toward a multi-modality approach to radiotherapy for cancer treatment in uk (unity is strength)...

Toward a multi-modality Toward a multi-modality approach to radiotherapyapproach to radiotherapyfor cancer treatment in UKfor cancer treatment in UK

(Unity is strength)(Unity is strength)

Barbara CamanziBarbara Camanzi

STFC – RAL & University of OxfordSTFC – RAL & University of Oxford

Barbara CamanziBarbara CamanziRAL & Oxford UniversityRAL & Oxford University

NPAE-Kyiv2010, Kiev,NPAE-Kyiv2010, Kiev, 7-12/06/10 7-12/06/10 22/30/30

OutlineOutline

Why cancerWhy cancerRadiotherapyRadiotherapyToward multi-modalityToward multi-modalityThe technological challenges: dosimetry and The technological challenges: dosimetry and

imagingimagingConclusionsConclusions



The challenge of cancer in UKThe challenge of cancer in UK Cancer is the leading cause of mortality in Cancer is the leading cause of mortality in

people under the age of 75. 1 in 4 people people under the age of 75. 1 in 4 people die of cancer overalldie of cancer overall

293k people/year diagnosed with cancer, 293k people/year diagnosed with cancer, 155k people/year die from cancer155k people/year die from cancer

Incidence of cancer is rising due to:Incidence of cancer is rising due to:1.1. Population ageingPopulation ageing2.2. Rise in obesity levelsRise in obesity levels3.3. Change in lifestyleChange in lifestyle

Cancer 3Cancer 3rdrd largest NHS disease programme largest NHS disease programme



RadiotherapyRadiotherapy



Radiotherapy and cancer in UKRadiotherapy and cancer in UK

RadiotherapyRadiotherapy given to 1/3 of cancer patients given to 1/3 of cancer patients (10-15% of all population)(10-15% of all population)

Overall cure rate = 40%. In some instances Overall cure rate = 40%. In some instances 90-95% (for ex. breast and stage 1 larynx 90-95% (for ex. breast and stage 1 larynx cancers)cancers)

Radiotherapy often combined with other Radiotherapy often combined with other cancer treatments: cancer treatments:

1.1. SurgerySurgery2.2. ChemotherapyChemotherapy3.3. Hormone treatmentsHormone treatments



Radiotherapy treatmentsRadiotherapy treatments External beam radiotherapy:External beam radiotherapy:

1.1. X-ray beamX-ray beam2.2. Electron beamElectron beam3.3. Proton/light ion beamProton/light ion beam

Internal radiotherapy:Internal radiotherapy:1.1. Sealed sources (brachytherapy)Sealed sources (brachytherapy)2.2. RadiopharmaceuticalsRadiopharmaceuticals

Binary radiotherapy: Binary radiotherapy: 1.1. BBoron Neutron Capture Therapy (BNCT)oron Neutron Capture Therapy (BNCT)2.2. Photon Capture Therapy (PCT) Photon Capture Therapy (PCT)



A new approach to radiotherapyA new approach to radiotherapy

Cure cancer & protect healthy tissuesCure cancer & protect healthy tissues• Dose escalation in tumourDose escalation in tumour

• Minimise dose to normal tissuesMinimise dose to normal tissues

Different treatment strategies are required Different treatment strategies are required depending on cancer type, stage and degree depending on cancer type, stage and degree of spread of spread

Radiotherapy treatments not linked = impact Radiotherapy treatments not linked = impact lowered = missed opportunitylowered = missed opportunity → New approach needed→ New approach needed



My vision: multi-modalityMy vision: multi-modality

Unified approach to radiotherapy needed to Unified approach to radiotherapy needed to maximise efficacymaximise efficacy and improve care and improve care

Multi-modality = bringing together the Multi-modality = bringing together the different forms of radiotherapy treatments:different forms of radiotherapy treatments:

1.1. Select best treatment depending on tumour typeSelect best treatment depending on tumour type

2.2. Combine different treatments when appropriateCombine different treatments when appropriate

Highly beneficial to patient: better local Highly beneficial to patient: better local control and lower toxicitycontrol and lower toxicity



