neutron interactions – part ii - uthgsbsmedphys.org– adenoidcystic carcinoma (cancer of parotid...

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Neutron Interactions – Part IINeutron Interactions – Part II

George Starkschall, Ph.D.George Starkschall, Ph.D.

Based on lectures by Rebecca Howell, PhD

Why do we care about neutronsWhy do we care about neutrons

• Neutrons in radiation therapy– Neutron Therapy

• Fast neutron therapy

• Boron neutron capture therapy

– Contamination neutrons• in x-ray therapy

• in proton therapy

• Neutron Shielding

• Neutron Dose

• Neutrons in radiation therapy– Neutron Therapy

• Fast neutron therapy

• Boron neutron capture therapy

– Contamination neutrons• in x-ray therapy

• in proton therapy

• Neutron Shielding

• Neutron Dose

Neutron RadiotherapyNeutron Radiotherapy

• Fast Neutron Therapy Beams

• Boron Neutron Capture Therapy

• History and Current Facilities

• Treatment sites

• Fast Neutron Therapy Beams

• Boron Neutron Capture Therapy

• History and Current Facilities

• Treatment sites

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Fast Neutrons Methods of Production


• Neutrons can be produced in a cyclotron by accelerating deuterons or protons and impinging them on a beryllium target.

• Protons or deuterons must be accelerated to ≥50 MeV to produce neutron beams with penetration comparable to megavoltage x-rays.

• Neutrons can be produced in a cyclotron by accelerating deuterons or protons and impinging them on a beryllium target.

• Protons or deuterons must be accelerated to ≥50 MeV to produce neutron beams with penetration comparable to megavoltage x-rays.



• Accelerating deuterons to ≥50MeV– Requires very large

cyclotron, too large for hospital.

• Accelerating deuterons to ≥50MeV– Requires very large

cyclotron, too large for hospital.

• Accelerating protons to ≥50MeV– Much smaller

cyclotron b/c proton has ½ the mass of deuteron.

• Accelerating protons to ≥50MeV– Much smaller

cyclotron b/c proton has ½ the mass of deuteron.

P+n

Fast Neutrons from Deuteron Bombardment of Be

Fast Neutrons from Deuteron Bombardment of Be

• Stripping Process –– Proton is stripped from the deuteron.

– Recoil neutron retains some of the incident kinetic energy of the accelerated deuteron.

– For each neutron produced, one atom of Be is converted to B.

• Stripping Process –– Proton is stripped from the deuteron.

– Recoil neutron retains some of the incident kinetic energy of the accelerated deuteron.

– For each neutron produced, one atom of Be is converted to B.

n

+

3

Fast Neutron Spectrafrom Deuteron Bombardment of Be

Fast Neutron Spectrafrom Deuteron Bombardment of Be

• Neutron spectra consists of a single peak, with a modal value of about 40% of the energy of the incident deuterons.

• Neutron spectra consists of a single peak, with a modal value of about 40% of the energy of the incident deuterons.

Hall, Fig 24.2a

Fast Neutrons from Proton Bombardment of Be

Fast Neutrons from Proton Bombardment of Be

• Knock-out Process – Protons impinge target of beryllium, where they

knock-out neutrons.

– For each neutron “knocked-out”, one atom of Be is converted to B.

• Knock-out Process – Protons impinge target of beryllium, where they

knock-out neutrons.

– For each neutron “knocked-out”, one atom of Be is converted to B.

nP+

+

Fast Neutron Spectrafrom Proton Bombardment of Be

Fast Neutron Spectrafrom Proton Bombardment of Be

• The neutron spectra spans a wide range of energies.

• Necessary to filter out the low energy neutrons to achieve acceptable depth dose distribution.

• The neutron spectra spans a wide range of energies.

• Necessary to filter out the low energy neutrons to achieve acceptable depth dose distribution.

Hall, Fig 24.2b

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Isodose Distribution

Isodose Distribution

• Neutron beam (produced from 50-MeV protons or deuterons) has comparable isodose distribution to 6MV photon beam.

• Neutron beam (produced from 50-MeV protons or deuterons) has comparable isodose distribution to 6MV photon beam.

