SummaryThis systematic review of studies compared magnetic resonance imaging (MRI), 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET), FDG-PET with computerized tomography (PET-CT) and CT with whole body X-Ray (WBXR) or (whole body) CT in order to provide evidencebased diagnostic guidelines in multiple myeloma bone disease. A comprehensive search of 3 bibliographic databases was performed; methodological quality was assessed using Quality Assessment of Diagnostic Accuracy Studies (QUADAS) criteria (score 1-14). Data from 32 directly comparative studies were extracted. The mean QUADAS score was 7Á1 (3-11), with quality hampered mainly by a poor description of selection and execution criteria. All index tests had a higher detection rate when compared to WBXR, with up to 80% more lesions detected by the newer imaging techniques; MRI (1Á12-1Á82) CT (1Á04-1Á33), PET (1Á00-1Á58) and PET-CT (1Á27-1Á45). However, the modern imaging techniques detected fewer lesions in the skull and ribs. In a direct comparison CT and MRI performed equally with respect to detection rate and sensitivity. This systematic review supports the International Myeloma Working Group guidelines, which recommend that WBCT can replace WBXR. In our opinion, the equal performance of MRI also indicates that it is a valuable alternative. As lesions of the skull and ribs are underdiagnosed by modern imaging techniques we advise additional X-rays of these regions. The consequences of this approach are discussed.

BACKGROUND:The goal of this study was to conduct a comparative analysis of whole body X-ray (WBXR) and 18 Ffluoro-deoxyglucose positron emission tomography ( 18 FDG PET) in staging and response assessment of multiple myeloma. METHODS: We performed a systematic review of studies comparing 18 FDG PET with WBXR and/or magnetic resonance imaging in terms of sensitivity for myeloma-related bone disease at staging and during follow-up. RESULTS: Eighteen studies involving 798 patients met the inclusion criteria. The mean Quality Assessment of Diagnostic Accuracy Studies (QUADAS) score, expressed as a percentage of the maximum score, was 61%. In 7 studies (n ¼ 242 patients), concordance assessment between WBXR and 18 FDG PET scan was possible, showing a higher sensitivity of the 18 FDG PET in the detection of myeloma bone lesions in 6 studies. The only study reporting on the prognostic value of 18 FDG PET at staging found that the number of FDG-avid focal lesions was an independent prognostic parameter. In addition, the limited studies on response monitoring showed that normalization of 18 FDG PET during treatment correlated with a superior clinical outcome. CONCLUSIONS: In general, 18 FDG PET has a superior sensitivity for myeloma bone lesions compared with WBXR. Future studies have to validate the additive value of myelomarelated bone disease detected on 18 FDG PET-computed tomography (CT) in predicting outcome. Response monitoring with the use of 18 FDG PET-CT during treatment is promising, allowing more precise prediction of prognosis compared with the standard response monitoring. In view of the expanding treatment options for multiple myeloma, this may provide important information for treatment decisions in the future.

BackgroundBone disease in multiple myeloma is characterized by reduced bone formation. The gold standard of bone formation is the mineral apposition rate (MAR), an invasive technique reflecting bone formation at a single site. We compared 18F-fluoride-PET with the MAR in myeloma patients.MethodsBone formation was measured before and after bortezomib treatment by determination of the MAR in iliac bone marrow biopsies and the measurement of 18F-uptake.ResultsThe inter- and intra-individual variations in 18F-uptake (SUVA50%) were pronounced as 33.50 (range 4.42 to 37.92) and 27.18 (range 4.00 to 31.18), respectively. A significant correlation between the MAR and 18F-uptake was found (r = 0.80, p = 0.017). There was a heterogeneous response after treatment varying from −2.20 to 4.53.ConclusionsIliac 18F-uptake was associated with the local MAR in myeloma patients. Furthermore, 18F-fluoride-PET demonstrated the heterogeneity of in vivo bone formation, enabling monitoring during treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-016-0197-4) contains supplementary material, which is available to authorized users.

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Considering the different treatment strategy for transformed follicular lymphoma (TF) as opposed to follicular lymphoma (FL), diagnosing transformation early in the disease course is important. There is evidence that 18 F-FDG has utility as a biomarker of transformation. However, quantitative thresholds may require inclusion of homogeneous non-Hodgkin lymphoma subtypes to account for differences in tracer uptake per subtype. Moreover, because proliferation is a hallmark of transformation, 3′-deoxy-3′-18 F-fluorothymidine ( 18 F-FLT) might be superior to 18 F-FDG in this setting. To define the best tracer for detection of TF, we performed a prospective a headto-head comparison of 18 F-FDG and 18 F-FLT in patients with FL and TF. Methods: 18 F-FDG and 18 F-FLT PET scans were obtained in 17 patients with FL and 9 patients with TF. We measured the highest maximum standardized uptake value (SUV max ), defined as the lymph node with the highest uptake per patient, and SUV range , defined as the difference between the SUV max of the lymph node with the highest and lowest uptake per patient. To reduce partial-volume effects, only lymph nodes larger than 3 cm 3 (A50 isocontour) were analyzed. Scans were acquired 1 h after injection of 185 MBq of 18 F-FDG or 18 F-FLT. To determine the discriminative ability of SUV max and SUV range of both tracers for TF, receiver-operatingcharacteristic curve analysis was performed. Results: The highest SUV max was significantly higher for TF than FL for both 18 F-FDG and 18 F-FLT (P , 0.001). SUV range was significantly higher for TF than FL for 18 F-FDG (P 5 0.029) but not for 18 F-FLT (P 5 0.075). The ability of 18 F-FDG to discriminate between FL and TF was superior to that of 18 F-FLT for both the highest SUV max (P 5 0.039) and the SUV range (P 5 0.012). The cutoff value for the highest SUV max of 18 F-FDG aiming at 100% sensitivity with a maximum specificity was found to be 14.5 (corresponding specificity, 82%). For 18 F-FLT, these values were 5.1 and 18%, respectively. When the same method was applied to SUV range , the cutoff values were 5.8 for 18 F-FDG (specificity, 71%) and 1.5 for 18 F-FLT (specificity, 36%). Conclusion: Our data suggest that 18 F-FDG PET is a better biomarker for TF than 18 F-FLT PET. The proposed thresholds of highest SUV max and SUV range should be prospectively validated.

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