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A model for the relative biological effectiveness of protons based on the linear energy transfer spectrum
ICTR-PHE 2016 of 5 mm3 the runtime of the reconstruction was about two days on a cluster.
Figure 1: Dose (left), γ-ray emissions (center), and reconstructed image (right) for the simulated patient case. Conclusions: By means of Geant4, an end-to-end test was performed which models clinical conditions. The impact of various parameters on the applicability of the Compton camera was evaluated. The reconstruction algorithm still has potential for improvements with respect to performance. Furthermore, in practice, the costs and the complexity of a Compton camera system could lead to the preference of simpler methods of PGI. Keywords: Compton camera, Geant4 simulations, image reconstruction References: [1] Kormoll T, Fiedler F, Schoene S, Wüstemann J, Zuber K and Enghardt W 2011 A Compton imager for in-vivo dosimetry of proton beams - A design study. Nucl. Instrum. Methods Phys. Res. A 626-627 114-119 [2] Llosá G, Cabello J, Callier S, Gillam JE, Lacasta C, Rafecas M, Raux L, Solaz C, Stankova V, Taille CL, Trovato M, Barrio J 2013 First Compton telescope prototype based on continuous LaBr3-SiPM detectors Nucl. Instrum. Meth. Phys. Res. Sec. A 718 130 – 133 [3] Thirolf PG, Lang C, Aldawood S, v.d. Kolff HG, Maier L, Schaart DR and Parodi K 2014 Development of a Compton Camera for Online Range Monitoring of Laser-Accelerated Proton Beams via Prompt-Gamma Detection. EPJ Web of Conferences 66(11036) [4] Hueso-González F, Golnik C, Berthel M, Dreyer A, Enghardt W, Fiedler F, Heidel K, Kormoll T, Rohling H, Schoene S, Schwengner R, Wagner A and Pausch G 2014 Test of Compton camera components for prompt gamma imaging at the ELBE bremsstrahlung beam. J. Instrum. 9 P05002 [5] Polf JC, Avery S, Mackin D and Beddar S 2015 Imaging of prompt gamma rays emitted during delivery of clinical proton beams with a Compton camera: feasibility studies for range verification. Phys Med Biol. 60(18) 7085-7099 [6] McCleskey M, Kaye W, Mackin DS, Beddar S, He Z and Polf JC 2015 Evaluation of a multistage CdZnTe Compton camera for prompt imaging for proton therapy. Nucl. Instrum. Methods Phys. Res. A 785 163-169 [7] Schoene S, Enghardt W, Fiedler F, Golnik C, Pausch G, Rohling H and Kormoll T 2015 An Evaluation System for Compton Camera Imaging for In-vivo Dosimetry of Therapeutic Ion Beams. Submitted to Trans. Nucl. Sci. 186 Design of electronic data processing system for radiotherapy study: lessons learned from VoxTox M. Romanchikova1, K. Harrison2, S.J. Thomas1, A. Bates3, M.P. Sutcliffe4, M.A. Parker2, N.G. Burnet4 1 Medical Physics and Clinical Engineering, Cambridge University Hospitals NHS Foundation Trust, United Kingdom 2 Cavendish Laboratory, University of Cambridge, United Kingdom 3 Cambridge Cancer Trials Centre, Cambridge University Hospitals NHS Foundation Trust, United Kingdom 4 Department of Engineering, University of Cambridge, United Kingdom 5 Department of Oncology, University of Cambridge, United Kingdom
S91 Radiotherapy (RT) research studies operate with vast amounts of imaging and planning data. A purpose-built electronic data processing system helps to eliminate errors, prevent data losses and achieve high data quality. This work presents methods and tools used in data processing pipeline for the VoxTox study. The study will include over 1000 patient data sets comprised of TomoTherapy® imaging and planning data. Data is collected at hospital site, anonymised, tested and transferred to Cavendish Laboratory for processing and storage. A pseudo-anonymisation system was designed, in which each patient identifier was substituted by a token that can be decrypted at the hospital site to re-identify the patient. A token is auto-generated upon adding patient details to the study master file and saved in a dedicated database. Patient imaging and planning data are extracted and converted to Digital Imaging and Communications in Medicine (DICOM) format by in-house developed software. The software tokenises data on-the-fly and makes use of DICOM private tags to add auxiliary data. Testing is performed before and after transfer between sites using MD5 hashes and file lists. As the time gap between RT completion and data collection is small, missing data are identified early and can be recovered. Daily doses are calculated using a modification of CheckTomo application distributed on a computer cluster with 228 job slots via GANGA job management tool originally developed for ATLAS project. The images are outlined using purpose-built Matlab software based on Chan-Vese segmentation algorithm. Both tools are user-interface (UI) free and configurable via text input files that can be auto-generated. Root framework is used for data analysis and visualisation. Toxicity data is collected in the clinic using MOSAIQ® oncology information system and collated with the patient reported outcomes in KeyPoint® software. The electroniconly data acquisition guarantees consistency of format and freedom from transcription errors. On average, VoxTox toolkit outperforms conventional tools used in the clinic by factor 6 (Table 1). Data retrieval is conventionally done via UI on TomoTherapy planning station. There is no tool to obtain TomoTherapy daily doses. Conventional contouring is performed by an experienced oncologist. Toxicity questionnaires are usually entered on paper forms and transcribed to electronic documents. Conventional data testing is a manual check of all files and folders in patient data set.
