6660 protocol review

ACRIN 6660 – Protocol ReviewACRIN 6660 – Protocol Review

Whole-Body MRI in the Evaluation Whole-Body MRI in the Evaluation of Pediatric Malignanciesof Pediatric Malignancies

Marilyn J. Siegel, M.D.Marilyn J. Siegel, M.D.Frederic Hoffer, M.D.Frederic Hoffer, M.D.

Brad Wyly, M.D.Brad Wyly, M.D.Alicia Y. Toledano, ScDAlicia Y. Toledano, ScD

American College of Radiology Imaging Network ACRIN: 6660 Pediatric MRI

AimsAims Primary AimPrimary 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 AimsSecondary 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.


Clinical SignificanceClinical Significance Accurate staging is critical to treatment Accurate staging is critical to treatment

planning.planning.

Conventional techniques have long imaging Conventional techniques have long imaging times and often use sedation and ionizing times and often use sedation and ionizing radiation.radiation.

If one imaging study can replace established If one imaging study can replace established imaging patterns this will have an impact on imaging patterns this will have an impact on the care of young cancer patients.the care of young cancer patients.


Imaging BackgroundImaging Background Studies in adult women with breast cancer show that Studies in adult women with breast cancer show that

whole body MRI with turbo STIR can serve as a whole body MRI with turbo STIR can serve as a single examination for stagingsingle examination for staging

SensitivitySensitivity• MRI>>95%• Conventional imaging=80%

Neuroblastoma Staging: RDOG (Radiology Diagnostic Neuroblastoma Staging: RDOG (Radiology Diagnostic Oncology Group) Results 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 usedSiegel MJ et al. Siegel MJ et al. Radio Radiol 2002; 223-168l 2002; 223-168


Daldrup-LinkDaldrup-Link AJR AJR 2001; 177:229 2001; 177:229

Imaging Background: PET vs MRIImaging Background: PET vs MRI 21 patients (51 bone metastases)21 patients (51 bone metastases)

Small cell tumorsSmall cell tumors

SensitivitySensitivity• 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 MRI and PET may improve detection of bone metastasesmetastases


Study OverviewStudy Overview Required Conventional Studies Required Conventional Studies

• Scintigraphy (Bone or MIBG or gallium)• Abdominal/Pelvic CT or MRI

Experimental StudiesExperimental Studies• Whole-Body Fast MRI• FDG-PET (optional)

Expected Accrual - 250 Patients in 12 MonthsExpected Accrual - 250 Patients in 12 Months• 50 Neuroblastomas • 30 Other sarcomas• 60 Rhabdomyosarcomas • 110 Lymphomas

Expected Stage IV DiseaseExpected Stage IV Disease• Neuroblastomas - 50% (25/100) • Other sarcomas - 20% (6/30)

• Rhabdomyosarcomas - 16% (10/60) • Lymphomas - 30% (33/110)


Eligibility CriteriaEligibility Criteria Age 21 years or younger.Age 21 years or younger. Proven rhabdomyosarcoma, Ewing’s sarcoma family of Proven rhabdomyosarcoma, Ewing’s sarcoma family of

tumors, neuroblastoma, Hodgkin’s disease, and non-Hodgkin’s tumors, neuroblastoma, Hodgkin’s disease, and non-Hodgkin’s lymphoma, or newly diagnosed mass strongly suspected to lymphoma, or newly diagnosed mass strongly suspected to represent any of these tumors.represent any of these tumors.

All examinations (CT, MRI, scintigraphy, and PET) must be All examinations (CT, MRI, scintigraphy, and PET) must be done prior to treatment and within 14 days of each other and done prior to treatment and within 14 days of each other and within 14 days of any diagnostic or operative procedure. within 14 days of any diagnostic or operative procedure.

Participants with CT studies, conventional MR, or Participants with CT studies, conventional MR, or scintigraphy, performed at outside institutions are eligible if scintigraphy, performed at outside institutions are eligible if these studies were performed with the same technical standards these studies were performed with the same technical standards specified in the protocol (see Appendix V).specified in the protocol (see Appendix V).

Signed informed consent by parent or child if older than 18.Signed informed consent by parent or child if older than 18.


Ineligibility CriteriaIneligibility Criteria Contraindications for MRI or CTContraindications for MRI or CT

• Includes active cardiac pacemakers or intracranial vascular clips

Lack of parental permission or participant assent Lack of parental permission or participant assent Patient has had a previous malignancyPatient has had a previous malignancy Patient has a CNS primary tumorPatient has a CNS primary tumor Patient is pregnant or nursingPatient is pregnant or nursing Patient has uncontrolled diabetes mellitus or has Patient has uncontrolled diabetes mellitus or has

controlled diabetes but with a fasting blood glucose controlled diabetes but with a fasting blood glucose value > 200 mg/dL, immediately before the injection value > 200 mg/dL, immediately before the injection of FDGof FDG


Image InterpretationImage Interpretation Local InterpretationLocal 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 InterpretationCentral 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


Positive FindingsPositive Findings Positive whole-body MRI or PET at initial staging 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 Positive whole-body MRI or PET at initial staging but no biopsy or imaging confirmation of diseasebiopsy or imaging confirmation of disease

• Repeat imaging with conventional studies recommended at 3 - 6 mos.

When abnormality is considered highly suspicious for When abnormality is considered highly suspicious for metastasis or when biopsy proof of that lesion is obtained, metastasis or when biopsy proof of that lesion is obtained, patient will receive treatment at discretion of the treating patient will receive treatment at discretion of the treating physicianphysician


The SarcomasThe Sarcomas Mandatory TestsMandatory Tests

• Chest CT (lung mets)

• Bone scintigraphy

• Whole-body MRI

• Plain radiographs if scintigraphy abnormal

Optional TestsOptional Tests• PET

• Abdominal CT or conventional MRI

• Brain CT or MRI


NeuroblastomaNeuroblastoma Mandatory TestsMandatory 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 TestsOptional Tests• PET• Chest or head CT, brain MRI


LymphomaLymphoma Mandatory TestsMandatory Tests

• Chest or abdominopelvic CT scans

• Gallium scintigraphy if PET not done

• Plain radiographs if scintigraphy abnormal

• Whole body MRI

Optional TestsOptional Tests• PET

• Brain CT or MRI


CT Imaging ProtocolCT Imaging Protocol Bowel OpacificationBowel Opacification

• Oral contrast medium whenever possible

Intravenous Contrast MediumIntravenous Contrast Medium• Not required for chest CT but can be given at the discretion

of the investigator• Required for abdominal/pelvic CT

Technical FactorsTechnical Factors• Abdomen, diaphragm to pubic symphysis• Chest, lung apices through liver• Minimum standards: 5 mm collimation, pitch 1.0, lowest

mAs and kVp possible


Conventional MR Imaging ProtocolConventional MR Imaging Protocol

Must be performed for primary soft tissue Must be performed for primary soft tissue tumors and may be performed for truncal tumors and may be performed for truncal neuroblastomasneuroblastomas

At a minimum, T1-weighted and T2-weighted At a minimum, T1-weighted and T2-weighted sequences in at least two planessequences in at least two planes

Section thickness determined by patient size Section thickness determined by patient size and the intent to cover the entire tumorand the intent to cover the entire tumor


Bone Scintigraphy Imaging ProtocolBone Scintigraphy Imaging Protocol

Tc-99m methylene diphosphonate (MDP) (or Tc-99m methylene diphosphonate (MDP) (or hydroxyethylene diphosphonate) hydroxyethylene diphosphonate)

Approximate dose 280 µCi/kg, with a Approximate dose 280 µCi/kg, with a minimum dose of 2.5 mCiminimum dose of 2.5 mCi

Imaging to begin about 2 hours after injectionImaging to begin about 2 hours after injection Large-field-of-view gamma cameraLarge-field-of-view gamma camera High-resolution collimator for children over High-resolution collimator for children over

age 2 years and a high-resolution or age 2 years and a high-resolution or converging collimator for younger childrenconverging collimator for younger children


Gallium ProtocolGallium Protocol IV dose of 140 µCi/kg, with a minimum dose IV dose of 140 µCi/kg, with a minimum dose

of 0.25 mCiof 0.25 mCi Imaging should be performed 3-5 days Imaging should be performed 3-5 days

following injectionfollowing injection SPECT suggested for localization of disease SPECT suggested for localization of disease

and for distinguishing between normal bowel and for distinguishing between normal bowel activity and pathologyactivity and pathology

Large-field-of-view multidetector gamma Large-field-of-view multidetector gamma camera with medium-energy collimator camera with medium-energy collimator recommended recommended


