Transcript Target Volumes - The Eastern Cancer Registration and

Oncology management
of CNS tumours
Neil Burnet
University of Cambridge Department of Oncology
& Oncology Centre, Addenbrooke’s Hospital
ECRIC CNS study day
7th April 2009
Introduction
• Treatment modalities for cancer
• What data do oncologists want?
• Examples of uses of Registry data
Cancer treatment modalities
Cancer treatment modalities
• Modalities
• (Surgery)
• Radiotherapy
• Chemotherapy
• Consider efficacy
• Consider costs
Oncology management
Radiotherapy
• Radiotherapy is an anatomical treatment
• Treats a specific area
• Localising the tumour target is crucial
• Imaging is key
• Better localisation – better outcome
• Localising normal structures allows avoidance
CT – the technology advance
Late 1970s
1980s
2003
Glioblastoma imaging
• T2
• T1
• T1 + Gd contrast
MR (magnetic resonance) imaging
Radiotherapy
• Immobilise the patient
• Relate today's patient position to tumour imaging
Radiotherapy
• High precision positioning
• Relocatable stereotactic frame
Radiotherapy
Radiotherapy imaging
CT
MRI
• GBM planning
• Using CT +MR together
MRI
CT
Radiotherapy imaging
• Pre-op CT
• Post-op planning CT
Target volume delineation
Radiotherapy
• Planning and delivery technology now very different
• Old ‘square’ planning
• Was conventional in 1960s – 1990s
• Conformal (dose conforms to shape of target in 3D)
• ‘Ultra-conformal’ (includes concave shape)
• known as IMRT (intensity modulated radiotherapy)
• 21st century technology
Treatment volumes compared
‘Square’ plan
Conformal
Ultra-conformal
IMRT
• Old ‘square’
planning
• Some
shielding
with ‘lead’
blocks
Treatment volumes compared
‘Square’ plan
Conformal
Ultra-conformal
IMRT
Conformal RT plan
IMRT plan (TomoTherapy)
• Ca nasopharynx
• 68 Gy to primary (34#)
• 60 Gy to nodes (34#)
• Cord dose < 45 Gy
• No field junctions
• No electrons
IMRT plan
• Skull base meningioma
• Shaping of dose around
optic nerves and chiasm
• Tumour ~ 60 Gy
• Optic chiasm 50 Gy
Radiotherapy dose
• Biological effect depends on
• Total dose
• Number of fractions
•
(Dose per fraction)
Overall treatment time
Complex relationship
Radiotherapy dose
• Single fraction
• Very destructive
• Known as radiosurgery
• Must physically avoid normal tissue
• Multiple fractions
• Spare normal tissue
• Enhances therapeutic radio
• Allows treatment including normal tissue
RT dose and fractions
• For a given dose,
Biologically
EffectiveEffective
Dose forDose
60 Gyfor 60 Gy
Biologically
for variable
fraction number
for variable
fraction number
• Actually depends
on dose/#
400
1200
Biological dose
Biological dose
and overall time,
1200
biological effect 1000
depends on
800
number of #
600
1000
Tumour
Tumour
Brain
Brain
800
600
400
200
200
0
0
1
5 1
10 5
15 10 20 15 25 20 30 25
Fractions Fractions
30
Chemotherapy
• Use in accordance with NICE Guidelines
• At first presentation, with (surgery &) RT
• Temozolomide
• Also at relapse
• PCV
• Monitor
• Blood count, nausea, liver function (+ other s/e)
• Progression
Chemotherapy
• Most chemo for CNS tumours is oral
• Temozolomide
• Invented in UK
• Revolutionised treatment of GBM
RT + TMZ for GBM
EORTC
Randomised trial results
P<0.001
Cancer cure and cost
Cancer cures by modality
References
• SBU. The Swedish council on technology assessment in health
care: Radiotherapy for Cancer. 1996
• Cancer Services Collaborative 2002
Funding World Class Cancer Care (Chapter 10)
Estimated total NHS spend on cancer care
27%
Inpatient costs (excluding those related to surgery) [1]
Surgery (including day cases and inpatient stays) [2]
22%
Drugs (cost of medicine, preparation and administration) [3]
18%
Outpatients (diagnostics, first and follow-up appointments) [4]
8%
Screening [5]
5%
Radiotherapy [6]
5%
Specialist Palliative Care (excluding voluntary sector) [7]
5%
Other [8]
10%
0
200
400
600
800
1000
1200
Cost (£ million per annum)

Total expenditure: Around £4.35bn pa in England.

