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The Use of High-Energy Protons in Cancer Therapy
The Use of High-Energy Protons in Cancer Therapy
World Wide Proton Treatments*
World Wide Proton Treatments*
LLUMC Proton Treatment Center
LLUMC Proton Treatment Center
LLUMC Proton Treatment Center
LLUMC Proton Treatment Center
LLUMC Proton Treatment Center
LLUMC Proton Treatment Center
LLUMC Proton Treatment Center
LLUMC Proton Treatment Center
CT Range Uncertainties
CT Range Uncertainties
CT Range Uncertainties
CT Range Uncertainties
Comparison of CT Calibration Methods
Comparison of CT Calibration Methods
Proton Beam Design
Proton Beam Design
Proton Beam Shaping Devices
Proton Beam Shaping Devices
Effect of Heterogeneities
Effect of Heterogeneities
Effect of Heterogeneities
Effect of Heterogeneities
Monte Carlo Dose Algorithm
Monte Carlo Dose Algorithm
Comparison of Dose Algorithms
Comparison of Dose Algorithms
Comparison of Dose Algorithms
Comparison of Dose Algorithms
Combination of Proton Beams
Combination of Proton Beams
Combination of Proton Beams
Combination of Proton Beams
Positron Emission Tomography (PET) of Proton Beams
Positron Emission Tomography (PET) of Proton Beams
PET Localization for Functional Proton Radiosurgery
PET Localization for Functional Proton Radiosurgery
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The Use of High-Energy Protons in Cancer Therapy

содержание презентации «The Use of High-Energy Protons in Cancer Therapy.ppt»
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1The Use of High-Energy Protons in 23fast. WED. ||. P. S.
Cancer Therapy. Reinhard W. Schulte Loma 24Effect of Heterogeneities.
Linda University Medical Center. 25Effect of Heterogeneities. Range
2A Man - A Vision. In 1946 Harvard Uncertainties (measured with PTR) > 5
physicist Robert Wilson (1914-2000) mm > 10 mm > 15 mm. Schneider U.
suggested*: Protons can be used clinically (1994), “Proton radiography as a tool for
Accelerators are available Maximum quality control in proton therapy,” Med
radiation dose can be placed into the Phys. 22, 353.
tumor Proton therapy provides sparing of 26Pencil Beam Dose Algorithm.
normal tissues Modulator wheels can spread Cylindrical coordinates Measured or
narrow Bragg peak. *Wilson, R.R. (1946), calculated pencil kernel Water-equivalent
“Radiological use of fast protons,” depth Accounts for multiple Coloumb
Radiology 47, 487. scattering more time consuming.
3History of Proton Beam Therapy. 1946 27Monte Carlo Dose Algorithm. Considered
R. Wilson suggests use of protons 1954 as “gold standard” Accounts for all
First treatment of pituitary tumors 1958 relevant physical interactions Follows
First use of protons as a neurosurgical secondary particles Requires accurate
tool 1967 First large-field proton cross section data bases Includes source
treatments in Sweden 1974 Large-field geometry Very time consuming.
fractionated proton treatments program 28Comparison of Dose Algorithms.
begins at HCL, Cambridge, MA 1990 First Protons. Petti P. (1991),
hospital-based proton treatment center “Differential-pencil-beam dose
opens at Loma Linda University Medical calculations for charged particles,” Med
Center. Phys. 19, 137.
4World Wide Proton Treatments*. Dubna 29Combination of Proton Beams.
(1967) 172 Moscow (1969) 3414 St. “Patch-field” design Targets wrapping
Petersburg (1969) 1029. Uppsala (1957): around critical structures Each beam
309 PSI (1984): 3935 Clatterbridge(1989): treats part of the target Accurate
1033 Nice (1991): 1590 Orsay (1991): 1894 knowledge of lateral and distal penumbra
Berlin (1998): 166. HCL (1961) 6174. LLUMC is critical. Urie M. M. et al (1986),
(1990) 6174. Chiba (1979) 133 Tsukuba “Proton beam penumbra: effects of
(1983) 700 Kashiwa (1998) 75. NAC (1993) separation between patient and beam
398. *from: Particles, Newsletter (Ed J. modifying devices,” Med Phys. 13, 734.
