WHOLE-BODY-LOW-DOSE MDCTWHOLE-BODY-LOW-DOSE MDCTIN THE INVESTIGATION OF IN THE INVESTIGATION OF MULTIPLE MYELOMA (MM) – MULTIPLE MYELOMA (MM) – A NEW APPROCH AND OUR EXPERIENCEA NEW APPROCH AND OUR EXPERIENCE

Kamenetsky Natalya (1), Kamenetsky Natalya (1), Rachmilewitz Eliezer (2),Rachmilewitz Eliezer (2),Katz Rama (1), Katz Rama (1),

(1)Department of Diagnostic Imaging(1)Department of Diagnostic Imaging(2) Department of Heamatology (2) Department of Heamatology E. Wolfson Medical Center, Holon, Israel.E. Wolfson Medical Center, Holon, Israel.

• The idea of our study came from lately The idea of our study came from lately published literature, especially the article:published literature, especially the article:

““Whole-body low dose multidetector row-Whole-body low dose multidetector row-CT CT

in the diagnosis of MM:in the diagnosis of MM: an alternative to conventional an alternative to conventional

radiography” radiography” EJR,2005.EJR,2005.

MM – Definition and MM – Definition and diagnosisdiagnosisUncontrolled proliferation of neoplasticUncontrolled proliferation of neoplastic

plasma cell clone in the bone marrow.plasma cell clone in the bone marrow.

DiagnosisDiagnosis based on laboratory and radiographic based on laboratory and radiographic findings:findings:

• Bone marrow containing more then 15% plasma Bone marrow containing more then 15% plasma cells (normally no more then 4%).cells (normally no more then 4%).

• Blood serum or urine containing an abnormal Blood serum or urine containing an abnormal protein (M protein, Bence-Jones protein).protein (M protein, Bence-Jones protein).

• Bone lesions found on skeletal survey as Bone lesions found on skeletal survey as generalized osteopenia or lytic bone deposits.generalized osteopenia or lytic bone deposits.

MM – Demographics:MM – Demographics:• Most common primary bone tumor in adult.Most common primary bone tumor in adult.

• Multifocal lesions more commonMultifocal lesions more common• Solitary (Plasmacytoma) less common: Solitary (Plasmacytoma) less common: may be Intra/Extraosseous. may be Intra/Extraosseous.

• Age: 40 years or older.Age: 40 years or older.• M:F = 2:1M:F = 2:1• More common in Afro-Americans then in More common in Afro-Americans then in

Caucasians. Less common in Asians.Caucasians. Less common in Asians.• Median survival: 3-4 years.Median survival: 3-4 years.

MM – Skeletal MM – Skeletal involvement:involvement:

Osteolytic Osteolytic lesionlesion (80%) -(80%) - found found

particularly with particularly with nodular marrow nodular marrow infiltrationinfiltration..

small discrete lytic areas of bone destruction small discrete lytic areas of bone destruction

with with no reactive bone formationno reactive bone formation..

Arises within the medulla, may progress to Arises within the medulla, may progress to

infiltrate the cortex and periosteum and be infiltrate the cortex and periosteum and be

accompanied with extraosseous soft tissue accompanied with extraosseous soft tissue masses.masses.

MM-Skeletal involvment:MM-Skeletal involvment:

•Diffuse osteopeniaDiffuse osteopenia (85%) (85%) is is associated with a associated with a packed patternpacked pattern of of marrow infiltrationmarrow infiltration – thinning of all – thinning of all trabeculae, vertebral body collapse.trabeculae, vertebral body collapse.

•OsteosclerosisOsteosclerosis – – rare (1-3%), may be rare (1-3%), may be focal or diffuse.focal or diffuse.

• Normal surveyNormal survey (10%). (10%).

Skeletal involvement in Skeletal involvement in MMMM::

Frequency in different bones correlates with Frequency in different bones correlates with normal sites of red marrow distribution :normal sites of red marrow distribution :

• Vertebra (66%).Vertebra (66%).

• Ribs (45%).Ribs (45%).

• Skull (40%).Skull (40%).

• Shoulder (40%).Shoulder (40%).

• Pelvis (30%).Pelvis (30%).

• Long bones (25%).Long bones (25%).

CT versus plain film:CT versus plain film:

• Bone lesions of the Bone lesions of the axial skeletonaxial skeleton, , are significantly better recognized byare significantly better recognized by CTCT by reducing the effects of overlying by reducing the effects of overlying soft tissue and bony structures.soft tissue and bony structures.

• Bone lesions of the Bone lesions of the appendicular appendicular skeletonskeleton are mostly well recognized are mostly well recognized in in both modalitiesboth modalities..

Roll of imaging in MM Roll of imaging in MM patients:patients:

• Diagnosis and staging.Diagnosis and staging.• Diagnosis of extramedullary or Diagnosis of extramedullary or

solitary plasmacytoma and directing solitary plasmacytoma and directing a biopsy if needed.a biopsy if needed.

