M Bhutani1, O Landgren. 1. Multiple Myeloma Section, Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 10/Room 13N240, 20892, Bethesda, MD, USA.
Abstract
CLINICAL ISSUE: Emerging clinical trial data support treatment of high-risk smoldering multiple myeloma (SMM) upon diagnosis, and not only at the time of progression to symptomatic complications (multiple myeloma). Early detection of bone and/or bone marrow involvement by sensitive imaging modalities may help define SMM patients at a high risk of progression. STANDARD RADIOLOGICAL METHODS: Current (2011) consensus guidelines recognize skeletal survey as a cornerstone modality for assessment of bone involvement at initial diagnosis and during follow-up of SMM. Skeletal survey has severe limitations related to underdetection of bone lesions and also provides no information on bone marrow abnormalities. METHODICAL INNOVATIONS: Modern imaging strategies such as fluorodeoxyglucose positron-emission tomography/CT (FDG PET/CT) and MRI, in conjunction with functional innovations, provide improved estimates of global abnormalities in the bone marrow and bone compartments. These methods have the potential to objectively quantify early transformation from SMM to multiple myeloma. PERFORMANCE: Although frequently used for staging and risk prognostication in multiple myeloma, modern imaging techniques have only been evaluated to a limited extent in SMM. Scant data in SMM indicate the prognostic value of two or more MRI-detected focal bone marrow abnormalities, which, if present, predict rapid progression to multiple myeloma. Data evaluating the role of FDG PET/CT in detecting early bone marrow abnormalities as an aid to predicting risk or directing treatment in SMM is currently lacking. ACHIEVEMENTS: The superior specificity and sensitivity of modern imaging techniques compared to skeletal survey suggest that these should have a place in standard practice management of patients at a high risk of SMM progression. The model imaging of the future should be an all-in-one strategy offering high diagnostic performance for bone marrow abnormalities and low-volume bone lesions, as well as allowing monitoring by minimizing radiation exposure and the need for contrast agents. PRACTICAL RECOMMENDATIONS: Newer imaging techniques need to be validated in prospective clinical trials assessing the SMM to multiple myeloma transition, with the aim of enabling appropriate management decisions. Efforts are also needed to improve the costs and availability of whole-body MRI and/or FDG PET/CT, in order to facilitate their widespread adoption as first-line detection modalities. Future clinical trials of therapeutic agents using earlier detection strategies will have to be carefully designed and take into consideration the risk of lead-time and length-time biases, which might falsely demonstrate longer overall survival. The English full text version of this article is available at SpringerLink (under "Supplemental").
CLINICAL ISSUE: Emerging clinical trial data support treatment of high-risk smoldering multiple myeloma (SMM) upon diagnosis, and not only at the time of progression to symptomatic complications (multiple myeloma). Early detection of bone and/or bone marrow involvement by sensitive imaging modalities may help define SMM patients at a high risk of progression. STANDARD RADIOLOGICAL METHODS: Current (2011) consensus guidelines recognize skeletal survey as a cornerstone modality for assessment of bone involvement at initial diagnosis and during follow-up of SMM. Skeletal survey has severe limitations related to underdetection of bone lesions and also provides no information on bone marrow abnormalities. METHODICAL INNOVATIONS: Modern imaging strategies such as fluorodeoxyglucose positron-emission tomography/CT (FDG PET/CT) and MRI, in conjunction with functional innovations, provide improved estimates of global abnormalities in the bone marrow and bone compartments. These methods have the potential to objectively quantify early transformation from SMM to multiple myeloma. PERFORMANCE: Although frequently used for staging and risk prognostication in multiple myeloma, modern imaging techniques have only been evaluated to a limited extent in SMM. Scant data in SMM indicate the prognostic value of two or more MRI-detected focal bone marrow abnormalities, which, if present, predict rapid progression to multiple myeloma. Data evaluating the role of FDG PET/CT in detecting early bone marrow abnormalities as an aid to predicting risk or directing treatment in SMM is currently lacking. ACHIEVEMENTS: The superior specificity and sensitivity of modern imaging techniques compared to skeletal survey suggest that these should have a place in standard practice management of patients at a high risk of SMM progression. The model imaging of the future should be an all-in-one strategy offering high diagnostic performance for bone marrow abnormalities and low-volume bone lesions, as well as allowing monitoring by minimizing radiation exposure and the need for contrast agents. PRACTICAL RECOMMENDATIONS: Newer imaging techniques need to be validated in prospective clinical trials assessing the SMM to multiple myeloma transition, with the aim of enabling appropriate management decisions. Efforts are also needed to improve the costs and availability of whole-body MRI and/or FDG PET/CT, in order to facilitate their widespread adoption as first-line detection modalities. Future clinical trials of therapeutic agents using earlier detection strategies will have to be carefully designed and take into consideration the risk of lead-time and length-time biases, which might falsely demonstrate longer overall survival. The English full text version of this article is available at SpringerLink (under "Supplemental").
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