Transcript Slide 1

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
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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
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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
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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 3 - 6 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
The Sarcomas
 Mandatory 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
American College of Radiology Imaging Network
ACRIN: 6660 Pediatric MRI
Neuroblastoma
 Mandatory 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
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ACRIN: 6660 Pediatric MRI
Lymphoma
 Mandatory 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
American College of Radiology Imaging Network
ACRIN: 6660 Pediatric MRI
CT Imaging Protocol
 Bowel Opacification
• 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
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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
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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
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
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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 70-140 µCi/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
• Dose is 14 µCi/kg, with a maximum dose of 1.0 mCi
• Images at 48 hours after tracer administration with a large-field-ofview gamma camera equipped with a high-energy collimator
• Additional images can be obtained at 72 hours, if necessary to clarify
findings at 48 hours
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ACRIN: 6660 Pediatric MRI
Fast MRI Techniques
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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
1
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
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.
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ACRIN: 6660 Pediatric MRI
Whole Body MR: Neuroblastoma CR
STIR
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OOPS T1
ACRIN: 6660 Pediatric MRI
11 Year Old, Stage 4 Neuroblastoma
STIR
IPS
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OOPS T1
ACRIN: 6660 Pediatric MRI
Lymphoma
WBMRI STIR then Fat Sat T1 + Gd for Biopsy
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ACRIN: 6660 Pediatric MRI
Non-Hodgkin's Lymphoma
STIR
OOPS T1
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Histoplasmosis
33ETL Turbo STIR 30 sec
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ACRIN: 6660 Pediatric MRI
Example-Ewing Sarcoma
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ACRIN: 6660 Pediatric MRI
Example-Rhabdomyosarcoma
MRI
CT
Mass
Mass
Renal Metastasis
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ACRIN: 6660 Pediatric MRI
Rhabdomyosarcoma
MR vs. PET:
no tumor found in right retroperitoneum
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ACRIN: 6660 Pediatric MRI
CT/PET vs. MRI: RMS Met Found
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ACRIN: 6660 Pediatric MRI
Non-Hodgkin’s Lymphoma
STIR MR
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PET
ACRIN: 6660 Pediatric MRI