• Monitoring treatment response.Monitoring treatment response.• Detection of relapse.Detection of relapse.• Assessing fracture risk and directing Assessing fracture risk and directing

prophylactic treatment.prophylactic treatment.

Staging by Durie and Staging by Durie and Saimon:Saimon:

Stage 1Stage 1:: Stage 3Stage 3:: (All) (1 or more) (All) (1 or more) HemoglobinHemoglobin >10g/100ml <8.5 g/100ml >10g/100ml <8.5 g/100ml Serum calciumSerum calcium <12mg/100ml >12mg/100ml <12mg/100ml >12mg/100ml M componentM component IgG: <5g/100ml >7g/100ml IgG: <5g/100ml >7g/100ml IgA:IgA: <3g/100ml >5g/100ml<3g/100ml >5g/100mlUrine light chainUrine light chain <4 g/24hr >12g/24hr <4 g/24hr >12g/24hr

Bone LesionBone Lesion none /solitarynone /solitary multiplemultiple

Stage 2Stage 2: : Between Stage 1 and 3.Between Stage 1 and 3.

MM – Staging:MM – Staging:

Patients with Patients with more then twomore then two unequivocal lytic lesions are unequivocal lytic lesions are classified as classified as stage 3stage 3, indicating , indicating immediate treatment.immediate treatment.

Different imaging Different imaging modalitiesmodalities in MM: in MM:

X-rayX-ray – Conventional plain film survey, – Conventional plain film survey, CT.CT.

MRIMRI

Radionuclid imagingRadionuclid imaging – Tc(99m)- MIBI, – Tc(99m)- MIBI,

F-18 FDG-PET.F-18 FDG-PET.

Plain film skeletal Plain film skeletal survey:survey:

Multiple lytic lesions (80%).Multiple lytic lesions (80%).Solitary (Plasmacytoma) expansible lytic lesion.Solitary (Plasmacytoma) expansible lytic lesion.Osteopenia (85%).Osteopenia (85%).Vertebral body collapse and pathological fractures.Vertebral body collapse and pathological fractures.Normal survey (10%).Normal survey (10%).

Shrinking or sclerosing deposits indicate a response.Shrinking or sclerosing deposits indicate a response.Residual osteolysis may persist in inactive phase of Residual osteolysis may persist in inactive phase of

disease. disease.

No detection of extraosseous involvement.No detection of extraosseous involvement.

CT Imaging:CT Imaging:

• Detect disease in bone, bone marrow and Detect disease in bone, bone marrow and extramedullary sites.extramedullary sites.

• Focal pattern – sharp, lytic lesions with no Focal pattern – sharp, lytic lesions with no sclerotic rim.sclerotic rim.

• Diffuse faint osteolysis.Diffuse faint osteolysis.• High (soft tissue) attenuation value of bone High (soft tissue) attenuation value of bone

marrow.marrow.

• Positive response to treatment – Shrinking or Positive response to treatment – Shrinking or sclerosing deposit, disappearance of soft tissue sclerosing deposit, disappearance of soft tissue masses, reappearance of cortical contour and masses, reappearance of cortical contour and fatty marrow content. fatty marrow content.

Our experience:Our experience:

• On April - November 2006 we performed On April - November 2006 we performed

41 CT skeletal surveys:41 CT skeletal surveys:

• 3030 patients with known diagnosis of MM. patients with known diagnosis of MM.

• 55 to exclude MM lesion in MGUS patients. to exclude MM lesion in MGUS patients.

• 66 in other patients. in other patients.

CT survey study CT survey study protocolprotocol::• Patient laying supine, cranio-caudal Patient laying supine, cranio-caudal

position, arms on abdomen. position, arms on abdomen. • Scan length from top of the skull down to Scan length from top of the skull down to

the end of the knees.the end of the knees.• With suspended respiration when possible.With suspended respiration when possible.• No oral or IV contrast material.No oral or IV contrast material.

CT survey study protocolCT survey study protocol:: * Low dose CT parameters are based on the article from EJR 2005.* Low dose CT parameters are based on the article from EJR 2005.

• MDCT 16 slices.MDCT 16 slices.• Surview 1536 mm.Surview 1536 mm.• 120 KV, 120 KV, 70 mAs (300 mAs in spine 70 mAs (300 mAs in spine

CT)CT)• Overall radiation dose of Overall radiation dose of 5 mSv.5 mSv.• 16*0.75mm collimation with 0.5 sec 16*0.75mm collimation with 0.5 sec

rotation time.rotation time.• Table speed – 18mm/sec.Table speed – 18mm/sec.• Slice thickness – 3mm. Slice thickness – 3mm. • Mean acquisition time – 38 sec.Mean acquisition time – 38 sec.

CT survey study CT survey study protocolprotocol::• Reconstruction was done from raw data.Reconstruction was done from raw data.• bone filter with B60f kernel.bone filter with B60f kernel.• F.O.V = 500mm max.F.O.V = 500mm max.

