Toward a multi-modality approach to radiotherapy for cancer treatment in UK (Unity is strength)

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

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Outline

Why cancer Radiotherapy Toward multi-modality The technological challenges: dosimetry and

imaging Conclusions


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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. Population ageing2. Rise in obesity levels3. Change in lifestyle

Cancer 3rd largest NHS disease programme


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Radiotherapy


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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. Surgery2. Chemotherapy3. Hormone treatments


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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)


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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


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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. Select best treatment depending on tumour type

2. Combine different treatments when appropriate

Highly beneficial to patient: better local control and lower toxicity


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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: 1. Proximity of organs at risk2. Tumour dimension and location3. Previous irradiation (recurrences)


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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. External beam therapy + brachytherapy

2. External beam therapy + radiopharmaceuticals


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The challenge


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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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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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State-of-the-Art


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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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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)


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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



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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


PET CT PET + CT


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The future


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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


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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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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


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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

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


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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


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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)

Hamamatsu Inc.

1x1 mm2

3x3 mm2


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Tests on TOF-PET prototypes

0

500

1000

1500

2000

2500

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-70

-60

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-20

-10 0 10 20 30 40 50 60 70 80 90 10

011

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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


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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

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3.5

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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


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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


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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.


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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)

Documents

Toward a multi-modality approach to radiotherapy for cancer treatment in UK (Unity is strength)