Clinical and prognostic significance of bone marrow abnormalities in the appendicular skeleton detected by low-dose whole-body multidetector computed tomography in patients with multiple myeloma

Multiple myeloma (MM) is a plasma cell disorder, characterized by clonal proliferation of malignant plasma cells in the bone marrow. Bone disease is the most frequent feature and an end-organ defining indicator of MM. In this context, imaging plays a pivotal role in the management of the malignancy. For several decades whole-body X-ray survey (WBXR) has been applied for the diagnosis and staging of bone disease in MM. However, the serious drawbacks of WBXR have led to its gradual replacement from novel imaging modalities, such as computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT). PET/CT, with the tracer 18F-fluorodeoxyglucose (18F-FDG), is now considered a powerful diagnostic tool for the detection of medullary and extramedullary disease at the time of diagnosis, a reliable predictor of survival as well as the most robust modality for treatment response evaluation in MM. On the other hand, 18F-FDG carries its own limitations as a radiopharmaceutical, including a rather poor sensitivity for the detection of diffuse bone marrow infiltration, a relatively low specificity, and the lack of widely applied, established criteria for image interpretation. This has led to the development of several alternative PET tracers, some of which with promising results regarding MM detection. The aim of this review article is to outline the major applications of PET/CT with different radiopharmaceuticals in the clinical practice of MM.

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The benefit of whole-body low-dose unenhanced multidetector computer tomography (WBLD-MDCT) for follow up and therapy response monitoring in patients with multiple myeloma: Correlation with hematologic parameters

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.7607 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 7607-7607

Author(s):

M. S. Horger ◽

C. Driessen ◽

C. Brodoefel ◽

C. Faul ◽

P. Pereira ◽

...

Keyword(s):

Multiple Myeloma ◽

Computer Tomography ◽

Low Dose ◽

Laboratory Data ◽

Whole Body ◽

Acquisition Time ◽

Bone Lesions ◽

Appendicular Skeleton ◽

Multidetector Computer Tomography

7607 Background: To assessthe value of whole-body low-dose multidetector computer tomography (WBLD-MDCT) as diagnostic and survey modality in multiple myeloma (MM), and as a one-stop alternative (Horger et al. EJR 2005;54:289–297) to established imaging techniques (e.g. x-ray and MRI). Methods: Between 7/2001 and 2/2005, WBLD-MDCT scans were obtained in 90 consecutive patients with histologically proven stage II-III MM, all patients having 2 or more scans (mean = 3,8; range = 2–6). CT-scans were performed using a standardized low-dose protocol and the number, size and density of focal or diffuse medullary (in the appendicular skeleton and pelvis) and extra-medullary lesions as well as osteolysis were analysed for each examination and at follow up. Results were correlated with current standard MM laboratory data and at follow up in order to assess correct temporal recognition of significant myeloma changes by both methods. Results: Detection and follow up of medullary and extra-medullary MM lesions and osteolysis by WBLD-MDCT resulted in a sensitivity of 92%, a specificity of 93%, a NPV of 95%, a PPV of 85% and a likelihood ratio for patients with CT-abnormalities to present changes in the course of their disease of 12. Results of radiologic and hematologic analysis showed high agreement at follow up (median, 3 mo). However, agreement of both techniques at the time of investigation was only moderate (κ = 0.629), with CT being correct in 60% of mismatching cases. Thus, CT enabled earlier detection of MM changes. WBLD-MDCT assessed correctly the course of disease in all 4 patients with nonsecretory MM. Evaluation of stability was optimal in all patients. Conclusions: WBLD-MD represents a reliable, widespread, quick (75s acquisition time), and cost-effective imaging technique in MM, allowing detection of bone marrow involvement, extra-medullary tumors and lytic bone lesions in different clinical settings (staging, follow up, therapy monitoring, evaluation of stability). WBLD-MDCT repeatedly allowed detection of changes in the course of the disease prior to laboratory data, especially in extramedullary MM relapse and nonsecretory MM. No significant financial relationships to disclose.

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Whole-Body Low-Dose Computed Tomography and Advanced Imaging Techniques for Multiple Myeloma Bone Disease

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-14-1692 ◽

2014 ◽

Vol 20 (23) ◽

pp. 5888-5897 ◽

Cited By ~ 39

Author(s):

Matthew J. Pianko ◽

Evangelos Terpos ◽

G. David Roodman ◽

Chaitanya R. Divgi ◽

Sonja Zweegman ◽

...

