Researchers Review Current Diagnostic Imaging Techniques For Multiple Myeloma

A group of European researchers recently published an extensive review of the imaging techniques currently used in the diagnosis and follow-up of multiple myeloma and related diseases.
The researchers assessed the benefits and limitations of several different imaging techniques, including traditional X-rays, computed tomography (CT), combined positron emission tomography and CT scanning (PET/CT), and magnetic resonance imaging (MRI).
According to the researchers, the whole-body X-ray skeletal survey remains the method of choice for the detection of bone lesions. However, they point out that whole-body CT may replace whole-body X-ray skeletal surveys, because CT scans are better able to detect lesions in the spine and pelvis.
The researchers also note that MRI and PET/CT are being explored as additional diagnostic tools for multiple myeloma. They add that MRI is the most effective tool for detecting bone lesions prior to any treatment. PET/CT scans, however, may be more useful for the assessment of treatment response.
The researchers also mention that PET/CT may be useful for the assessment of minimal residual disease.
However, the researchers explain that standards for the interpretation and reporting of imaging results are necessary to ensure further use of these techniques in daily practice.
The report by the European researchers is valuable not only because it is so detailed, but also because it is available online, in its entirety, at no charge (see below for the report's complete reference information).
Background
Multiple myeloma patients typically undergo skeletal surveys or CT scans at diagnosis for the assessment of their disease. These techniques, however, mainly find lytic lesions, which are lesions in a patient’s outer (hard) bone, rather than the bone marrow.
Recent research has shown that MRI scans, on the other hand, can be an effective method for identifying lesions within the bone marrow. Such lesions are typically called focal lesions. The presence of focal lesions has important implications in plasma cell disorders.
The number of focal lesions detected by MRI has been linked, for example, to the risk of progression in patients with smoldering myeloma (see related Beacon news), and to overall survival in myeloma patients who have undergone stem cell transplantation (see related Beacon news).
Spinal MRI is commonly recommended for detecting focal lesions in patients with the myeloma precursor diseases monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma.
In addition, PET scans have been shown to be useful in determining the remission status of multiple myeloma patients after stem cell transplantation (see related Beacon news).
In the current study, a group of European researchers assessed the advantages and disadvantages of each of these techniques in regard to multiple myeloma and its precursor diseases.
Study Design And Results
The researchers conducted a search of two medical literature databases and abstracts presented at American Society of Hematology annual meetings to identify studies that used imaging techniques in the diagnosis and monitoring of patients with multiple myeloma or one of its precursor diseases.
Advantages and Disadvantages Of Imaging Techniques
Traditional X-Rays and Skeletal Surveys
According to current guidelines from the International Myeloma Working Group, whole body X-ray skeletal surveys should be considered the gold standard for detecting lytic bone lesions in patients.
However, the authors of the review point out that this imaging technique has several limitations. First, they note that X-ray skeletal surveys are not sensitive enough to detect early, developing bone lesions, and therefore underestimate bone involvement.
Furthermore, an X-ray skeletal survey typically takes much longer than other imaging techniques because it usually requires at least 20 separate scans.
In addition, the investigators explain that X-ray skeletal surveys are limited in their ability to assess a myeloma patient’s response to treatment, since bone lesions may not necessarily change following treatment.
Computed Tomography
The investigators also assessed computed tomography (CT), another common imaging technique that is more sensitive than traditional X-rays. CT can detect smaller bone lesions and can better assess the fracture risk of a patient.
CT scans can also reveal extramedullary disease, which occurs when myeloma cells form tumors outside of a patient’s bones.
According to the researchers, the one major disadvantage with CT is that, like traditional x-rays, it involves exposing a patient to radiation.
PET/CT
A positron emission tomography (PET) scan is a type of imaging test that detects the level of cell activity throughout the body. Patients undergoing a PET scan typically receive an injection of a radioactive sugar molecule called fluorodeoxyglucose (FDG), which accumulates more in cancer cells than in healthy cells. The PET scan then reveals the activity and locations of cancer cells in different parts of the body based on detected radioactivity levels.
PET scans provide more detailed results when combined with a computerized tomography (CT) scan. A PET scan plus a CT scan is called a PET/CT scan.
The European researchers point out that PET/CT scanning permits the direct visualization of how extensively myeloma is present in a patient's body, a concept known as "tumor burden." However, the researchers caution that PET/CT scans can overestimate a patient's tumor burden if the patient is experiencing infections or other inflammatory processes.
MRI
Magnetic resonance imaging (MRI) uses magnetic fields to repetitively excite atoms in a patient's body. The excited atoms emit radio signals, which are detected by the MRI scanner.
Atoms in different types of body tissue take different amounts of time to return to their normal state when the MRI scanner's magnetic field is switched from on to off. The scanner detects these differences and uses them to determine the presence of different kinds of body tissue.
