Gliomas / Glioblastoma Multiforme (GBM)

FACTS

  • GBM can be primary or a transformation of diffuse infiltrating astrocytoma (Grade 2/3)
    • primary: EGFR mutation; elderly usually primary
    • secondary: TP53 mutations
  • mechanisms of spread: subarachnoid seeding (via CSF), white matter
How gliomas spread through white matter
Spread through…
Leads to involvement in …
peduncles
brainstem
genu / body of corpus callosum
bilateral frontal lobes (”butterfly glioma”)
splenium of corpus callosum
parietal / occipital lobes
notion image
 
  • How gliomas spread via white matter
Spread through…
Leads to involvement in …
peduncles
brainstem
genu / body of corpus callosum
frontal lobes
splenium of corpus callosum
parietal / occipital lobes

HPI

universal ROS
  • KPS

PHYSICAL EXAM

universal exam
  • Visual fields / acuity
  • speech (naming, repetition)

IMAGING

MR spectroscopy:
  • NAA/Creatine peaks DECREASED as grade INCREASES
  • Choline peak INCREASED
    • NOTE: [11c] choline has high diagnostic accuracy in detecting relapse from radiation induced necrosis
MRI without contrast:
  • HGG are DWI restricting (unlike LGG)

A/P

  • First line treatment: Stupp Protocol
    • Maximal safe excision
    • Concurrent TMZ (temozolomide) + XRT (60 Gy over 30 sessions: 5d x 6 wks)
  • counsel: prognosis depends a lot on KPS, grade, neurologic deficit, histology, EOR, genetics (IDH, MGMT)
    • IDH mutation is good
    • MGMT mutation is good
  • Recurrences vs. pseudoprogression (Treatment effect, radiation necrosis)
    • Order MRI spectroscopy to help distinguish
    • Tx for pseudoprogression:
      • steroids
      • bevacazumab (Avastin)
      • LITT
      • ?hyper-baric O2

Notes

Temozolomide
  • MOA: alkalating agent → deposits methyl on DNA → cytotoxic lesions → cell death
    • MGMT removes these lesions, hence it’s better to have an MGMT mutation

References

Stupp Protocol
Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987-96. doi: 10.1056/NEJMoa043330. PMID: 15758009.    Radiotherapy for glioblastoma in the elderly. NEJM. 2007 Apr 12; 356(15):1527-35