Very High Energy Electrons ( >100 MeV)
in Radiation Therapy
What? Are you nuts? We don’t even like 20 MeV very much!
Colleen DesRosiers
06/14/2017
“Imagination
is more important than
knowledge.”
AAMD Annual Meeting, June, 2017
Albert Einstein, Ph.D.
Introduction
Very High Energy Electrons
(VHEE)
AAMD Annual Meeting, June, 2017
The idea…
Best treatment available in
radiation therapy using photons
(linac based):
•IMRT
•VMAT
– Specialty units
•Cyberknife
•Tomotherapy
•View Ray
•Gamma Knife/ Perfexion
AAMD Annual Meeting, June, 2017
Limitations for photons
– Photons are not charged – cannot be “scanned”
– Modulated treatment delivery relies heavily on
mechanical motion!!
• Mechanical motion is slow – inefficient
– Interplay effects with patient motion
– Patient throughput
• Precision – width of MLC
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Alternatives to photon therapy
• Brachytherapy
• Electrons
• Heavy particles
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Brachytherapy limitations
• Accessibility to target
• Proximity to radiation source
• Control of dose distribution
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Electron beam therapy limitations
• Depth of target
• High surface dose
• High penumbra (scattering in air)
• Bulging effect
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Heavy Particle therapy limitations
•Cost
– Facility
– treatment
•Sensitivity to patient /target motion
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Depth Dose curves
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The optimum therapy characteristics
• Optimum dose distribution
1.
2.
3.
Heavy particles (SOBP) for depth dose
Small beams – high modulation
Large number of beam directions
• Quickest treatment delivery
– Reduce motion effects
– Patient throughput
– Electromagnetically (or otherwise approaching speed of light)
scanned
• Cost competitive with photon beams
AAMD Annual Meeting, June, 2017
Consideration of electron beams
Limitations of clinical electrons
• High relative surface dose
• Shallow penetration/short range
• Range straggling (no Bragg peak)
• High penumbra
• Bulging effect
• Spread of beam in air (why we have cones)
Limitations of electron beams due to energy –
what happens if the electron energy is increased??
AAMD Annual Meeting, June, 2017
Thought experiment…
What will happen if the energy of the electrons is
increased (100+ MeV)?
• Increases depth of penetration
• No range straggling if beam penetrates through patient
• Ability to control position electromagnetically
•
•
Scanning beams more easily done than heavy particles
Speed of electromagnetic scanning allows for ~ 100X more beams
delivered in the same time as photons
• Lower beam spread and reduced bulging effect
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Courtesy of the imagination of
Lech Papiez, PhD, 1998
Thought experiment… (continued)
While maintaining some low energy characteristics
• Can produce pencil beams
• High surface dose
• Less costly than heavy particles
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Courtesy of the imagination of
Lech Papiez, Ph.D., 1998
Materials and Methods 1
Indiana University
Oak Ridge National Laboratory
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Initial VHEE experiments
• Monte Carlo simulations with PENELOPE
• Physical measurements at Oak Ridge National
Laboratory electron linear accelerator (ORELA)
•Solid water
•Gaf-Chromic film
•150 MeV
•Estimated 100 Gy dose
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Monte Carlo comparison with measured
ORELA facility
Varian Linear accelerator
Accelerator structure length = 17 meters
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DesRosiers, Moskvin, Papiez, 2000
PENELOPE data
Electron Beams of 200 MeV in Water Phantom
Radius 5 cm
Radius1 cm
DesRosiers, Moskvin, Papiez, 2000
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Depth distribution various modalities
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Subiel, et al, Radiation Research Annual Meeting, Sept. 2014
Angular spread of VHEE
The relationship
between electron
energy, spread of
beam in air and
distance
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DesRosiers, Moskvin, Papiez, 2000
cm 4
Air
Tissue
3
15 MV
2
1
0.5
0.9
0
0.8
-1
-2
0.7
-14 -13 -12 -11 -10
cm 4
Tissue
3
-9
-8
-7
Air
-6
-5
-4
cm
200 MeV
2
1
0.9
0
-1
-2
0.5
0.8
