Guidelines for the Use of Imaging In the Management of Myeloma Department of Haematology, University College Hospital, London, UK British Journal of Haematology, 137, 49–63, 2007

Introduction Multiple myeloma : plasma cell tumor - plasma cell BM infiltration - osteolytic lesion - monoclonal protein in serum or urine - Solitary plasmacytoma - Non-secretory myeloma British Committee for Standard in Haematology, 2001 BCSH - plain X-ray as standard skeletal survey method - emergent CT or MRI in the setting of cord compression

Purpose of imaging in the management of myeloma - assessment of the extent and severity of the disease - identification of complication - assessment of treatment response Newer diagnostic imaging method - PET/CT - 99Technetium -2-methoxy-isobutyl-isonitrile (MIBI) Other consideration for choice of imaging test - cost - exposure to radiation

Typical effective doses of common diagnostic Radiological procedures

Use of Imaging at Diagnosis Diagnosis & Staging of multiple myeloma - BM exam for assessment of degree of plasma cell infiltration - quantification of the amount of monoclonal protein - imaging of skeleton for evidence of osteolytic lesions

Algorithm of Suggested Recommendations

Skeletal Survey - standard method for radiological screening at diagnosis - extent of disease – number of lytic lesions - tumor load - positive for almost 80% of patients Affecting sites with radiological identification - vertebrae (66%) > ribs (45%) > skull / shoulder > pelvis > long bone International Myeloma Working Group, classification of patient with bone disease and no clinical symptoms  as a “symptomatic” : requiring treatment

Prediction of likelihood of fracture in long bone Disadvantage - low sensitivity - showing other combined non-specific bony lesion

Recommendations For skeletal survey chest PA C / T / L - spine AP / Lateral veiw Humerus and Femur AP / Lateral view Skull AP / Lateral view Pelvis AP any other symptomatic areas

MRI Technique of choice ! - for evaluation of spinal cord compression Evaluation of disease within the bone marrow - reflection of trabecular bone, fat, water and other marrow change - typical myeloma lesion ; low signal density on T1-weighted images high signal density on T2-weighted images

Significance of using MRI screening - very sensitive : possible detection of bone lesion with negative plain radiography  Detection of occult disease with accurate disease progression rate  Staging of solitary bone plasmacytoma ---- Aid to decision making about Local VS Systemic therapy  Non-secretory myeloma (1% of total multiple myeloma) : non-detectable serum/urine monoclonal protein ---- Follow-up with serial MRI with/without sequential BM biopsy

Recommendations Suspected cord compression - urgent MRI as a diagnostic procedure All patients with solitary plasmacytoma - whole spine MRI with routine skeletal survey For clarification of ambiguous CT finding

CT Conventional CT - higher sensitivity than plain radiograph - presence and extent of extra-osseous extensions of disease - high predictive value of suspected area with normal plain film or unavailable region with plain film (scapula, sternum, rib etc.) - availability for CT – giuded biopsy - complemetary imaging information with MRI - not available as a screening test due to high level of radiation exposure

Recommendations Urgent CT for suspected cord compression in case of unavailable MRI (pt intolerance or metallic foreign body) Spine CT for suspected with negative MRI result Indication in the case of ambiguous plain film results : symptomatic area despite of normal X-ray finding Identification of extent and nature of soft tissue disease and CT – guided biopsy

Bone scintigraphy Using Technitium 99-phosphorus compound - incorporation into bone areas of increased mineralization - lytic lesion in myeloma : excessive bone resorption with lack of osteoblastic activity  Lower sensitivity for myeloma evaluation Recommenations Typically normal or decreased uptake in myeloma  little value of routine staging of myeloma

DEXA scanning Dual Energy X-ray Absorptiometry scanning - gold standard procedure for osteoporosis - Ablidgaard et al, 2004 ; correlation of reduced L-spine BMD with increased risk of vertebral collapse in multiple myeloma - not adequately confirmed by other study ; controversial - more ambiguous due to universal use of bisphosphonates NOT Recommended

PET & MIBI Scanning - one of recently emerging test Positron Emission Tomography - detection of early BM involvement in solitary plasmacytoma - extramedullary involvement detection - evaluation of treatment response Limitation of PET - undetectable for very small lytic lesion  false negative result - spatial resolution  supported by PET/CT fusion scan - false positive : inflammatory change, chemotherapy, radiotherapy - too expensive

99 Technetium sestamibi (MIBI) imaging - alternative tumor-seeking tracer - uptake of Tc-99 ; correlation with extent of disease and other disease marker (LDH, ß 2 microglobulin etc) - sensitivity 90~100% specificity 83~93% for the detection of myeloma PET vs MIBI scan : better correlation with MIBI scan Recommendations Neither PET nor MIBI scan recommended for routine screening : possible only within clinical trials

Serum amyloid P component scintigraphy AL (immunoglobulin light chain) amyloidosis - most common, serious type of systemic amyloidosis - association with monoclonal gammopathy - localization of amyloid deposit by whole body scanning with radio-labelled serum amyloid P - diagnostic yield > 90% in liver, spleen, bone, adrenal gland, kidney - insufficient spatial resolution with nerve, gut, skin involvement - poor demonstration of cardiac involvement due to motion artifact

Recommendations Indication of diagnostic SAP (serum amyloid P) scan - all patient with suggestive of AL amyloidosis in addition to biopsy Follow-up SAP scan - every 6~12months for assess response to therapy

Use of Imaging in the Management of Vertebral Collapse Acute Vertebral Collapse - incidence of up to 70% of patients - cord compression in 25% of patient with vertebral body collapse - MRI for choice of diagnostic test Vertebral collapse unresponsive to conservative management  percutaneous vertebroplasty or kyphoplasty - C / T / L – spine AP/Lateral view - Cross-sectional MRI of affected vertebral body| - Bone SPECT for distinguish acute or chronic lesion - Calculation of percentage loss of vertebral height on MRI image

Recommendations Urgent MRI - diagnostic procedure for suspected cord compression in myeloma patient with vertebral collapse - No Role for prediction of likelihood of collapse or level of spinal column Patient being considered for percutaneous vertebroplasty - plain spine x-ray and spine CT / MRI to exclude cord compression

Assessment of Response to Therapy and Disease Relapse Skeletal survey - limited value due to little reflection of healing lytic lesion on plain flim - new vertebral compression fracture ; not always evidences of disease progression presented even after effective therapy - repetitive skeletal survey : exhausting and potentially painful experience to patients

Recommendations Little benefit of routine follow up to asymptomatic patient without disease progression In case of disease progression - repeat skeletal survey as part of restaging process - no need of additional evaluation within 3 month since disease progression and without any new symptoms

MRI - reflection of wide spectrum of treatment-induced marrow change - correlation with treatment reponse : reduction of signal intensity in T2WI Recommendations Insufficient evidence to recommend routine MRI for follow-up of treated disease

CT - more discriminating than plain film - disappearance of extraosseous or extramedullary masses - reappearance of continuous cortical outline and fatty marrow PET & MIBI Scanning - controversial despite of emerging report about correlation with therapy response NOT Recommendation of CT or PET with routine follow-up test