Gliomas

IMAGING

Histology CT description
Juvenile pilocytic astrocytoma "classic " cyst-with-mural nodule appearance. (ie. part of the cyst wall may not enhance)
Low-grade astrocytoma hypointense on pre-contrast T1
nonenhancing on post- T1 imaging
Optic Glioma isointense to the cortex (ie. hypointense to orbital fat) on T1
isointense to hyperintense to white matter and the cortex on T2
Meningioma Isointense on pre-contrast T1
brightly enhancing on post-contrast T1
GBM Mixed isointense on T1
ring enhancing on post-T1

PATHOLOGY AND HISTOLOGY

Pathologic Classification of Astrocytoma
Pilocytic astrocytoma (non-invasive, WHO grade I)

  • hemispheric
  • diencephalic
  • optic
  • brain stem
  • cerebellar

Astrocytoma (WHO grade II)

  • variants: protoplasmic, gemistocytic, fibrillary, mixed

Anaplastic (malignant) astrocytoma (WHO grade III)

  • hemispheric
  • diencephalic
  • optic
  • brain stem
  • cerebellar

Glioblastoma multiforme (WHO grade IV)

  • variants: giant cell glioblastoma, gliosarcoma

Astrocytes provide physical support to neurons and clean up debris within the brain.
oligodendrocytes are the myelin producing cells of the central nervous system
Microglia are the smallest of the glial cells. Some act as phagocytes cleaning up CNS debris.

Grading

Astrocytomas have great variation in their presentation. The World Health Organization acknowledges the following grading system for astrocytomas:

  • Grade 1 — pilocytic astrocytoma - primarily pediatric tumor, with median age at diagnosis of 12
  • Grade 2 — diffuse astrocytoma
  • Grade 3 — anaplastic (malignant) astrocytoma
  • Grade 4 — glioblastoma multiforme (most common)

Median Survival

Histology Survival in Months
Low-grade Oligodendroglioma 120
Low-grade Astrocytoma 60
Anaplastic Oligodendroglioma 60
Anaplastic Astrocytoma 36
glioblastoma multiforme 10
Histology Median Survival yrs Histology Median Survival yrs
Pilo-A 10+
Oligo-A 7 Oligodendorglioma 10
Diff-A 4.7
AA 3 anaplastic oligodendroglioma 5
GBM 1

A – Astrocytoma
AA – Anaplastic Astocytoma

RPA Classification

Class Patient Characteristics Median Survival (mo)
I, II Anaplastic astrocytoma
- Age <= 50, nl mental status
- Age > 50, KPS > 70, symptoms > 3mo.
40-60
III, IV Anaplastic astrocytoma
- Age <= 50, abnormal mental status
- Age > 50, symptoms < 3mo.
Glioblastoma
- Age < 50
- Age > 50, KPS => 70
11-18
V, VI Glioblastoma
- Age > 50, KPS <70 or abnormal MS
5-9

LOW GRADE GLIOMAS

General

  • Astrocytomas: fibrillary, protoplastic, gemistocytic (transform into anaplastic form), pilocytic (young patients).
  • 20-40 years old
  • Typically in the cerebral hemisphere.

Mayo Experience: Surival of Low-Grade Supratentorial Gliomas

Survival Pilo-A Diff-A OA O
Median (y) 4.7 7.1 9.8
2 y (%) 88 80 89 93
5 y(%) 85 46 63 73
10 y (%) 79 17 33 49
15 y(%) 79 7 17 49

O, oligodendroglioma
OA, oligoastrocytoma

Malignant transformation

  • 9% with RT vs 18% with surgery alone (Reichenthal)

Diagnosis

  • Pilocytic Astrocytomas are enhancing lesions with cysts.
  • The others are diffuse non-enhancing lesions that are poorly defined and are low signal on T1 and increased intensity on T2 images.

Surgery

  • Diagnosis and removal of symptomatic area.
  • Pilo-A is cured with complete resection if possible and with PR the survival is 80-90%. For other tumors, a CR results in survival of 80%

Radiation Dose and field

  • 2 Randomized negative trials for dose escalation
  • EORTC: 45 VS 59.4 58% VS 59% OS-5 NS
  • NCCTG: 50.4 VS 64.8 73% VS 68% OS-5 NS
  • Current dose: RTOG chose a 54 Gy dose to T2-weighted MR + 2 cm margin

Radiation Timing

  • EORTC 22845 phase III 54 Gy adjuvant vs at progression: 55% vs 35% PFS-5 in favor of adjuvant RT but median survival time 7.4 was not affected.
  • Observation is reasonable in adults with asymptomatic supratentorial low-grad glioma

Chemotherapy

  • used to delay radiation; carboplatin and vincristine shows 3-yr PFS of 77% (Packer 1997).

