The Royal Marsden
Applying new techniques to
radiotherapy for early breast
cancer
Dr Ellen Donovan
Physics Department
Research Coaching Session 22.07.2011
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Contents
1. Introduction
2. Background
3. Advances in Radiotherapy technology
4. How can we use these advances for early breast
cancer patients?
5. Summary
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Introduction
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My Background
– Physics degree
– MSc in Medical Physics
– PhD investigating how radiotherapy for early breast
cancer can be improved
– Clinical physicist since 1992; RMH from 1995
– Head of RT treatment machine QA until November
2009; clinical trials in radiotherapy for breast
cancer
– Career break
– CSO/NIHR Healthcare Scientist Post Doctoral fellow
until 2013
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Why does treating cancer need physics?
What is Physics?
– n. “the science dealing with the properties and
interactions of matter and energy”
– Oxford English Dictionary
– “If it moves, it's biology. If it stinks, it's chemistry.
If it doesn't work, it's physics.“
– Handy Guide to Modern Science
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What is Physics?
– Symmetries
–
–
–
–
Laws of nature don’t change with time
Laws of nature don’t change with position
Laws of nature don’t change with rotation
Describing fundamental particles
– Conservation laws
–
–
–
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Conservation of energy
Conservation of momentum
Conservation of angular momentum
Description of all interactions of matter and energy –
“Standard model”
Slide courtesy of Professor Phil Evans
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What is Medical Physics?
– Application of physics/technology
– Involves engineering, computer science, biology,
chemistry, mathematics
– Much more complex than solely energy and
matter
– Interactions of energy and matter are central for
much of RMH/ICR physics
Imaging (low energy)
Treatment (high energy)
Slide courtesy of Professor Phil Evans
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Why does treating cancer need physics?
Imaging
– Measure interaction of energy with body and
detectors
– Ultrasound – acoustic energy
– Magnetic Resonance (MR)– magnetic fields, radio
waves
– Computed Tomography (CT), Radiology, Nuclear
Medicine – x,  rays
Treatment
– Control interaction of energy with body
– Ultrasound therapy – acoustic energy
– Radiotherapy – x,  rays, ,  particles
Slide courtesy of Professor Phil Evans
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Year of Radiotherapy 2011
– An initiative by Cancer Research UK (CRUK) and the
National Radiotherapy Implementation Group (NRIG)
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–
–
–
–
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Radiotherapy : significant part in the treatment of 40% of
patients who are cured
more targeted than chemotherapy,
less invasive than surgery,
most cost effective method of treating cancer.
Good example of the beneficial and often unpredictable spinoffs of fundamental physics research
Without investment in nuclear and particle physics in the
twentieth century, we would not have radiotherapy
treatments today.
From Institute of Physics and Engineering in Medicine
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Role of Physics in Radiotherapy
–
Plan radiotherapy treatments for individual patients
–
Ensure that multimillion pound items of radiotherapy
equipment are selected, commissioned, maintained and that
they deliver the correct amount of radiation for each
treatment.
–
Advice and guidance
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IT systems - support treatment planning and verify that the
complex treatment machine set-ups required for modern
radiotherapy match the patient prescription.
–
Advise on the use of images from different imaging techniques
(e.g. CT and MRI) for accurate treatment planning.
–
Bring together knowledge of radiation physics, understanding
of radiotherapy technology, and expertise in the interaction of
radiation with the human body : new developments are
implemented safely in clinical practice.