Bewley, Fig 4.3

Long Treatment DistancesLong Treatment Distances

• Neutron beam treatment distances are 100 to 140 cm due to large collimator size

• Neutron beam treatment distances are 100 to 140 cm due to large collimator size

Long Treatment DistancesLong Treatment Distances

• Collimator materials:– Hydrogenous material to slow the

neutrons

– Absorber material to remove thermal neutrons

– Pb or other high Z material to absorb -ray component (remember that activation follows absorption, -photon is often the result)

• Collimator materials:– Hydrogenous material to slow the

neutrons

– Absorber material to remove thermal neutrons

– Pb or other high Z material to absorb -ray component (remember that activation follows absorption, -photon is often the result)

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Clinical Experience with Fast Neutrons


• Early experiences:–First experience at Lawrence

Berkeley Laboratory

–Hammersmith Hospital in London

• Early experiences:–First experience at Lawrence

Berkeley Laboratory

–Hammersmith Hospital in London



• 3 Neutron Therapy Facilities in the US– Northern Illinois University Institute for

Neutron Therapy at Fermilab

– University of Washington Medical Center

– Gershenson Radiation Oncology Center, Detroit

• 3 Neutron Therapy Facilities in the US– Northern Illinois University Institute for

Neutron Therapy at Fermilab

– University of Washington Medical Center

– Gershenson Radiation Oncology Center, Detroit

Modern Neutron Therapy Facilities

Modern Neutron Therapy Facilities

University of Washington Medical

Center

• Cyclotron accelerates protons (50.5 MeV)

• Rotating gantry

• MLC equipped

University of Washington Medical

Center

• Cyclotron accelerates protons (50.5 MeV)

• Rotating gantry

• MLC equipped

Gershenson Radiation Oncology

Center

• Superconducting cyclotron accelerates deuterons (48.5 MeV)

• Rotating Gantry

• MLC equipped

Gershenson Radiation Oncology

Center

• Superconducting cyclotron accelerates deuterons (48.5 MeV)

• Rotating Gantry

• MLC equipped

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Fast Neutron TherapyFast Neutron Therapy

Considerations:

• Who should be treated with neutrons?– Subgroups of patients that may benefit from

neutrons.• Slower growing tumors.

• Cancers w/ good response to neutron Therapy:– adenoidcystic carcinoma (cancer of parotid glands)

– locally advanced prostate cancer

– locally advanced head and neck tumors

– inoperable sarcomas

– cancer of the salivary glands

Considerations:

• Who should be treated with neutrons?– Subgroups of patients that may benefit from

neutrons.• Slower growing tumors.

• Cancers w/ good response to neutron Therapy:– adenoidcystic carcinoma (cancer of parotid glands)

– locally advanced prostate cancer

– locally advanced head and neck tumors

– inoperable sarcomas

– cancer of the salivary glands

A few references on neutrons in radiation therapy

A few references on neutrons in radiation therapy

• Fast neutron radiotherapy for locally advanced prostate cancer. Final report of Radiation Therapy Oncology Group randomized clinical trial. (American Journal of Clinical Oncology. 1993 Apr; 16(2):164-7)

• Fast neutron irradiation of metastatic cervical adenopathy: The results of a randomized RTOG study. (International Journal of Radiation Oncology Biology Physics, Vol. 9, pp. 1267-1270)

• Neutron versus photon irradiation for unresectable salivary gland tumors: Final report of an RTOG-MRC randomized clinical trial. (International Journal of Radiation Oncology Biology Physics, Vol. 27, pp. 235-240)

• Fast neutron radiotherapy for soft tissue and cartilaginous sarcomas at high risk for local recurrence. (International Journal of Radiation Oncology Biology Physics, Vol. 50, No. 2, pp. 449–456)

• Photon versus fast neutron external beam radiotherapy in the treatment of locally advanced prostate cancer: results of a randomized prospective trial. (International Journal of Radiation Oncology Biology Physics, Vol. 28, pp. 47-54)