Initial research involving MRI scanning and multiple myeloma focused on MRI scans of the spine and pelvis (axial MRI). More recently, studies have investigated the potential value of whole body MRI scans.
MRI scans are particularly useful for visualizing the bone marrow in myeloma patients. In this regard, the technique is considered more sensitive than either X-ray skeletal surveys or CT scanning.
The authors of the current study note that additional advantages of MRI include the fact that it does not involve radiation and that it is a fairly quick procedure.
Application Of Imaging Techniques In Myeloma And Myeloma-Related Diseases
In their review, the researchers discuss the application of the different imaging techniques in symptomatic multiple myeloma and other myeloma-related diseases.
Solitary Plasmacytoma
In patients with solitary bone plasmacytoma, abnormal plasma cells in the bone marrow aggregate to form a single tumor in any bone in the body.
Most commonly, the tumor develops in a bone along the spinal column. In order of decreasing frequency, the tumor may also develop in the pelvis, ribs, upper extremities, face, skull, femur, and sternum.
According to the authors of the review, whole-body x-ray skeletal survey and axial MRI should be performed in patients with a solitary plasmacytoma to exclude the possibility of additional lesions.
In addition, they recommend that PET/CT be performed, if available, since this technique can detect both extramedullary and medullary (bone) disease.
Smoldering Myeloma
Smoldering, or asymptomatic, myeloma is a precursor to multiple myeloma in which the patient experiences none of the four symptoms typically associated with active (symptomatic) multiple myeloma. These "CRAB" symptoms, as they are commonly known, include elevated calcium levels, kidney (renal) failure, anemia, and bone lesions.
Smoldering myeloma is characterized by an excess of monoclonal protein in the blood and urine. A diagnosis of smoldering multiple myeloma is made when a patient’s monoclonal protein level is at least 3 g/dL or the proportion of plasma cells in the bone marrow is at least 10 percent, but the patient does not exhibit any of the "CRAB" symptoms of multiple myeloma.
According to the authors of the review, diagnostic imaging techniques are crucial in smoldering myeloma patients because they can detect focal bone lesions and provide prognostic information on the risk of progression.
The researchers believe that, once initial imaging has been carried out to ensure that a smoldering patient does not have symptomatic myeloma, MRI is the most effective imaging technique for such patients.
Specifically, studies have shown that focal lesions detected by MRI tend to be strongly correlated with the potential for progression of the disease to symptomatic myeloma. However, the researchers believe there is currently insufficient evidence to justify active treatment of smoldering myeloma in patients who show focal lesions on MRI.
The researchers add that, to their knowledge, there are currently no major studies being conducted on the use of PET/CT in smoldering myeloma patients.
Symptomatic Multiple Myeloma
For patients with symptomatic multiple myeloma, the European researchers believe that screening using either whole-body x-ray or low-dose CT should be mandatory at the time of diagnosis.
However, they point out that both PET/CT and MRI have been found to be more sensitive, and have shown a higher detection rate of lesions in symptomatic patients, than X-rays and CT alone.
Based on these findings, they recommend that MRI be considered as a complementary diagnostic tool, given that it provides excellent results when used to image the spine and pelvis.
Furthermore, the researchers state that both PET/CT and MRI can provide useful prognostic information. Studies have shown a link, for example, between the number of lesions detected by either of these imaging techniques at diagnosis and a patient's expected progression-free and overall survival.
Studies also have shown that how a patient's bone marrow appears in MRI scans may have an impact on prognosis. If myeloma cells are scattered throughout the marrow, causing the bone marrow to appear "diffuse" in MRIs, this can be a sign of more aggressive disease.
There also have been studies investigating the value of MRI and PET/CT for evaluating a myeloma patient's response to treatment. Currently, the evidence suggests that, of the two, PET/CT may be more effective at tracking treatment response.
At least two studies have shown, for example, that patients whose PET/CT scans continue to show a tumor burden ("abnormal FDG uptake") after treatment tend to have a higher risk of progression, and shorter overall survival, in comparison of patients with no abnormal FDG uptake after treatment.
That said, studies on the use of PET/CT in response assessment have been limited to patients who have received a stem cell transplant. Thus, the authors of the current study encourage additional research of PET/CT in the follow-up of transplant-ineligible patients.
For more information, please refer to the study by Caers, J. et al., “The role of positron emission tomography-computed tomography and magnetic resonance imaging in diagnosis and follow up of multiple myeloma,” in Haematologica, April 1, 2014 (full text).
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For my myeloma diagnosis 3 years ago, PET scan combined with MRI was the choice. This was a good choice as it turns out. I have always been one to avoid X-rays so I am pleased to see the researchers also recognizing the radiation exposure issue. Good analysis of the pro and con side of each technique. Keep the research coming!
Any chance that this allow for the tracking needed to allow for non secretory patients to be involved with clinical trials? Seems like there is so much hope in these trials and so many are doing well, not having that option is limiting?
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