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1426 poster LET AND DOSE DEPENDENCE OF THE OXYGEN ENHANCEMENT RATIO IN ION BEAM RADIATION THERAPY
S 530
P ROTON AND ION THERAPY: P HYSICS
in a water bath generated by an x-ray beam, and (b) gold nanoparticles in a tissue-equivalent phantom irradiated by a proton beam at the Clatterbridge Centre for Oncology. Results: Simulations indicated that the dose to the patient resulting from xray emissions from gold seeds will be negligible. X-ray energies were high enough to penetrate several cm of tissue to enable external monitoring. Simulation of a water phantom (blue box) containing a gold marker (yellow cylinder), with a proton beam. Gamma emissions(green lines) and other secondary particles are tracked
Materials: This presentation will provide an overview of the project with brief highlights from all work-packages including results of simulations of lasertarget interactions indicating the potential advantages of radiation pressure acceleration over the standard mode of target-normal sheath acceleration and examples of the levitation and transport of micron scale aluminium targets. However the main content will be the approaches taken to provide high quality dosimetry in this highly challenging environment where instantaneous dose-rates are of the order of 109 Gys-1 . The development of a methodology to provide reliable dose estimates for cell irradiations from individual laser shots will be explained in detail. This methodology uses a combination of a stack of gaf-chromic film and detailed simulations with the Monte Carlo code FLUKA, and experiments performed on the TIRANIS laser at Queens University Belfast. Results: Results to-date indicate that with suitable magnetic separation, low energy beams with a spectral width of a few MeV can be generated and used to irradiate cell cultures in mono-layer. Doses of up to approximately 5 Gy can be delivered to cells in a single laser shot. The largest correction factors which are necessary to derive the final dose estimates area) a) correction for the under-response of the selected gaf-chromic film when irradiated with low-energy protonsb) b) allowance for the thickness of the cell medium which overlays the cells and provides nutrition during irradiation (variations in this thickness also provide the largest dosimetry uncertainty in the pilot experiments performed to-date Conclusions: Technical challenges are being solved so the ultimate aim of a clinical proton treatment facility based on laser-induced proton emission remains possible. Dosimetry methods which can cope with the very high dose rates are proving successful. 1426 poster LET AND DOSE DEPENDENCE OF THE OXYGEN ENHANCEMENT RATIO IN ION BEAM RADIATION THERAPY T. Wenzl1 , J. Wilkens1 1 K LINIKUM RECHTS DER I SAR , TU M ÜNCHEN, Department of Radiation Oncology, München, Germany
Conclusions: Preliminary experiments demonstrated measurable x-ray fluorescence is emitted from a solution containing gold, thus potentially allowing in-vivo dosimetry. We are extending the analysis to correct for the effect of overlying tissues to relate dose at the gold marker to fluorescent intensity. References: [1] K Pepper, et al ’A system for x-ray diffraction imaging of nanoparticle biomarkers’, IEEE Nuc Sci & Med Im Conf 2010. 1425 poster LASER-PLASMA ACCELERATION OF PARTICLES FOR PROTON AND ION-BEAM RADIOTHERAPY: AN UPDATE FROM THE LIBRA CONSORTIUM S. Green1 , M. Borghesi2 , D. Neely3 , P. McKenna4 , Z. Najmudin5 , C. Palmer5 , I. Sari6 , M. Tolley3 , A. Ward3 , D. Carroll4 , S. Kar7 , D. Doria7 , J. Green3 , C. Brenner3 , D. Kirby8 , F. Fiorini8 , K. Kirkby9 , M. Merchant9 , C. Jeynes9 , H. Palmans10 , D. Shipley10 , R. Nutbrown10 , R. Thomas10 , M. Kraft6 , K. Kakolee11 , R. Prasad11 1 H ALL E DWARDS R ADIOTHERAPY R ESEARCH G ROUP, U NIVERSITY H OSPITAL B IRMINGHAM NHS T RUST, Department of Medical Physics and Radiation Safety, Birmingham, United Kingdom 2 S CHOOL OF P HYSICS AND M ATHEMATICS , Q UEENS U NIVERSITY B ELFAST, Belfast, United Kingdom 3 RUTHERFORD A PPLETON L ABORATORY, Central Laser Facility, Didcot, United Kingdom 4 U