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International Myeloma Working Group Consensus Statement and Guidelines Regarding the Current Role of Imaging Techniques in the D Leukemia (2009) 23, 1545–1556 & 2009 Macmillan Publishers Limited All rights reserved 0887-6924/09 $32.00 www.nature.com/leu REVIEW International myeloma working group consensus statement and guidelines regarding the current role of imaging techniques in the diagnosis and monitoring of multiple Myeloma M Dimopoulos1, E Terpos1, RL Comenzo2, P Tosi3, M Beksac4, O Sezer5, D Siegel6, H Lokhorst7, S Kumar8, SV Rajkumar8, R Niesvizky9, LA Moulopoulos10 and BGM Durie11 On behalf of the IMWG 1Department of Therapeutics, Alexandra Hospital, Athens, Greece; 2Blood Bank and Stem Cell Processing Laboratory, Tufts Medical Center, Boston, MA, USA; 3Institute of Hematology and Medical Oncology, University of Bologna, Bologna, Italy; 4Ankara University, Cebeci Yerles¸kesi, Ankara, Turkey; 5Department of Hematology/Oncology, Charite´-University Hospital, Berlin, Germany; 6Division of Multiple Myeloma, Hackensack University Medical Center, Hackensack, NJ, USA; 7Department of Hematology, University Hospital Utrecht, Utrecht, The Netherlands; 8Department of Hematology, Mayo Clinic, Rochester, MN, USA; 9Center for Lymphoma and Myeloma, Weill Medical College of Cornell University, New York, NY, USA; 10Department of Radiology, Alexandra Hospital, Athens, Greece and 11Aptium Oncology Inc., Cedars-Sinai Outpatient Cancer Center at the Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA, USA Several imaging technologies are used for the diagnosis and the arms and legs.2 Furthermore, almost 10% of the patients management of patients with multiple myeloma (MM). Conven- present with diffuse osteopenia or osteoporosis at diagnosis.3 tional radiography, computed tomography (CT), magnetic reso- nance imaging (MRI) and nuclear medicine imaging are all used Myeloma bone destruction represents a major cause of in an attempt to better clarify the extent of bone disease and soft morbidity and mortality. Progression of skeletal disease is often 4 tissue disease in MM. This review summarizes all available data not affected by chemotherapy even in responding patients. The in the literature and provides recommendations for the use of mechanisms of bone destruction are related to increased each of the technologies. Conventional radiography still remains osteoclastic bone resorption, which is accompanied by an the ‘gold standard’ of the staging procedure of newly diagnosed exhausted osteoblast function and reduced bone formation.5–7 and relapsed myeloma patients. MRI gives information comple- mentary to skeletal survey and is recommended in MM patients Thus, a characteristic feature of myeloma bone disease is that with normal conventional radiography and in all patients with an the lesions rarely heal even when the patients are in complete 3,8 apparently solitary plasmacytoma of bone. Urgent MRI or CT remission. This finding is in keeping with the observation that (if MRI is not available) is the diagnostic procedure of choice to bone scans are often negative in myeloma patients who have assess suspected cord compression. Bone scintigraphy has no extensive lytic lesions, and offer very little in the follow-up of place in the routine staging of myeloma, whereas sequential bone disease in these patients.9 Appropriate use of imaging dual-energy X-ray absorptiometry scans are not recommended. Positron emission tomography/CT or MIBI imaging are also not techniques is essential in the identification and characterization recommended for routine use in the management of myeloma of the skeletal complications resulting from MM and in patients, although both techniques may be useful in selected determination of the extent of intramedullary bone disease. cases that warrant clarification of previous imaging findings, but Imaging also is critical for detection of extramedullary foci, such an approach should ideally be made within the context of a identification and characterization of infectious and other clinical trial. complications and evaluation of progression of the disease. Leukemia (2009) 23, 1545–1556; doi:10.1038/leu.2009.89; published online 7 May 2009 However, we lack a consensual and standardized imaging Keywords: multiple myeloma; conventional radiography; computed protocol for both newly diagnosed myeloma patients or for tomography; magnetic resonance imaging; nuclear medicine following patients in the course of treatment and disease imaging progression.10 Lytic lesions are generally diagnosed by radiographic analysis. One weakness of radiographic detection is that it may reveal lytic disease only when over 30% of the trabecular bone has been lost.11 This results in suboptimal assessment of generalized osteopenia, which affects MM patients and corre- Introduction lates with an increased