Transcript NPAE2010 Kiev Version 1

Toward a multi-modality
approach to radiotherapy
for cancer treatment in UK
(Unity is strength)
Barbara Camanzi
STFC – RAL & University of Oxford
Outline
 Why cancer
 Radiotherapy
 Toward multi-modality
 The technological challenges: dosimetry and
imaging
 Conclusions
Barbara Camanzi
RAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10
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The challenge of cancer in UK
 Cancer is the leading cause of mortality in
people under the age of 75. 1 in 4 people
die of cancer overall
 293k people/year diagnosed with cancer,
155k people/year die from cancer
 Incidence of cancer is rising due to:
1.
2.
3.
Population ageing
Rise in obesity levels
Change in lifestyle
 Cancer 3rd largest NHS disease programme
Barbara Camanzi
RAL & Oxford University
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Radiotherapy
Barbara Camanzi
RAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10
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Radiotherapy and cancer in UK
 Radiotherapy given to 1/3 of cancer patients
(10-15% of all population)
 Overall cure rate = 40%. In some instances
90-95% (for ex. breast and stage 1 larynx
cancers)
 Radiotherapy often combined with other
cancer treatments:
1.
2.
3.
Surgery
Chemotherapy
Hormone treatments
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RAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10
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Radiotherapy treatments
 External beam radiotherapy:
X-ray beam
2. Electron beam
3. Proton/light ion beam
1.
 Internal radiotherapy:
Sealed sources (brachytherapy)
2. Radiopharmaceuticals
1.
 Binary radiotherapy:
Boron Neutron Capture Therapy (BNCT)
2. Photon Capture Therapy (PCT)
1.
Barbara Camanzi
RAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10
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A new approach to radiotherapy
 Cure cancer & protect healthy tissues
• Dose escalation in tumour
• Minimise dose to normal tissues
 Different treatment strategies are required
depending on cancer type, stage and degree
of spread
 Radiotherapy treatments not linked = impact
lowered = missed opportunity
→ New approach needed
Barbara Camanzi
RAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10
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My vision: multi-modality
 Unified approach to radiotherapy needed to
maximise efficacy and improve care
 Multi-modality = bringing together the
different forms of radiotherapy treatments:
1.
2.
Select best treatment depending on tumour type
Combine different treatments when appropriate
 Highly beneficial to patient: better local
control and lower toxicity
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RAL & Oxford University
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Multi-modality: selection
 External beam and internal radiotherapy
best for localised diseases
 Binary therapy best for locally spread
diseases with high degree of infiltration
 Proton/light ion therapy very promising for
paediatric tumours
 Some other considerations:
Proximity of organs at risk
2. Tumour dimension and location
3. Previous irradiation (recurrences)
1.
Barbara Camanzi
RAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10
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Multi-modality: combination
 Combination of different sources → dose
escalation
 Different organs at risk for various
treatments → toxicity not increased
 Some examples:
1.
2.
External beam therapy + brachytherapy
External beam therapy + radiopharmaceuticals
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RAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10
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The challenge
Barbara Camanzi
RAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10
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The technological challenges
 The challenge of radiotherapy from the
patient end
Make sure that the right dose is delivered at
the right place = improved dosimetry +
improved imaging
 The challenge of early diagnosis
“See” smaller tumours = improved imaging
 New advanced technologies desperately
needed for dosimetry and imaging
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RAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10
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How particle physics can help
"The significant advances achieved during the last decades in
material properties, detector characteristics and high-quality
electronic system played an ever-expanding role in different
areas of science, such as high energy, nuclear physics and
astrophysics. And had a reflective impact on the development
and rapid progress of radiation detector technologies used in
medical imaging."
“The requirements imposed by basic research in particle physics
are pushing the limits of detector performance in many regards,
the new challenging concepts born out in detector physics are
outstanding and the technological advances driven by
microelectronics and Moore's law promise an even more
complex and sophisticated future.”
D. G. Darambara "State-of-the-art radiation detectors for medical imaging: demands and trends"
Nucl. Inst. And Meth. A 569 (2006) 153-158
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RAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10
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State-of-the-Art
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RAL & Oxford University
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Dosimetry
 All external dosimeters
placed on patient skin:
• TLDs
• Diodes
• MOSFETs
 Disadvantages:
• No reading at tumour site
• No real-time information
for some (TLDs)
• Difficult to use (wires:
diodes, MOSFETs)
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RAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10
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Imaging
 Most medical imaging systems, CT, gamma
cameras, SPECT, PET, use particle physics
technologies: scintillating materials, photon
detectors, CCDs, etc.
CT scanner
Scintillator
Gamma
camera
(SPECT)
Diode
Collimator
Courtesy Mike Partridge
(RMH/ICR)
Barbara Camanzi
RAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10
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Positron Emission Tomography

