1. ANDY LIM Surgical HMO2

2.  Classification  Clinical presentation  Investigations  Management

4.  Glial cells ◦ Astrocytes  Anchor neurons to blood supply  Regulate chemical environment  May regulate vasoconstriction ◦ Oligodendrocytes  Coats axons in CNS - myelin  Insulation  Propagation of electrical signals ◦ Ependymal cells  Walls of ventricles – CSF

5.  Neuroepithelial tumours ◦ Gliomas  Astrocytoma (including glioblastoma)  Oligodendroglioma  Ependymoma ◦ Pineal tumours ◦ Neuronal tumours ◦ Medulloblastoma  Pituitary tumours  Nerve sheath tumours (Schwannoma)  Meningeal tumours (meningioma)  Metastatic tumours

6. WHO designationWHO grade 1993Kernohan Grade 1949 Pilocytic astrocytomaII AstrocytomaIII, II Anaplastic astrocytoma IIIII, III Glioblastoma multiforme IVIII, IV

8.  Classification  Clinical presentation  Investigations  Management

9.  Raised intracranial pressure  Focal neurological deficit  Epilepsy

10.  Raised ICP ◦ Headache ◦ Vomiting ◦ Drowsiness ◦ Papilloedema

12.  Mass effect ◦ Tentorial herniation  Lateral  Central ◦ Subfalcine herniation ◦ Tonsillar herniation

13.  Management of raised ICP ◦ Steroids ◦ Sedation  Propofol  Thiopentone ◦ Hypothermia ◦ Hyperventilation ◦ Mannitol infusion ◦ CSF withdrawal ◦ Decompressive craniectomy

14.  Focal neurology ◦ Personality change ◦ Limb paresis ◦ Visual defects ◦ Speech disturbance

15.  Epilepsy ◦ Generalised ◦ Partial  Simple  Complex ◦ Partial to generalised

16.  Classification  Clinical presentation  Investigations  Management

17.  CT brain  MRI brain

23.  Classification  Clinical presentation  Investigations  Management

24.  Surgery  Adjuvant radiotherapy  Chemotherapy ◦ Temozolomide

25.  Surgery ◦ Aims  Definitive diagnosis  Sterotactic biopsy (CRW system)  Small, deep seated, diffuse, highly eloquent areas  Biopsy during radical excision  Alleviate symptoms of raised ICP  Precursor to adjuvant therapy ◦ Specific complications  Haematoma  Cerebral oedema

26.  Radiotherapy ◦ Effective in rapidly growing tumours III & IV ◦ Extends survival, does not cure ◦ Dose-effect relationship ◦ Minimise high-dose regions in normal brain

27.  Chemotherapy ◦ 5-10% brain tumour cells in active growth phase ◦ Initial trials  A survival benefit was initially demonstrated using the nitrosurea carmustine ◦ Subsequent trials  Have established the role of temozolomide as the current standard for adjuvant chemotherapy

28.  Temozolomide  Alkylating agent – damages DNA – triggers cell death  100% bioavailability  Enters CSF  No hepatic activation required  In vitro antitumour activity against highly resistant malignancies  Potential for combination treatments currently being investigated

29.  Temozolamide phase III study ◦ Stupp et al Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. NEJM 2005; 352:987 ◦ Stupp et al Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 2009; 10:459

30.  Temozolamide phase III study ◦ 573 newly dx GDM ◦ Random assignment  1) post-op RTx (60 Gy in daily 30 fractions)  2) RTx + temozolamide (75mg/m2 daily up to 49 days) then up to six cycles temozolamide 150-200mg/m2 daily for 5/7, every 28/7 ◦ Results at 1 year  27 vs 11% ◦ Results at 5 years  10 vs 2% ◦ Benefits in all patient subsets ◦ No negative effect on health-related quality of life

31.  4 different grades of increasing biological aggressiveness  Clinical presentation can be a combination of raised ICP, focal neurology or epilepsy  Imaging modality of choice is CT/MRI  Management includes surgery, radiation and chemotherapy