Expenditure per head of population = £80 (compared with £121 in France and
£143 in Germany)
The Cancer Reform Strategy
Prof. Mike Richards 2007
1400
Effectiveness and cost
% cures
% of cancer
care cost
Ratio
• Radiotherapy
40%
5%
8.0
• Chemotherapy
11%
18%
0.6
• Surgery
49%
22%
2.2
What data do oncologists really want?
What data do oncologists really want?
• What data do oncologists really want or need?
• Types of CNS tumour
• Prognostic factors
• Treatment intent
• Treatment details
• Dates
Tumour types in oncology clinic
•
Note ~20% with benign tumours
CNS tumour types - 1
• Glial tumours
•
•
•
•
•
•
•
Astrocytoma (inc Pilocytic & Juvenile Pilocytic)
Oligodendroglioma
Oligo-astrocytoma
Glioblastoma (GBM)
Ependymoma (+ subependymoma)
Meningioma
Pituitary adenoma + Craniopharyngioma
CNS tumour types - 2
• Vestibular schwannoma (aka acoustic neuroma)
• Medulloblastoma
• Germinoma + teratoma
• Lymphoma
• Neurocytoma + Ganglioglioma
• Pineoblastoma
• Primitive neuro-ectodermal tumour (PNET)
• (Chordoma + chondrosarcoma)
• (Metastases)
CNS tumour types - 3
• Many tumour types
• Prognosis varies enormously
• Survival from “days to weeks” to cure
• Affected by tumour type
• Grade (ie how malignant)
• Essential to know detail
• Detail must be collected
Grade affects prognosis
• High grade glioma
• Grade III
• Grade IV = GBM
- Surgery + RT only
- Radical treatment
- Addenbrooke’s data
Grade affects prognosis
• Histology is not
the only tumour
feature which
affects outcome
Radiotherapy & Oncology 2007; 85:371-378
• Radiology adds
to pathology
grade
• Need to include
information
from imaging
What data do oncologists really want?
• Prognostic factors
•
•
•
•
Age
Performance status
? Size
Extent of surgical resection (hard to evaluate)
• Treatment intent
• Radical
• Palliative
What data do oncologists really want?
•
•
Treatment intent
• Might be clear from treatment
• GBM – RT 60 Gy (30#) = radical
30 Gy (6#) = palliative
Need to know if intent changes
• eg due to progression
Radiotherapy details
• Area treated
• Total dose
• Number of fractions
• Overall treatment time
• Dates
• Time (delay) to start RT
• Overall time (duration) of RT
Chemotherapy details
• Drug(s)
• Dose
• Number of cycles given
• Dates
Examples of Registry data use
• Measuring disease burden - AYLL
• GBM outcome
• Modelling chemotherapy use
1
Measuring disease burden
• Simple mortality figures do not tell the whole story
• Other measures show alternative aspects of mortality:
• Burden on society
• Burden to the individual affected
• With particular thanks to Peter Treasure at ECRIC
Measuring disease burden
• Method
• Detail deaths from specific tumour type
• Compare to standardised matched population
• Sum the difference
Diagnosis
Death
Life expectancy at diagnosis
Years of Life Lost
Measuring disease burden
• CNS tumours
• 2% of cancer deaths – simple mortality
• 3% of the years of life lost - YLL
• YLL shows the burden on society
Average Years of Life Lost
• Divide YLL by number of affected patients
• Average Years of Life Lost – AYLL
• AYLL shows the burden to the affected person
• Easily understood measure, including by patients
• CNS tumours account for ~ 20 years of lost life
• This is higher than any other adult tumour type
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Average Years of Life Lost per affected individual
Average Years of Life Lost
Average Years of Life Lost for 17 cancer sites
25.0
20.0
15.0
10.0
5.0
0.0
Measuring disease burden
• CNS tumours
• 2% of cancer deaths
• 3% of the years of life lost – YLL
• ~ 20 years of lost life per individual - AYLL
Average Years of Life Lost
• In the 2007 Cancer Reform Strategy reference made
to the poor overall outcome of brain & CNS tumours
in terms of AYLL ¶
• Encouraging that alternative measures of mortality
are being acknowledged by the government
¶
UK Government Department of Health (2007)
http://www.dh.gov.uk/en/Publicationsandstatistics/Lettersandcirculars/Dear
colleagueletters/DH_080975
Measuring disease burden
• AYLL is an effective measure of disease burden to
the affected person
• AYLL has other uses
• Compare disease burden with research spending
• AYLL does not match NCRI research spending
• The mis-match is most extreme for CNS tumours
Average Years of Life Lost per affected patient versus %NCRI spending
Burnet et al. Br J Cancer 2005; 92(2): 241-5
2
GBM outcome
GBM outcome
• GBM – traditionally terrible
outloook
• Addition of temozolomide
(TMZ) chemotherapy has
transformed the outlook
• Can we reproduce trial
results?
