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The Use of High-Energy Protons in Cancer Therapy
The Use of High-Energy Protons in Cancer Therapy
A Man - A Vision
A Man - A Vision
History of Proton Beam Therapy
History of Proton Beam Therapy
World Wide Proton Treatments*
World Wide Proton Treatments*
LLUMC Proton Treatment Center
LLUMC Proton Treatment Center
Main Interactions of Protons
Main Interactions of Protons
Why Protons are advantageous
Why Protons are advantageous
Uncertainties in Proton Therapy
Uncertainties in Proton Therapy
Treatment Planning
Treatment Planning
Treatment Delivery
Treatment Delivery
Computed Tomography (CT)
Computed Tomography (CT)
Processing of Imaging Data
Processing of Imaging Data
CT Calibration Curve
CT Calibration Curve
CT Calibration Curve Stoichiometric Method*
CT Calibration Curve Stoichiometric Method*
CT Calibration Curve Stoichiometric Method
CT Calibration Curve Stoichiometric Method
CT Range Uncertainties
CT Range Uncertainties
Proton Transmission Radiography - PTR
Proton Transmission Radiography - PTR
Comparison of CT Calibration Methods
Comparison of CT Calibration Methods
Proton Beam Computed Tomography
Proton Beam Computed Tomography
Proton Beam Computed Tomography
Proton Beam Computed Tomography
Proton Beam Design
Proton Beam Design
Proton Beam Shaping Devices
Proton Beam Shaping Devices
Ray-Tracing Dose Algorithm
Ray-Tracing Dose Algorithm
Effect of Heterogeneities
Effect of Heterogeneities
Effect of Heterogeneities
Effect of Heterogeneities
Pencil Beam Dose Algorithm
Pencil Beam Dose Algorithm
Monte Carlo Dose Algorithm
Monte Carlo Dose Algorithm
Comparison of Dose Algorithms
Comparison of Dose Algorithms
Combination of Proton Beams
Combination of Proton Beams
Combination of Proton Beams
Combination of Proton Beams
Lateral Penumbra
Lateral Penumbra
Lateral Penumbra
Lateral Penumbra
Nuclear Data for Treatment Planning (TP)
Nuclear Data for Treatment Planning (TP)
Nuclear Data for Proton Therapy
Nuclear Data for Proton Therapy
Selection of Elements
Selection of Elements
Nuclear Data for Proton Therapy
Nuclear Data for Proton Therapy
Nonelastic Nuclear Reactions
Nonelastic Nuclear Reactions
Nonelastic Nuclear Reactions
Nonelastic Nuclear Reactions
Proton Beam Activation Products
Proton Beam Activation Products
Positron Emission Tomography (PET) of Proton Beams
Positron Emission Tomography (PET) of Proton Beams
PET Dosimetry and Localization
PET Dosimetry and Localization
PET Localization for Functional Proton Radiosurgery
PET Localization for Functional Proton Radiosurgery
Relative Biological Effectiveness (RBE)
Relative Biological Effectiveness (RBE)
Linear Energy Transfer (LET) vs
Linear Energy Transfer (LET) vs
RBE vs
RBE vs
RBE of a Modulated Proton Beam
RBE of a Modulated Proton Beam
Open RBE Issues
Open RBE Issues
Summary
Summary

Презентация: «The Use of High-Energy Protons in Cancer Therapy». Автор: Reinhard Schulte. Файл: «The Use of High-Energy Protons in Cancer Therapy.ppt». Размер zip-архива: 4062 КБ.

The Use of High-Energy Protons in Cancer Therapy

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1 The Use of High-Energy Protons in Cancer Therapy

The Use of High-Energy Protons in Cancer Therapy

Reinhard W. Schulte Loma Linda University Medical Center

2 A Man - A Vision

A Man - A Vision

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.