Tissue
-14
Bone
Monte Carlo
simulation results
comparing 15 MV
photon distribution
to 200 MeV
electron beams
0.7
Tissue
-13 -12
-11 -10
-9
-8
-7
-6
-5
-4
cm
DesRosiers, Moskvin, Papiez, 2000
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Lung phantom MC study
Comparison of 6 MV, 15 MV, 200
MeV in RPC Lung phantom
Given same target dose coverage, VHEE
shows some reduced normal tissue dose
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DesRosiers, et al, ASTRO annual meeting, 2008
Review of literature
AAMD Annual Meeting, June, 2017
Stanford University
• Treatment planning papers
– Bazalova-Carter, et al (2015)
– Schuller, et al. (2017)
• Conclusions
– Developed treatment planning system with VHEE pencil
beams by linking EGSnrc Monte Carlo with research
version of Ray Station
– Demonstrate equivalent or superior dose distributions
as compared with 6 MV and 15 MV VMAT
– Demonstrate some improvement compared with protons
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Pediatric brain treatment
VHEE specifications
• 100 MeV beams
• 36 beams
• 1mm beam diameters
• 2 mm spacing between
beams
• 9200 beamlets total
VMAT specifications
• 6 MV photons
• Clinically used plan
Reprinted with permission, Bazalova-Carter, et al., MedPhys
Lung and Prostate comparisons
The 100 MeV VHEE lung plan
resulted in mean dose decrease
to all OARs by up to 27% for the
same target coverage compared
to the clinical 6 MV flattening
filter-free (FFF) VMAT plan.
The 100 MeV prostate plan
resulted in 3% mean dose
increase to the penile bulb and
the urethra, but all other OAR
mean doses were lower
compared to the 15 MV VMAT
plan.
Reprinted with permission, Bazalova-Carter, et al., MedPhys
More conclusions …
Rapid dose delivery can be achieved using current linacs
(>100 Gy/s) – how?
• Fewer electrons needed to produce the same dose as
photons
• Efficiency of x-ray production low (6%)
Why is this important?
– Allows for a large number of treatment beams to be
treated
– Patient/target motion effects are reduced or eliminated
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Bazalova-Carter, et al., MedPhys
Equipment Design
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Methods for producing VHEE
• Linear accelerators
• Microtrons
• Laser Plasma
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Linear accelerator
• Electron gun produces
microsecond pulses
• Length of tube
proportional to beam
energy
Linac accelerator
structure = 15 – 20
meters long!!
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Figure from
http://static.bitlanders.com/users/galleries/301941/301941_gallery_541d2e8821727_jpg_fa_rszd.jpg
Microtron
Electrons produced in microsecond
pulses typically
Accelerated by applied magnetic field
Racetrack microtron for 150 MeV design proposed
by Washio, et al. (non-medical application)
Highest energy medical microtron MM50 at
University of Michigan, 50 MeV
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Figure 4.11 from Khan, The Physics of Radiation Therapy, 4th edition
A new type of medical accelerator
Laser Wakefield Plasma
Accelerator
(LWFA)
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What is laser plasma acceleration?
Plasma acceleration is a technique for
accelerating charged particles using an
electric field associated with electron plasma
wave or other high-gradient plasma structures
Plasma = ionized gas
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Some FAQs about Laser plasma technology
• Who first introduced the technology?
– Introduced by Tajima & Dawson, UCLA in 1979
• What is the pulse frequency?
– Ultrashort laser pulses (femtosecond = 10-15 sec)
• What kind of a laser is used?
– Titanium sapphire crystal laser (Terawatt = 1012 W)
• Helium plasma
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Laser Electron Accelerator T. Tajima and J. M. Dawson
Phys. Rev. Lett. 43, 267 – Published 23 July 1979
An intense electromagnetic pulse can create a wake of plasma oscillations
through the action of the nonlinear ponderomotive force. Electrons trapped in
the wake can be accelerated to high energy. Existing glass lasers of power
density 1018 W/cm2 shone on plasmas of densities 1018 cm−3 can yield GeV of
electron energy per centimeter of acceleration distance. This acceleration
mechanism is demonstrated through computer simulation. Applications to
accelerators and pulsers are examined.