Sisterson), No. 28. July 2001. 30Combination of Proton Beams. Excellent
5LLUMC Proton Treatment Center. sparing of critical structures No perfect
6Main Interactions of Protons. match between fields Dose non-uniformity
Electronic (a) ionization excitation at field junction “hot” and “cold” regions
Nuclear (b-d) Multiple Coulomb scattering are possible Clinical judgment required.
(b), small q Elastic nuclear collision 31Lateral Penumbra. Penumbra factors:
(c), large q Nonelastic nuclear Upstream devices scattering foils range
interaction (d). shifter modulator wheel bolus Air gap
7Why Protons are advantageous. Patient scatter.
Relatively low entrance dose (plateau) 32Lateral Penumbra. Thickness of bolus
Maximum dose at depth (Bragg peak) Rapid ?, width of air gap ? ? lateral penumbra ?
distal dose fall-off Energy modulation Dose algorithms can be inaccurate in
(Spread-out Bragg peak) RBE close to predicting penumbra. Russel K. P. et al
unity. (2000), “Implementation of pencil kernel
8Uncertainties in Proton Therapy. and depth penetration algorithms for
Patient related: Physics related: Machine treatment planning of proton beams,” Phys
related: Biology related: Patient setup Med Biol 45, 9.
Patient movements Organ motion Body 33Nuclear Data for Treatment Planning
contour Target definition Relative (TP). Experiment. Theory. Evaluation. †
biological effectiveness (RBE). CT number e.g., ICRU Report 63 ‡ e.g., Peregrine.
conversion Dose calculation. Device Validation. Quality Assurance. Radiation
tolerances Beam energy. Transport Codes for TP‡. Recommended
9Treatment Planning. Acquisition of Data†. Integral tests, benchmarks.
imaging data (CT, MRI) Conversion of CT 34Nuclear Data for Proton Therapy.
values into stopping power Delineation of Application Quantities needed Loss of
regions of interest Selection of proton primary protons Total nonelastic cross
beam directions Design of each beam sections Dose calculation, radiation Diff.
Optimization of the plan. and doublediff. cross sections transport
10Treatment Delivery. Fabrication of for neutron, charged particles, and g
apertures and boluses Beam calibration emission Estimation of RBE average
Alignment of patient using DRRs energies for light ejectiles product
Computer-controlled dose delivery. recoil spectra PET beam localization
11Computed Tomography (CT). Faithful Activation cross sections.
reconstruction of patient’s anatomy 35Selection of Elements. Element Mainly
Stacked 2D maps of linear X-ray present in ’ H, C, O Tissue, bolus N, P
attenuation Electron density relative to Tissue, bone Ca Bone, shielding materials
water can be derived Calibration curve Si Detectors, shielding materials Al, Fe,
relates CT numbers to relative proton Cu, W, Pb Scatterers, apertures, shielding
stopping power. X-ray tube. Detector materials.
array. 36Nuclear Data for Proton Therapy.
12Processing of Imaging Data. SP = Internet sites regarding nuclear data:
dE/dxtissue /dE/dxwater. H = 1000 mtissue International Atomic Energy Agency
/mwater. Relative proton stopping power (Vienna) Online telnet access of Nuclear
(SP). CT Hounsfield values (H). Data Information System Brookhaven
Calibration curve. Dose calculation. National Laboratory Online telnet access
Isodose distribution. of National Nuclear Data Center Los Alamos
13CT Calibration Curve. Proton National Laboratory T2 Nuclear Information
interaction ? Photon interaction Bi- or System. OECD Nuclear Energy Agency NUKE -
tri- or multisegmental curves are in use Nuclear Information World Wide Web.
No unique SP values for soft tissue 37Nonelastic Nuclear Reactions. Remove
Hounsfield range Tissue substitutes ? real primary protons Contribute to absorbed
tissues Fat anomaly. dose: 100 MeV, ~5% 150 MeV, ~10% 250 MeV,
14CT Calibration Curve Stoichiometric ~20% Generate secondary particles neutral
Method*. Step 1: Parameterization of H (n, g) charged (p, d, t, 3He, a, recoils).
Choose tissue substitutes Obtain 38Nonelastic Nuclear Reactions. Total
best-fitting parameters A, B, C. H = Nerel Nonelastic Cross Sections. Source: ICRU
{A (ZPE)3.6 + B (Zcoh)1.9 + C}. Rel. Report 63, 1999.
electron density. Photo electric effect. 39Proton Beam Activation Products.
