squeezing the proton

Squeezing the proton towards small proton therapy systems

Roelf Slopsema. M.Sc. / UF Health Proton Therapy Institute

Disclosures

• I worked as an R&D physicist for IBA from 2002 until 2004

• I have received a research grant from IBA in 2007

• I have performed paid consultancy work for MevIon in 2013

• I work at a center that has IBA equipment

• I like protons

• I am not a PhD

Learning objectives

• …. know what proton therapy is

• …. have an overview of the historical development of proton accelerators and proton therapy

• .... have an understanding of the different factors driving the development of smaller PT systems

• …. know the different technologies applied to make PT systems smaller

• …. have an idea of the small proton therapy systems available now, in the near future, and in the distant future

After this presentation you…….

Overview

• what is proton therapy?

• technical challenges of proton therapy systems

• history of proton accelerators and PT systems

• rationale for smaller PT systems

• technology for smaller PT systems

o limited-angle gantry

o superconducting cyclotrons

o linear accelerators

o laser-accelerated protons

• current status and outlook for the future

What is proton therapy? (1)

• Proton therapy (PT) = type of radiotherapy that uses high-energy protons to irradiate diseased tissue

• The process through which high-energy protons loose energy while traversing matter results in a distinct depth dose distribution called the Bragg peak

• The penetration depth of the Bragg peak can controlled with the entrance energy, allowing for complete sparing of structures distal to the target

PT depth dose distribution

PT delivery techniques

Several different delivery techniques are applied in PT:

• 3D conformal proton therapy : using a block (aperture) and range compensator to conform the dose to the target

– passive scattering

– uniform scanning

• Spot scanning : using many, scanned, small beams of varying energy to ‘paint in the target’ (allows for IMPT)

PT dose distribution

3D conformal XT IMRT 3D conformal PT

http://www.cancernetwork.com/articles/improving-therapeutic-ratio-hodgkin-lymphoma-through-use-proton-therapy/page/0/2

PT dose distribution

Ek : kinetic energy E0: rest energy electrons: E0 = 0.511 MeV protons: E0 = 938.3 MeV

Technical challenges of PT delivery (1)

Energy loss in coulomb interactions with shell electrons for electrons1 or protons2:

1: Moeller cross section ; 2 Bethe equation (http://pdg.lbl.gov/2014/reviews/rpp2014-rev-passage-particles-matter.pdf)

At same kinetic energy protons lose much more energy than electrons because of higher mass.

10 MeV electrons: =0.93 → 1/2=1.2 10 MeV protons: =0.14 → 1/2= 51 1700 MeV protons: =0.93 → 1/2= 1.2

2.0 MeV/cm

46 MeV/cm

2.1 MeV/cm


Range:

You need large proton energy to get sufficient range in the body.

dE/dx ↑ → RCSDA↓

2.5 cm (EYE) : Ek ≥55 MeV 16 cm (BRAIN): Ek ≥160 MeV 32 cm (ABDOMEN): Ek ≥230 MeV

Note: Compared to electrons, protons scatter little allowing deep penetration with little lateral deflection around the initial beam direction.


Magnetic rigidity of a charged particle –

charge 1, rest energy E0, kinetic energy Ek:

For example, bending a 250 MeV proton with a 1.5 T field results in a bending radius of 1.6 m, requiring a 2.5 m long magnetic field for a 90◦ bend

High E0 and Ek results in high BR


1. You need high proton energy to achieve sufficient range inside the patient

→ large accelerator

2. The high proton kinetic and rest energy results in large magnetic rigidity

→ large bending radii / large magnets

3. Clinical applications require beam delivery from different angles with respect to patient

→ large gantry structures

Invention of the cyclotron

• invented in 1931 by Lawrence & Livingstone

• Noble prize in 1939

• 4.5 inch, 80 keV

Ernest Lawrence 4.5-inch cyclotron

1931 / 11 inch cyclotron / protons to 1 MeV

1937 / 37 inch cyclotron / deutrons to 8 MeV

"He creates and destroys."

