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A Systematic Literature Review of Imaging Definitions for Detection of Bone and Bone Marrow Metastases in Neuroblastoma Patients

Gitta Bleeker, Doris Heijkoop, Elvira C van Dalen, Leontien C Kremer, Anne M Smets, Eline E Deurloo, Berthe L Van Eck-Smit, Huib N Caron and Godelieve A Tytgat

Objective: The presence of bone and bone marrow (BM) metastases in neuroblastoma patients are independent adverse prognostic factors, so precise and consistent definitions of both categories on imaging are important. The objectives of this systematic review were to identify all definitions reported for detection of bone and bone marrow metastases on imaging in neuroblastoma to determine diagnostic accuracies of the most frequently used definitions for detection of bone and/or BM metastases on each imaging technique.

Methods: We searched MEDLINE/PubMed (1945 to April 2013) and EMBASE/Ovid (1980 to April 2013). Full-text original studies were included if they reported definitions of bone and/or BM metastases on diagnostic imaging of children with suspected metastatic neuroblastoma. As reference standard for bone metastases bone scintigraphy was used and for bone marrow metastases bone marrow biopsies/aspirates. Methodological quality was assessed.

Results: Of 403 identified studies (plus one relevant reference), 131 were assessed in full-text and 31 finally included, 23 described BM metastases and 18 bone metastases. No uniform definitions of bone and bone marrow metastases were reported for each imaging method. On MIBG scintigraphy bone metastases were mostly defined as “focal” and BM metastases as “diffuse” and on MRI both definitions were used for BM metastases. The diagnostic accuracy of different diagnostic methods to detect bone (reference test bone scintigraphy) or BM (reference test bone marrow biopsies/ trephines) metastases varied widely.

Conclusion: No uniform definitions of bone and bone marrow metastases were reported for each imaging method and concerning the diagnostic accuracy no general conclusions could be drawn.