The scream – Edvard Munck
TMZ + RT for GBM
EORTC
Randomised trial results
P<0.001
TMZ + RT for GBM
Addenbr RT alone
TMZ + RT for GBM
Addenbr RT + TMZ
Addenbr RT alone
TMZ + RT for GBM
Addenbr RT+TMZ
P<0.001
GBM outcome
• Our results match the
international trial
• Endorsement of our
treatment pathway
• Good news for patients !
Patient photo
3
Modelling chemotherapy use
Modelling chemotherapy use
• TMZ chemo combined with RT (& surgery) has
revolutionised the outcome for patients with GBM
• TMZ is given in 2 parts
• Concurrent daily with RT
• Adjuvant for 6 cycles after RT
• Are both parts of value?
TMZ treatment schema
• Chemo-RT programme with temozolomide (TMZ)
RT
TMZ
Week 0
•
6
10
Component 1
• Concurrent with RT
• Daily for 42 days
14
18
•
22
26
30
34
Component 2
• Adjuvant
• 5 days every 28, x 6 cycles
Modelling chemotherapy use
• Build model of patient survival
• Allow treatment with RT and with chemo
• Fit model to Kaplan Meier survival curves to derive
values for tumour growth and response to treatment
• Test
• TMZ + RT = concurrent
• RT followed by TMZ = adjuvant
EORTC trial
Model - RT + concurrent TMZ
RT + concurrent TMZ
near perfect fit
Modelling chemotherapy use
• RT + concurrent TMZ produces near perfect fit
• Suggests concurrent TMZ is the effective component
• Suggests adjuvant TMZ may not add anything
• Omitting 6 cycles of adjuvant TMZ would:
• Spare toxicity
• Improve QoL (likely) - finish treatment 6/12 earlier
• Save money
Modelling chemotherapy use
• Incidence of GBM
• 33 cases per million population per annum
• Cost of TMZ – 1 course
• Concurrent £3900
• Adjuvant
£7100
•
With thanks to:
• David Greenberg & Peter Treasure,
Eastern Cancer Registration & Information Centre (ECRIC), Cambridge
• Brendan O’Sullivan,
Chemotherapy Pharmacist, Addenbrooke’s Hospital
Modelling chemotherapy use
• UK
•
•
•
•
Population
GBM cases (33 x 60)
GBM patients treated radically
Number ‘requiring’ TMZ
60 m
1,980 p.a.
50%
990 p.a.
Modelling chemotherapy use
• UK
•
•
•
•
Population
GBM cases (33 x 60)
GBM patients treated radically
Number ‘requiring’ TMZ
• Cost TMZ
• Saving by using only
concurrent TMZ
60 m
1,980 p.a.
50%
990 p.a.
£11 m p.a.
£ 7 m p.a.
Improving survivorship
Patient photo
Photo of patient
and family
•
AW on the beach
•
AS at
Christmas
Acknowledgements
•
•
•
•
Colleagues
• Sarah Jefferies
• Raj Jena
• Fiona Harris
• Phil Jones
•
•
•
•
Peter Treasure
Norman Kirkby
Lara Barazzuol
EORTC
National Institute for Health Research (NIHR) Cambridge
Biomedical Research Centre
RJ is supported by The Health Foundation, UK
NFK was supported by an EPSRC discipline-hopping grant