From Institute of Physics and Engineering in Medicine
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Role of Physics in Radiotherapy
‘Behind every successful man there is an unseen
but successful woman’
‘Behind every successful
radiotherapy treatment there is
an unseen, but successful,
physics department’
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Background
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Radiotherapy : Linear Accelerator
–
Generate high intensity,
high energy x-rays
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Fire several beams into
tumour – crossfire
– High dose to tumour
and spare “normal”
tissues
–
Complex sequence of
events for successful
treatment
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Cross fire effect
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Patient Treatment
Radiotherapy is given after the tumour has been removed
Tangential fields (beams) to the left breast
Medial field
Lateral field
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Transverse Contour Through Breast
Breast
Beam
direction 1
Heart
Lung
Beam
direction 2
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Breast Treatments
Approach same for all patients
Whole breast treated with two
beams
Make treatment plan based on a
contour of centre plane of breast
Wedge in treatment machine to
even out dose in central plane
Little or no access to CT ;
detailed information about
anatomy not available
Patients with spread to nodes –
additional beams to
supraclavicular region and axilla
Boost dose to tumour bed after
whole breast radiotherapy
Post mastectomy - same
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Whole Breast RT After Tumour Excision in pN+/- Cancer (N=7311)
Local relapse
Breast cancer mortality
All mortality
5.3
5.4
21.7
EBCTCG Lancet, 2005, 366, 2087-2016
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Breast Treatments – Traditional
Successful –
Early Breast Trials Collaborative
Group Overview
Radiotherapy - for every 4 local
recurrences prevented : 1 breast
cancer death prevented
48,000 new cases in UK in 2008
1.3
Issues –
Changes in response to radiation
Cardiac damage
1.8
Contralateral breast cancer
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Advances in
Radiotherapy
Technology
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Treatment Delivery : Multileaf collimator
– Direct beams from
various angles
Each leaf moves
– Shape beams
independently
– Multileaf
collimator (MLC)
– Vary intensities
– Intensity
Modulated
Radiotherapy
(IMRT)
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Treatment Delivery :
Intensity Modulated Radiotherapy
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–
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Revolutionises radiotherapy as treatment agent
Can deliver almost any dose distribution we want
Many methods and now available on commercial systems
Slide courtesy of Professor Phil Evans
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IMRT can be used to shape a dose distribution
Regions
to be
treated
Regions
to be
spared
dose
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How can we
apply our ability
to shape the dose
delivered?
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Two examples
1. Removing unplanned dose variation
2. Shaping the dose distribution
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1. Removing unplanned dose
variation
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What is the effect of the traditional
technique on the dose variation in the
breast?
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Unplanned RT Dose Variation can be eliminated
3D
2D
Sup
Ant
Inf
90
95
98
100
102
105
110
112
Donovan 2007
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Unplanned RT Dose Variation is Eliminated using MLC and
IMRT methods
– Start with standard
method
– If there is too much
dose variation - IMRT
– Use MLC to block
regions of high dose
– Use more than one
beam from each side
– Solution for each
patient
– individualising
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Does
the unplanned
variation of dose in
the whole breast
matter?
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Breast Dosimetry Trial
Does improved radiation dose uniformity
delivered by
intensity modulated radiotherapy (IMRT) results
in less detectable injury to healthy breast
tissue than standard RT?
Set up null
hypothesis :
There is no
difference in the
risk of normal
tissue injury
with IMRT
compared to the
standard method
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Eligibility
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Early breast cancer (T1-3a, N0-1, M0)
Confirmation of invasive carcinoma
Breast-preserving surgery
Higher than average risk of radiation normal
tissue changes due to breast size/shape
– Radiotherapy to the breast +/- lymphatics
– Written informed consent
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Primary Endpoint
– Change in breast appearance (none, mild,
marked) scored blind to treatment allocation
After surgery,
before RT
Several years
later...
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Secondary Endpoints
– Patient selfassessments of
breast discomfort
and hardness
– Clinical assessments
of breast hardness
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Results: Patient Demographics
– N = 306 patients, both Sutton and Chelsea
– Mean age 55.7 years (range 28 – 83)
– Breast size, axillary surgery, cytotoxic &
endocrine therapies balanced between
treatment arms
– Supraclavicular and axillary radiotherapy
balanced between treatment arms
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Effect of using IMRT on dose variation
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25
% volume of
breast outside 95105%
Standard Treatment
IMRT Treatment
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15
10
5
0
1
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17 18 19 20
Patient Number
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Dose variation with region in the breast
Percentage of Patients
100%
90%
80%
95-105%
70%
105-110%
60%
>110%
50%
40%
30%
20%
10%
0%
Upper
breast
Lower
breast
CONTROL
Upper
breast
Lower
breast
IMRT
Dose
prescribed
to 100%
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Change in Breast Appearance at Year 5
Control
IMRT
No change
51
71
Mild and marked
change
71
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Total
122
118
Control arm 1.7 (1.2 to 2.5) times more likely to
have had change
p = 0.008 for any change versus none
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Change in Breast Appearance at Year 5
Dose < 105%
Dose > 105%
No change
68
50
Mild and marked
change
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68
Total
110
118
Dose > 105% 1.9 (1.3 to 2.9) times more likely to have
had change than dose < 105%
p = 0.002 for any change versus none
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Conclusions
– Reduction in risk of change in breast
appearance at 5 years after IMRT
– Analysis suggests that this difference is
unlikely to be a chance effect
– Confirmatory studies are needed to address
clinical benefits and cost-effectiveness
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Impact of trial
– Recommended method in all new UK technical RT trials
for breast cancer
– E.g.