1939 / 60 inch cyclotron / deutrons to 16 MeV

"I must confess that one reason we have undertaken this biological work is that we thereby have been able to get financial support for all of the work in the laboratory. As you know, it is much easier to get funds for medical research." —Lawrence to Niels Bohr, 1935

Atomic explosion over Hiroshima.

1946 / 184 inch synchrocyclotron / protons to 340 MeV

Evolution of accelerator energy

Birth of proton therapy

‘Radiological Use of Fast Protons’, R.R. Wilson, Radiology 47(1946), 487-491 http://users.physics.harvard.edu/~wilson/cyclotron/bobwilsn.html

Robert Wilson: “Higher-energy machines are now under construction, however, and the ions from them will in general be energetic enough to have a range in tissue comparable to body dimensions. It must have occurred to many people that the particles themselves now become of considerable therapeutic interest.”

Birth of proton therapy

Robert Stone and John Lawrence, Ernest's brother, treat a patient with neutrons from the 60-inch cyclotron.

• 1954 first patient treated with protons at Berkeley Radiation Laboratory

• irradiation to destroy the pituitary gland in patients with hormone-sensitive metastatic breast cancer

Development of proton therapy

• 1957 : results from Berkeley duplicated in Uppsala, Sweden

• 1961: Harvard Cyclotron facility starts PT

• 1990: first hospital-based PT system opens at Loma Linda University, CA

• 2001 : PT starts at MGH

• 2006-2014: an additional 10 large, hospital-based PT centers are opened in the U.S. (I.U., M.D. Anderson, UF, Upenn, Hampton Uni., …)

• 2013 onwards: introduction of smaller, one-room PT systems

IBA cyclotron: 230 MeV, 220 tons

IBA gantry: 38 feet tall by 35 feet wide, >200,000 pounds

http://www.varian.com/us/oncology/proton/technology.html / http://www.scripps.org/services/cancer-care__proton-therapy

Five-room proton therapy center as installed at Scripps (San Diego, CA)

Rationale for smaller systems


High cost of PT equipment limits widespread adaptation of proton therapy.

Linear accelerator: $2.8 million (2.4-3.0) 1

1 Modern Healthcare / ECRI Institute Technology Price Index July 2013 (http://www.modernhealthcare.com/article/20130724/NEWS/307249943) 2 http://www.proton-therapy.org/zapper.htm

5-room PT system: $144 million 2

http://www.modernhealthcare.com/article/20130724/NEWS/307249943


‘smaller systems’ can reduce cost by…..

• reducing foot print of building

• eliminating need for construction of dedicated building/room

• reduction in #components

• making PT available for smaller centers (one room) or as extra modality in existing centers (economy of scale)

• make proton therapy more compatible with conventional forms of RT


1. You need high proton energy to achieve sufficient range inside the patient

→ large accelerator

2. The high proton kinetic and rest energy results in large magnetic rigidity

→ large bending radii / large magnets

3. Clinical applications require beam delivery from different angles with respect to patient

→ large gantry structures

Approaches to smaller PT systems

1. Limit the number of treatment rooms

2. Reduce the foot print of the building (land/shielding)

• accelerator under gantry • accelerator on gantry • reduce required shielding (proton absorption / degradation)

3. Shrink the size of the accelerator • superconducting cyclotron • linear accelerator with very high potential gradient • laser-accelerated protons

4. Shrink the size of gantry structure / beamline • short gantries • limited-angle gantries / fixed beam line

Limit the number of treatment rooms

Take a multi-room facility and strip away all tx rooms except one.... → smaller, but not very cost effective

IBA Proteus system with four rooms

IBA Proteus system with one room

Reducing foot print - cyclo under room

http://lightions.com/news/sumitomo-proton-therapy-system-clears-fda-510k/16

Sumitomo PT system:

• single gantry

• double-decker

• small vault foot print: 16mx20m

Shrink size gantry – Sumitomo short gantry

http://www.aapm.org/meetings/2013AM/documents/Sumitomo.pdf

Shrink size gantry – few fixed angles


IBA – inclined beam line:

• two fixed beam lines (90 and 30deg)

• limited-angle gantry that rotates just nozzle (not beam line)

• robotic positioner

• often in centers with additional ‘full gantry rooms’

