Multifocal Glioblastoma Multiforme Eric Wing Sun Tam The

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Multifocal Glioblastoma Multiforme

• Eric Wing Sun Tam
• The Chinese University of Hong Kong

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The Patient

• E.C. F 71
• Presented with ataxia and poor penmanship
• 1 episode of focal motor seizure of left leg
• Hemochromatosis, No PMH of Malignancy
• FH of malignancy
• 4/5 Iliopsoas and hamstrings
• Unsteady wide-based gait
• MRI showed multiple homogenously brightly
  enhancing masses
• CT torso, mammogram negative

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Differential Diagnosis

• CNS Lymphoma
• Multiple Metastases
• Multifocal Glioblastoma

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Differential Diagnosis

• CNS Lymphoma
• Multiple Metastases
• Multifocal Glioblastoma

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Multifocal GBM - Definition

• Batzdorf et al. (1963) distinguish between
  "Multicentric" and "Multifocal"
• Showalter et al. (2007) suggests that "the
  clinical utility of this... may be scant."
• Lim et al. (2007) hypothesize that multifocal GBM
  is a subtype of GBM arising from Subventricular
  zone (SVZ) stem cells

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Questions

• Does surgical resection prolong survival in
  patients with conventional glioblastoma?
• Does surgical resection prolong survival in
  patients with multifocal glioblastoma?

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Design of these studies

• volumetric or non-volumetric ways

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Non-Volumetric Studies
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Sanai et al.
Surgery No Increased Survival
Surgery Increased Survival
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Non-volumetric studiesSurgery Increased
Survival
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Surgery better than Biopsy - WHO Grade IV,
plt0.05 in multivariate

• Study Year Sample size Survival Benefit
• Shibamoto et al. 1990 135 4 months
• Simpson et al. 1993 645 4.7 months
• Jeremic et al. 1994 86 6.7 months
• Ushio et al. 2005 105 12 months

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Non-volumetric studiesSurgery No Increased
Survival
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Volumetric Studies
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• Sanai et al. (2008)

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Limitations of these studies

• Study Design
• RCT impossible
• Selection bias
• Keles et al. include only patients with KPS gt 70
• Assessment method
• The true outer border of the tumor?
• CT and MRI are used in the same study
• Post-op treatment
• Up to 1/3 of patients in some studies did not
  receive Chemo

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Questions

• Does surgical resection prolong survival in
  patients with conventional glioblastoma?
• Does surgical resection prolong survival in
  patients with multifocal glioblastoma?

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The Role of Surgery in Multifocal GBM

• No RCT to date
• Surgery (/-RT/CT) vs Biopsy (/-RT/CT)
• Pro-surgery Salvati et al. (2003)
• Pro-biopsy Timothy et al. (2007)

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Pro-surgery

• Salvati et al. (2003)
• Sample size 25
• Both Grade III and Grade IV included
• Survival
• Biopsy only mean 2.8 months
• Aggressive surgery mean 9.5 months
• Long term survivor

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Pro-surgery
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Pro-surgery

• Limitations
• small sample size
• Both group III and IV are included
• no selection criteria for surgery
• no multivariate analysis
• no p-value or CI provided (probably NS)
• confounding factors affecting survival
• those who underwent SB only tend not to receive
  RT
• those who underwent surgery tend to receive RT

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Pro-biopsy

• Showalter et al.
• Retrospective cohort
• 50 out of 497 patients are multifocal GBM
• WBRT or 3D-CRT
• Multivariate analysis
• No difference in survival regardless of extent of
  surgery in (p 0.238)
• GTR prolongs time to progression
• No difference in survival regardless of WBRT or
  3D-CRT (p 0.331)

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Pro-conservative treatment

• Limitations
• Primary purpose is not to assess the role of
  surgery in multifocal GBM
• No description of how to determine GTR or STR

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Conclusions

• Multifocal GBM is likely a more migratory and
  invasive type of GBM arising from SVZ stem cells
• Controversy still exists regarding the role of
  surgery in prolonging survival in conventional
  GBM
• Surgery probably prolongs survival, albeit
  modestly, in conventional GBM based on
  accumulating evidence
• Limited data on whether surgery prolongs survival
  in multifocal GBM
• Attaining gross (close to) total resection in
  multifocal GBM is difficult and thus surgery may
  be of limited value in multifocal GBM

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Acknowledgements

• Dr. Chen

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References

• Lim et al Relationship of glioblastoma
  multiforme to neural stem cell regions predicts
  invasive and multifocal tumor phenotype. Neuro
  Oncol. 2007 October 9(4) 424429.
• Nadar Sanai, et al Glioma Extent of Resection
  and its impact on patient outcome. Neurosurgery
  62753 - 766, 2008
• Michel Lacroix, et al A multivariate analysis of
  416 patients with glioblastoma multiforme
  prognosis, extent of resection, and survival. J
  Neurosurg 95190198, 2001G.
• Evren Keles et al Effect of Extent of Resection
  on Time to Tumor Progression and Survival in
  Patients with Glioblastoma Multiforme of the
  Cerebral Hemisphere. Surg Neurol 1999523719
• Timothy N. Showalter et al Multifocal
  Glioblastoma Multiforme Prognostic Factors and
  Patterns of Progression. Int. Journal of
  Radiation Oncology 69820-824, 2007
• Salvati et al. Multicentric glioma our
  experience in 25 patients and critical review of
  the literature. Neurosurg Rev. 2003
  Oct26(4)275-9. Epub 2003 Jul 26.