– FAST and FAST Forward (looking at number of RT
treatments in a course)
– IMPORT LOW trial (looking at the effect of
irradiating only part of the breast)
– IMPORT High trial (looking at giving a higher dose
to the tumour bed)
– Included in the latest International Commission on
Radiation Units (ICRU) recommendations on IMRT
– Widespread adoption in UK centres for routine
treatment
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2. Shaping the dose distribution
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Risk Adapted Radiotherapy : planning a dose
variation in the breast
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Patients with high risk
of local recurrence
given additional
radiotherapy to the
tumour bed : the ‘boost’
Most recurrences occur
near the tumour bed
Can the radiotherapy
dose be varied across
the breast to map the
recurrence risk?
Can we escalate the
dose to the tumour bed
by giving less dose to
regions of the breast
further away?
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Risk Adapted Radiotherapy :technical requirements
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Internal markers in tumour bed
–
Requires the new physics
methods
– Intensity Modulated RT :
planning
– Image Guided RT :
verifying
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Physics/maths analysis tools
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IMPORT High verification
Treatment
beam
Imaging
beam
The smallest volume of the treatment
only has a margin of 5 mm
Reduce the day to day variation in
patient position using imaging
Make a correction so that the systematic
error due to set up is small ~ 1mm
EBCTCG, Lancet 2005; 366, 2087-2106
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Current status
– Recruitment to July 2011
– ~300 patients
– 12 centres
– ~80 patients from Royal Marsden
– Total recruitment = 840
– Trial will remain open until 2013
– 250 patient datasets to be used in Image Guided
RT study
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Impact of trial
–
Pilot study set the standard for use of surgical clips in tumour bed
– Feasibility study : In Press Coles et al Radiotherapy and
Oncology 2011
– British Association of Surgical Oncology (BASO) guidelines :
Surgical guidelines for the management of breast cancer. Eur J Surg
Oncol, 2009. 35 Suppl 1.
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–
–
Physics analysis of marker movement
– Harris et al International Journal of Radiation Oncology Biology
Physics 73(3) 2009
Physics planning methods
– Donovan et al International Journal of Radiation Oncology
Biology Physics 79(4) 2011
Use of Image Guidance in breast radiotherapy
– Trial beginning to set the standard
– NIHR/MRC Efficacy and Mechanism Evaluation Programme
Grant
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Summary
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Summary
–Physics is crucial for high quality radiotherapy
–Physics and technology advances have meant a move
towards even more personalisation of treatment in
radiotherapy
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–
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based on recurrence risk
patient specific dosimetry
tailor the dose variation to the patient
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Acknowledgements
–
Mrs Helen Convery,
Senior Dosimetrist,
Royal Marsden (Sutton), UK.
Mr Jim Warrington,
Head of Radiotherapy Physics, Royal
Marsden (Sutton), UK.
–
Ms Sally Eagle,
Superintendent Radiographer, Royal
Marsden (Sutton), UK.
–
Professor John Yarnold,
Professor of Clinical Oncology,
Institute of Cancer Research, UK.
–
–
Dr Charlotte Coles,
Clinical Oncologist,
Addenbrookes Hospital, Cambridge, UK.
Dr Emma Harris,
Post Doctoral Fellow
Royal Marsden / Institute of Cancer
Research, UK.
–
Professor Philip Evans,
Professor of Medical Radiation Physics,
Institute of Cancer Research, UK.
–
Dr Ellen Donovan is funded by a Post
Doctoral Research Fellowship award from
the National Institute for Health Research*
–
Our patients, and all the radiotherapy and physics staff at
Sutton and Chelsea
Institute of Cancer Research
* This report is independent research arising from a Healthcare Scientist Research Fellowship
supported by the National Institute for Health Research and the CSO. The views expressed in
this publication are those of the author and not necessarily those of the NHS, the National
Institute for Health Research or the Department of Health.