Transcript NPAE Kiev Version 2

Toward a multi-modality
approach to radiotherapy
for cancer treatment in UK
(Unity is strength)
Barbara Camanzi
STFC – RAL & University of Oxford
Outline
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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
2/30
The challenge of cancer in UK
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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.
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Population ageing
Rise in obesity levels
Change in lifestyle
Cancer 3rd largest NHS disease programme
Barbara Camanzi
RAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10
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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
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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
Barbara Camanzi
RAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10
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Radiotherapy treatments
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External beam radiotherapy:
X-ray beam
2. Electron beam
3. Proton/light ion beam
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Internal radiotherapy:
1.
2.
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Sealed sources (brachytherapy)
Radiopharmaceuticals
Binary radiotherapy:
1.
2.
Boron Neutron Capture Therapy (BNCT)
Photon Capture Therapy (PCT)
Barbara Camanzi
RAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10
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A new approach to radiotherapy
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Cure cancer & protect healthy tissues
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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
7/30
My vision: multi-modality
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Unified approach to radiotherapy needed to
maximise efficacy and improve care
Multi-modality = bringing together the
different forms of radiotherapy treatments:
1.
2.
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Select best treatment depending on tumour type
Combine different treatments when appropriate
Highly beneficial to patient: better local
control and lower toxicity
Barbara Camanzi
RAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10
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Multi-modality: selection
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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:
1.
2.
3.
Proximity of organs at risk
Tumour dimension and location
Previous irradiation (recurrences)
Barbara Camanzi
RAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10
9/30
Multi-modality: combination
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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
Barbara Camanzi
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
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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
Barbara Camanzi
RAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10
12/30
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
NPAE-Kyiv2010, Kiev, 7-12/06/10
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Dosimetry
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All external dosimeters
placed on patient skin:
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TLDs
Diodes
MOSFETs
Disadvantages:
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No reading at tumour site
No real-time information
for some (TLDs)
Difficult to use (wires:
diodes, MOSFETs)
Barbara Camanzi
RAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10
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Imaging
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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
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511 keV g
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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
17/30
Conventional PET
Conventional PET scanner:
1.
2.
3.
Coincidences formed within a very
short time window
Straight line-of-response reconstructed
Position of annihilation calculated
probabilistically
Courtesy Mike Partridge (RMH/ICR)
PET
Barbara Camanzi
RAL & Oxford University
CT
PET + CT
NPAE-Kyiv2010, Kiev, 7-12/06/10
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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
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The requirements for new dosimeters:
1.
2.
3.
4.
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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
20/30
In-vivo dosimetry
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Radiation sensitive MOSFET
transistors (RadFETs) used
in particle physics experiments
(BaBar, LHC, etc.) for real-time,
online radiation monitoring
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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
Barbara Camanzi
RAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10
21/30
The imaging challenge
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The requirements for new imaging systems:
1.
2.
3.
4.
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More accurate, more quantitative and highly
repeatable imaging
Imaging during treatment: organ movement
(breathing), patient set-up, tumour shrinkage
Image smaller lesions (early diagnosis)
Treatment specific requirements (for ex. Bragg
position in proton/light ion therapy)
The answer: higher spatial resolution, higher
linearity, lower noise, less drift, faster imaging
Barbara Camanzi
RAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10
22/30
Time-Of-Flight PET (TOF-PET)
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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
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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
Barbara Camanzi
RAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10
23/30
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
Barbara Camanzi
RAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10
24/30
Photon detectors: SiPMs
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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.
Barbara Camanzi
RAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10
25/30
Tests on TOF-PET prototypes
2500
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Barbara Camanzi
RAL & Oxford University
2000
Counts
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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
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
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NPAE-Kyiv2010, Kiev, 7-12/06/10
Time Difference (ps)
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Preliminary results
SiPM timing resolution with blue LED
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600.00
Timing resolution (ps)
500.00
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400.00
1.
SiPM single
300.00
Best SiPMs: Hamamatsu (electrical
problem with 11-25) and SensL
Best timing resolutions measured:
SiPM pair
2.
200.00
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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
20 ps for single SiPM
40 ps for pairs of SiPMs
Hamamatsu performance as function
of pitch still under investigation
Phot
33
2-channel prototype timing resolution with sources
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Prototypes with Hamamatsu
best of all. SensL blind to LaBr3
Best timing resolutions measured:
1.
2.
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mm3
430 ps with 3x3x10
LYSO
3
790 ps with 3x3x30 mm LaBr3
Performance of prototypes with LaBr3
highly dependent from SiPM-crystal
coupling
Barbara Camanzi
RAL & Oxford University
4
3.5
Timing resolution (ns)
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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
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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
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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
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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)
Barbara Camanzi
RAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10
30/30