Multi-modality: selectionMulti-modality: selection

External beam and internal radiotherapy External beam and internal radiotherapy best for localised diseasesbest for localised diseases

Binary therapy best for locally spread Binary therapy best for locally spread diseases with high degree of infiltrationdiseases with high degree of infiltration

Proton/light ion therapy very promising for Proton/light ion therapy very promising for paediatric tumourspaediatric tumours

Some other considerations: Some other considerations: 1.1. Proximity of organs at riskProximity of organs at risk2.2. Tumour dimension and locationTumour dimension and location3.3. Previous irradiation (recurrences)Previous irradiation (recurrences)



Multi-modality: combinationMulti-modality: combination

Combination of different sources Combination of different sources → → dose dose escalationescalation

Different organs at risk for various Different organs at risk for various treatments treatments → → toxicity not increasedtoxicity not increased

Some examples:Some examples:1.1. External beam therapy + brachytherapyExternal beam therapy + brachytherapy

2.2. External beam therapy + radiopharmaceuticalsExternal beam therapy + radiopharmaceuticals



The challengeThe challenge



The technological challengesThe technological challenges

The challenge of radiotherapy from the The challenge of radiotherapy from the patient endpatient end Make sure that the right dose is delivered at Make sure that the right dose is delivered at the right place = improved dosimetry + the right place = improved dosimetry + improved imagingimproved imaging

The challenge of early diagnosisThe challenge of early diagnosis “See” smaller tumours = improved imaging“See” smaller tumours = improved imaging

New advanced technologies desperately New advanced technologies desperately needed for dosimetry and imaging needed for dosimetry and imaging



How particle physics can helpHow particle physics can help

"The significant advances achieved during the last decades in "The significant advances achieved during the last decades in material properties, detector characteristics and high-quality material properties, detector characteristics and high-quality electronic system played an ever-expanding role in different electronic system played an ever-expanding role in different areas of science, such as high energy, nuclear physics and areas of science, such as high energy, nuclear physics and astrophysics. And had a reflective impact on the development astrophysics. And had a reflective impact on the development and rapid progress of radiation detector technologies used in and rapid progress of radiation detector technologies used in medical imaging."medical imaging."

““The requirements imposed by basic research in particle physics The requirements imposed by basic research in particle physics are pushing the limits of detector performance in many regards, are pushing the limits of detector performance in many regards, the new challenging concepts born out in detector physics are the new challenging concepts born out in detector physics are outstanding and the technological advances driven by outstanding and the technological advances driven by microelectronics and Moore's law promise an even more microelectronics and Moore's law promise an even more complex and sophisticated future.”complex and sophisticated future.”

D. G. Darambara "State-of-the-art radiation detectors for medical imaging: demands and trends" D. G. Darambara "State-of-the-art radiation detectors for medical imaging: demands and trends" Nucl. Inst. And Meth. A 569 (2006) 153-158Nucl. Inst. And Meth. A 569 (2006) 153-158



State-of-the-ArtState-of-the-Art



All external dosimeters All external dosimeters placed on patient skin:placed on patient skin:• TLDsTLDs

• DiodesDiodes

• MOSFETsMOSFETs

Disadvantages:Disadvantages:• No reading at tumour siteNo reading at tumour site

• No real-time information No real-time information for some (TLDs)for some (TLDs)

• Difficult to use (wires: Difficult to use (wires: diodes, MOSFETs)diodes, MOSFETs)

DosimetryDosimetry



ImagingImaging

Most medical imaging systems, CT, gamma Most medical imaging systems, CT, gamma cameras, SPECT, PET, use particle physics cameras, SPECT, PET, use particle physics technologies: scintillating materials, photon technologies: scintillating materials, photon detectors, CCDs, etc.detectors, CCDs, etc.

