Prognostic significance of focal lesions and diffuse infiltration on MRI for multiple myeloma: a meta-analysis

Abstract

Objectives

MRI of bone marrow of the axial skeleton is recommended for evaluation of multiple myeloma. The impact of bone marrow involvement pattern on MRI for determining progression-free survival (PFS) and overall survival (OS) is not yet clear.

Methods

We performed a meta-analysis of research on the prognostic significance of MRI patterns for OS and PFS using a random effects model. Databases searched without language restriction were MEDLINE, EMBASE, and the Cochrane Library (January 1976 to April 2014). Manual searches were also conducted.

Results

Of 10,953 citations identified in the original search, 10 cohort studies for a total of 2015 patients met the inclusion criteria. Nine of the 10 included studies are from three research groups. Pooled hazard ratios were 1.80 (95 % confidence interval [CI] 1.32–2.46; P < 0.001) for OS and 2.30 (95 % CI 1.65–3.20; P < 0.001) for PFS for focal lesions on MRI; and 1.70 (95 % CI 1.30–2.21; P < 0.001) for OS and 1.74 (95 % CI 1.07–2.85; P = 0.03) for PFS for diffuse infiltration on MRI. No significant heterogeneity was observed among studies.

Conclusions

This meta-analysis demonstrated an association between focal lesions and diffuse infiltration and poor prognosis in this population.

Key Points

MRI findings of multiple myeloma include normal, focal, variegated and diffuse infiltration

Focal lesions and diffuse infiltration on MRI were poor prognostic factors

Bone marrow involvement pattern on MRI can help physicians assess prognosis

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Abbreviations

CRAB:

Hypercalcemia, renal failure, anemia and bone lesions

CT:

Computed tomography

HR:

Hazard ratio

IMWG:

International Myeloma Working Group

ISS:

International staging system

MGUS:

Monoclonal gammopathy of undetermined significance

MRI:

Magnetic resonance imaging

OS:

Overall survival

PFS:

Progression-free survival

QUIPS:

Quality in prognosis studies

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Acknowledgments

The scientific guarantor of this publication is Hyun-Jung Kim. The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article. The authors state that this work has not received any funding. One of the authors has significant statistical expertise. Methodology: retrospective, performed at one institution.

Author information

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Authors

Corresponding author

Correspondence to Hyun-Jung Kim.

Appendices

Appendix 1 Search strategy for each database

  1. 1.1.

    MEDLINE

    1. 1.

      ("Multiple Myeloma"[Mesh:NoExp]) OR "Bone Marrow Neoplasms"[Mesh]

    2. 2.

      "Bone Marrow Neoplasms/secondary"[Mesh]

    3. 3.

      1 NOT 2

    4. 4.

      ("Monoclonal Gammopathy of Undetermined Significance"[Mesh]) OR "Plasmacytoma"[Mesh]

    5. 5.

      "Bone Marrow Neoplasms"[tiab] OR "Bone Marrow Neoplasm"[tiab] OR "Myeloma"[tiab] OR "Myelomas"[tiab] OR "Monoclonal Gammopathy"[tiab] OR "Monoclonal Gammapathies"[tiab] OR "plasmacytoma"[tiab] OR "Plasmocytomas"[tiab]

    6. 6.

      3 OR 4 OR 5

    7. 7.

      (((("Magnetic Resonance Imaging"[Mesh:NoExp]) OR "Bone Marrow"[Mesh]) OR "Bone and Bones"[Mesh:NoExp]) OR "Spine"[Mesh]) OR "Bone Density"[Mesh]

    8. 8.

      marrow[tiab] OR Spine[tiab] OR Spinal[tiab] OR Vertebra*[tiab] OR "Magnetic Resonance"[tiab] OR "MRI"[tiab] OR "MR"[tiab] OR "MRIs"[tiab] OR "Bones"[tiab] OR "Bone"[tiab]

    9. 9.

      7 OR 8

    10. 10.

      6 AND 9

    11. 11.

      Prognosis[tiab] OR Predictive Value[tiab] OR Progression[tiab] OR Progressions[tiab] OR Risk[tiab] OR Risks[tiab] OR Survival[tiab] OR Survivals[tiab]

    12. 12.

      (((("Prognosis"[Mesh:NoExp]) OR "Survival Analysis"[Mesh]) OR "Risk"[Mesh]) OR "Predictive Value of Tests"[Mesh]) OR "Disease Progression"[Mesh]

    13. 13.

      11 or 12

    14. 14.

      mortality[MeSH Terms] OR follow up studies[MeSH:noexp] OR prognos*[tiab] OR predict*[tiab] OR course*[tiab]

    15. 15.

      13 OR 14

    16. 16.

      15 AND 10

    17. 17.

      16/humans

  2. 1.2

    EMBASE

    1. 1.

      'multiple myeloma'/exp OR 'bone marrow cancer'/exp

    2. 2.

      'monoclonal immunoglobulinemia'/exp OR 'plasmacytoma'/exp

    3. 3.

      'Bone Marrow Neoplasms':ab,ti OR 'Bone Marrow Neoplasm':ab,ti OR 'Myeloma':ab,ti OR 'Myelomas':ab,ti OR 'Monoclonal Gammopathy':ab,ti OR 'Monoclonal Gammapathies':ab,ti OR 'plasmacytoma':ab,ti OR 'Plasmocytomas':ab,ti

    4. 4.

      1 OR 2 OR 3

    5. 5.

