6660Protocol review

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 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

American College of Radiology Imaging Network

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
American College of Radiology Imaging Network

ACRIN: 6660 Pediatric MRI


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

American College of Radiology Imaging Network

ACRIN: 6660 Pediatric MRI


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

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 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-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

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.

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 4 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