• Fast neutron radiotherapy for locally advanced prostate cancer. Final report of Radiation Therapy Oncology Group randomized clinical trial. (American Journal of Clinical Oncology. 1993 Apr; 16(2):164-7)

• Fast neutron irradiation of metastatic cervical adenopathy: The results of a randomized RTOG study. (International Journal of Radiation Oncology Biology Physics, Vol. 9, pp. 1267-1270)

• Neutron versus photon irradiation for unresectable salivary gland tumors: Final report of an RTOG-MRC randomized clinical trial. (International Journal of Radiation Oncology Biology Physics, Vol. 27, pp. 235-240)

• Fast neutron radiotherapy for soft tissue and cartilaginous sarcomas at high risk for local recurrence. (International Journal of Radiation Oncology Biology Physics, Vol. 50, No. 2, pp. 449–456)

• Photon versus fast neutron external beam radiotherapy in the treatment of locally advanced prostate cancer: results of a randomized prospective trial. (International Journal of Radiation Oncology Biology Physics, Vol. 28, pp. 47-54)

Boron-Neutron Capture TherapyBoron-Neutron Capture Therapy

• Preferentially deliver boron-containing drug to the tumor.

• Then deliver thermal (0.025 eV) neutrons, which interact with the boron to produce alpha particles.– Recall 10B has large thermal cross section: = 3837

barns

• 10B absorbs the thermal energy neutron and ejects energetic alpha particle (1.47MeV) and lithium ion (0.84MeV) which deposit most of their energy within the cell containing the original 10B atom.

• Preferentially deliver boron-containing drug to the tumor.

• Then deliver thermal (0.025 eV) neutrons, which interact with the boron to produce alpha particles.– Recall 10B has large thermal cross section: = 3837

barns

• 10B absorbs the thermal energy neutron and ejects energetic alpha particle (1.47MeV) and lithium ion (0.84MeV) which deposit most of their energy within the cell containing the original 10B atom.

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Why Boron?Why Boron?Several nuclides have high thermal neutron , but 10B is the best choice for several reasons:

1. it is non-radioactive and readily available, comprising approximately 20% of naturally occurring boron;

2. Emitted particles ( and 7Li) have high LETCombined path lengths are approximately one cell diameter; i.e., about 12 microns, theoretically limiting the radiation effect to those tumor cells that have taken up a sufficient amount of 10B, and simultaneously sparing normal cells

3. Chemistry of boron is well understood and allows it to be readily incorporated into a multitude of different chemical structures.

Several nuclides have high thermal neutron , but 10B is the best choice for several reasons:

1. it is non-radioactive and readily available, comprising approximately 20% of naturally occurring boron;

2. Emitted particles ( and 7Li) have high LETCombined path lengths are approximately one cell diameter; i.e., about 12 microns, theoretically limiting the radiation effect to those tumor cells that have taken up a sufficient amount of 10B, and simultaneously sparing normal cells

3. Chemistry of boron is well understood and allows it to be readily incorporated into a multitude of different chemical structures.

Boron-Neutron Capture TherapyBoron-Neutron Capture Therapy

• Beam Energy Selection– Limited penetration of thermal neutrons.

• Thermal neutrons rapidly attenuated by tissue.

• HVL only about 1.5cm.

• Not possible to treat depths greater than a few cm.

– Can use epithermal neutrons (1 eV-10 keV), which are thermalized by tissue (via collisions with H).

• Peak in dose occurs at 2 to 3cm; – Avoid high surface doses, but still poorly penetrating!

• Beam Energy Selection– Limited penetration of thermal neutrons.

• Thermal neutrons rapidly attenuated by tissue.

• HVL only about 1.5cm.

• Not possible to treat depths greater than a few cm.

– Can use epithermal neutrons (1 eV-10 keV), which are thermalized by tissue (via collisions with H).

• Peak in dose occurs at 2 to 3cm; – Avoid high surface doses, but still poorly penetrating!

Boron-10 Neutron InteractionBoron-10 Neutron Interaction

• An epithermal beam rapidly loses energy by elastic scattering in tissue.