3 History of Proton Beam Therapy

History of Proton Beam Therapy

1946 R. Wilson suggests use of protons 1954 First treatment of pituitary tumors 1958 First use of protons as a neurosurgical tool 1967 First large-field proton treatments in Sweden 1974 Large-field fractionated proton treatments program begins at HCL, Cambridge, MA 1990 First hospital-based proton treatment center opens at Loma Linda University Medical Center

4 World Wide Proton Treatments*

World Wide Proton Treatments*

Dubna (1967) 172 Moscow (1969) 3414 St. Petersburg (1969) 1029

Uppsala (1957): 309 PSI (1984): 3935 Clatterbridge(1989): 1033 Nice (1991): 1590 Orsay (1991): 1894 Berlin (1998): 166

HCL (1961) 6174

LLUMC (1990) 6174

Chiba (1979) 133 Tsukuba (1983) 700 Kashiwa (1998) 75

NAC (1993) 398

*from: Particles, Newsletter (Ed J. Sisterson), No. 28. July 2001

5 LLUMC Proton Treatment Center

LLUMC Proton Treatment Center

6 Main Interactions of Protons

Main Interactions of Protons

Electronic (a) ionization excitation Nuclear (b-d) Multiple Coulomb scattering (b), small q Elastic nuclear collision (c), large q Nonelastic nuclear interaction (d)

7 Why Protons are advantageous

Why Protons are advantageous

Relatively low entrance dose (plateau) Maximum dose at depth (Bragg peak) Rapid distal dose fall-off Energy modulation (Spread-out Bragg peak) RBE close to unity

8 Uncertainties in Proton Therapy

Uncertainties in Proton Therapy

Patient related:

Physics related:

Machine related:

Biology related:

Patient setup Patient movements Organ motion Body contour Target definition Relative biological effectiveness (RBE)

CT number conversion Dose calculation

Device tolerances Beam energy

9 Treatment Planning

Treatment Planning

Acquisition of imaging data (CT, MRI) Conversion of CT values into stopping power Delineation of regions of interest Selection of proton beam directions Design of each beam Optimization of the plan

10 Treatment Delivery

Treatment Delivery

Fabrication of apertures and boluses Beam calibration Alignment of patient using DRRs Computer-controlled dose delivery

11 Computed Tomography (CT)

Computed Tomography (CT)

Faithful reconstruction of patient’s anatomy Stacked 2D maps of linear X-ray attenuation Electron density relative to water can be derived Calibration curve relates CT numbers to relative proton stopping power

X-ray tube

Detector array

12 Processing of Imaging Data

Processing of Imaging Data

SP = dE/dxtissue /dE/dxwater

H = 1000 mtissue /mwater

Relative proton stopping power (SP)

CT Hounsfield values (H)

Calibration curve

Dose calculation

Isodose distribution

13 CT Calibration Curve

CT Calibration Curve

Proton interaction ? Photon interaction Bi- or tri- or multisegmental curves are in use No unique SP values for soft tissue Hounsfield range Tissue substitutes ? real tissues Fat anomaly

14 CT Calibration Curve Stoichiometric Method*

CT Calibration Curve Stoichiometric Method*

Step 1: Parameterization of H Choose tissue substitutes Obtain best-fitting parameters A, B, C

H = Nerel {A (ZPE)3.6 + B (Zcoh)1.9 + C}

Rel. electron density

Photo electric effect

Coherent scattering

Klein-Nishina cross section

*Schneider U. (1996), “The calibraion of CT Hounsfield units for radiotherapy treatment planning,” Phys. Med. Biol. 47, 487.

15 CT Calibration Curve Stoichiometric Method

CT Calibration Curve Stoichiometric Method

Step 2: Define Calibration Curve select different standard tissues with known composition (e.g., ICRP) calculate H using parametric equation for each tissue calculate SP using Bethe Bloch equation fit linear segments through data points

Fat

16 CT Range Uncertainties

CT Range Uncertainties

Two types of uncertainties inaccurate model parameters beam hardening artifacts Expected range errors

Soft tissue Bone Total H2O range abs. error H2O range abs. Error abs. error (cm) (mm) (cm) (mm) (mm) Brain 10.3 1.1 1.8 0.3 1.4 Pelvis 15.5 1.7 9 1.6 3.3