Courtesy Mike Partridge (RMH/ICR)

Collimator

Scintillator

Diode

CT scanner Gamma

camera (SPECT)



Positron Emission TomographyPositron Emission Tomography 1818F labelled glucose given to patients: F labelled glucose given to patients:

ee++ annihilates in two back-to-back annihilates in two back-to-back 511 keV 511 keV

AA ring of scintillating crystals and ring of scintillating crystals and PMTs detects the PMTs detects the

511 keV

511 keV




Conventional PETConventional PET

Conventional PET scanner:Conventional PET scanner: 1.1. Coincidences formed within a very Coincidences formed within a very

short time windowshort time window

2.2. Straight line-of-response reconstructedStraight line-of-response reconstructed

3.3. Position of annihilation calculated Position of annihilation calculated probabilisticallyprobabilistically


PET CT PET + CT



The futureThe future



The dosimetry challengeThe dosimetry challenge

The requirements for new dosimeters:The requirements for new dosimeters:1.1. Measure dose at tumour site and not at skinMeasure dose at tumour site and not at skin

2.2. Measure total dose (including during imaging Measure total dose (including during imaging procedures)procedures)

3.3. Measure in real-time and not long time after Measure in real-time and not long time after each treatment fractioneach treatment fraction

4.4. System easy to useSystem easy to use

The answer: in-vivo dosimetryThe answer: in-vivo dosimetry



In-vivo dosimetryIn-vivo dosimetry

Radiation sensitive MOSFET Radiation sensitive MOSFET transistors transistors (RadFETs) used (RadFETs) used in particle in particle physics experiments physics experiments (BaBar, LHC, etc.) for (BaBar, LHC, etc.) for real-time, real-time, online radiation monitoring online radiation monitoring

Development of RadFET based miniaturised Development of RadFET based miniaturised wireless dosimetry systems to be implanted in wireless dosimetry systems to be implanted in patient body at tumour site for real-time, online, patient body at tumour site for real-time, online, in-vivo dosimetry in-vivo dosimetry → → Seek fundingSeek funding



The imaging challengeThe imaging challenge

The requirements for new imaging systems:The requirements for new imaging systems:1.1. More accurate, more quantitative and highly More accurate, more quantitative and highly

repeatable imagingrepeatable imaging2.2. Imaging during treatment: organ movement Imaging during treatment: organ movement

(breathing), patient set-up, tumour shrinkage(breathing), patient set-up, tumour shrinkage3.3. Image smaller lesions (early diagnosis)Image smaller lesions (early diagnosis)4.4. Treatment specific requirements (for ex. Bragg Treatment specific requirements (for ex. Bragg

position in proton/light ion therapy)position in proton/light ion therapy)

The answer: higher spatial resolution, The answer: higher spatial resolution, higher linearity, lower noise, less drift, faster higher linearity, lower noise, less drift, faster imagingimaging



Time-Of-Flight PET (TOF-PET)Time-Of-Flight PET (TOF-PET) TOF-PET scanner:TOF-PET scanner:

1.1. Time difference between signals from two crystals measured Time difference between signals from two crystals measured 2.2. Annihilation point along line-of-response directly calculated Annihilation point along line-of-response directly calculated

Goal: 100 ps timing resolution (ideally 30 ps and below) = 3 cm Goal: 100 ps timing resolution (ideally 30 ps and below) = 3 cm spatial resolution (ideally sub-cm)spatial resolution (ideally sub-cm)

Advantages: higher sensitivity and specificity, improved S/NAdvantages: higher sensitivity and specificity, improved S/N Technology needed: fast scintillating materials and fast photon Technology needed: fast scintillating materials and fast photon

detectorsdetectors

D2

line of response

time-of-flight envelope

D1



Fast scintillating materialsFast scintillating materialsDecay 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



Photon detectors: SiPMsPhoton detectors: SiPMs

Hamamatsu Inc.

