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).