AAMD Annual Meeting, June, 2017
Laser propagating in underdense
plasma generates plasma waves
C. Hackenberger
Plasma waves are just like waves
formed behind a boat
Electrons can surf the electric field of the
wave’s wake and can be accelerated up to
hundreds GeV/m
Subiel, et al, Radiation Research Annual Meeting, Sept. 2014
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Acceleration Mechanism
• Intense laser pulse drives the wakefield
• Plasma bubbles (dark blue circles) are formed (contains positive and negative ions)
• Electrons are expelled by laser and encircle plasma bubbles
• Electrons form a density spike and will be injected into the bubble when a threshold
level is reached, producing further acceleration
Reprinted with permission from V. Malka et al. “Ultra-short electron beams based
spatio-temporal radiation biology and radiotherapy” Mutation Research 704 (2010)
142–151, Figures 1, 3 and text
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LWFA are typically built on a “table top”
University of Strathclyde, Glasgow, UK
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University of Texas LWFA
Laser plasma (LWFA) comparison with linear
accelerators (Linac)
• Plasma can handle much heavier energy flow, less prone
to structural failure
• More efficient accelerator
– Linac: 10 MeV/meter
– LWFA: GeV/cm = 100,000X more efficient than a linac
• Pulse width
– Linac: 10-6 seconds
– LWFA: 10-15 seconds
• Electrons may be positioned electromagnetically or by
controlling laser position
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Methods of acceleration comparison
Parameter
Linac
Microtron
Cyclotron
Laser
plasma
Pulse size
10-6 sec
10-6 sec
10-12 sec
10-8 sec
10-15
seconds
Charge per
pulse
1011
electrons
1011
electrons
700 protons 107
electrons
Instantaneous
charge rate
0.016 A
0.01 A –
1.6x104A
11 nA
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1.6x103 A
Energy deposition
• Low LET
– Spurs = 4 nm (2x DNA diameter), 100 eV, 3 ion pairs,
95% energy deposition with photons
• High LET
– Blob = 7 nm, 100-500 eV, 12 ion pairs, neutrons and alpha
– Will the nature of the energy deposition be
impacted by the intense electric fields?
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Materials and Methods 2
University of Strathclyde Experiment
Glasgow, Scotland
2011-2014
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Experiment supported by Clarian Values Fund VFR 273
VHEE (> 100 MeV)
• Initial experiments using VHEE have been carried out using
the ALPHA-X laser-plasma wakefield accelerator beam line
at the University of Strathclyde, Glasgow, UK.
• The purpose of this investigation is to use Monte Carlo
simulations to compare with characterization of the
interaction of the VHEE beam using a BANG3Pro polymer gel
dosimeter dosimeter.
• MC simulations do not account for spatial/temporal effects
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Bang gel dosimetry
• BANG® gels are muscle-tissueequivalent chemical dosimeters
• Optical density per unit length is
proportional to radiation dose
• Dose response is based on
radiation-induced polymerization of
monomers which are dispersed in
the gel
MGS Research
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Bang gel experiment layout
Schematic for experiment layout
Photo of actual experiment
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LET sensitive gel dosimetry
• Dependent on the method
employed in the reading of the
optical density of the gels
• Theory
– High LET radiations produce “blobs” which
scatter light mostly in the forward
direction
– Low LET radiation produce “spurs” which
scatter light isotropically
Results from these experiments indicate that VHEE
behave more like heavy particles producing molecular
scattering favoring the forward direction
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Spatio temporal radiation biomedicine
• Femtolysis (Gauduela et. al) femto second radiolysis
•
•
•
•
•
•
Mutagenic DNA lesions
Cell signalling
Genomic instability
Apoptosis
Microenvironment
Bystander effects
• Calls for “intensive development of ultra short laser
technologies and advanced high time resolved spectroscopic
methods” for the purpose of observing “short lived
nonequilibrium radical trajectories” on the “molecular motion
scale”
AAMD Annual Meeting, June, 2017
Laser plasma accelerator for medical applications
The treatment of cancerous tumors
using lasers offers the potential to
significantly downscale the size and
the cost of proton therapy
infrastructures. This could lead to
high dissemination in hospitals, as
compared to more conventional
systems based on RF acceleration
that require the construction of large
infrastructures.
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http://loa.ensta-paristech.fr/applications_lang_EN_menu_3
Stanford University (SLAC) - 2013
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Summary
• VHEE for radiotherapy
• Somewhere between photons and heavy particles
• Finest IMRT
• Quick treatment delivery
• Low cost
• May offer improved dose distributions in brain, lung and
prostate as compared with photon beams
• VHEE using LWFA may offer unique dosimetric benefits
due to intense electron fluence
• Comparable to heavy particles?
