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Astrocytoma
05 November 2004
The most common cerebral tumor
INCIDENCE OF CEREBRAL TUMORS Astrocytoma 45% (Malignant 25%, low grade 20%) Metastatic 15% Meningioma 15%
CLASSIFICATION
KERNOHAN (1949) 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.
RINGERTZ Well differentiated astrocytoma Anaplastic astrocytoma: nuclear polymorphism, mitoses Glioblastoma multiforme: endothelial proliferation, necrosis.
WHO CLASSIFICATION Grade 1: pilocytic astrocytoma Grade II: astrocytoma Grade III: anaplastic astrocytoma Grade IV: glioblastoma multiforme
SPECIAL ASTROCYTOMAS 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 Pathologic classification Radiotherapy dose & field size Extent of surgical resection Location of lesion Control groups
RISK FACTORS Age Male (60:40) Phakomatoses (Tuberous sclerosis) Neurofibromatosis Type 1 Lynch syndrome (HNPCC) Li Fraumenni syndrome Previous radiation Turcot syndrome
Low Grade Astrocytoma Management
SURGERY 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 Cytoreduction Improved survival with attempted total resection on retrospective studies Improved neurological symptoms
RADIOTHERAPY 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 BCNU Vincristine & procarbazine Immunotherapy Brachytherapy Hyperthermia
HIGH GRADE ASTROCYTOMA
SURGERY 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
RADIOTHERAPY 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
INTERSTITIAL BRACHYTHERAPY 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 30% radionecrosis
CHEMOTHERAPY 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) Hyperthermia Photactivated chemotherapy Immunotherapy Retroviral vectors
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.
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