A new pet for myeloma

Positron emission tomography (PET) is a tomographic nuclear imaging procedure that uses positrons as radiolabels and positron-electron annihilation reaction gamma rays to locate the radiolabels. A low dose of a radiopharmaceutical labeled with a positron emitter, such as F18-fluorodeoxyglucose (FDG), is injected into the patient, who is scanned by a tomographic system. The advent of fusion scanning combining both PET and computed tomography (CT) addresses the issue of limited spatial resolution, which was a major limitation of PET.²  The sensitivity of FDG-PET/CT in detecting myelomatous involvement is approximately 85% and its specificity is 90% to 95%.³  PET/CT is also more sensitive than other imaging modalities for localizing extramedullary disease, and it reveals additional lesions in almost 30% of the patients who had been diagnosed with solitary plasmacytoma by magnetic resonance imaging (MRI).⁴ 

The first assessment of FDG-PET/CT in myeloma showed that this examination identified patients with high-risk myeloma, could be used to monitor nonsecretory myeloma, and could detect residual disease in patients with immunofixation negative complete response (CR).⁵  Larger studies of PET/CT in myeloma confirmed these data. Thus, PET/CT was included as an option for the diagnosis and monitoring of myeloma patients according to the National Comprehensive Cancer Network (NCCN) guidelines. The National Oncologic PET Registry, a large prospective program, enrolled 22 975 cancer patients, including more than 1300 patients with myeloma, and revealed that 36.5% of the time, treating physicians changed the intended management on the basis of PET/CT results.⁶  But is this justified for myeloma patients? The study by Bartel et al gives us important information for the use of FDG-PET/CT in myeloma patients treated with both novel agents and high-dose therapy. In 239 patients who underwent total therapy 3 (TT3), the authors performed standard skeletal survey, MRI, and FDG-PET/CT at baseline and then at specified points in their multiphased treatment. The presence of more than 3 focal lesions (FLs) in the PET/CT (PET-FL) independently predicted for inferior overall survival (OS) and event-free survival (EFS). Furthermore, complete FDG suppression in PET-FL before transplantation conferred superior OS and EFS. As in other studies, the presence of FLs in MRI and of lytic lesions in plain radiography (MBS-osteolytic lesions [OLs]) also predicted for shorter survival in the univariate analysis. However, the logistic regression analysis showed that although PET-FL was independently positively linked to both MRI-FLs and MBS-OL, only PET-FL retained its independent predictive value for survival, identifying a subset of patients with otherwise low-risk myeloma who had inferior survival. In addition, CR based on PET/CT criteria (absence of PET-FL and extramedullary disease) occurred more rapidly than the clinical CR or near CR and especially than the MRI-CR status among patients presenting with MRI-FL. Do these data indicate that PET/CT is superior to MRI in patients with myeloma? All reported studies to date have confirmed the superiority of PET/CT over conventional radiography (see figure).³  However, these studies have also revealed that if PET/CT was the sole imaging procedure, it would have missed additional small lytic skeletal lesions and diffuse spine involvement, which is readily detected by MRI.^3,7  Another disadvantage of PET/CT is the false positive results especially in areas of inflammation or infection, deposits of brown fat, postsurgical changes, vertebroplasty changes, and occasionally other benign or malignant processes.⁸  In a prospective comparison among FDG-PET/CT, MRI, and conventional radiography, PET-CT was superior to plain radiographs, but, in 30% of patients, PET-CT scans of the spine and pelvis failed to show abnormal findings in areas in which MRI revealed an abnormal pattern of bone marrow involvement, more frequently of diffuse type. In contrast, in 35% of patients, PET-CT enabled the detection of myelomatous lesions in areas that were outside the field of MRI. By combining MRI of the spine-pelvis and PET-CT, the ability to detect sites of active multiple myeloma (MM), both medullary and extramedullary, was as high as 92%. After autologous stem cell transplantation, 15 of 23 patients had negative PET-CT scans (including 13 with very good partial response or near CR), while only 8 had normal MRI.⁹ 

The results of the study by Bartel et al are important as they reveal PET/CT as a technique that could lead to individualized therapeutic decisions especially in patients who have residual disease detected only by this procedure. Furthermore, PET/CT is the procedure of choice when extramedullary involvement is suspected (ie, in patients with rising serum LDH). However, further studies are needed before the recommendation of using PET/CT as the standard tool in both diagnosis and follow-up of MM patients.