NIVERSITY OF S TRATHCLYDE, Department of Physics, Glasgow, United Kingdom 5 I MPERIAL C OLLEGE L ONDON, Physics, London, United Kingdom 6 U NIVERSITY OF S OUTHAMPTON, Electronics And Computer Science, University of Southampton, United Kingdom 7 Q UEEN ’ S U NIVERSITY B ELFAST, Physics, Belfast , United Kingdom 8 U NIVERSITY OF B IRMINGHAM, Physics and Astronomy, Birmingham, United Kingdom 9 U NIVERSITY OF S URREY, Ion Beam Centre, Guildford, United Kingdom 10 N ATIONAL P HYSICAL L ABORATORY, Radiation dosimetry, Teddington, United Kingdom 11 Q UEEN ’ S U NIVERSITY B ELFAST, Mathematics and Physics, Belfast , United Kingdom Purpose: The LIBRA Consortium is exploring the generation of intense high energy beams of protons, ions, and x-rays from the interaction of high power short-pulse laser beams with solid targets. The team is focussed particularly on fabrication, manipulation and delivery of suitable targets into the correct position for laser-ablation, on the development of suitable diagnostics and dosimetry approaches for these beams, radiobiological characterisation of the emitted particle beams and techniques to minimise and manage the debris produced during target ablation. The consortium is now entering the final year of its initial 4-year programme.
Purpose: The increased resistance of hypoxic cells to ionizing radiation is believed to be the primary reason for treatment failure in tumors with oxygendeficient areas. This oxygen effect can be expressed by the oxygen enhancement ratio (OER), which is defined as the ratio of doses given under hypoxic and aerobic conditions to produce the same biological effect. The OER depends on the type of ionizing radiation and decreases with increasing linear energy transfer (LET) which suggests a potential advantage of high-LET radiotherapy with ion beams. The purpose of this work is to develop a simple phenomenological model based on experimental data from the literature, which enables us to estimate the clinical impact of OER variations depending on LET, level of hypoxia and applied dose. Materials: Our calculations use the standard linear-quadratic (LQ) model with its two parameters alpha and beta. To describe the oxygen effect depending on the tissue oxygenation status we suggest the Alper-Howard-Flanders dependence of both alpha and the square root of beta on the oxygen partial pressure (pO2). Furthermore, in the clinical relevant LET region we assume a linear dependence of alpha on LET and suppose beta to be independent of LET. Results: The OER decreases with increasing LET with the steepest slope at approx. 100 keV/μm. However, the strong LET dependence seen in experiments in vitro is much smaller in vivo because of the large difference between the oxygen partial pressure in cell experiments compared to the clinical situation. This is demonstrated for a common clinical setup with a carbon ion spread-out Bragg peak (SOBP). Furthermore, according to our calculations the OER decreases with increasing dose per fraction for low-LET radiation, and increases with dose for high-LET. Though, this behavior depends on the cell line or more specifically on the given alpha/beta ratios under hypoxic and aerobic conditions. Conclusions: The proposed model is a simple tool to estimate OER values in both low- and high-LET radiotherapy. To exploit the full potential of the reduced OER with increasing LET, very high LET values are necessary that are typically not found in carbon ion therapy. The OER in the most distal tenth of the carbon ion SOBP can be reduced up to 40% compared with the OER for protons. However, for the mean OER in the target volume the clinical advantage of carbon ions might be relatively moderate, with OER values about 1-15% smaller than for protons. The benefit of proton compared to conventional photon radiotherapy is rather marginal (up to 3% reduction in the OER). Regarding the dose dependence, the oxygen effect in clinical practice is not very sensitive to the choice of dose per fraction in both low- and high-LET radiotherapy. Acknowledgement: Supported by DFG Cluster of Excellence: Munich-Centre for Advanced Photonics.
