Brain Tumours for Psychologists

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Brain Tumours for Psychologists

• Allan James
• Consultant Clinical Oncologist
• Beatson Oncology Centre

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Why suspect a Brain Tumour ?

• Headaches are common, very few caused by tumour
• Look for acute onset, particular pattern,
  association with other symptoms / signs
  
• Although seizures are dramatic, very few are
  caused by brain tumours
  
• Scan all with new onset seizures with no adequate
  explanation of cause
  
• Personality changes are common in older age
• Brain tumours are a rare cause
• VIGILANCE
• is the key

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Some imaging is a little more accurate still
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Baseline
Week 6
Week 24
Week 40
Week 56
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LOH 1p 19q is becoming A useful clinical marker
Both for prognosis
And therapeutic decisions
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There is no more Powerful prognostic Marker in
GBM
Than AGE
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THUS
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Introduction to GliomaTreatment
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Introduction to GliomaTreatment
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Introduction to GliomaTreatment
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Introduction to GliomaTreatment
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Introduction to GliomaTreatment
Frame based Image Guided Brain Biopsy 1980
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Introduction to GliomaTreatment
Image guidance has simplified the biopsy or ex
cision of supratentorial
lesions
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Introduction to GliomaTreatment
Awake craniotomy for brain mapping and tumour
excision cortical stimulation and
language testing during craniotomy
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Introduction to GliomaTreatment
A Biopsy only B Maximal debulking C Various p
ercentage debulking
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Introduction to GliomaTreatment
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Introduction to GliomaTreatment

• Glioma Historical perspective
• Situation around 2000
• HGG
• Age
• Age 70 PS 0 or 1
• Young but PS 1
• Age 70 WHO 1 Supportive care
• Chemotherapy at relapse
• Survival 12months (Gd IV) 1-4 years (Gd III
  OOAA)
  

Highly palliative 6 XRT
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Introduction to GliomaTreatment
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Introduction to GliomaTreatment
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Introduction to GliomaTreatment
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Introduction to GliomaTreatment

• Radiotherapy of Primary Brain tumours
• What do we achieve

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Chemotherapy for Brain Tumours
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Chemotherapy for Brain Tumours

• Can we give chemotherapy with / after XRT to
  improve outcome in High Grade Gliomas?
  
• Meta-analysis of several small trials in 1990s
  suggested small survival advantage (6) at 1
  year, halved, barely significant at 2 years, gone
  by 3 years
• Chemo was 9 months of 3 drug regimen with GI
  side effects, marrow suppression, diet
  restrictions
  
• Interpreted differently in UK (Europe), chemo
  witheld until relapse in US, survival advantage,
  therfore adjuvant PCV offered
  
• BUT, TIMES HAVE CHANGED

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Chemotherapy for Brain Tumours
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Chemotherapy for Brain Tumours
Concomitant TMZ/RT
Adjuvant TMZ
R
0
Weeks
6
10
14
18
22
26
30
RT Alone
Temozolomide 75 mg/m2 po qd for 6 weeks,
then 150200 mg/m2 po qd d15 every 28 days for 6
cycles
Focal RT daily 30 x 200 cGy Total dose 60 Gy
PCP prophylaxis was required for patients
receiving TMZ during the concomitant phase.
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2001 2003 EORTC 26981Progression Free Survival
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2001 2003 EORTC 26981Overall Survival

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RT TMZ/RT Median OS, mo 12.1 14.6 2-yr surviva
l 10 26 HR 95 C.I. 0.63 0.52-0.75 p 0.0001
90
80
70
60

50
40
30
TMZ/RT
20
RT
10
0
0
6
12
18
24
30
36
42
months
RT
TMZ/RT
Stupp et al. N Engl J Med 2005, 352987-996
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Concomitant Chemoradiotherapy

• Concomitant Chemoradiotherapy
• First trial in 25 years to show significant
  survival advantage (Walker, XRT, 1978)
  
• Temozolomide developed in UK
• Expensive - 15-18k per course

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Concomitant Chemoradiotherapy

• Concomitant Chemoradiotherapy
• First trial in 25 years to show significant
  survival advantage (Walker, XRT, 1978)
  
• Temozolomide developed in UK
• Expensive - 15-18k per course

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Concomitant Chemoradiotherapy

• Concomitant Chemoradiotherapy
• First trial in 25 years to show significant
  survival advantage (Walker, XRT, 1978)
  
• Temozolomide developed in UK
• Expensive - 15-18k per course
• There is a potential target population
• ie a way of identifying responders, thus
  targetting resources and identifying patients in
  whom we must take a different approach
  

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MGMT Promoter Methylation Predicts Benefit from
TMZ Treatment?
Unmethylated MGMT
Randomization RT TMZ/RT Median OS, mo 11.8 12
.7
2-yr survival 1.9 13.8
100
100
90
90
Logrank p 0.062
Logrank p 0.0074
80
80
70
70
TMZ/ RT
60
60
50
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Overall Survival
TMZ/ RT
40
40
30
30
RT alone
RT alone
20
20
10
10
0
0
0
4
8
12
16
20
24
28
32
36
40
0
5
10
15
20
25
30
35
40
months
months
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Management of (High Grade) Glioma whats new

• MGMT (methyl guanine methyl transferase)
• Repairs damage inflicted on DNA by Temozolomide
  (methyl group attached on Guanine)
  
• Suicide enzyme
• If MGMT expressed in cells, they can repair TMZ
  damage, and thus are resistant to chemotherapy
  
• If MGMT gene promoter is methylated, it is not
  expressed in those cells, therefore they will not
  be able to repair TMZ damage, and thus will
  respond to chemotherapy

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Management of (High Grade) Glioma whats new

• UK / Scottish History of Concomitant Therapy
• 2001-2003 Randomised Phase 3 study
• 2004 Results first presented at ASCO
• Late 2004 First cases treated in Glasgow
• March 2005 Definitive paper published in NEJM
  with the MGMT paper
  
• Feb 2006 NICE fail to recommend use of regime in
  any category. Use stops in Glasgow.
  
• April 2006 SMC follow suite but 8 point criticism
  submitted to NICE
  
• December 2006 SMC and subsequently NICE finally
  approve use in newly diagnosed GBM of PS 0 or 1

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Gliadel
But 2 year data less convincing
And compare with Stupp trial curve
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Thus age remains the strongest prognostic factor
in
HGG survival, despite advances in therapy
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Low Grade Glioma
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Compare with GBM data already given
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