Study

RTOG 9802 (Favorable Study) [1]
Patients

  • Favorable patients (pts) (age <40 years [yrs] who undergo gross total resection [GTR])

Treatment

  • observed postoperatively in a single arm Phase II study (Arm 1).

Results

  • Arm 1, OS at 2- and 5-yrs is 99% and 94%. PFS at 2- and 5-yrs is 82% and 50%.

RTOG 9802 (Unfavorable Study) [1]
Patients

  • Unfavorable pts (age ≥40 who have subtotal resection [STR] or biopsy [B])

Treatment

  • randomized to either RT alone (54Gy in 30 fractions to a local treatment field) (Arm 2) or RT followed by 6 cycles of standard dose PCV (Arm 3).

Results

  • Arms 2 (RT alone) and 3 (RT+PCV), there was no difference in OS or PFS. OS at 2- and 5-yrs was 87% and 61% with RT alone versus (vs) 86% and 70% with RT+PCV (p=0.72).

TECTAL GLIOMA

THALAMIC GLIOMA

  • Thalamic and brain stem tumors constitute 10-15% of primary intracranial gliomas of childhood, with a dominant age being 4-14 years.
  • Adult thalamic and brain stem tumors constitute 35% of intracranial gliomas
  • Due to their critical location, thalamic tumors often require treatment without biopsy confirmation. However, autopsy results and more recently stereotactic biopsy have revealed that the majority of the tumors are glial neoplasms
  • Total surgical resections are generally less feasible because of the resulting neurological deficits.
  • Treatment is as per pathology

OPTIC PATH GLIOMA

  • Epidemiology
    • 5% of pediatric brain tumors
    • nearly all are found in patients younger than 20 years of age and mostly 10 years of age.
    • 20-40% associated with NF-1
    • 5-10% of patient with NF-1 have optic path glioma
    • patients with NF-1 have more indolent course
  • Presentation
    • loss of visual acuity 70%, strabismus and nystagmus 33%, visual field impariment 8%
    • developmental delay, macrocephaly, ataxia, hemiparesis, proptosis, and precocious puberty
    • upto 30% of children with optic chiasm (73% of cases) involvement initially present with precocious puberty.
    • NF-1 patients have anterior > posterior visual pathways involved.
  • Gliomas along te anterior visual pathway occurred in 15% of NF-1 patients and were occasionally bilateral.
  • Biopsy not needed
  • Treatment
    • Carboplatin and vincristine to delay radiation in pre-pubertal patients
    • 3 years progression free survival rate of 77%
    • 50-54 Gy in 150 to 180 cGy per fraction
    • 45 Gy at 1.5 Gy per fraction for < 3 year-old.

OLIGODENDRIOGLIOMAS

General

  • 20-50 years
  • Loss of 1p and 19q
  • 80% are in the white matter
  • Typically presents with seizures
  • From oligodendrocytes which mylelinate the neurons.

Pathology

  • Small round cells with perinuclear halo and can see calcifications.
  • Grade: either low (5 year survival of 75%) or anaplastic OG (45%).
  • If have astrocytomas + ependymomas elements then called a mixed OG with survival of 65%.
  • If recurs then GBM or anaplastic astrocytoma.

Diagnosis

  • CT or MRI scan shows an enhancing lesion with hemorrhage or necrotic area.
  • MR specttroscopy shows
    • reduction in N-acetyle asparate (NAA) signal
    • increase in choline peak

Treatment

  • Surgery: goal is CR
  • Radiotherapy: Added if PR or if intact with 54 for LG and 60 for the anaplastic tumors.
  • Chemotherapy: PCV is useful in this group of patients especially 1p 19q deletions
Bibliography
1. E. G. Shaw, B. Berkey, S. W. Coons, D. Brachman, J. C. Buckner, K. J. Stelzer, G. R. Barger, P. D. Brown, M. R. Gilbert and M. Mehta. Initial report of Radiation Therapy Oncology Group (RTOG) 9802: Prospective studies in adult low-grade glioma (LGG). Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 24, No 18S (June 20 Supplement), 2006: 1500.
Unless otherwise stated, the content of this page is licensed under Creative Commons Attribution-Share Alike 2.5 License.