toward a multi-modality approach to radiotherapy for cancer treatment in uk (unity is strength)
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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. - PowerPoint PPT PresentationTRANSCRIPT
Toward a multi-modality approach to radiotherapyfor cancer treatment in UK
(Unity is strength)Barbara Camanzi
STFC – RAL & University of Oxford
Barbara CamanziRAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10 2/30
Outline
Why cancer Radiotherapy Toward multi-modality The technological challenges: dosimetry and
imaging Conclusions
Barbara CamanziRAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10 3/30
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. Population ageing2. Rise in obesity levels3. Change in lifestyle
Cancer 3rd largest NHS disease programme
Barbara CamanziRAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10 4/30
Radiotherapy
Barbara CamanziRAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10 5/30
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. Surgery2. Chemotherapy3. Hormone treatments
Barbara CamanziRAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10 6/30
Radiotherapy treatments
External beam radiotherapy:1. X-ray beam2. Electron beam3. Proton/light ion beam
Internal radiotherapy:1. Sealed sources (brachytherapy)2. Radiopharmaceuticals
Binary radiotherapy: 1. Boron Neutron Capture Therapy (BNCT)2. Photon Capture Therapy (PCT)
Barbara CamanziRAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10 7/30
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 CamanziRAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10 8/30
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. Select best treatment depending on tumour type
2. Combine different treatments when appropriate
Highly beneficial to patient: better local control and lower toxicity
Barbara CamanziRAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10 9/30
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: 1. Proximity of organs at risk2. Tumour dimension and location3. Previous irradiation (recurrences)
Barbara CamanziRAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10 10/30
Multi-modality: combination
Combination of different sources → dose escalation
Different organs at risk for various treatments → toxicity not increased
Some examples:1. External beam therapy + brachytherapy
2. External beam therapy + radiopharmaceuticals
Barbara CamanziRAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10 11/30
The challenge
Barbara CamanziRAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10 12/30
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
Barbara CamanziRAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10 13/30
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
Barbara CamanziRAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10 14/30
State-of-the-Art
Barbara CamanziRAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10 15/30
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)
Barbara CamanziRAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10 16/30
Imaging
Most medical imaging systems, CT, gamma cameras, SPECT, PET, use particle physics technologies: scintillating materials, photon detectors, CCDs, etc.
Courtesy Mike Partridge (RMH/ICR)
Collimator
Scintillator
Diode
CT scanner Gamma camera (SPECT)
Barbara CamanziRAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10 17/30
Positron Emission Tomography 18F labelled glucose given to patients:
e+ annihilates in two back-to-back 511 keV
A ring of scintillating crystals and PMTs detects the
511 keV
511 keV
Courtesy Mike Partridge (RMH/ICR)
Barbara CamanziRAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10 18/30
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 CT PET + CT
Barbara CamanziRAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10 19/30
The future
Barbara CamanziRAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10 20/30
The dosimetry challenge
The requirements for new dosimeters:1. Measure dose at tumour site and not at skin
2. Measure total dose (including during imaging procedures)
3. Measure in real-time and not long time after each treatment fraction
4. System easy to use
The answer: in-vivo dosimetry
Barbara CamanziRAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10 21/30
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
Barbara CamanziRAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10 22/30
The imaging challenge
The requirements for new imaging systems:1. 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)
The answer: higher spatial resolution, higher linearity, lower noise, less drift, faster imaging
Barbara CamanziRAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10 23/30
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
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
D2
line of response
time-of-flight envelope
D1
Barbara CamanziRAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10 24/30
Fast scintillating materials
Decay time (ns)
Light Yield (/keV)
Density (g/cm3)
att 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 CamanziRAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10 25/30
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)
Hamamatsu Inc.
1x1 mm2
3x3 mm2
Barbara CamanziRAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10 26/30
Tests on TOF-PET prototypes
0
500
1000
1500
2000
2500
-80
-70
-60
-50
-40
-30
-20
-10 0 10 20 30 40 50 60 70 80 90 10
011
0
Time Difference (ps)
Co
un
ts
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
Barbara CamanziRAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10 27/30
Preliminary results
SiPM timing resolution with blue LED
0.00
100.00
200.00
300.00
400.00
500.00
600.00
Ham11-100
Ham11-50
Ham11-25
Ham33-100
Ham33-50
Ham33-25
SensL11
SensL33
Phot11
Phot33
Tim
ing
res
olu
tio
n (
ps)
SiPM single
SiPM pair
Prototypes with Hamamatsu 3x3mm2 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 SiPM-crystal coupling
Best SiPMs: Hamamatsu (electrical problem with 11-25) and SensL
Best timing resolutions measured:1. 20 ps for single SiPM
2. 40 ps for pairs of SiPMs Hamamatsu performance as function
of pitch still under investigation
2-channel prototype timing resolution with sources
0
0.5
1
1.5
2
2.5
3
3.5
4
Ham11-100
Ham11-50
Ham11-25
Ham33-100
Ham33-50
Ham33-25
SensL11
SensL33
Phot11
Phot33
Tim
ing
res
olu
tio
n (
ns)
LYSO 5mm Na22
LYSO 10mm Na22
LaBr3 Na22
LYSO 5mm F18
LaBr3 F18
Barbara CamanziRAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10 28/30
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 CamanziRAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10 29/30
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 CamanziRAL & Oxford University
NPAE-Kyiv2010, Kiev, 7-12/06/10 30/30
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)