1x1 mm2

3x3 mm2

Array of Silicon Photodiodes Array of Silicon Photodiodes on common substrate each on common substrate each operating in Geiger modeoperating in Geiger mode

SiPMs have high speed (sub SiPMs have high speed (sub ns) and gain (10ns) and gain (1066) and work in ) and work in high magnetic fields (7T)high magnetic fields (7T)



Tests on TOF-PET prototypesTests 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

LaBrLaBr33(Ce) and LYSO scintillating (Ce) and LYSO scintillating

crystals from Saint-Gobaincrystals from Saint-Gobain SiPMs from Hamamatsu, SensL SiPMs from Hamamatsu, SensL

and Photonique and Photonique Various two-channel demonstrator Various two-channel demonstrator

systems tested at RAL and RMHsystems tested at RAL and RMH Timing resolution analysis still Timing resolution analysis still

ongoingongoing



Preliminary resultsPreliminary resultsSiPM 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 3x3mmPrototypes with Hamamatsu 3x3mm2 2 best best of all. SensL blind to LaBrof all. SensL blind to LaBr33

Best timing resolutions measured:Best timing resolutions measured:1.1. 430 ps with 3x3x10 mm430 ps with 3x3x10 mm33 LYSO LYSO

2.2. 790 ps with 3x3x30 mm790 ps with 3x3x30 mm33 LaBr LaBr33

Performance of prototypes with LaBrPerformance of prototypes with LaBr33

highly dependent from SiPM-crystal highly dependent from SiPM-crystal couplingcoupling

Best SiPMs: Hamamatsu (electrical Best SiPMs: Hamamatsu (electrical problem with 11-25) and SensLproblem with 11-25) and SensL

Best timing resolutions measured:Best timing resolutions measured:1.1. 20 ps for single SiPM20 ps for single SiPM

2.2. 40 ps for pairs of SiPMs40 ps for pairs of SiPMs

Hamamatsu performance as function Hamamatsu performance as function of pitch still under investigationof 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



Where next with TOF-PETWhere next with TOF-PETPreliminary results very encouraging. Next Preliminary results very encouraging. Next

step: dual-head demonstrator system. Two step: dual-head demonstrator system. Two planar heads with identical number of channels planar heads with identical number of channels → Funded by → Funded by FP7 as part of ENVISION FP7 as part of ENVISION ((European NoVel Imaging Systems for ION European NoVel Imaging Systems for ION therapy)therapy)

Use of fast scintillators can be expanded to Use of fast scintillators can be expanded to other imaging systems (CT, SPECT, etc.)other imaging systems (CT, SPECT, etc.)

Use of SiPMs opens up the possibility of Use of SiPMs opens up the possibility of designing a compact PET/MRI scannerdesigning a compact PET/MRI scanner



ConclusionsConclusions

Cancer is a leading cause of mortality in UK. Cancer is a leading cause of mortality in UK. Its incidence is rising.Its incidence is rising.

Radiotherapy is and will be given to a large Radiotherapy is and will be given to a large number of patients.number of patients.

Patients will benefit from a multi-modality Patients will benefit from a multi-modality approach to radiotherapy. This requires the approach to radiotherapy. This requires the development of new, advanced technologies.development of new, advanced technologies.

Particle physics holds the key to the Particle physics holds the key to the development of these technologies.development of these technologies.



AcknowledgementsAcknowledgements

Dr Phil Evans and Dr Mike Partridge (Royal Dr Phil Evans and Dr Mike Partridge (Royal Marsden Hospital / Institute of Cancer Marsden Hospital / Institute of Cancer Research - UK)Research - UK)

Prof Ken Peach (John Adams Institute - UK)Prof Ken Peach (John Adams Institute - UK)Prof Bleddyn Jones (Radiation Oncology and Prof Bleddyn Jones (Radiation Oncology and

Biology Institute - UK) Biology Institute - UK) The STFC Futures Programme team (UK)The STFC Futures Programme team (UK)Dr John Matheson and Mr Matt Wilson Dr John Matheson and Mr Matt Wilson

(STFC-RAL - UK)(STFC-RAL - UK)

toward a multi-modality approach to radiotherapy for cancer treatment in uk (unity is strength)...

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