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Whole-Body MRI in the Evaluation of Pediatric Malignancies

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1 Whole-Body MRI in the Evaluation of Pediatric Malignancies
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

2 Aims Primary Aim Secondary Aims
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.

3 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.

4 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;

5 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

6 Study Overview Required Conventional Studies Experimental Studies
Scintigraphy (Bone or MIBG or gallium) Abdominal/Pelvic CT or MRI Experimental Studies Whole-Body Fast MRI FDG-PET (optional) Expected Accrual Patients in 12 Months 50 Neuroblastomas • 30 Other sarcomas 60 Rhabdomyosarcomas • 110 Lymphomas Expected Stage IV Disease Neuroblastomas - 50% (25/100) • Other sarcomas - 20% (6/30) Rhabdomyosarcomas - 16% (10/60) • Lymphomas - 30% (33/110)

7 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.

8 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

9 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

10 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

11 The Sarcomas Mandatory Tests Optional Tests Chest CT (lung mets)
Bone scintigraphy Whole-body MRI Plain radiographs if scintigraphy abnormal Optional Tests PET Abdominal CT or conventional MRI Brain CT or MRI

12 Neuroblastoma Mandatory Tests Optional Tests
Chest or abdominopelvic CT or MRI, depending on site of primary tumor Skeletal and/or MIBG scintigraphy to screen for skeletal mets Plain radiographs if scintigraphy abnormal Whole body MRI Optional Tests PET Chest or head CT, brain MRI

13 Lymphoma Mandatory Tests Optional Tests
Chest or abdominopelvic CT scans Gallium scintigraphy if PET not done Plain radiographs if scintigraphy abnormal Whole body MRI Optional Tests PET Brain CT or MRI

14 CT Imaging Protocol Bowel Opacification Intravenous Contrast Medium
Oral contrast medium whenever possible Intravenous Contrast Medium Not required for chest CT but can be given at the discretion of the investigator Required for abdominal/pelvic CT Technical Factors Abdomen, diaphragm to pubic symphysis Chest, lung apices through liver Minimum standards: 5 mm collimation, pitch 1.0, lowest mAs and kVp possible

15 Conventional MR Imaging Protocol
Must be performed for primary soft tissue tumors and may be performed for truncal neuroblastomas At a minimum, T1-weighted and T2-weighted sequences in at least two planes Section thickness determined by patient size and the intent to cover the entire tumor

16 Bone Scintigraphy Imaging Protocol
Tc-99m methylene diphosphonate (MDP) (or hydroxyethylene diphosphonate) Approximate dose 280 µCi/kg, with a minimum dose of 2.5 mCi Imaging to begin about 2 hours after injection Large-field-of-view gamma camera High-resolution collimator for children over age 2 years and a high-resolution or converging collimator for younger children

17 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

18 MIBG Protocol Saturated potassium iodide solution (SSKI) or other sources of free iodide the day before and 7 days after study I-123 MIBG preferred Dose is µCi/kg, with a minimum dose of 1.0 mCi Images at 24 hours following tracer administration with a large-field-of-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 Dose is 14 µCi/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

19 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 ~ minutes

20 OOPS Why OOPS? OOPS Interruption
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

21 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* Contrast None Anatomic coverage Whole body (cranial vertex to feet) TE (msec) 30-77 TR (msec) 4-7 TI (msec) Flip angle 80 70-75 Echo train length 7-33 1 Number of slices 3-10 10-17 slices 10-20 slices Slice thickness (mm) 5-10 4-6 Spacing/gap (mm) 2-5 Field of View (FOV) mm 500 Matrix (phase x frequency) 128 x 256 x 256 x 256 Scan (Acquisition) Time 6-20 sec. 2-3 minutes 15-25 sec.

22 Whole Body MR: Neuroblastoma CR

23 11 Year Old, Stage 4 Neuroblastoma

24 Lymphoma WBMRI STIR then Fat Sat T1 + Gd for Biopsy

25 Non-Hodgkin's Lymphoma

26 Histoplasmosis 33ETL Turbo STIR 30 sec

27 Example-Ewing Sarcoma

28 Example-Rhabdomyosarcoma
MRI CT Mass Mass Renal Metastasis

29 Rhabdomyosarcoma MR vs. PET: no tumor found in right retroperitoneum

30 CT/PET vs. MRI: RMS Met Found

31 Non-Hodgkin’s Lymphoma

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