current glioma management - briz brain & spine · 2015-07-01 · shortens survival in patients...
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Current glioma management
David Walker
MBBS PhD FRACS
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Overview
• Defining prognosis
• Classification
• Treatment options for
glioma
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Prognosis
• Traditionally
–
–
• Quality of Life
–
–
–
• Family concerns
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Basic Classification of Glioma (WHO)
• Grade I
– Pilocytic astrocytoma
• Grade II
– Astrocytoma
– Oligodendroglioma
– Mixed
• Grade III
– Anaplastic astrocytoma / oligodendroglioma
• Grade IV
– Glioblastoma multiforme (GBM)
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Common Themes in Improved Management
•Earlier and more accurate diagnosis
•Safer Surgery
- Stereotaxis
- Minimally invasive techniques
- Functional mapping
•Safer and more effective radiotherapy and chemotherapy
•Better follow up
•Multidisciplinary care
•Brain Tumour Nurse Practitioner
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Stereotaxis
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Techniques to Improve Outcome
Minimally invasive techniques •Shave
•Incision
•Craniotomy
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Functional mapping - Awake craniotomy
•Aims to identify CRITICAL areas of the brain and AVOID them – MINIMIZE THE RISK
• Areas controlling movement and speech
• Cortical Stimulation – identify motor areas
• Awake craniotomy – for speech areas
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Cortical stimulation
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Awake craniotomy (cont’d)
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Low grade glioma
• Observation
• Biopsy
• Resection
• Radiotherapy
• Chemotherapy
• Optimal management is – Maximal safe resection
– Radiotherapy
– 6 m chemotherapy
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Glioblastoma Multiforme
• A diagnosis of despair ? –
•
–
» Median Survival <12 months
• Modern Approach –
–
» Median Survival 17 months
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Stummer et al 2006. Lancet Oncology
GLIOLAN - fluorescent
Guided tumour resection
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Chemotherapy improves outcome
(months)
0 6 12 18 24 30 36 42 0
10
20
30
40
50
60
70
80
90
100
N Number of patients at risk :
286 240 144 59 23 2 0 287 246 174 109 57 27 4
RT TMZ/RT
Median OS, mo: 12.1 14.6
2-yr survival: 10.4% 26.5%
HR [95% C.I.]: 0.63 [0.52-0.75]
p <0.001
TMZ/RT
RT
TMZ/RT
%
RT
Stupp R et al. NEJM 2005;352:987-96.
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Local therapies
Have a role
Gliadel - wafers
CCNU
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Comparison to Other Studies
Stupp
(RT
alone)
Westp
hal
(GBM)
Stupp
(TMZ+R
T)
La
Rocca
(40 pts)
McGirt
2009 (33
pts)
Pan (21
pts)
Walker
(15 pts)
Overall
survival
(m)
12.1 13.1 14.6 18.6 20.7 17 17.6
PFS (m) 5.0 6.9 7.2 8.5 11.3
18/12
survival
(%)
25 23 44 55 58 45 53
24/24
survival
(%)
10.4 16 26 29 36 39 53*
QUADRUPLE THERAPY
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Irwin et al. Delay in radiotherapy
shortens survival in patients with high
grade glioma. (2007) J. Neurooncol.
Walker et al. An analysis of
dose-effect relationship in the
radiotherapy of malignant
gliomas. (1979)
Int.J.Radiat.Biol.Phys.
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Bevacizumab (AVASTIN): precise VEGF inhibition
Recombinant humanised monoclonal anti-VEGF antibody developed from murine anti-VEGF MAb A4.6.11
• 93% human, 7% murine
• recognises all major isoforms of human VEGF, Kd = 8 x 10–10M
• terminal half-life 17–21 days
1. Presta, et al. Cancer Res 1997
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Significant responses seen often after AVASTIN
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Recurrent GBM : What do I do?
Surgery Whenever possible (good and intermediate patients)
Add Gliadel whenever possible (including when used before)
Chemotherapy Recommend considering 2nd line agents or protocols
Bevacizimab has important role Options very limited when/if this fails
SRS – rarely indicated but consider when possible
Consider eligibility for trials
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Dendritic Cell Vaccine Temozolomide
29/7/03 23/10/03 30/12/03 17/3/04
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HCMV infection in GBM tissues CMV seropositive CMV seronegative
CMV IE-1
Control
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Synthetic
Viral peptides
Cultured together in
GMP facility
+
Activated anti-viral
CD8+ T cells
Inject back into
the patient
GBM
patient Blood
lymphocytes
HCMV-specific T cell expansion strategy
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Pre-Therapy Post-Therapy Post-Therapy
April 2009 (1 m post T cell therapy) (6 m post T cell therapy)
Clinical response: pre- and post-T cell therapy
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Brain Tumour Nurse Practitioner
•Education -Preoperative -Perioperative -Postoperative
•Support for patient and family •Coordination of Care
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What should be done?
63 female 35 male
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