We created a system that is modular, robust and efficient. All processing tools can run on a single computer or be deployed in a job management system on a cluster. Utilization of existing tools and staff skills minimizes project costs and accelerates the development. Key design elements such as pseudo-anonymisation, text-based inputs, batch processing and electronic data entry can be applied to any RT study. Keywords: DICOM, automated processing, TomoTherapy 187 A model for the relative biological effectiveness of protons based on the linear energy transfer spectrum E. Rørvik1, K.S. Ytre-Hauge1 1 Department of Physics and Technology, University of Bergen, Norway
S92 Purpose: In proton therapy a generic relative biological effectiveness (RBE) of 1.1 has traditionally been clinically applied, implying that protons are slightly more effective than photons. However, there exist large amounts of data, mainly from in vitro studies, demonstrating that the RBE is variable and dependent on a set of factors, including the radiation quality of the beam. Most of the phenomenological models made for estimating the RBE use the dose average Linear Energy Transfer (LETd) as a parameter for the radiation quality. However, such a simplified description of the quality might lead to inaccurate RBE. In this work a new RBE model for proton therapy has been developed, utilizing the dose weighted LET spectrum (d(L)) to describe the radiation quality. Materials/methods: A new formalism for RBE calculation is introduced, based on the concept of RBEmax and the usage of biological weighting functions. RBEmax is found by weighting the LET spectrum by rmax(L), a smooth continuous function for the full LET range of protons (0-83 keV/μm). We assumed that rmax(L) is nonlinear and symmetric around a turnover point (LETu). A quantitative description of rmax(L) was found by making a regression fit to the α/αx of 96 data points, where the α and αx are coefficients of the linear-quadratic model, for proton and photon irradiation respectively. These points were extracted from experiments with semimonoenergetic proton beams found in literature. In our model we have assumed that β = βx and thus RBEmin = 1. A Fluka Monte Carlo simulation was done to check the new calculation method was benchmarked against a constant RBE of 1.1 and an existing LETd based model for variable RBE (McNamara et al., 2015). Results: By fitting rmax(L) to the data, we found a peak at LETu=34.5 keV/μm. The fit had a R2 value of 0.634. In the simulated example, the new model estimated a RBE of 1.001.02 in the entrance region. The RBE rises from 1.05 to 1.6 along the SOBP. This indicates that a constant RBE of 1.1 leads to an overestimate of the dose to the normal tissue, as well to the proximal part of the tumour. Compared to the LETd based model, the RBE is approximately 9-11% lower at all depths. Conclusions: A dose and tissue dependent RBE model, based on the LET spectrum has been developed for application in proton therapy. Compared to LETd–based model, this approach might give a better estimation of the biological dose in a mixed radiation field. The model could be further optimized, by adjusting the definition of rmax(L) and introducing a term for rmin(L), taking into account a variable LET dependent β parameter. Keywords: RBE, dose average LET, LET spectrum References: [1] A.L. McNamara et al, Phys. Med. Biol. 60, 8399. (2015) 188 DoPET: an in-treatment monitoring system for particle therapy V.Rosso1*,G. Battistoni2, N. Belcari1, N. Camarlinghi1, G.A.P. Cirrone3, F. Collini4, G. Cuttone3, M.Ciocca5, A. Del Guerra1, A. Ferrari6, S. Ferretti1, A.C. Kraan1, A. Mairani5, M. Pullia5, S. Molinelli5, F. Romano3, P. Sala6, G. Sportelli1, E. Zaccaro1 1 Department of Physics, University of Pisa and INFN, Pisa, Italy. 2 INFN Milano, Milano, Italy 3 INFN - Laboratori Nazionali del Sud, Catania, Italy 4 Department of Physical Sciences, Earth and Environment, University of Siena and INFN, Pisa, Italy 5 CNAO Foundation, Pavia, Italy 6 CERN, Geneva, Switzerland Purpose: The growing interest in charged particle therapy has led to the development of dedicated systems able to monitor the dose delivered to the patient. Positron Emission Tomography (PET) is a non-invasive way for in-vivo verification of the dose delivery. In fact, during particle + irradiation, various ß -emitting isotopes (15O, 11C etc.) are
