International Myeloma Working Group Guidelines on Imaging Techniques in the Diagnosis and Monitoring of Multiple Myeloma 1

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Edwina Matthews
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1 Internatinal Myelma Wrking Grup Guidelines n Imaging Techniques in the Diagnsis and Mnitring f Multiple Myelma 1 Up t 90% f myelma patients develp stelytic lesins, a majr cause f mrbidity and mrtality, during the curse f their disease. 2 Apprpriate use f imaging techniques is essential t identify and characterize skeletal cmplicatins resulting frm MM, t determine the extent f intramedullary and extramedullary fci, and t evaluate disease prgressin. Several imaging techniques are used t clarify bne and sft tissue disease in the diagnsis and management f myelma: cnventinal radigraphy, cmputed tmgraphy (CT), magnetic resnance imaging (MRI), and nuclear medicine imaging. The fllwing Internatinal Myelma Wrking Grup (IMWG) guidelines prvide recmmendatins fr the use f each f the technlgies. The apprpriate use f these varius technlgies fr each individual patient shuld be discussed directly with the treating physician. 1. CONVENTIONAL RADIOGRAPHY Cnventinal radigraphy is still cnsidered the "gld standard" fr the determinatin f the extent f MM bne disease at diagnsis. In a cmplete skeletal survey, it is imprtant t include all areas f pssible myelma invlvement: cervical, thracic, and lumbar spine; skull, chest, pelvis, humeri, and femra. Cnventinal radigraphy reveals lytic disease nly when ver 30% f the trabecular bne has been lst. This and ther limitatins f cnventinal radilgy are listed in Table 1. Table 1: Cnventinal Radilgy: Limitatins Sme areas nt well visualized Limited sensitivity: 10-20% f lesins/abnrmalities missed Reduced specificity vs. benign causes f stepenia (e.g. sterids/pst-menpausal) Observer dependent Time/Tlerance fr standard survey nt ideal 1

2 Usually fail t shw respnse t treatment 2. COMPUTED TOMOGRAPHY CT scanning allws excellent 3D recnstructin f images. In sme institutins, CT scanning has replaced cnventinal radigraphy as the initial imaging tl used in patients with disease related prblems f the spine r pelvis. Advantages f CT are detailed in Table 2. Table 2: Advantages f Cmputed Tmgraphy (CT) Detects small stelytic lesins Faster than standard radigraphic survey Prvides 3D recnstructin f images Shws assciated sft tissue disease Greater sensitivity and specificity versus standard radigraphy Allws estimatin f fracture risk Excellent fr raditherapy planning and fr surgical interventin A negative pint is that the radiatin dse with CT is times higher than that delivered during standard radigraphy. 3. MAGNETIC RESONANCE IMAGING MRI allws visualizatin f the medullary cavity and a direct assessment f the degree f MM cell infiltratin befre bne destructin becmes visible n plain radigraphs, withut radiatin expsure. MRI can be used fr the accurate illustratin f the vertebral fracture r the percentage f lss f vertebral height befre vertebrplasty r kyphplasty. Whle-bdy MRI is superir t whle-bdy MDCT, a very sensitive CT methdlgy. 3 MRI is useful in determining prgnsis based n the number, size, and pattern f MR bne marrw lesins. Fr a list f ther advantages f MRI in myelma, see Table 3. 2

3 Table 3: Rle f Magnetic Resnance Imaging (MRI) Mre sensitive than standard radigraphy Excellent imaging f axial skeletn Discriminates myelma vs. nrmal marrw Excellent diagnstic discriminatin fr spinal crd/nerve cmpressin issues, as well as sft tissue disease Can detect avascular necrsis f the femral head Can detect amylid/light chain depsits in the heart and ther sites Can be used t assess disease status in MGUS, asymptmatic myelma and fr slitary plasmacytmata f bne Can be used t mnitr respnse (althugh imprvements can be delayed) Caveats: A questin was raised at the ASH meeting in December, 2009, regarding the use f gadlinium enhancement in MRI in light f its prmtin f myelma cell grwth in vitr. 4 The main methdlgical cnsideratin with MRI imaging is the lack f specificity f the findings. MRI must be perfrmed at least ne mnth after G-CSF administratin; diffuse r fcal marrw changes after treatment with G-CSF cannt be easily distinguished frm active disease. Cntraindicatins t MRI include patient intlerance, cardiac pacemakers, and intra-rbital freign bdies 4. NUCLEAR MEDICINE IMAGING Technetium bne scintigraphy The specificity and sensitivity f technetium bne scintigraphy at the time f initial diagnsis, in fllw-up studies, and in the evaluatin f bne pain is lwer cmpared t cnventinal radigraphy. Technetium bne scintigraphy is related mainly t steblastic prcess. Since myelma is characterized by steblast dysfunctin, bne scintigrapy is nt recmmended fr the assessment f myelmatus bne disease. 3

