General MM

Whole body computed tomography (WBCT) shows increased benefit over conventional skeletal survey (CSS), for the identification of bone lesions in MM

Routinely, CSS has been used as the standard imaging technique for the detection of bone disease in Multiple Myeloma (MM), and involves conventional X-ray of several skeletal sites. Limitations of this method have become apparent, with new techniques such as computed tomography (CT) proving more sensitive and able to provide three-dimensional information of the scanned areas. In addition, protocols using lower doses of radiation and whole body scanning have been developed, and provide enhanced sensitivity. However, it has been argued that such enhanced detection may lead to patients with smoldering multiple myeloma (SMM) being classified as having progressive MM much earlier and treated as such with no added benefit.

In a recent study published in Blood Cancer Journal, a comparison was made between conventional skeletal survey (CSS) and whole body computed tomography (WBCT), in terms of sensitivity levels and whether the identification of additional lesions was of prognostic relevance. The study was carried out by Jens Hillengass from the Department of Hematology and Oncology, University Hospital Heidelberg, Germany, and supported by the International Myeloma Working Group.

Key Highlights:

  • Data was assessed from patients (pts) that had both conventional X-ray and WBCT within 30 days
  • CSS and WBCT data was collected from 283 patients, from 8 different centers worldwide
  • Pts with MM = 212 (159 were untreated at time of imaging); and with SMM = 66 (54 of these were untreated and included in the analysis)
  • No lytic bone lesions detected with either technique = 103 pts (48.6%)
  • Lesions detected with both CSS and WBCT = 43 pts (20.3%)
  • Lytic lesions observed in CSS but not by WBCT = 12 pts (5.7%)
  • Lytic lesions observed by WBCT but not by CSS = 54 pts (25.5%); (odds ratio = 4.50 (2.38–9.24); P<0.0001)
  • Out of 12 pts for which WBCT was negative, only 5 pts had lesions considered ‘definitely present’ by CSS, 5 had lesions defined as ‘probably present’ and 1 ‘probably absent’
  • Lesions located in the long bones (clavicle, femur, humerus, ribs) = 11/21 and 10 in the axial skeleton (skull, spine, pelvis)
  • No lesions were identified by either CSS or WBCT in 42/54 untreated SMM pts (77.8%)  
  • Osteolytic lesions were identified in 12 pts (22.2%) by WBCT; CSS was by definition negative (P = 0.0005)
  • Sensitivity of WBCT was most noticeably superior to CSS in the spine and pelvis
  • Osteoporosis detected by both methods = 14 SMM patients; 12 pts by WBCT only, and 12 pts by CSS only (odds ratio = 12.0; P = 0.003).
  • WBCT showed osteoporosis with a fracture in 4 pts; CSS did not detect anything
  • SMM pts with lytic bone lesions on WBCT had a higher probability of progression to symptomatic myeloma than those with none by WBCT (log-rank P = 0.05); no prognostic significance for overall survival
  • SMM patients with lytic bone lesions vs SMM pts without lytic bone lesions:
    • Median time to progression (TTP) = 38 vs 82 months
    • PFS (2-year) = 58% vs 33%
  • Osteoporosis was not of prognostic significance, but presence of an osteoporotic fracture was: HR = 2.03; (95% CI 0.57–7.24), although numbers are very small
  • Untreated MM patients (n = 79): osteolysis by CT = 48 pts (60.8%); osteolysis by CSS = 40 pts (50.6%)
  • A difference between both imaging techniques was found with CT positivity and CSS negativity in 16 (20.3%) and CSS positivity with CT negativity in 8 (10.1%) of MM patients, respectively
  • No prognostic significance was found for the presence of lytic bone lesions identified by either technique (PFS: P = 0.3 and OS: P = 0.4)
Conclusion

Due to the enhanced sensitivity of CT imaging, this is now included in the new IMWG guidelines for the diagnosis of MM. This study reinforces that decision and showed that in 20–25% of patients with negative CSS, WBCT can detect destructive bone lesions. Differences between WBCT and CSS were dependent on the location of the lesions. WBCT was overall more superior, especially in the axial skeleton, although CSS was more effective at identifying lesions in the humeri. To maximise the potential of WBCT for plasma cell disorders, it has been suggested that the patients’ arms should be placed alongside the body so that the scans include both the skull up to the vertex, as well as the entire femora and knees. 

References
  1. Hillengass J.et al. Whole-body computed tomography versus conventional skeletal survey in patients with multiple myeloma: a study of the International Myeloma Working Group. Blood Cancer J. 2017 Aug 25;7(8):e599. doi: 10.1038/bcj.2017.78
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