risk of early vertebral collapse.12 The morbidity of vertebral collapse is significant. Chronic pain, Multiple myeloma (MM) is a plasma-cell malignancy and is functional limitations and respiratory compromise, which characterized by the presence of lytic bone disease causing increase the risk of pulmonary infections are typical clinical severe bone pain, pathological fractures, spinal cord compres- sequelae of vertebral compression fractures. Due to the sion and hypercalcemia. Up to 90% of myeloma patients limitations of standard radiographic analysis, computed tomo- 1 develop osteolytic lesions during the course of their disease. graphy (CT) or magnetic resonance imaging (MRI) have been These lesions occur predominantly in the axial skeleton, that is, used to increase the sensitivity and specificity of early detection skull, spine, rib cage and pelvis, as well as the proximal areas of of myeloma-associated bone destruction. CT and MRI also allow discrimination of malignant and benign compression fractures, Correspondence: Dr M Dimopoulos, Department of Clinical Ther- visualization of soft tissue involvement and spinal cord and/or apeutics, University of Athens School of Medicine, 80 Vas. Sofias, nerve root compression or jeopardy. Athens, 11528, Greece. In recent years, positron emission tomography (PET) has also E-mail: [email protected] Submitted on behalf of the International Myeloma Working Group been used in MM imaging. 18F-fluorodeoxyglucose (FDG) is Received 2 March 2009; accepted 5 March 2009; published online 7 taken up by metabolically active cells, which can then be May 2009 imaged using PET. High uptake by tumor cells is visible on PET Role of imaging techniques in multiple myeloma M Dimopoulos et al 1546 imaging, as they have increased metabolic rates. This review reproducibility of the results is very low between different summarizes all available data for the role of imaging in MM and centers and in a recent study an expert radiological review of aims to provide practical information for the usage of these skeletal surveys was able to detect additional abnormalities in techniques by clinicians who manage myeloma patients. 23% of the studied cases.22 A major disadvantage of conven- tional X-rays is that almost 20 separate films/exposures are needed, requiring a lengthy period on the radiographic table. Conventional radiology The patient’s ability to tolerate the standard bone survey is an important issue because myeloma patients can experience Since 1903, when Weber first observed that myeloma lesions severe pain when they are rotated and positioned for multiple are evident on radiographs, X-rays have been extensively used individual radiographic exposures. To override this problem, to identify myeloma-related bone lesions both at diagnosis and some centers have introduced a whole-body conventional during disease course. Lytic lesions on plain X-rays are typically radiographic skeletal survey, the low-dose whole-body radio- holes – that is, punched-out lesions with absent reactive graphic system (Statscan) for the detection of focal metastatic sclerosis of the surrounding bone – in the flat bones of the skull deposits in cancer and myeloma patients, which can give a high and pelvis.13 In the long bones, there is a range of appearances quality imaging of the bones in less than 5 min.23 In a study of from endosteal scalloping, to discrete small (o1 cm) lytic 30 patients with solid tumors metastatic to the skeleton and MM, lesions, to mottled areas of multiple small lesions, to large the whole-body radiography was found as effective as CT or MRI destructive lesions.14 These lesions correspond to nodular in revealing focal lesions,23 a result that has not yet been replacement of marrow by plasma cells with entire bone confirmed by others.10 Furthermore, plain X-rays cannot be used destruction.15 Conventional radiography may also reveal diffuse for the assessment of response to therapy as the lytic bone osteoporosis, which is best recognized in the spine.16 lesions seldom show evidence of healing,8 whereas new The presence of lytic lesions is a criterion for myeloma compression vertebral fractures do not always indicate disease diagnosis, whereas the extent of lytic disease is included in progression and may occur due to ongoing bone loss or Durie–Salmon staging system.17 Therefore, it is important to reduction of tumor mass that supports the bony cortex.24 For include in a ‘complete skeletal survey’ all areas of possible all these reasons, although conventional X-rays are considered myeloma involvement, such as the cervical, thoracic and as a ‘gold standard’ for the determination of the extent of lumbar spine, skull, chest, pelvis, humeri and femora. Almost myeloma bone disease at diagnosis, further imaging is needed 80% of patients with myeloma will have radiological
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