• Groups at Laboratoire d’Optique and SLAC working
AAMD Annual
Meeting, medical
June, 2017
towards
applications LWFA
Acknowledgements
Indiana University
• Lech Papiez, Ph.D.
University of Strathclyde
• Dino Jaroszynski, Ph.D.
• Vadim Moskvin, Ph.D.
• Anna Subiel, Ph.D.
• Marc Mendonca, Ph.D.
• Gregor H Welsh, Ph.D.
Purdue University
• Sylvia Cipiccia, Ph.D.
• Collins Yeboah, Ph.D.
• George Sandison, Ph.D.
• David Reboredo, Ph.D.
UCLA
• Chan Joshi, Ph.D.
• Chris Clayton, Ph.D.
• Annette Sorensen, Ph.D.
• Marie Boyd, Ph.D.
MGS Research
• Marek Maryanski, Ph.D.
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References
•
Bazalova-Carter, et al, “Treatment planning for radiotherapy with very high-energy electron beams and
comparison of VHEE and VMAT plans” Med. Phys. 42, 2615 (2015)
•
C. DesRosiers, et al., “150–250 MeV electron beams in radiation therapy,” Phys. Med. Biol. 45, 1781 2000
•
Y.A. Gauduela, Y. Glinec, J.-P. Rousseau, F. Burgy, and V. Malka. High energy radiation femtochemistry of
water molecules: early electron-radical pairs processes. Eur. Phys. J. D 60, 121–135 (2010)
•
Y.A. Gauduel*, V Malka. Ultrafast sub-nanometric spatial accuracy of a fleeting quantum probe interaction
with a biomolecule: innovating concept for spatio-temporal radiation biomedicine. SPIE annual meeting
2014 proceedings, 8954-9, 2014
•
Glinec,et al, “Radiotherapy with laser-plasma accelerators: Monte Carlo simulation of dose deposited by an
experimental quasimonoenergetic electron beam” Medical Physics, 33(1), 155-162 (2006)
•
V. Malka et al. “Ultra-short electron beams based spatio-temporal radiation biology and radiotherapy”
Mutation Research 704 (2010) 142–151
•
V. Malka,et al, “Electron acceleration by a wake field forced by an intense ultrashort laser pulse,” Science
298, 1596-1600 (2002)
•
Maryanski et al, Radiation Therapy Dosimetry using Magnetic Resonance Imaging of Polymer Gels.
Med.Phys. 23 (5), pp.699-705, (1996)
•
V. Moskvin, et al. Characterization of the Very High Energy Electrons, 150 - 250 MeV (VHEE) beam generated
by ALPHA-X laser wakefield accelerator beam line for utilization in Monte Carlo simulation for biomedical
experiment planning, AAPM Annual Meeting, 2012
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References
•
Richter, C. et al., “Dosimetry of laser-accelerated electron beams used for in vitro cell irradiation
Experiments”, Radiation Measurements, 46, 2006-09 (2011)
•
O Rigaud et al., Exploring ultrashort high-energy electron-induced damage in human carcinoma cells.
Cell Death and Disease (2010)
•
Schuler, et al., “Very high-energy electron (VHEE) beams in radiation therapy; Treatment plan
comparison between VHEE, VMAT, and PPBS”, Med.Phys. June 2544-55 (2017)
•
A. Subiel, et al., “Calibration and dosimetry of very high energy electrons as a new treatment modality
for radiotherapy”, Radiation Research Annual Meeting, Las Vegas, NV (2014)
•
M. Washio, et al., “Simulations of racetrack microtron for acceleration of picosecond electron pulse,”
Proceedings of the 1999 Particle Accelerator Conference, 2298-3000 (1999)
•
Wilson, P, Nunan, C. The racetrack microtron as a negative pion source for radiotherapy,
https://accelconf.web.cern.ch/accelconf/p73/PDF/PAC1973_1018.PDF, IEEE, 1973
•
Xu et al, Performance of a commercial optical CT scanner and polymer gel dosimeters for 3D dose
verification. Med. Phys 31 (11), pp.3024-3033
•
C. Yeboah, G. A. Sandison, and V. Moskvin, “Optimization of intensitymodulated very high energy 50–
250 MeV electron therapy,” Phys. Med. Biol. 47, 1285 2002.
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Questions?:
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Boldly stolen from Bartlett, et al. AAMD presentation 2017