P ROTON AND ION THERAPY: P HYSICS
in a water bath generated by an x-ray beam, and (b) gold nanoparticles in a tissue-equivalent phantom irradiated by a proton beam at the Clatterbridge Centre for Oncology. Results: Simulations indicated that the dose to the patient resulting from xray emissions from gold seeds will be negligible. X-ray energies were high enough to penetrate several cm of tissue to enable external monitoring. Simulation of a water phantom (blue box) containing a gold marker (yellow cylinder), with a proton beam. Gamma emissions(green lines) and other secondary particles are tracked
Materials: This presentation will provide an overview of the project with brief highlights from all work-packages including results of simulations of lasertarget interactions indicating the potential advantages of radiation pressure acceleration over the standard mode of target-normal sheath acceleration and examples of the levitation and transport of micron scale aluminium targets. However the main content will be the approaches taken to provide high quality dosimetry in this highly challenging environment where instantaneous dose-rates are of the order of 109 Gys-1 . The development of a methodology to provide reliable dose estimates for cell irradiations from individual laser shots will be explained in detail. This methodology uses a combination of a stack of gaf-chromic film and detailed simulations with the Monte Carlo code FLUKA, and experiments performed on the TIRANIS laser at Queens University Belfast. Results: Results to-date indicate that with suitable magnetic separation, low energy beams with a spectral width of a few MeV can be generated and used to irradiate cell cultures in mono-layer. Doses of up to approximately 5 Gy can be delivered to cells in a single laser shot. The largest correction factors which are necessary to derive the final dose estimates area) a) correction for the under-response of the selected gaf-chromic film when irradiated with low-energy protonsb) b) allowance for the thickness of the cell medium which overlays the cells and provides nutrition during irradiation (variations in this thickness also provide the largest dosimetry uncertainty in the pilot experiments performed to-date Conclusions: Technical challenges are being solved so the ultimate aim of a clinical proton treatment facility based on laser-induced proton emission remains possible. Dosimetry methods which can cope with the very high dose rates are proving successful. 1426 poster LET AND DOSE DEPENDENCE OF THE OXYGEN ENHANCEMENT RATIO IN ION BEAM RADIATION THERAPY T. Wenzl1 , J. Wilkens1 1 K LINIKUM RECHTS DER I SAR , TU M ÜNCHEN, Department of Radiation Oncology, München, Germany
Conclusions: Preliminary experiments demonstrated measurable x-ray fluorescence is emitted from a solution containing gold, thus potentially allowing in-vivo dosimetry. We are extending the analysis to correct for the effect of overlying tissues to relate dose at the gold marker to fluorescent intensity. References: [1] K Pepper, et al ’A system for x-ray diffraction imaging of nanoparticle biomarkers’, IEEE Nuc Sci & Med Im Conf 2010. 1425 poster LASER-PLASMA ACCELERATION OF PARTICLES FOR PROTON AND ION-BEAM RADIOTHERAPY: AN UPDATE FROM THE LIBRA CONSORTIUM S. Green1 , M. Borghesi2 , D. Neely3 , P. McKenna4 , Z. Najmudin5 , C. Palmer5 , I. Sari6 , M. Tolley3 , A. Ward3 , D. Carroll4 , S. Kar7 , D. Doria7 , J. Green3 , C. Brenner3 , D. Kirby8 , F. Fiorini8 , K. Kirkby9 , M. Merchant9 , C. Jeynes9 , H. Palmans10 , D. Shipley10 , R. Nutbrown10 , R. Thomas10 , M. Kraft6 , K. Kakolee11 , R. Prasad11 1 H ALL E DWARDS R ADIOTHERAPY R ESEARCH G ROUP, U NIVERSITY H OSPITAL B IRMINGHAM NHS T RUST, Department of Medical Physics and Radiation Safety, Birmingham, United Kingdom 2 S CHOOL OF P HYSICS AND M ATHEMATICS , Q UEENS U NIVERSITY B ELFAST, Belfast, United Kingdom 3 RUTHERFORD A PPLETON L ABORATORY, Central Laser Facility, Didcot, United Kingdom 4 U NIVERSITY OF S TRATHCLYDE, Department of Physics, Glasgow, United Kingdom 5 I MPERIAL