17 Proton Transmission Radiography - PTR

Proton Transmission Radiography - PTR

First suggested by Wilson (1946) Images contain residual energy/range information of individual protons Resolution limited by multiple Coulomb scattering Spatial resolution of 1mm possible

18 Comparison of CT Calibration Methods

Comparison of CT Calibration Methods

PTR used as a QA tool Comparison of measured and CT-predicted integrated stopping power Sheep head used as model Stoichiometric calibration (A) better than tissue substitute calibrations (B & C)

19 Proton Beam Computed Tomography

Proton Beam Computed Tomography

Proton CT for diagnosis first studied during the 1970s dose advantage over x rays not further developed after the advent of X-ray CT Proton CT for treatment planning and delivery renewed interest during the 1990s (2 Ph.D. theses) preliminary results are promising further R&D needed

20 Proton Beam Computed Tomography

Proton Beam Computed Tomography

Conceptual design single particle resolution 3D track reconstruction Si microstrip technology cone beam geometry rejection of scattered protons & neutrons

21 Proton Beam Design

Proton Beam Design

22 Proton Beam Shaping Devices

Proton Beam Shaping Devices

Wax bolus

Cerrobend aperture

Modulating wheels

23 Ray-Tracing Dose Algorithm

Ray-Tracing Dose Algorithm

One-dimensional dose calculation Water-equivalent depth (WED) along single ray SP Look-up table Reasonably accurate for simple hetero-geneities Simple and fast

WED

||

P

S

24 Effect of Heterogeneities

Effect of Heterogeneities

25 Effect of Heterogeneities

Effect of Heterogeneities

Range Uncertainties (measured with PTR) > 5 mm > 10 mm > 15 mm

Schneider U. (1994), “Proton radiography as a tool for quality control in proton therapy,” Med Phys. 22, 353.

26 Pencil Beam Dose Algorithm

Pencil Beam Dose Algorithm

Cylindrical coordinates Measured or calculated pencil kernel Water-equivalent depth Accounts for multiple Coloumb scattering more time consuming

27 Monte Carlo Dose Algorithm

Monte Carlo Dose Algorithm

Considered as “gold standard” Accounts for all relevant physical interactions Follows secondary particles Requires accurate cross section data bases Includes source geometry Very time consuming

28 Comparison of Dose Algorithms

Comparison of Dose Algorithms

Protons

Petti P. (1991), “Differential-pencil-beam dose calculations for charged particles,” Med Phys. 19, 137.

29 Combination of Proton Beams

Combination of Proton Beams

“Patch-field” design Targets wrapping around critical structures Each beam treats part of the target Accurate knowledge of lateral and distal penumbra is critical

Urie M. M. et al (1986), “Proton beam penumbra: effects of separation between patient and beam modifying devices,” Med Phys. 13, 734.

30 Combination of Proton Beams

Combination of Proton Beams

Excellent sparing of critical structures No perfect match between fields Dose non-uniformity at field junction “hot” and “cold” regions are possible Clinical judgment required

31 Lateral Penumbra

Lateral Penumbra

Penumbra factors: Upstream devices scattering foils range shifter modulator wheel bolus Air gap Patient scatter

32 Lateral Penumbra

Lateral Penumbra

Thickness of bolus ?, width of air gap ? ? lateral penumbra ? Dose algorithms can be inaccurate in predicting penumbra

Russel K. P. et al (2000), “Implementation of pencil kernel and depth penetration algorithms for treatment planning of proton beams,” Phys Med Biol 45, 9.

