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
STIR OOPS T1

23. 11 Year Old, Stage 4 Neuroblastoma
STIR IPS OOPS T1

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

25. Non-Hodgkin's Lymphoma
STIR OOPS T1

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
STIR MR PET