• An epithermal beam rapidly loses energy by elastic scattering in tissue.

http://web.mit.edu/nrl/www/bnct/info/description/description.html

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• The thermal neutrons are captured by the 10B nuclei, which become 11B nuclei in an excited state for a very short time (~ 10-12 s).

• The thermal neutrons are captured by the 10B nuclei, which become 11B nuclei in an excited state for a very short time (~ 10-12 s).



• The 11B nuclei then splits into alpha particles, 7Li recoil nuclei and in 94% of the reactions, gamma rays.

• The 11B nuclei then splits into alpha particles, 7Li recoil nuclei and in 94% of the reactions, gamma rays.


Treatment Sites for BNCTTreatment Sites for BNCT

• Clinical Trials for:– Glioblastoma Multiforme (GBM)

• Sweet and colleagues first demonstrated that certain boron compounds would concentrate in human brain tumor relative to normal brain tissue.1

– Melanoma

• Clinical Trials for:– Glioblastoma Multiforme (GBM)

• Sweet and colleagues first demonstrated that certain boron compounds would concentrate in human brain tumor relative to normal brain tissue.1

– Melanoma

1(Sweet, W.H., Javid, M., "The possible use of neutron-capturing Isotopes such as boron-10 in the treatment of neoplasms," I. Intracranial Tumors, J. Neurosurg., 9:200-209, (1952) )

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Production of Secondary NeutronsProduction of Secondary Neutrons

Secondary Neutrons in Radiation Therapy


• X-Ray Therapy– Neutrons can be produced via (n)

reactions primarily with high atomic number materials within the treatment head.

• X-Ray Therapy– Neutrons can be produced via (n)

reactions primarily with high atomic number materials within the treatment head.



• Proton Therapy– Neutrons can be produced via (pn)

reactions, not limited to high Z materials.• At the high energies other reactions

are also possible

• Proton Therapy– Neutrons can be produced via (pn)

reactions, not limited to high Z materials.• At the high energies other reactions

are also possible

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Production of Neutrons Production of Neutrons

(,n) Reactions(,n) Reactions

Bremsstrahlung SpectrumBremsstrahlung Spectrum

0.0%

0.5%

1.0%

1.5%

2.0%

2.5%

3.0%

3.5%

4.0%

4.5%

5.0%

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19

per

cen

t p

ho

ton

flu

ence

(%

)

energy (MeV)

Particle Production Cross Sections


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0.0%

1.0%

2.0%

3.0%

4.0%

5.0%

6.0%

7.0%

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19

perc

ent

phot

on f

luen

ce (

%)

energy (MeV)

18MV 15MV

(-n) Reaction Cross-Sections Elements in Tissue (C,O,N)

(-n) Reaction Cross-Sections Elements in Tissue (C,O,N)

Note:

• Threshold energies are much higher compared to high Z

• The magnitude of the reaction x-sections are an order of magnitude lower than for high Z (0.005 – 0.02).

•These data are from the T-2 Nuclear Information Service.

Secondary Neutron Spectra from Clinical Photon beamsSecondary Neutron Spectra from Clinical Photon beams

• The initial distribution of secondary neutrons generated in the linac head from (,n) reactions is approximately isotropic and resembles a fission spectrum.

• The initial distribution of secondary neutrons generated in the linac head from (,n) reactions is approximately isotropic and resembles a fission spectrum.

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Secondary Neutron Spectra from Clinical Photon beamsSecondary Neutron Spectra from Clinical Photon beams• The neutron energy decreases as a

consequence of neutron transport through the components of the treatment head (primary collimators, flattening filter, secondary jaws, MLC, etc). – The primary mechanisms of energy loss in

high Z materials in the linac head are inelastic scattering and (n,2n) reactions.

• The neutron energy decreases as a consequence of neutron transport through the components of the treatment head (primary collimators, flattening filter, secondary jaws, MLC, etc). – The primary mechanisms of energy loss in

high Z materials in the linac head are inelastic scattering and (n,2n) reactions.

Photoneutron SpectraEffect of collimators and room shielding

Photoneutron SpectraEffect of collimators and room shielding• Photoneutron spectrum

for 15 MeV electrons striking W target (designated 15MeV W PN bare)– Spectrum with 10 cm of W

shielding surrounding W target.