      'nuclear magnetic resonance imaging'/de OR 'bone marrow'/exp OR 'bone'/de OR 'spine'/exp OR 'bone density'/exp

    6. 6.

      marrow:ab,ti OR Spine:ab,ti OR Spinal:ab,ti OR Vertebra*:ab,ti OR 'Magnetic Resonance':ab,ti OR 'MRI':ab,ti OR 'MR':ab,ti OR 'MRIs':ab,ti OR 'Bones':ab,ti OR 'Bone':ab,ti

    7. 7.

      5 OR 6

    8. 8.

      7 AND 8

    9. 9.

      Prognosis:ab,ti OR Predictive Value:ab,ti OR Progression:ab,ti OR Progressions:ab,ti OR Risk:ab,ti OR Risks:ab,ti OR Survival:ab,ti OR Survivals:ab,ti

    10. 10.

      'cancer prognosis'/exp OR 'survival'/exp OR 'risk'/de OR 'risk assessment'/exp OR 'risk factor'/exp OR 'predictive value'/exp OR 'disease course'/exp OR 'cancer mortality'/exp

    11. 11.

      prognos*:ab,ti OR predict*:ab,ti OR course*:ab,ti

    12. 12.

      9 OR 10 OR 11

    13. 13.

      12 AND 8

    14. 14.

      13/humans

  3. 1.3

    Cochrane library

    1. 1.

      MeSH descriptor: [Multiple Myeloma] this term only

    2. 2.

      MeSH descriptor: [Bone Marrow Neoplasms] explode all trees

    3. 3.

      #1 or #2

    4. 4.

      MeSH descriptor: [Bone Marrow Neoplasms] explode all trees and with qualifier(s): [Secondary]

    5. 5.

      #3 not #4

    6. 6.

      MeSH descriptor: [Monoclonal Gammopathy of Undetermined Significance] explode all trees

    7. 7.

      MeSH descriptor: [Plasmacytoma] explode all trees

    8. 8.

      #6 or #7

    9. 9.

      "Bone Marrow Neoplasms" or "Bone Marrow Neoplasm" or "Myeloma" or "Myelomas" or "Monoclonal Gammopathy" or "Monoclonal Gammapathies" or "plasmacytoma" or "Plasmocytomas":ti,ab,kw (Word variations have been searched)

    10. 10.

      #5 or #8 or #9

    11. 11.

      MeSH descriptor: [Magnetic Resonance Imaging] this term only

    12. 12.

      MeSH descriptor: [Bone Marrow] explode all trees

    13. 13.

      MeSH descriptor: [Bone and Bones] this term only

    14. 14.

      MeSH descriptor: [Spine] explode all trees

    15. 15.

      MeSH descriptor: [Bone Density] explode all trees

    16. 16.

      #11 or #12 or #13 or #14 or #15

    17. 17.

      "marrow" or "Spine" or "Spinal" or "Vertebra*" or "Magnetic Resonance" or "MRI" or "MR" or "MRIs" or "Bones" or "Bone":ti,ab,kw (Word variations have been searched)

    18. 18.

      #16 or #17

    19. 19.

      #10 and #18

    20. 20.

      "Prognosis" or "Predictive Value" or "Progression" or "Progressions" or "Risk" or "Risks" or "Survival" or "Survivals":ti,ab,kw (Word variations have been searched)

    21. 21.

      MeSH descriptor: [Prognosis] this term only

    22. 22.

      MeSH descriptor: [Survival Analysis] explode all trees

    23. 23.

      MeSH descriptor: [Risk] explode all trees

    24. 24.

      MeSH descriptor: [Predictive Value of Tests] explode all trees

    25. 25.

      MeSH descriptor: [Disease Progression] explode all trees

    26. 26.

      #21 or #22 or #23 or #24 or #25

    27. 27.

      MeSH descriptor: [Mortality] explode all trees

    28. 28.

      MeSH descriptor: [Follow-Up Studies] this term only

    29. 29.

      "prognos*" or "predict*" or "course*":ti,ab,kw (Word variations have been searched)

    30. 30.

      #27 or #28 or #29

    31. 31.

      #26 or #30

    32. 32.

      #19 and #31

    33. 33.

      #32/trials

Appendix 2 Funnel Plots

2.1. Funnel plot of pooled studies with OS related to focal lesion on MRI in patients with multiple myeloma.

figurea

2.2. Funnel plot of pooled studies with PFS related to focal lesion on MRI in patients with multiple myeloma.

figureb

2.3. Funnel plot of pooled studies with OS related to diffuse infiltration on MRI in patients with multiple myeloma.

figurec

2.4. Funnel plot of pooled studies with PFS related to diffuse infiltration on MRI in patients with multiple myeloma.

figured

2.5. Funnel plot of pooled studies with PFS related to focal lesion on MRI in patients with asymptomatic multiple myeloma.

figuree

2.6. Funnel plot of pooled studies with OS related to focal lesion on MRI in patients with symptomatic multiple myeloma.

figuref

2.7. Funnel plot of pooled studies with PFS related to diffuse infiltration on MRI in patients with asymptomatic multiple myeloma.

figureg

2.8. Funnel plot of pooled studies with OS related to diffuse infiltration on MRI in patients with symptomatic multiple myeloma.

figureh

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Lee, SY., Kim, HJ., Shin, Y.R. et al. Prognostic significance of focal lesions and diffuse infiltration on MRI for multiple myeloma: a meta-analysis. Eur Radiol 27, 2333–2347 (2017). https://doi.org/10.1007/s00330-016-4543-8

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Keywords

  • Multiple myeloma
  • MRI
  • Prognosis
  • Bone marrow
  • Meta-analysis