 4-7 4200-6800 120-150 TI (msec) Flip angle 140-150 80 Echo train length 150-180 70-75 7-33 Number of slices 3-10 10-17 slices 10-20 slices Slice thickness (mm) 5-10 4-6 4-6 Spacing/gap (mm) 2-5 1 Field of View (FOV) mm 500 200-500 200-500 Matrix (phase x frequency) 128 x 256 128-140 x 256 150-180 x 256 Scan (Acquisition) Time 6-20 sec 2-3 minutes 15-25 sec American College of Radiology Imaging Network ACRIN: 6660 Pediatric MRI Whole Body MR: Neuroblastoma CR STIR American College of Radiology Imaging Network OOPS T1 ACRIN: 6660 Pediatric MRI 11 Year Old, Stage Neuroblastoma STIR IPS American College of Radiology Imaging Network OOPS T1 ACRIN: 6660 Pediatric MRI Lymphoma WBMRI STIR then Fat Sat T1 + Gd for Biopsy American College of Radiology Imaging Network ACRIN: 6660 Pediatric MRI Non-Hodgkin's Lymphoma STIR OOPS T1 American College of Radiology Imaging Network ACRIN: 6660 Pediatric MRI Histoplasmosis 33ETL Turbo STIR 30 sec American College of Radiology Imaging Network ACRIN: 6660 Pediatric MRI Example-Ewing Sarcoma American College of Radiology Imaging Network ACRIN: 6660 Pediatric MRI Example-Rhabdomyosarcoma MRI CT Mass Mass Renal Metastasis American College of Radiology Imaging Network ACRIN: 6660 Pediatric MRI Rhabdomyosarcoma MR vs PET: no tumor found in right retroperitoneum American College of Radiology Imaging Network ACRIN: 6660 Pediatric MRI CT/PET vs MRI: RMS Met Found American College of Radiology Imaging Network ACRIN: 6660 Pediatric MRI Non-Hodgkin’s Lymphoma STIR MR American College of Radiology Imaging Network PET ACRIN: 6660 Pediatric MRI