• multiplanar reformatted (MPR) whole body multiplanar reformatted (MPR) whole body images were reconstructed in sagital and coronal images were reconstructed in sagital and coronal planes. planes.

Divided into 3 different body parts:Divided into 3 different body parts:• Head and neck, including cervical spineHead and neck, including cervical spine• Chest and abdomen including the relevant spinal Chest and abdomen including the relevant spinal

column and armscolumn and arms• pelvis and thighs.pelvis and thighs.

Plain film skeletal survey Plain film skeletal survey protocolprotocol::

• Skull – AP and lateral.Skull – AP and lateral.• Vertebral column – AP and lateral for each level.Vertebral column – AP and lateral for each level.• Ribs – AP and oblique.Ribs – AP and oblique.• Pelvis – AP.Pelvis – AP.• Upper and lower extremities – AP and lateral.Upper and lower extremities – AP and lateral.

• Overall - 20 different plain films per Overall - 20 different plain films per patient.patient.

• Radiation dose of Radiation dose of 2.4 mSv.2.4 mSv.

Our experience – results:Our experience – results:

• The majority had IgG gammopathy and The majority had IgG gammopathy and suffered from both osteopenia and lytic suffered from both osteopenia and lytic lesions.lesions.

• 12 (29%) patients had vertebral collapse.12 (29%) patients had vertebral collapse.

• 5 (12%) patients had large vertebral lytic 5 (12%) patients had large vertebral lytic lesion at high risk for collapse.lesion at high risk for collapse.

Results:Results:

In 7 (17%) patients we detected In 7 (17%) patients we detected significant extramedullary finding: significant extramedullary finding:

• 2 (4%) as part of the MM dieses 2 (4%) as part of the MM dieses itself.itself.

• 55 (12%) not directly relevant to MM (12%) not directly relevant to MM but demand forwarder investigation.but demand forwarder investigation.

CT versus plain film CT versus plain film survey:survey:• 16 MM patients had a conventional plain film 16 MM patients had a conventional plain film

survey done no more than two weeks before survey done no more than two weeks before the CT.the CT.

Comparing the two imaging modalities we Comparing the two imaging modalities we found: found:

• In 5 (31%) patients lytic lesion that where In 5 (31%) patients lytic lesion that where not found on the conventional survey.not found on the conventional survey.

• In 2 (12.5%) patients vertebral lytic lesion in In 2 (12.5%) patients vertebral lytic lesion in risk of collapse that were not found on the risk of collapse that were not found on the plain film survey.plain film survey.

CT versus plain film CT versus plain film survey:survey:Advantage: Advantage:

• More sensitive and accurate in identifying and More sensitive and accurate in identifying and characterizing lytic lesions.characterizing lytic lesions.

• Especially important in the evaluation of vertebral Especially important in the evaluation of vertebral collapse and their possible complications. collapse and their possible complications.

• Most beneficial in the diagnosis of large lytic Most beneficial in the diagnosis of large lytic lesions in risk of phatological fracture.lesions in risk of phatological fracture.

CT versus plain film survey:CT versus plain film survey:

Advantage: Advantage: • Identify extramedullary involvement of Identify extramedullary involvement of

the dieses itself or incidental finding that the dieses itself or incidental finding that may be important.may be important.

• Guide biopsies.Guide biopsies.

Disadvantage:Disadvantage: • Higher radiation dose.Higher radiation dose.

Radiation dose of X-ray Radiation dose of X-ray ImagingImaging::

Exam Exam typetype

Plain Plain film film

survey survey

CTCT low low dosedose

70 mAs70 mAs

CT high CT high dosedose

250 250 mAsmAs

RadiatiRadiation doseon dose

2.4 2.4 mSvmSv

5 5 mSvmSv

25.5 25.5 mSvmSv

Summary:Summary:

• Accurate detection of skeletal lesions is Accurate detection of skeletal lesions is essential for the diagnosis, staging and essential for the diagnosis, staging and treatment in MM.treatment in MM.

• The number, size and anatomic location of The number, size and anatomic location of the lesions are important to evaluate the the lesions are important to evaluate the patient’s prognosis and quality of life.patient’s prognosis and quality of life.

• Whole body low dose CT is much more Whole body low dose CT is much more sensitive and accurate than the classic sensitive and accurate than the classic plain film survey.plain film survey.

Summary:Summary:

• In low dose CT the radiation dose is about In low dose CT the radiation dose is about twice that of a plain film survey but much twice that of a plain film survey but much lower than conventional skeletal CT.lower than conventional skeletal CT.

• As in the literature, we propose this study As in the literature, we propose this study as an efficient and relatively available in as an efficient and relatively available in compare to other imaging modalities, for compare to other imaging modalities, for MM patients.MM patients.

MERCI! THANK YOU!MERCI! THANK YOU!

!!!!תודהתודה

MERCI! THANK MERCI! THANK YOUYOU!!

תודה!!תודה!!