05 November 2004
The most common cerebral tumor
INCIDENCE OF CEREBRAL TUMORS
(Malignant 25%, low grade 20%)
Grade 1: increased cellularity of astrocytes
Grade 2: mild – mod nuclear polymorphism, no mitotic figures
Grade 3: 50-75% astrocytes are normal, frequent mitotic figures, increased vascularity, necrosis.
Grade 4: marked cellular pleomorphism, extensive endothelial proliferation, numerous mitotic figures, necrosis.
Well differentiated astrocytoma
Anaplastic astrocytoma: nuclear polymorphism, mitoses
Glioblastoma multiforme: endothelial proliferation, necrosis.
Grade 1: pilocytic astrocytoma
Grade II: astrocytoma
Grade III: anaplastic astrocytoma
Grade IV: glioblastoma multiforme
Gemistocytic astrocytoma: classed as low grade but high incidence of conversion to malignant forms
Pilocytic: good prognosis
Ganglioglioma: good prognosis
Pleomorphic xanthoastrocytoma: good prognosis
DIFFICULTIES OF LITERATURE INTERPRETATION
Uniformity of patient selection
Uniformity of patients’ neuro status
Radiotherapy dose & field size
Extent of surgical resection
Location of lesion
Phakomatoses (Tuberous sclerosis)
Neurofibromatosis Type 1
Lynch syndrome (HNPCC)
Li Fraumenni syndrome
Low Grade Astrocytoma Management
Early surgical intervention does not improve survival?
Useful for: Confirming diagnosis
CT: 30% absent enhancement in high grade astro
MRI: 5% incorrect evaluation
Low grade astro can have pockets of high grade
Improved survival with attempted total resection on retrospective
Improved neurological symptoms
60 Gy in 30 fractions
5 yr survival from 38% to 49%
9% complicated by radiation necrosis
Side effects: psychomotor slowing, radiation induced meningioma & gliomas
Hyperfractionation, accelerated, photosensitisers showed no extra benefit
ADJUNCTIVE THERAPY OF NO BENEFIT
Vincristine & procarbazine
HIGH GRADE ASTROCYTOMA
Surgery improves survival, reduces morbidity & confirms the diagnosis
Reoperation adds a further 3 months
Reoperation plus adjuvant therapy adds up to 37 weeks.
Reoperation morbidity 8% at 30 day
Reoperation mortality rate 2.7% at 30 day
60 Gy over 30 fractionated doses
Radiation is the single most effective treatment for astrocytoma
Median survival of surgery alone is 17 weeks
Median survival of surgery & radiotherapy is 37.5 weeks
Hyperfractionation, accelerated protocols, photosensitisers (metronidazole, misonidazole) show no extra benefit
20-30% are eligible (ltd by size, patient condition); used for rescue therapy
Limitations of technique are limitations of the study: unifocal, <5cm, susceptible to catheter implantation
Provides an extra mean survival time of 9 months
BCNU(carmustine) first drug used & still the gold standard albeit a poor one
Surgery & radiation & chemotherapy compared to surgery & radiotherapy extends 9.25 to 10 months.
Other agents trialled with less success: CCNU, procarbazine,, intracarotid infusion, manipulation of blood brain barrier, paclitaxel, adriamycin, etoposide.
ADJUNCTIVE THERAPY (WITHOUT SUCCESS)
Multicentre phase II trial of temozolomide in patients with anaplastic astrocytoma at first relapse.
Journal of Clinical Oncology: 17(9):2762-71, 1999 Sept.
DNA mismatch repair and O6-alkylguanine-DNA alkyltransferase analysis and response to Temodal in newly diagnosed malignant glioma.
Journal of Clinical Oncology: 16(12):3851-7, 1998 Dec.