Coherent scattering. Klein-Nishina cross Activation Product Application /
section. *Schneider U. (1996), “The Significance Short-lived b+ emitters
calibraion of CT Hounsfield units for in-vivo dosimetry (e.g., 11C, 13N, 18F)
radiotherapy treatment planning,” Phys. beam localization 7Be none Medium mass
Med. Biol. 47, 487. products none (e.g., 22Na, 42K, 48V, 51Cr)
15CT Calibration Curve Stoichiometric Long-lived products in radiation
Method. Step 2: Define Calibration Curve protection collimators, shielding.
select different standard tissues with 40Positron Emission Tomography (PET) of
known composition (e.g., ICRP) calculate H Proton Beams. Reaction Half-life Threshold
using parametric equation for each tissue Energy (MeV) e 16O(p,pn)15O 2.0 min 16.6
calculate SP using Bethe Bloch equation 16O(p,2p2n)13N 10.0 min 5.5 16O(p,3p3n)13C
fit linear segments through data points. 20.3 min 14.3 14N(p,pn)13N 10.0 min 11.3
Fat. 14N(p,2p2n)11C 20.3 min 3.1 12C(p,pn)17N
16CT Range Uncertainties. Two types of 20.3 min 20.3.
uncertainties inaccurate model parameters 41PET Dosimetry and Localization.
beam hardening artifacts Expected range Experiment vs. simulation activity plateau
errors. Soft tissue Bone Total H2O range (experiment) maximum activity (simulation)
abs. error H2O range abs. Error abs. error cross sections may be inaccurate activity
(cm) (mm) (cm) (mm) (mm) Brain 10.3 1.1 fall-off 4-5 mm before Bragg peak. Del
1.8 0.3 1.4 Pelvis 15.5 1.7 9 1.6 3.3. Guerra A., et al. (1997) “PET Dosimetry in
17Proton Transmission Radiography - PTR. proton radiotherapy: a Monte Carlo Study,”
First suggested by Wilson (1946) Images Appl. Radiat. Isot. 10-12, 1617.
contain residual energy/range information 42PET Localization for Functional Proton
of individual protons Resolution limited Radiosurgery. Treatment of Parkinson’s
by multiple Coulomb scattering Spatial disease Multiple narrow p beams of high
resolution of 1mm possible. energy (250 MeV) Focused shoot-through
18Comparison of CT Calibration Methods. technique Very high local dose (> 100
PTR used as a QA tool Comparison of Gy) PET verification possible after test
measured and CT-predicted integrated dose.
stopping power Sheep head used as model 43Relative Biological Effectiveness
Stoichiometric calibration (A) better than (RBE). Clinical RBE: 1 Gy proton dose ?
tissue substitute calibrations (B & 1.1 Gy Cobalt g dose (RBE = 1.1) RBE vs.
C). depth is not constant RBE also depends on
19Proton Beam Computed Tomography. dose biological system (cell type)
Proton CT for diagnosis first studied clinical endpoint (early response, late
during the 1970s dose advantage over x effect).
rays not further developed after the 44Linear Energy Transfer (LET) vs.
advent of X-ray CT Proton CT for treatment Depth.
planning and delivery renewed interest 45RBE vs. LET. Source: S.M. Seltzer,
during the 1990s (2 Ph.D. theses) NISTIIR 5221.
preliminary results are promising further 46RBE of a Modulated Proton Beam.
R&D needed. Source: S.M. Seltzer, NISTIIR 5221.
20Proton Beam Computed Tomography. 47Open RBE Issues. Single RBE value of
Conceptual design single particle 1.1 may not be sufficient Biologically
resolution 3D track reconstruction Si effective dose vs. physical dose Effect of
microstrip technology cone beam geometry proton nuclear interactions on RBE Energy
rejection of scattered protons & deposition at the nanometer level -
neutrons. clustering of DNA damage.
21Proton Beam Design. 48Summary. Areas where (high-energy)
22Proton Beam Shaping Devices. Wax physics may contribute to proton radiation
bolus. Cerrobend aperture. Modulating therapy: Development of proton computed
wheels. tomography Nuclear data evaluation and
23Ray-Tracing Dose Algorithm. benchmarking Radiation transport codes for
One-dimensional dose calculation treatment planning In vivo localization
Water-equivalent depth (WED) along single and dosimetry of proton beams Influence of
ray SP Look-up table Reasonably accurate nuclear events on RBE.
for simple hetero-geneities Simple and
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The Use of High-Energy Protons in Cancer Therapy

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