MIBG ProtocolMIBG Protocol Saturated potassium iodide solution (SSKI) or other sources of Saturated potassium iodide solution (SSKI) or other sources of

free iodide the day before and 7 days after studyfree iodide the day before and 7 days after study I-123 MIBG preferredI-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-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 usedIf 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


Fast MRI TechniquesFast MRI Techniques Whole Body ImagingWhole Body Imaging Vertex to toesVertex to toes Coronal plane imagesCoronal plane images Body Coil; phased array coils allowed unless lengthened time Body Coil; phased array coils allowed unless lengthened time

of examof exam Breath hold on scans under 30Sec onlyBreath hold on scans under 30Sec only Scans performed on a 1.5 TScans performed on a 1.5 T Localizer scanLocalizer scan Turbo STIR (water sensitive image) Turbo STIR (water sensitive image) Out-of-phase (OOPS) better than in phase (IPS) for detecting Out-of-phase (OOPS) better than in phase (IPS) for detecting

metastasesmetastases Images acquired in 3-4 stationsImages acquired in 3-4 stations Total Imaging time ~ 10-15 minutesTotal Imaging time ~ 10-15 minutes


OOPSOOPS Why 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 InterruptionOOPS 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


Whole Body MRI Technical FactorsWhole Body MRI Technical FactorsPatient PositionPatient Position Supine, arms down at sidesSupine, arms down at sides

Imaging PlaneImaging Plane Coronal, sagittal or Coronal, sagittal or multiplane Scoutmultiplane Scout

Coronal STIRCoronal STIR Coronal T1 OOPSCoronal T1 OOPS

Coil(s)Coil(s) Body coil*Body coil* Body coil*Body coil* Body coil*Body coil*

ContrastContrast NoneNone NoneNone NoneNone

Anatomic coverageAnatomic coverage Whole body (cranial vertex to feet)Whole body (cranial vertex to feet)

TE (msec)TE (msec) 1.9-3.051.9-3.05 30-7730-77 2.2-2.42.2-2.4

TR (msec)TR (msec) 4-74-7 4200-68004200-6800 120-150120-150

TI (msec)TI (msec) 140-150140-150

Flip angleFlip angle 8080 150-180150-180 70-7570-75

Echo train lengthEcho train length 7-337-33 11

Number of slicesNumber of slices 3-103-10 10-17 slices10-17 slices 10-20 slices10-20 slices

Slice thickness (mm)Slice thickness (mm) 5-105-10 4-64-6 4-64-6

Spacing/gap (mm)Spacing/gap (mm) 2-52-5 11 11

Field of View (FOV) mmField of View (FOV) mm 500500 200-500200-500 200-500200-500

Matrix (phase x frequency)Matrix (phase x frequency) 128 x 256 128 x 256 128-140 x 256128-140 x 256 150-180 x 256150-180 x 256

Scan (Acquisition) TimeScan (Acquisition) Time 6-20 sec.6-20 sec. 2-3 minutes2-3 minutes 15-25 sec.15-25 sec.


Whole Body MR: Neuroblastoma CRWhole Body MR: Neuroblastoma CR

STIR STIR OOPS T1 OOPS T1


11 Year Old, Stage 4 Neuroblastoma11 Year Old, Stage 4 Neuroblastoma

STIR IPS OOPS T1STIR IPS OOPS T1


LymphomaLymphomaWBMRI STIR then Fat Sat T1 + Gd for BiopsyWBMRI STIR then Fat Sat T1 + Gd for Biopsy


Non-Hodgkin's LymphomaNon-Hodgkin's Lymphoma

STIR OOPS T1STIR OOPS T1


Histoplasmosis Histoplasmosis

33ETL Turbo STIR 30 sec33ETL Turbo STIR 30 sec


Example-Ewing SarcomaExample-Ewing Sarcoma


Example-Rhabdomyosarcoma Example-Rhabdomyosarcoma

Renal MetastasisRenal Metastasis

CTCTMRIMRI

MassMass


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


CT/PET vs. MRI: RMS Met FoundCT/PET vs. MRI: RMS Met Found


Non-Hodgkin’s LymphomaNon-Hodgkin’s Lymphoma

STIR MR PETSTIR MR PET

6660 protocol review

Health & Medicine

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relative accuraciesof

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