Shrink size gantry – limited angle


IBA Proteus One : 220 degrees MevIon S250: 180 degrees

Reducing foot print – shrinking beamline


scanning magnets

degrader

energy-selection system

IBA Proteus One:

• incorporate energy-selection system into gantry

• move scanning magnets from nozzle to gantry

• conventional to superconducting cyclotron

• limited-angle gantry

Reducing foot print – IBA Proteus One

http://www.aapm.org/meetings/2013AM/documents/IBA.pdf

Shrink size accelerator – superconducting cyclo

Revolution period: T = 2πm/B

But for relativistic energies: m = γm0 → T increases with energy

To compensate for mass increase with radius you need to either….

• decrease RF frequency with radius > synchrocyclotron

• increase magnetic field with radius > isochronous cyclotron

First some cyclo basics….


Isochronous cyclotron • continuous beam (~100 MHz) • increasing magnetic field causes vertical defocusing > need for complex

magnet shape

Synchrocyclotron • pulsed beam structure (kHz region) • lower RF power • simpler magnet design (weak focusing)

• earliest cyclotrons used for PT were synchrocyclotrons

• later commercial cyclotrons are isochronous

IBA C230 isochronous cyclotron

…some more cyclo basics….


• superconductivity allows increase of magnetic field above levels obtainable with conventional electromagnets (several T)

• higher magnetic field results in smaller bending radius (at same energy) r = mv/B

• But, increased magnetic field makes vertical focusing difficult

saturated poles > limit on field gradient between hills/valleys

limit in spiral design

• To account for this you either…

stay with an isochronous cyclotron, but limit the magnetic field increase

use a synchrocyclotron design allowing for higher magnetic fields



Varian SC isochronous cyclotron

MevIon TriNiobium Core SC synchrocyclotron

IBA S2C2 SC synchrocyclotron


http://www.aapm.org/meetings/2013AM/documents/CyclotronProsandCons.pdf /

Manufact. Model Super-conducting

Type Energy [MeV]

Weight [tons]

Diam. [m]

Peak B [T]

IBA C230 NO isochronous 230 220 4.3 2.2

Varian YES isochronous 250 90 3.1 <4

MevIon S250

YES synchro 250 20 1.8 ~9

IBA S2C2 YES synchro 230 <50 2.5 ~6.6

Comparison of normal and superconducting cyclotrons used for proton therapy

Reducing foot print - cyclo on gantry

MevIon S250 system

Shrink size accelerator – proton linacs

Issues with proton linear accelerators….

• long or high field gradients needed

• protons move at relatively low speed (up to of 60% of speed of light) > large variation in speed along accelerator

Potential benefits….

• variable energy without degrader (neutrons, shielding)

• fast energy change

• light: no need for (heavy) magnets in accelerator

Different approaches….

• long cavity-coupled linac

• dielectric wall accelerator

Proton Linacs - LIGHT

http://www.advancedoncotherapy.com/Our-LIGHT-system/Product-overview

• LIGHT = Linac Image Guided Hadron Technology

• Spin-off from LHC project (R&D facility at CERN)

• LIGHT components:

– Radio-frequency quadrupole ‘injector’ (4.5 MeV)

– Side-couple drift tube linac (35 MeV)

– Cavity-Coupled linacs (10 accelerators > 230 MeV)

• Potential benefits1

– lower shielding requirements (no absorbers for energy modulation)

– fast energy changes (2-3 ms)

– (modular)

– (more compact)

– (lower cost) ‘We estimate that the cost of a LIGHT facility will be in the region of US$40m vs. US$160-200m for those using cyclotrons or synchrotrons’

Linear accelerators- LIGHT

Proton Linacs – Dielectric wall accelerator

STATUS OF THE DIELECTRIC WALL ACCELERATOR, G. Caporaso et al, Proceedings of PAC09, Vancouver, BC, Canada

Principles of dielectric wall accelerator…

• developed at Lawrence Livermore National Laboratory

• uses fast switched high voltage transmission lines to generate pulsed electric fields on the inside of a high gradient insulating (HGI) acceleration tube

• high electric field gradients are achieved by the use of alternating dielectric insulators and conductors and short pulse times