511 keV g
18F
labelled glucose given to patients:
e+ annihilates in two back-to-back
511 keV g
 A ring of scintillating crystals and
PMTs detects the g
511 keV g
Courtesy Mike Partridge (RMH/ICR)
Barbara Camanzi
RAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10
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Conventional PET
Conventional PET scanner:
1.
Coincidences formed within a very
short time window
2.
Straight line-of-response reconstructed
3.
Position of annihilation calculated
probabilistically
Courtesy Mike Partridge (RMH/ICR)
PET
Barbara Camanzi
RAL & Oxford University
CT
PET + CT
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The future
Barbara Camanzi
RAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10
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The dosimetry challenge
 The requirements for new dosimeters:
1.
2.
3.
4.
Measure dose at tumour site and not at skin
Measure total dose (including during imaging
procedures)
Measure in real-time and not long time after
each treatment fraction
System easy to use
 The answer: in-vivo dosimetry
Barbara Camanzi
RAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10
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In-vivo dosimetry
 Radiation sensitive MOSFET
transistors (RadFETs) used
in particle physics experiments
(BaBar, LHC, etc.) for real-time,
online radiation monitoring
 Development of RadFET based miniaturised
wireless dosimetry systems to be implanted
in patient body at tumour site for real-time,
online, in-vivo dosimetry → Seek funding
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RAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10
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The imaging challenge
 The requirements for new imaging systems:
More accurate, more quantitative and highly
repeatable imaging
2. Imaging during treatment: organ movement
(breathing), patient set-up, tumour shrinkage
3. Image smaller lesions (early diagnosis)
4. Treatment specific requirements (for ex. Bragg
position in proton/light ion therapy)
1.
 The answer: higher spatial resolution,
higher linearity, lower noise, less drift, faster
imaging
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RAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10
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Time-Of-Flight PET (TOF-PET)
 TOF-PET scanner:
1. Time difference between signals from two crystals measured
2. Annihilation point along line-of-response directly calculated
time-of-flight
envelope
D1
line of
response
D2
 Goal: 100 ps timing resolution (ideally 30 ps and below) = 3 cm
spatial resolution (ideally sub-cm)
 Advantages: higher sensitivity and specificity, improved S/N
 Technology needed: fast scintillating materials and fast photon
detectors
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RAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10
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Fast scintillating materials
Decay time
(ns)
Light Yield
(g/keV)
Density
(g/cm3)
latt at 511keV
(cm)
LaBr3(Ce)
BrilLanCeTM380
16
63
5.3
2.23
LYSO
PreLudeTM420
41
32
7.1
1.20
LSO
40
27
7.4
1.14
BGO
300
9
7.1
1.04
GSO
60
8
6.7
1.61
BaF2
0.8
1.8
4.9
2.27
NaI(Tl)
250
38
3.7
2.91
BrilLanCeTM380 and PreLudeTM420 produced by Saint-Gobain Cristaux et Detecteurs
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RAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10
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Photon detectors: SiPMs
 Array of Silicon Photodiodes
on common substrate each
operating in Geiger mode
 SiPMs have high speed (sub
ns) and gain (106) and work in
high magnetic fields (7T)
1x1 mm2
3x3 mm2
Hamamatsu Inc.
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RAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10
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Tests on TOF-PET prototypes
2500
Barbara Camanzi
RAL & Oxford University
Counts
2000
1500
1000
500
0
-8
0
-7
0
-6
0
-5
0
-4
0
-3
0
-2
0
-1
0
0
10
20
30
40
50
60
70
80
90
10
0
11
0
 LaBr3(Ce) and LYSO scintillating
crystals from Saint-Gobain
 SiPMs from Hamamatsu, SensL
and Photonique
 Various two-channel demonstrator
systems tested at RAL and RMH
 Timing resolution analysis still
ongoing
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Time Difference (ps)
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Preliminary results
SiPM timing resolution with blue LED

600.00
Timing resolution (ps)
500.00

400.00
Best SiPMs: Hamamatsu (electrical
problem with 11-25) and SensL
Best timing resolutions measured:
SiPM single
300.00
1. 20 ps for single SiPM
2. 40 ps for pairs of SiPMs
SiPM pair
200.00

100.00
0.00
Ham
Ham
11-100 11-50
Ham
Ham
Ham
11-25 33-100 33-50
Ham
33-25
SensL SensL
11
33
Phot
11
Phot
33
Hamamatsu performance as
function of pitch still under
investigation
2-channel prototype timing resolution with sources

Prototypes with Hamamatsu
best of all. SensL blind to LaBr3
Best timing resolutions measured:
1. 430 ps with 3x3x10 mm3 LYSO
2. 790 ps with 3x3x30 mm3 LaBr3

Performance of prototypes with
LaBr3 highly dependent from SiPMcrystal coupling
Barbara Camanzi
RAL & Oxford University
4
3.5
Timing resolution (ns)

3x3mm2
3
LYSO 5mm Na22
2.5
LYSO 10mm Na22
2
LaBr3 Na22
LYSO 5mm F18
1.5
LaBr3 F18
1
0.5
0
Ham Ham Ham Ham Ham Ham
11-100 11-50 11-25 33-100 33-50 33-25
NPAE-Kyiv2010, Kiev, 7-12/06/10
SensL SensL
11
33
Phot
11
Phot
33
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Where next with TOF-PET
 Preliminary results very encouraging. Next
step: dual-head demonstrator system. Two
planar heads with identical number of
channels → Funded by FP7 as part of
ENVISION (European NoVel Imaging
Systems for ION therapy)
 Use of fast scintillators can be expanded to
other imaging systems (CT, SPECT, etc.)
 Use of SiPMs opens up the possibility of
designing a compact PET/MRI scanner
Barbara Camanzi
RAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10
28/30
Conclusions
 Cancer is a leading cause of mortality in UK.
Its incidence is rising.
 Radiotherapy is and will be given to a large
number of patients.
 Patients will benefit from a multi-modality
approach to radiotherapy. This requires the
development of new, advanced technologies.
 Particle physics holds the key to the
development of these technologies.
Barbara Camanzi
RAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10
29/30
Acknowledgements
 Dr Phil Evans and Dr Mike Partridge (Royal
Marsden Hospital / Institute of Cancer
Research - UK)
 Prof Ken Peach (John Adams Institute - UK)
 Prof Bleddyn Jones (Radiation Oncology and
Biology Institute - UK)
 The STFC Futures Programme team (UK)
 Dr John Matheson and Mr Matt Wilson
(STFC-RAL - UK)
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RAL & Oxford University
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