33 Nuclear Data for Treatment Planning (TP)

Nuclear Data for Treatment Planning (TP)

Experiment

Theory

Evaluation

† e.g., ICRU Report 63 ‡ e.g., Peregrine

Validation

Quality Assurance

Radiation Transport Codes for TP‡

Recommended Data†

Integral tests, benchmarks

34 Nuclear Data for Proton Therapy

Nuclear Data for Proton Therapy

Application Quantities needed Loss of primary protons Total nonelastic cross sections Dose calculation, radiation Diff. and doublediff. cross sections transport for neutron, charged particles, and g emission Estimation of RBE average energies for light ejectiles product recoil spectra PET beam localization Activation cross sections

35 Selection of Elements

Selection of Elements

Element Mainly present in ’ H, C, O Tissue, bolus N, P Tissue, bone Ca Bone, shielding materials Si Detectors, shielding materials Al, Fe, Cu, W, Pb Scatterers, apertures, shielding materials

36 Nuclear Data for Proton Therapy

Nuclear Data for Proton Therapy

Internet sites regarding nuclear data: International Atomic Energy Agency (Vienna) Online telnet access of Nuclear Data Information System Brookhaven National Laboratory Online telnet access of National Nuclear Data Center Los Alamos National Laboratory T2 Nuclear Information System. OECD Nuclear Energy Agency NUKE - Nuclear Information World Wide Web

37 Nonelastic Nuclear Reactions

Nonelastic Nuclear Reactions

Remove primary protons Contribute to absorbed dose: 100 MeV, ~5% 150 MeV, ~10% 250 MeV, ~20% Generate secondary particles neutral (n, g) charged (p, d, t, 3He, a, recoils)

38 Nonelastic Nuclear Reactions

Nonelastic Nuclear Reactions

Total Nonelastic Cross Sections

Source: ICRU Report 63, 1999

39 Proton Beam Activation Products

Proton Beam Activation Products

Activation Product Application / Significance Short-lived b+ emitters in-vivo dosimetry (e.g., 11C, 13N, 18F) beam localization 7Be none Medium mass products none (e.g., 22Na, 42K, 48V, 51Cr) Long-lived products in radiation protection collimators, shielding

40 Positron Emission Tomography (PET) of Proton Beams

Positron Emission Tomography (PET) of Proton Beams

Reaction Half-life Threshold Energy (MeV) e 16O(p,pn)15O 2.0 min 16.6 16O(p,2p2n)13N 10.0 min 5.5 16O(p,3p3n)13C 20.3 min 14.3 14N(p,pn)13N 10.0 min 11.3 14N(p,2p2n)11C 20.3 min 3.1 12C(p,pn)17N 20.3 min 20.3

41 PET Dosimetry and Localization

PET Dosimetry and Localization

Experiment vs. simulation activity plateau (experiment) maximum activity (simulation) cross sections may be inaccurate activity fall-off 4-5 mm before Bragg peak

Del Guerra A., et al. (1997) “PET Dosimetry in proton radiotherapy: a Monte Carlo Study,” Appl. Radiat. Isot. 10-12, 1617.

42 PET Localization for Functional Proton Radiosurgery

PET Localization for Functional Proton Radiosurgery

Treatment of Parkinson’s disease Multiple narrow p beams of high energy (250 MeV) Focused shoot-through technique Very high local dose (> 100 Gy) PET verification possible after test dose

43 Relative Biological Effectiveness (RBE)

Relative Biological Effectiveness (RBE)

Clinical RBE: 1 Gy proton dose ? 1.1 Gy Cobalt g dose (RBE = 1.1) RBE vs. depth is not constant RBE also depends on dose biological system (cell type) clinical endpoint (early response, late effect)

44 Linear Energy Transfer (LET) vs

Linear Energy Transfer (LET) vs

Depth

45 RBE vs

RBE vs

LET

Source: S.M. Seltzer, NISTIIR 5221

46 RBE of a Modulated Proton Beam

RBE of a Modulated Proton Beam

Source: S.M. Seltzer, NISTIIR 5221

47 Open RBE Issues

Open RBE Issues

Single RBE value of 1.1 may not be sufficient Biologically effective dose vs. physical dose Effect of proton nuclear interactions on RBE Energy deposition at the nanometer level - clustering of DNA damage

48 Summary

Summary

Areas where (high-energy) physics may contribute to proton radiation therapy: Development of proton computed tomography Nuclear data evaluation and benchmarking Radiation transport codes for treatment planning In vivo localization and dosimetry of proton beams Influence of nuclear events on RBE

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