4 99mTc-sestamibi 99mTc-sestamibi (MIBI) imaging clsely reflects myelma disease activity in bne marrw with very high sensitivity and specificity. 5,6 MIBI is nt useful in MGUS wrk-up, since it is always negative and cannt be used t predict MGUS transfrmatin. MIBI scanning has inferir value cmpared t FDG-PET/CT, and is inferir t MRI in assessing the extent f myelmatus bne marrw infiltratin in the spine. MIBI scre is significantly related t ISS, bne marrw bipsy infiltratin rate, and serum B2M. MIBI washut may predict fr respnse t cnventinal r high-dse chemtherapy. MIBI scan was f prgnstic value in ISS stage II MM patients, but added n relevant infrmatin t ISS in patients with stages I and III. MIBI cannt detect ONJ (stenecrsis f the jaw) in myelma patients. Psitrn emissin tmgraphy (PET) Subcentimeter lytic lesins seen n plain radigraph may nt be detectable n PET scanning. Fusin scanning cmbining bth PET and CT addresses the issue f limited spatial reslutin and takes less time than (apprximately 30 minutes) than a PET scan alne (apprximately ne hur). PET/CT allws identificatin f high-risk myelma and can be used t mnitr nn-secretry myelma as well as patients in CR withut measurable M-cmpnent. PET/CT studies are mre sensitive than ther imaging mdalities fr lcalizing extramedullary disease; they reveal additinal lesins in almst 30% f patients wh had been diagnsed with slitary plasmacytma by MRI. In 30% f newly diagnsed patients, PET/CT scans f the spine and pelvis failed t shw abnrmal findings in areas in which MRI revealed an abnrmal pattern f bne invlvement. Cmbining PET/CT with MRI f the spine and pelvis increases the ability t detect sites f active MM, bth medullary and extramedullary. 4

5 PET/CT has false psitive results, particularly in areas f inflammatin r infectin. PET/CT is mre sensitive than MRI fr making the diagnsis f mandibular stenecrsis. Further studies are needed befre the use f PET as a standard tl in bth diagnsis and fllw-up f MM is recmmended. The use f MIBI PET shuld particularly be cnsidered in the evaluatin f a patient with an early-stage MM t exclude the presence f mre extensive disease. Dual-energy X-ray absrptimetry (DEXA) DEXA may influence the decisin t begin bisphsphnate treatment. DEXA is a quick, nninvasive investigatin that uses a small dse f radiatin. Its use is limited by spinal disease and the difficulty f distinguishing myelma steprsis frm malignant steprsis. Sequential DEXA-scans are nt recmmended because they shw hetergeneus lcal BMD changes, and cannt predict disease prgressin. 1 Dimpuls MA et al.internatinal myelma wrking grup cnsensus statement and guidelines regarding the current rle f imaging techniques in the diagnsis and mnitring f multiple myelma, Leukemia (2009), Terps E, Dimpuls MA. Myelma bne disease: pathphysilgy and management. Ann Oncl 2005: 16: Bauer-Melnyk A et al. Whle-bdy MRI versus whle-bdy MDCT fr staging f multiple myelma. AJR Am J Rentgenl 2008; 190: Fulciniti M et al. Gadlinium Cntaining Cntrast Agent Prmtes Multiple Myelma Cell Grwth: Implicatin fr Clinical Use f MRI in Myelma. ASH abstract 1809, 51st annual ASH meeting, pster sessin n Bilgy and Pathphysilgy f Myelma 5

6 5 Balleari E et al. Technetium-99-sestaMIBI scintigraphy in multiple myelma and related gammpathies: a useful tl fr the identificatin and fllw-up f myelma bne disease. Haematlgica 2001; 86: Tiravla EB et al. The use f 99m-Tc-MIBI scanning in multiple myelma. Br J Cancer 1996; 74:

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