Keyword(s):

Computed Tomography ◽

Multiple Myeloma ◽

Bone Disease ◽

Low Dose ◽

Imaging Techniques ◽

Whole Body ◽

Advanced Imaging ◽

Myeloma Bone Disease ◽

Low Dose Computed Tomography

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Longitudinal whole body MRI (wbMRI) in monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.8590 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 8590-8590

Author(s):

Maximilian Merz ◽

Barbara Wagner-Gund ◽

Kai Neben ◽

Anthony D. Ho ◽

Hartmut Goldschmidt ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Marrow ◽

Prognostic Significance ◽

Progression Free Survival ◽

Whole Body ◽

Rank Test ◽

Focal Lesions ◽

Patients At Risk ◽

Initial Work

8590 Background: The detection of bone marrow focal lesions (FLs) by MRI at the initial work up has prognostic significance in multiple myeloma (MM), smoldering MM as well as MGUS. Currently, there are no data available on the predictive relevance of new FLs or FLs increasing in size in longitudinally performed wbMRIs for the follow-up of sMM and MGUS. Methods: We retrospectively analyzed 87 patients (sMM n=65; MGUS n=22) that received at least 2 (up to 5) wbMRIs for follow-up. The date of progression into MM requiring systemic therapy was defined as event for the analysis of progression free survival (PFS). Radiological progressive disease (rPD) was defined as the appearance of novel FLs or increase in size of preexisting FLs. Kaplan-Meier plots of PFS for patients with rPD and patients without rPD were analyzed using the log-rank test for significant differences. Results: Median follow-up was 61 months (9.8-101) with a median time between follow-up wbMRIs of 15.8 months (1-73). Progression from sMM/MGUS into MM was found in 28 patients (sMM 40%; MGUS 9%). Using wbMRI, rPD was found in 21 patients (sMM 32%; MGUS 0%). Of all patients, 76% (n=16) with rPD and 16% (n= 9) without rPD progressed into MM during the observation period. Analysis of Kaplan Meyer plots for PFS revealed a highly significant shorter PFS for patients with rPD (32 months) compared to patients with radiological stable disease in wbMRI (PFS not reached; p<0.0001). New appearance or progression of diffuse bone marrow infiltration was not associated with a shorter PFS (not reached; p>0.05). Conclusions: In our study, the appearance of novel FLs or progression of preexisting FLs was highly predictive for progression from sMM into MM requiring systemic treatment. We conclude that wbMRI is effective for the longitudinal follow-up of patients with sMM and MGUS and identifies a group of patients at risk for progression into MM.

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Image Quality in Low-dose Multidetector Computed Tomography: A Pilot Study to Assess Feasibility and Dose Optimization in Whole-body Bone Imaging

Canadian Association of Radiologists Journal ◽

10.1016/j.carj.2010.01.003 ◽

2010 ◽

Vol 61 (5) ◽

pp. 258-264 ◽

Cited By ~ 19

Author(s):

Tadhg G. Gleeson ◽

Brenda Byrne ◽

Pat Kenny ◽

Jason Last ◽

Patricia Fitzpatrick ◽

...

Keyword(s):

Computed Tomography ◽

Image Quality ◽

Multidetector Computed Tomography ◽

Low Dose ◽

Interobserver Agreement ◽

Skeletal Survey ◽

Whole Body ◽

Altman Plot ◽

Low Dose Ct ◽

Effective Doses

Objective To study the impact of dose parameters on image quality at whole-body low-dose multidetector computed tomography (CT) in an attempt to derive parameters that allow diagnostic quality images of the skeletal system without incurring significant radiation dose in patients referred for investigation of plasma cell dyscrasias. Methods By using a single cadaver, 14 different whole-body low-dose CT protocols were individually assessed by 2 radiologists, blinded to acquisition parameters (kVp and mAs, reconstruction algorithm, dose reduction software). Combinations of kVps that range from 80-140 kVp, and tube current time product from 14–125 mAs were individually scored by using a Likert scale from 1–5 in 4 separate anatomical areas (skull base, thoracic spine, pelvis, and distal femora). Correlation between readers scores and effective doses were obtained by using correlation coefficient statistical analysis, statistical significance was considered P < .01. Interobserver agreement was assessed by using a Bland and Altman plot. Interobserver agreement in each of the 4 anatomical areas was assessed by using kappa statistics. A single set of parameters was then selected for use in future clinical trials in a cohort of patients referred for investigation of monoclonal gammopathy, including multiple myeloma. Results Several sets of exposure parameters allowed low-dose whole-body CT to be performed with effective doses similar to skeletal survey while preserving diagnostic image quality. Individual reader's and average combined scores showed a strong inverse correlation with effective dose (reader 1, r = −0.78, P = .0001; reader 2, r = −0.75, P = .0003); average combined scores r = −0.81, P < .0001). Bland and Altman plot of overall scores shows reasonable interobserver agreement, with a mean difference of 1.055. Conclusion Whole-body low-dose CT can be used to obtain adequate CT image quality to assess normal osseous detail while delivering effective doses similar to those associated with conventional radiographic skeletal survey.

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