C OLLEGE L ONDON, Physics, London, United Kingdom 6 U NIVERSITY OF S OUTHAMPTON, Electronics And Computer Science, University of Southampton, United Kingdom 7 Q UEEN ’ S U NIVERSITY B ELFAST, Physics, Belfast , United Kingdom 8 U NIVERSITY OF B IRMINGHAM, Physics and Astronomy, Birmingham, United Kingdom 9 U NIVERSITY OF S URREY, Ion Beam Centre, Guildford, United Kingdom 10 N ATIONAL P HYSICAL L ABORATORY, Radiation dosimetry, Teddington, United Kingdom 11 Q UEEN ’ S U NIVERSITY B ELFAST, Mathematics and Physics, Belfast , United Kingdom Purpose: The LIBRA Consortium is exploring the generation of intense high energy beams of protons, ions, and x-rays from the interaction of high power short-pulse laser beams with solid targets. The team is focussed particularly on fabrication, manipulation and delivery of suitable targets into the correct position for laser-ablation, on the development of suitable diagnostics and dosimetry approaches for these beams, radiobiological characterisation of the emitted particle beams and techniques to minimise and manage the debris produced during target ablation. The consortium is now entering the final year of its initial 4-year programme.
Purpose: The increased resistance of hypoxic cells to ionizing radiation is believed to be the primary reason for treatment failure in tumors with oxygendeficient areas. This oxygen effect can be expressed by the oxygen enhancement ratio (OER), which is defined as the ratio of doses given under hypoxic and aerobic conditions to produce the same biological effect. The OER depends on the type of ionizing radiation and decreases with increasing linear energy transfer (LET) which suggests a potential advantage of high-LET radiotherapy with ion beams. The purpose of this work is to develop a simple phenomenological model based on experimental data from the literature, which enables us to estimate the clinical impact of OER variations depending on LET, level of hypoxia and applied dose. Materials: Our calculations use the standard linear-quadratic (LQ) model with its two parameters alpha and beta. To describe the oxygen effect depending on the tissue oxygenation status we suggest the Alper-Howard-Flanders dependence of both alpha and the square root of beta on the oxygen partial pressure (pO2). Furthermore, in the clinical relevant LET region we assume a linear dependence of alpha on LET and suppose beta to be independent of LET. Results: The OER decreases with increasing LET with the steepest slope at approx. 100 keV/μm. However, the strong LET dependence seen in experiments in vitro is much smaller in vivo because of the large difference between the oxygen partial pressure in cell experiments compared to the clinical situation. This is demonstrated for a common clinical setup with a carbon ion spread-out Bragg peak (SOBP). Furthermore, according to our calculations the OER decreases with increasing dose per fraction for low-LET radiation, and increases with dose for high-LET. Though, this behavior depends on the cell line or more specifically on the given alpha/beta ratios under hypoxic and aerobic conditions. Conclusions: The proposed model is a simple tool to estimate OER values in both low- and high-LET radiotherapy. To exploit the full potential of the reduced OER with increasing LET, very high LET values are necessary that are typically not found in carbon ion therapy. The OER in the most distal tenth of the carbon ion SOBP can be reduced up to 40% compared with the OER for protons. However, for the mean OER in the target volume the clinical advantage of carbon ions might be relatively moderate, with OER values about 1-15% smaller than for protons. The benefit of proton compared to conventional photon radiotherapy is rather marginal (up to 3% reduction in the OER). Regarding the dose dependence, the oxygen effect in clinical practice is not very sensitive to the choice of dose per fraction in both low- and high-LET radiotherapy. Acknowledgement: Supported by DFG Cluster of Excellence: Munich-Centre for Advanced Photonics.