• use of laser-controlled switching to ‘fire’ acceleration in phase with proton propagation and energy

• DWAs are expected to reach acceleration gradients around 100 MV/m

Proton Linacs – Dielectric wall accelerator

AAPM presentation, R. Mackie, ‘Dielectric wall accelerator and distal edge tracking proton therapy system’

Proton Linacs – TomoTherapy PT system

• proton arc therapy

• using ‘distal edge tracking’

Proton Linacs – CPAC system

CPAC = Compact Particle Acceleration Corporation using dielectric wall technology

http://www.cpac.pro/index.htm / http://www.gizmodo.com.au/2012/03/the-petite-particle-accelerator-a-proton-gun-for-killing-tumours/ml

Shrink accelerator – laser-accelerated protons

Principles of laser accelerated protons…

• Target Normal Sheath Acceleration (TNSA)

• ultra-intense laser pulse hits thin foil >1019 W/cm2

• plasma plume created in focal region

• laser accelerates plasma electrons

• electrons exit on other side creating strong electric field TV/m

• protons (ion) are pulled out and accelerated under the influence of created electric field


Characteristics current experimental systems…

• maximum proton energy of 70 MeV for a 100 TeraWatt laser

• development of PetaWatt lasers underway enough for clinical PT energies

• high power requires pulsed lasers

• 10 Hz repetition for ultra-short pulses (50 fs)

• few pulses per minute for long pulses (700 fs)

• biology experiments have been performed

Proton Accelerators, M. Schippers, in Proton Therapy Physics, Ed. H. Paganetti, 2012 / A compact solution for ion beam therapy with laser accelerated protons, U. Masood et al, Appl. Phys. B (2014) 117:41-52


Benefits of laser-accelerated protons….

• no need for accelerator

• no/less need of particle transport (mirrors

instead of magnets)

Proton Accelerators, M. Schippers, in Proton Therapy Physics, Ed. H. Paganetti, 2012 / A compact solution for ion beam therapy with laser accelerated protons, U. Masood et al, Appl. Phys. B (2014) 117:41-52

Challenges of laser-accelerated protons….

• laser power and maximum energy

→ need 1022 W/cm2 to get 200 MeV protons

• energy spread → loss of bragg peak

• ultra-short pulsed beam → extreme

instantaneous dose rates 1010 Gy/s (biology/dosimetry)

PT system with laser-accelerated protons

A compact solution for ion beam therapy with laser accelerated protons, U. Masood et al, Appl. Phys. B (2014) 117:41-52

‘Our proposed design for laser-driven beams results in a substantial reduction in size by a factor of 2-3, and hence weight, compared to the most compact conventional Ion Beam Therapy gantry systems….’

Current status and outlook

• Currently most PT centers are large, multi-room facilities

• Recently the first one-room systems have started operation and several more are under construction

Research-facility PT systems

Operational

12 http://www.ptcog.ch/index.php/facilities-in-operation

Multi-room hospital-based systems (IBA Proteus , Varian ProBeam, Hitachi ProBeat)

Operational

http://www.ptcog.ch/index.php/facilities-in-operation

27

Multi-functional one-room systems (MevIon S250, Proteus One)

Operational

2 http://www.ptcog.ch/index.php/facilities-in-operation

One-room systems (MevIon S250, Proteus One, single gantry)

Research-facility based systems

Multi-room hospital-based systems (Proteus, Varian , Hitachi ProBeat)

Under construction / Planned

http://www.ptcog.ch/index.php/facilities-under-construction http://www.iba-protontherapy.com/why-iba / http://www.mevion.com/s250-map

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Current status and outlook

• Several new technologies (laser-accelerated protons, LINACS) are interesting, but are likely not ready for clinical application in the next 5-10 years

• How much these new technologies will reduce the cost of PT systems, remains to be seen

• The continued growth of proton therapy will depend on both….

– the results of the effort of cost reduction and

– the clinical outcome of PT

– ‘politics’

• Currently most PT centers are large, multi-room facilities

• Recently the first one-room systems have started operation and several more are under construction

You never know, the next break through in proton delivery might be just around the corner……

Thank you for your attention.

squeezing the proton

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