– Spectrum with 10 cm of W shielding surrounding W target inside a concrete room

• A 252Cf fission spectrum shown for comparison

• Photoneutron spectrum for 15 MeV electrons striking W target (designated 15MeV W PN bare)– Spectrum with 10 cm of W

shielding surrounding W target.

– Spectrum with 10 cm of W shielding surrounding W target inside a concrete room

• A 252Cf fission spectrum shown for comparison

NCRP-79 Fig 25

Secondary Neutron SpectraMeasured for Varian 18MV

Linac

Secondary Neutron SpectraMeasured for Varian 18MV

Linac

• Howell et al. Medical Physics, Vol. 36, No. 9, 4027-4038 (2009)• Howell et al. Medical Physics, Vol. 36, No. 9, 4027-4038 (2009)

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Production of Neutrons Production of Neutrons

(p,n) Reactions(p,n) Reactions

Proton SpectraProton Spectra

• Clinical proton beams have a much smaller energy spread compared to photon beams (Gaussian distribution).

• Also, the maximum energies are considerably higher and clinical beam energies may include 100 MeV, 160 MeV, 200 MeV, and 250 MeV beams.

• Clinical proton beams have a much smaller energy spread compared to photon beams (Gaussian distribution).

• Also, the maximum energies are considerably higher and clinical beam energies may include 100 MeV, 160 MeV, 200 MeV, and 250 MeV beams.



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November 2007 Rebecca M. Howell, Ph.D.



Secondary Neutron Spectra for Clinical Proton Beams

Secondary Neutron Spectra for Clinical Proton Beams

• Zhang et al. Phys. Med. Biol. 53 (2008) 187–201• Zhang et al. Phys. Med. Biol. 53 (2008) 187–201

ReferencesReferences• Eric J. Hall. Radiobiology for the Radiologist 5th Ed. (2000)• Frank H. Attix. Introduction to Radiological Physics and Radiation

Dosimetry. (1986)• Patton H. McGinley. Shielding Techniques for Radiation Oncology Facilities

2nd ed.• D.K. Bewley. The Physics and Radiobiology of Fast Neutron Beams (1989)• AAPM Report 7 Protocol for Neutron Beam Dosimetry• ICRU 45 Clinical Neutron Dosimetry• NCRP 79 Neutron Contamination from Medical Electron Accelerators• NCRP 151 Structural Shielding Design and Evaluation for Megavoltage X-

and Gamma-Ray Radiotherapy Facilities (2005)• ICRP74/ICRU57 (Jointly published by both ICRU and ICRP) Conversion

Coefficients for use in Radiological Protection against External Radiation• ICRP 60 Recommendations of the International Commission on Radiological

Protection• ICRU 66 Determination of Operational Dose Equivalent Quantities for

Neutrons• http://web.mit.edu/nrl/www/bnct/info/description/description.html• T2.lanl.gov• http://www.nndc.bnl.gov/nudat2

• Eric J. Hall. Radiobiology for the Radiologist 5th Ed. (2000)• Frank H. Attix. Introduction to Radiological Physics and Radiation

Dosimetry. (1986)• Patton H. McGinley. Shielding Techniques for Radiation Oncology Facilities

2nd ed.• D.K. Bewley. The Physics and Radiobiology of Fast Neutron Beams (1989)• AAPM Report 7 Protocol for Neutron Beam Dosimetry• ICRU 45 Clinical Neutron Dosimetry• NCRP 79 Neutron Contamination from Medical Electron Accelerators• NCRP 151 Structural Shielding Design and Evaluation for Megavoltage X-

and Gamma-Ray Radiotherapy Facilities (2005)• ICRP74/ICRU57 (Jointly published by both ICRU and ICRP) Conversion

Coefficients for use in Radiological Protection against External Radiation• ICRP 60 Recommendations of the International Commission on Radiological

Protection• ICRU 66 Determination of Operational Dose Equivalent Quantities for

Neutrons• http://web.mit.edu/nrl/www/bnct/info/description/description.html• T2.lanl.gov• http://www.nndc.bnl.gov/nudat2

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