Assessment of myeloma bone disease
Early detection, ideally before symptoms develop, and thorough functional imaging are essential so that the most appropriate intervention for each myeloma patient can be initiated as soon as possible to prevent or minimise the effects of any skeletal-related events.
Blood
Elevated serum calcium (normal corrected level 2.2 – 2.6 mmol/L) results from a blood test often provide an early indication of active myeloma bone disease before specific skeletal assessments are carried out. Patients should then be assessed for symptoms of hypercalcaemia including:
- Loss of appetite
- Fatigue/weakness
- Excessive thirst/urination
- Mental confusion
- Acute renal insufficiency
It has been shown however, that the commonest cause of raised calcium in patients with a plasma cell disorder is hyperparathyroidism. It is therefore important to check parathyroid hormone levels.
Imaging
The current gold standard and recommended imaging at diagnosis for all patients with myeloma is whole-body MRI. If not available, whole-body low dose CT or FDG PET-CT should be used as an alternative. Additional imaging tests are often also warranted to check particular areas more thoroughly, fracture risks and for managing and monitoring disease and response to treatment. These are described in the sections below.
X-rays
A skeletal survey involving a series of X-ray imaging used to be the standard of screening at diagnosis however it is no longer considered sufficient for myeloma bone disease detection. An immediate X-ray may be used to assess whether a patient has a lytic lesion breaching the cortex and therefore presents a fracture risk.
Where facilities and local expertise exist, the recommended imaging options for the diagnosis of myeloma are:
Whole-body MRI
Whole-body magnetic resonance imaging (MRI) utilising the MY-RADS protocol (Messiou et al 2019) is recommended by NICE as the first-choice imaging technique because of its improved detection of bone lesions and ability to determine the amount of myeloma cell infiltration in the bone marrow before bone destruction is evident. Where whole-body MRI is not available, MRI of the spine and pelvis may be performed although this may not detect lesions located in the limbs.
Whole-body MRI is also the technique of choice for patients with suspected spinal cord compression. It is also useful for assessing disease burden in patients with non-secretory or oligo-secretory myeloma and for evaluating extramedullary plasmacytomas.
MRI, although a powerful imaging technique, is contra-indicated for patients with pacemakers and certain metal prostheses. It is also not recommended for patients with inability to lie still for a prolonged period of time and/or patients who are claustrophobic as MRI scans can take up to an hour to complete. It is important that patients are informed of the scanning procedure and are advised to take analgesia beforehand if required. If patients are going from the ward, analgesia should be administered 30-60 minutes before the scan is planned.
Spinal MRI
If whole-body MRI is not available, a spinal MRI should be performed for those presenting with suspected spinal cord compression in the emergency setting within 24 hours. It may also be used for procedure planning such as vertebral augmentation.
CT scanning
CT scanning uses X-rays to create cross-sectional images of the body. The amount of radiation used in a CT scan is much greater but it is more sensitive and can detect bone lesions more accurately than a traditional X-ray, as well as allow and assessment of bone stability and fracture risk.
Whole-body low-dose CT
Whole-body low-dose computerised tomography (CT) is recommended by NICE as first-line imaging for newly diagnosed myeloma patients if whole body MRI is not suitable. As with whole-body MRI, whole body low-dose CT allows for the assessment of bone involvement with greater sensitivity and coverage, and it also has the advantage of being able to detect extramedullary disease in many cases.
Fluorodeoxyglucose positron emission tomography CT (FDG PET-CT)
Positron emission tomography is a nuclear imaging technique involving the administration of a radioactive substance such as 18fluorodeoxyglucose (FDG) into the patient followed by tomographic scanning 10 – 40 minutes later. Cancer cells have a high metabolic rate and rapidly take up the 18FDG because of their high glucose demand, allowing them to be distinguished from normal cells. The dose of radioactivity injected is low and is equivalent to that in an X-ray.
Of the various imaging methods available to myeloma patients, FDG PET scanning is the most sensitive in terms of being able to identify the metabolic activity of a lesion and in detecting extramedullary plasmacytomas. The main limitation of FDG PET is the poor spatial resolution but to overcome this, it is combined with CT scanning. This allows an image that determines both tumour activity (FDG PET) and structural changes (CT). Like whole-body MRI, FDG PET-CT is also able to identify active disease before patients become symptomatic.
Summary
Imaging plays a crucial role in the assessment of myeloma. Assessment of the bones should enable weaknesses and risks associated with fractures to be identified and interventions considered, as well as confirming existing fractures for which prompt treatment is needed. Bone disease (focal and/or diffuse) can involve any part of the skeleton and its accurate delineation can inform prognosis and contribute towards risk stratification and clinical management. In clinical trials, imaging is used as part of the assessment of response to treatment and can help guide follow-up management decisions particularly for high-risk patients.
Wherever possible, FDG PET-CT should be used alongside whole-body MRI as they have complementary roles in providing a full picture of myeloma bone disease and capturing tumour infiltration before significant bone destruction arises. Both are also recommended for patients with non-secretory myeloma or soft-tissue plasmacytomas.