A Comparison of PET-CT to Whole Body Diffusion Weighted MRI in the Diagnosis of Plasma Cell Dyscrasias

Abstract Introduction Functional imaging techniques such as 18fluoro-deoxyglucose positron emission tomography-computed tomograpthy (PET-CT) and whole body diffusion weighted magnetic resonance imaging with background subtraction (DWIBS) are useful in the detection and enumeration of active disease sites in multiple myeloma (MM). To date few formal comparisons of the two techniques have been performed. Methods The ability of PET-CT and DWIBS to determine disease activity defined as focal lesions (FLs) and background bone marrow (BM) abnormalities was studied in82 cases presenting for plasma cell dyscrasia evaluation. All had PET-CT, DWIBS, BM and pertinent laboratory tests performed within 3 days of each other. Using conventional diagnostic criteria, 19 (23%) had MGUS, 7 (9%) SMM, 51 (62%) active MM and 5 (6%) MM in stringent complete response (sCR) defined by IMWG criteria using flow cytometry (sensitivity of 10-5). For both PET-CT and DWIBS, the background BM signal and the presence of FLs were examined. A number of normalization approaches were investigated including comparison of involved areas to the liver, spleen, vertebral bodies and brachial plexus. Reporting radiologists were blinded to the clinical, laboratory and other imaging information. Statistical analysis was performed using R 3.3.1. Results Both PET-CT and DWIBS were able to detect FLs and abnormal diffuse background BM signal. For PET-CT, a BMmax to liver SUVmean ratio of 1.2 or greater best separated cases with active MM from MGUS/SMM and MM in sCR. Of the 51 MM patients, 28 were considered PET-CT positive: 17 with FLs, 1 with diffuse abnormal BM uptake and 10 with both. Using this ratio all SMM and MM in sCR patients were negative. 1/19 MGUS cases were positive with evidence of a FL. A BMmax / liver SUVmean ratio 1.2 or greater therefore had a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 55%, 97%, 97% and 57% respectively with regards to correctly categorizing active MM. The other normalization approaches were less specific and less clinically useful as more patients without active MM had higher ratios. For DWIBs, a BM signal greater than or equal to the splenic signal best separated the patient groups. Of the 51 active MM patients, 13 patients had FLs, 10 had diffuse abnormal BM signal, and 10 had both. All SMM patients were negative, one patient with MGUS was found to be positive, and all other non-active MM patients were negative. Therefore the DWIBS criteria of the presence of FLs greater than 1.5 cm, BM signal greater than or equal to spleen, or both, had a sensitivity, specificity, PPV and NPV of 65%, 97%, 97% and 63% respectively. When looking at the overall concordance between the two techniques in 82 cases, 23 patients were positive by both, 42 negative by both and 17 positive with one or other method.Both techniques were able to accurately characterize SMM and MM in sCR. One MGUS was misclassified. The most variation was seen when looking at just MM with active disease (n=51), 23 patients were positive by both and 13 patients negative by both techniques. 15 cases were positive with one or other technique. When comparing the ability of each technique to detect background BM infiltration, a number of cases were noted to be discordant (n=21). More cases were noted to have an abnormal BM infiltration pattern by DWIBS than by PET (n=20 vs 11), suggesting DWIBS is more sensitive at detecting background BM infiltration. DWIBS were also able to detect more FLs than PET, with 12 cases having more lesions on DWIBS than PET-CT. In some instances, however, FLs were seen on the PET-CT and not on the DWIBS (7 cases). When the number of FLs were summarized within ranges, i.e. 0, 1-5, 5-20, >20, PET-CT and DWIBS agreed on focal lesion counts for 63/82 (77%) patients. Conclusions When comparing the ability of PET-CT and DWIBS to detect the different disease patterns (abnormal BM infiltration alone, FLs alone, both abnormal BM infiltration and FLs, or neither), the overall concordance was 53/82 (65%). Although DWIBS had a higher sensitivity for detecting diffuse disease compared to PET-CT, both technologies were at least equal in sensitivity for detecting FLs. This suggests that both modalities are required to accurately detect and describe the imaging features of MM, and that the whole body functional imaging approaches provide complementary approaches for the assessment of plasma cells dyscrasias. Disclosures Davies: Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Morgan: Takeda: Consultancy, Honoraria; Bristol Myers: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding.