Dong Introduction to proton therapy...

6/30/2012

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Introduction to Proton Therapy

Lei Dong, Ph.D.Scripps Proton Therapy Center

San Diego, California

ASRT/MDCB Lecture UCSD, June 30, 2012

Objectives

Learn about the basic principle of proton therapy

Introduce different delivery modes in proton therapy

Understand the advantages and disadvantages of proton therapy

Outline

A brief history

Proton advantages

Hardware: Cyclotron or Synchrotron?

Delivery modes: PSPT; US; PBS

Overall workflow comparison

CT-Simulation

IGRT

Treatment planning

Future development

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A Condensed History

1904 Bragg & Kleeman report ion energy loss curves

1919 Rutherford proposes existence of the proton

1932 Lawrence & Livingston report 1st cyclotron

1946 Wilson proposes proton therapy

1954 Tobias et al treat patients w/ 340 MeV p at LBL

1990 First hospital-based proton treatment facility at Loma Linda University Medical Center

2006 Proton facilities open at MD Anderson and Univ. of Florida

2007 19 facilities worldwide (5 in US)

2012 10 operational + 12 being considered in US

Wilson proposes proton therapy In 1946 Harvard physicist

Robert Wilson (1914-2000) suggested*: Protons can be used clinically

Accelerators are available

Maximum radiation dose can be placed into the tumor

Proton therapy provides sparing of normal tissues

Modulator wheels can spread narrow Bragg peak

*Wilson, R.R. (1946), “Radiological use of fast protons,” Radiology 47, 487.

commissioned PT facilities (5)

2. MGH (IBA)

3. MPRI (‘in house’)

4. MD Anderson (Hitachi)

5. UFPTI (IBA)1. LLMUC (Optivus)

PT facilities to be commissioned (5+)

Procure Oklahoma (IBA)

UPenn (IBA)

RWJUH (StillRiver)

ProCure Illinois (IBA)St. Louis (StillRiver)

Prototype (6-8)

2007

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MSKCC May 2008

Bill Chu LBL

100,000th patient in 2012

Proton Advantages

Pristine Bragg Peak Anatomy

From Newhauser, NPTC Internal Report

A complete Bragg peak

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Why Protons are advantageous?

Maximum dose at depth (Bragg peak)

Relatively low entrance dose (plateau)

Rapid distal dose fall-off

RBE close to unity

Comparable lateral penumbra

Energy modulation

Clinical relevance of intensity-modulated therapy (protons vs photons)

Con

form

ality

Integral dose

high

low high

3D CRT

IMXT3D PT

IMPT

J Loeffler, T Bortfeld

• Complex anatomies/geometries (e.g., head & neck) with multiplecritical structures

• Cases where Tx can be simplified, made faster

• Cases where integral dose is limiting (e.g., pediatric tumors)

• Cases where it may be possible to reduce side-effects (improve patient’s quality of life)

Medulloblastoma (3 y old boy)

Protons(SOBP, 1 field)

Photon IMRT(15 MV, 9 field)

Photons(6 MV, 1 field)

Miralbell et al., IJROBP 2002

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IMRT Proton87.5 Gy Plans

ProtonIMRT

Dong

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

0 1000 2000 3000 4000 5000 6000 7000 8000 9000 10000

Dose (cGy)

Fra

ctio

n

Heart (IMRT)

Heart (Proton)

Body (IMRT)

Body (Proton)

Spinal Cord (IMRT)

Spinal Cord (Proton)

Esophagus (IMRT)

Esophagus (Proton)

Dosimetric Comparison: 87.5 Gy in 35 fxs

IMRT (dashed)vs.Proton (solid)

Dong

How to produce protons?

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How to change the direction of a proton?

Magnetic Field (B)

Protons at relatively low energies are injected into the center of the cyclotron. The protons are accelerated each time they cross the gap between the dees until the radius of the path is large enough for the protons to be extracted from the cyclotron.

Classic Cyclotron Design

How Cyclotron Works?

Beam Exit

Alternating Radio Frequency (RF)voltage accelerates protons whenthey go across the gap in each turn.

2/3 speed of light

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ProBeam Varian Medical Systems

19

Cancer ForefrontIMPTVarian AdvantageScanning BeamProton Platform

Varian ProBeam™

Superconducting Cyclotron

20

Beamline Under Construction

21

Beam Steering by Magnetic Fields

• Dipoles: for bending the beam

• Quadruples: focusing the beam

• Vacuum pumps to keep beamline under very high level of vacuum (think about outer space)

• Beam profile monitors to measure beam along the central tube Dipoles

Quadruples

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Relativistic increase in mass

E0 = m0c2 where m0 is the proton rest mass

ET = E0 + T where T is the kinetic energy

m = m0, where = m/m0 = ET/E0 = (E0 + T)/E0

m = m0/sqrt(1 - 2), where = v/c

IBA C230

First commercially available cyclotron for PT

230 MeV protons

Dedicated to therapy

ACCEL/VARIAN K250

Compact 250 MeV superconducting cyclotron

Higher magnetic field - less volume/mass

High extraction efficiency and reproducible beam parameters

THE FUTURE?• Energy: 250 MeV Protons• Diameter: 1.7 m• Magnetic field: 8.5 Tesla• Beam structure: Pulsed, 1 kHz

Modern Hospital-Based Cyclotrons

The Principle of SynchrotronsHitachi and Siemens Synchrotrons:

Both designs use 7 MeV multi-turn injection for higher intensity: 1.2 x 1011 protons per pulse (Hitachi) Both use RF driven extraction for turning beam on and off quickly ( < 200 μsec) and for gated respirationBoth are strong focusing with similar magnet layout and beam optical

LLUMC Synchrotron:Uses slow extraction with 0.2 – 0.5 sec every 2.2 sec weak focusing

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Proton beam delivery system at PTC-H

PROBEAT, Hitachi Ltd.

Accelerator Type Slow-cycling Synchrotron

Injector 7MeV Linac

Output Energy 70-250MeV

Circumference 23m

Repetition cycle 2-7secPhoto by Umezawa@HitachiHitachi Ltd.

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Cyclotron vs Synchrotron

Cyclotron

• Fixed output energy and “continuous” beam

• Energy variation requires post acceleration energy selector. Activation “problem”

Synchrotron

• Energy variable from pulse to pulse

• Pulsed beam (difficult for motion mgr)

Multi-Room Configuration

Passive Scattering Port

Pencil Beam Scanning Port

Large Fixed Port Eye Port

Experimental Port

Accelerator System(slow cycle synchrotron)

PTC-H3 Rotating Gantries1 Fixed Port1 Eye Port1 Experimental Port

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Multi-room Systems

• Hitachi 270 MeV proton synchrotron• IBA 230MeV cyclotron• Mitsubishi 235 MeV proton synchrotron• Mitsubishi* 320MeV/u synchrotron (20 cm – 12C)• Optivus 250 MeV proton synchrotron• ProTom 330 MeV/u proton synchrotron• Siemens * 430 MeV/u synchrotron (30 cm – 12C)• Varian/Accel 250MeV superconducting cyclotron

* Proton and 12C

Single Room Systems

• Mevion• 250 MeV gantry mounted compact

superconducting synchrocyclotron. In production.

• Tomotherapy 250 MeV Dielectric Wall Accelerator.Compact linear accelerator. Feasibility testing.

Proton Beam Delivery Mode• Passive Scatter (PS)

– Use scatter technique to create a large treatment field

– Range modulation is required

• Pencil Beam Scanning (PBS)– Use magnetic field to scan the treatment field

– Energy (range) can be changed spot-by-spot

• Uniform Scanning (US)– Pre-programmed PBS with beam aperture

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Comparisons

PS US PBSFlexibility in shaping the dose distribution

** ** ***

Dose conformity ** ** ***No/reduced need for patient-specific hardware

* * ***

Speed in energy changes *** * *Speed in overall dose delivery *** ** **Ease of commissioning * ** **Maturity of the technique *** ** *

Passive Double Scattering System

PS system

Beam Gating to Achieve Desired SOBP Width

• The RMW rotates

• The beam is turned on at the thinnest part of the wheel

• The beam is then gated off at a predetermined the modulator steps

• The process is repeated 6 times for each revolution

• Sum of Bragg peaks (called “layers” in the TPS) = SOBP

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Compensated (constant scattering for all thicknesses) bimaterial modulation wheel used for first scatterer

• 400 RPM

• 6 modulations per cycle

• Up to 16 cm modulation

• Beam gated for smaller modulation

G2-NZL AT2.2 Modulat ion　 Test (A-2) UF18E250 Range27.0[ cmH2O]

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

110%

0 50 100 150 200 250 300 350

Dept h in Wat er [ mmH2O]

SOBP16cm ⇒16.2cm T0524A+B

SOBP8cm ⇒8cm T0521F+G+H

SOBP4cm ⇒4.2cm T0521I+J+K

G2-NZL AT2.10 Lateral Penumbra Test(A-1) /UF25E250/Inline R24.9(MAX)

0%

20%

40%

60%

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100%

120%

-200 -150 -100 -50 0 50 100 150 200Inline[mm]

Rel

ativ

e D

ose

[%]

Inline(SOBPCenter) Inline+:6.75mm Inline-:6.64mm T0519I

Constant Range Modulation Widthand Passive Range Compensation

• Usually use range modulator wheels

• 3-d range compensator (usually plastic or wax)

• Automatically designed and machined

• Very simple and clinically effective Chu, Ludewigt, Renner - Rev. Sci. Instr.

MSKCC May 2008

Aperture and Compensating Bolus

Lateral Field Edge Shaping Distal Field Edge Shaping

~$800 / field

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: pencil beam scanning nozzle for MGH

• Continuous scanning. Modulation in current and speed.• Pencil beam spot width () at the isocenter: ~4-10 mm• Several identical paintings (frames) of the same target

slice (layer)• Max patient field (40x30) cm2

Beam monitor

Intensity Modulated

BeamZ

X

Y

Fast Slow

Scanning Magnets

Pair of Quads

Vacuum Chamber

Scattering vs Scanning

• Scattering – no problem with organ motion.• Scanning requires gating to overcome organ

motion problems.• Scanning – better conformation to target

volume.• Scanning - patient safety is a bigger problem

than with scattering.• Scanning – suitable for large volumes.• Scanning – allows for IMPT

Motivation for Pencil Beam Scanning

• Fewer neutrons

• Sparing of healthy tissues proximal to the target

• Intensity modulated proton therapy (IMPT)

Martin Bues, PhD,

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Martin Bues, PhD,

Step and shoot delivery of proton beam scanning

target

layer

Dynamic scanning is achievedwith discrete spot scanning method.

spot

layer

proton beamBeam OFFscanner setting

proton beam

Repeating many static irradiationsSpeedy beam switching with RF Driven Extraction technique

Beam OFFscanner setting

proton beam

Hitachi, Ltd.

Proton Beam Characteristics

Proton interaction with matter

Electromagnetic interaction with orbiting electrons-ionization and excitation

Secondary electrons- short ranged and deposit energy locally

Sharp increase in energy deposition as proton comes to rest

Multiple Coulomb scattering, small angle Gaussian lateral spread-out, = 5% of the range Elastic nuclear collision, large angle scattering Nonelastic nuclear interactions, nuclear fragments

deposit dose locally Statistical fluctuation in energy loss leads to range

straggling-blurring of the peak (1% of range)

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Energy Transfer Mechanisms

Excitation Elastic scattering with nucleus

IonizationBrems-strahlung

Most energy loss is via coulombic interactions with atomic electrons.

Small deflections are caused by coulombic interactions with nucleus.

Nuclear reactions play only a small role.

Proton dose distribution in water

PTCH-G2, Pristine Bragg Peaks

0

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40

60

80

100

120

0 50 100 150 200 250 300 350

Depth (mm)

PD

D

100MeV_RMW15_Range 4.3 cm

250MeV_RMW91_Range 28.5 cm

N. Sahoo/MDACC

PTCH-G2, Pristine Bragg Peaks

0.0

20.0

40.0

60.0

80.0

100.0

120.0

0 50 100 150 200 250 300 350

Depth (mm)

PD

D

100MeV 200MeV 250MeV

More Pristine Peaks

N. Sahoo/MDACC

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Generation of Spread-Out-Bragg-Peak (SOBP) with Energy Modulation of the Bragg Peak

PDD as a function of SOBP Widths

Note increase in entrance dose with increase in modulation.

Sahoo/MDACC

G2_250MeV_RMW91_range28.5cm_mediumsnout@5cm

0

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40

60

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0 50 100 150 200 250 300 350

Depth (mm)

PD

D SOBP 4 cm, Measured 4.2 cmSOBP 10 cm, Measure 10.2 cmSOBP 16 cm, Measured 16.1cmSOBP 12 cm, Measured 12.0 cmSOBP 8 cm, Measured 8.1 cmSOBP 6 cm, Measured 6.1 cmSOBP 14 cm, Measured 14.3 cm

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Protons vs Carbon

Alex Trofimov MGH

Workflow

Clinical Workflow

New Patient Consultation

Diagnostic Imaging and

staging

Treatment Delivery

Treatment Planning

Simulation

Patient Referral

Completion of Treatment

Course

Designing treatment

Immobilization, CT scanning, scheduling

Imaging, testing, and staging

Networking/insurance

Initial clinical evaluation

1 – 40 treatments

Review and follow-up

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Patient Treatment Information FlowPassive Scattering

Clinical Proton Therapy Physics with Emphasis on Spot Scanning - 2012

Machine Shop

Elekta

Patient Treatment Information FlowScanning Beam


Elekta

ProBeam Varian Medical Systems

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Cancer ForefrontIMPTVarian AdvantageScanning BeamProton Platform

Varian Advantage—Varian Integrated Oncology NetworkProBeam™

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CT Simulation

(a)

(d)(c)

(b)

125 kVp CT

320 kVp CT

125 kVp CT

320 kVp CT

Yang et al. Med Phys 35 (5):1932-1941, 2008.

CT number to SPR Conversion

Degeneracy problem HU (ρ1, Z1) = HU (ρ2,Z2)

SPR(ρ1, Z1) ≠ SPR(ρ2,Z2)

60

Thyroid

Skin

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Variations in Human Tissue Composition

Summary of CT# Variation

Patient size is the dominating factor

Uncertainty is a function of tissue types

Tissue Groups

Time and Scanner

Size PositionCouch

PositionRoot-Sum-

Square (RSS)

CT#

Lung 1.0% 4.4% 2.2% 1.8% 5.3%

Soft 0.3% 0.5% 0.1% 0.4% 0.7%

Bone 0.6% 2.4% 1.3% 0.7% 2.9%

SPR

Lung 1.0% 4.5% 2.2% 1.8% 5.4%

Soft 0.3% 0.3% 0.1% 0.3% 0.5%

Bone 0.4% 1.6% 0.9% 0.5% 1.9%

Yang M. et al.

Uncertainty Category Uncertainty Source

CT imaging uncertainties The deviation of HU value from its calibrated value

when imaging a patient.

Uncertainties in predicting

theoretical CT numbers using tissue

substitute phantoms

This includes the uncertainties in the definition and

measurement using CT imaging for a tissue

substitute phantom, including the parameterization

of equation

Uncertainties to calculate SPRs of

human tissues

The uncertainties caused by modeling SPR and

variations of tissue composition in patient

population.

Uncertainties in mean excitation

energies

The value of mean excitation energy is critical in

calculating SPR

Uncertainties caused by an

assumption used in a dose

calculation algorithm

For simplicity, some treatment planning systems

ignored the SPR dependency on proton energy.

Comprehensive analysis of the stoichiometric calibration. Yang M. et al.

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Newhauser et al. PMB 53 (2008) 2327-2344

Mitigation of CT imaging uncertainties

Distal and proximal margins

Site-specific CT calibration (small phantom vs. large phantom)

In patient calibration of CT numbers for known anatomy (Moyer et al. 2010)

Avoiding couch or immobilization device outside CT scanner’s FOV

SPR uncertainties have a significant impact on proton dose distributions

Commonly it’s not visible on proton plans

-3.5% +3.5%

0% uncertainty Dong/MDACC

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IGRT

Cage Source

Cage Detector

Nozzle Detector

Nozzle Source

Hitachi gantrytwo X-ray systems extended


Thoracic

CSI

Prostate

Patient Setup

H&N

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Setup Error and Positional Variation of Immobilization Device

Couch Edge Effect

H. Yu et al.

(A) (B)

(C)

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Low Z fiducial markers

Free breathing treatment

Impact of Organ Motion To Proton Dose Distributions

Tsunashima/MDACC

Gated treated on exhale

Free breathing Treatment

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Treatment Planning

(to minimize treatment uncertainties)

Treatment Planning System Varian Eclipse Planning System:

Pencil beam algorithm for dose calculation

Passive scatter and PBS

Similar workflow in planning Passive Scatter (PS): technique similar to

3DCRT

IMPT: similar to IMRT (inverse planning)

Evaluation of a proton plan

Including robustness in planning

Trofimov et al. IJROBP 69(2): 444-453. (2007)

PS vs. IMPT

IMPTConventional PT

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Photons vs. Protons

Bortfeld T. IMRT: “A review and a preview”, Phys. Med. Biol. 51(13), 2006.

80

RC smear: 7.5 mm

Setup error: 0 mmTumor motion: 0 mm

AP margin: 7.5 mmRC smear: 7.5 mm

Setup error: 5 mmTumor motion: 5 mm

AP margin: 7.5 mm

20508095

100

Isodoselevels

PLANNED “DELIVERED”

Compensator Smearing and Aperture Expansion

Courtesy of Martijn Engelsman (MGH)

Single PTV?

Field A

Field B

CTV PTV A

PTV B

Beam specific PTV’s cannot easily be added and used for plan evaluation.

PTV A

PTV B

Single encompassing PTV is not appropriate

Addition of PTV’s not appropriate

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xxxx

Beam-specific PTV varies depending on beam angle and local heterogeneity

P. Park et al. 2011

Proton Lateral Penumbra vs. Distal Falloff

95-50% ~ 10 mm 95-50% ~ 4 mm

Dong

Inter-fractional Variations

Planning contours mapped to 24 in-room CTs Dong

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Simulation CT is a snapshot of patient’s anatomy!

Planning CT



Simulation CT is a snapshot of patient’s anatomy!

Original Proton PlanDose recalculated on the new anatomy

Bucci/Dong et al. ASTRO Abstract, 2007

Impact of Tumor Shrinkage on Proton Dose Distribution

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Smearing to Ensure Target Coverage

The bolus thickness at point P, as calculated by the ‘simple’ technique, is replaced by the thinnest bolus thickness calculated anywhere within d of the point P

Urie, et al Phys. Med. Biol., 1983.

Typical proton dose distributions

Dong/MDACC

An example of Robust IMPT planning

Beam 1 Beam 3Beam 2

Total dose:

Bortfeld

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nominal range 5 mm undershoot 5 mm overshoot

Conventional IMPT without Robust Planning

IMPT with Robust Planning

Improving Proton Therapy

Anatomy variations IGRT/adaptive radiotherapy

Robust optimization

Intra-fractional motion Gating, coaching, tracking…

Accurate stopping power ratios (CT number conversion)

Scanning pencil beams (IMPT)

Main differences between photons and protons

Factors Protons Photons

1CT # and stopping powers accuracy

Sensitive - affect range, distal target coverage or distal normal tissue sparing Not sensitive

2Target motion normal to beam

Affects margin, may affect dose distribution distal to target Affects margin

3Normal structure motion orthogonal to beam

Affects range, dose distribution distal to structure Minimal effect

4Target motion along beam direction No effect Affects margin

5Normal structure motion along beam direction No effect Minimal effect

6Complex inhomogeneities

Not well characterized, perturb dose distributions, degrade distal edge Well understood, effect not strong

7Anatomy changes over course of RT Affect dose distribution Minimal effect

8 Plan Evaluation

Impact of uncertainties significant, PTV concept not valid, validity of initial nominal plan questionable

PTV concept valid, dose distributions relatively invariant to uncertainties, initial plan acceptable approximations

Dong/Mohan/MDACC

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Summary of Proton Beam Properties

Proton beams stop - no exit dose

Although we don’t know exactly where they stop

Proton beams are more sensitive to

CT number accuracy

Organ motion

Anatomy changes

Proton plans are difficult to evaluate

Proton demonstrated excellent low dose sparing

IMPT shows additional benefits both in low dose sparing and

high dose conformality

IGRT and Adaptive RT will play an important role

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