ICTR-PHE 2016 generated in the patient and this activity distribution can be related to the delivered dose. Materials/methods: A compact PET system was developed to be installed close to the patient. The PET system, DoPET, is based on two planar heads. Over the years the dimension of the heads was increased, from 5cm x 5cm, to 10cm x10cm and finally to the dimension of 15cm x 15cm per head. The heads result from the assembly of several detecting modules: in the present prototype there are 9 modules (3x3) per head. Each detecting module, (5cm x 5cm) consists of a segmented LYSO crystal matrix (2 mm pitch) coupled to a PSPMT. The readout is performed by custom electronics, and the data acquisition was designed to cope with the high fluxes present during the treatment plan (TP) delivery. The + data reconstruction of the measured 3-D ß -activity distribution, based on a MLEM-OSEM 3D algorithm takes less than one minute. The system was mostly characterized for proton therapy applications: at CATANA, a cyclotron-based center(LNSINFN Catania, Italy), and at CNAO a synchrotron-based center (Pavia, Italy). Preliminary characterization for carbon irradiations were also performed. Results: The DoPET spatial resolution guarantees the reconstruction of the distal fall activity profile with a sensibility of 1 mm, operating in-treatment [1, 2]. The intreatment data were useful. In fact, DoPET provided information on a whole protonTP and on its very early phases [3]. A study was done delivering only the proton TP Highest Energy Layer: thanks to the sharp shape of the mono-energetic activity fall- off profile, the shift due to the presence of a small air cavity was evident. + The experimental ß -activity profiles were also compared to calculated data obtained with FLUKA Monte Carlo, with very satisfactory agreement [3]. Conclusions: DoPET represents a reliable and fast intreatment monitoring system that could act as an image guidance in the case of hypo-fractionation scheme. The present head dimension allows studies with anthropomorphic phantoms that will be done before moving onto patients. Keywords: Particle therapy monitoring, on-line PET References: [1] N. Camarlinghi et al. An In-beam PET System For Monitoring Ion-beam Therapy: Test On Phantoms Using Clinical 62 MeV Protons; JINST 9 C04005 (2014) 1-12 [2] G. Sportelli et al. First full-beam PET acquisitions in proton therapy with a modular dual-head dedicated system; Phys. Med. Biol. 59 (2014) 43–60; [3] A.C. Kraan et al. First tests for an on line treatment monitoring system with in-beam PET for proton therapy; JINST, 10, C01010 (2015) 1-11
189 Design of an innovative beam monitor for particle therapy for the simultaneous measurement of beam fluence and energy R. Sacchi1,2, N.Cartiglia1, F. Cenna1, L. Fanola1,2, M. Ferrero2, S. Giordanengo1, F. Marchetto1, V. Monaco1,2, A. Vignati1, M. Varasteh Anvar1,2, R. Cirio1,2 1 Istituto Nazionale di Fisica Nucleare (INFN), division of Torino, Torino, Italy 2 Department of Physics, University of Torino, Torino, Italy
Figure 1: Dose (left), γ-ray emissions (center), and reconstructed image (right) for the simulated patient case. Conclusions: By means of Geant4, an end-to-end test was performed which models clinical conditions. The impact of various parameters on the applicability of the Compton camera was evaluated. The reconstruction algorithm still has potential for improvements with respect to performance. Furthermore, in practice, the costs and the complexity of a Compton camera system could lead to the preference of simpler methods of PGI. Keywords: Compton camera, Geant4 simulations, image reconstruction References: [1] Kormoll T, Fiedler F, Schoene S, Wüstemann J, Zuber K and Enghardt W 2011 A Compton imager for in-vivo dosimetry of proton beams - A design study. Nucl. Instrum. Methods Phys. Res. A 626-627 114-119 [2] Llosá G, Cabello J, Callier S, Gillam JE, Lacasta C, Rafecas M, Raux L, Solaz C, Stankova V, Taille CL, Trovato M, Barrio J 2013 First Compton telescope prototype based on continuous LaBr3-SiPM detectors Nucl. Instrum. Meth. Phys. Res. Sec. A 718 130 – 133 [3] Thirolf PG, Lang C, Aldawood S, v.d. Kolff HG, Maier L, Schaart DR and Parodi K 2014 Development of a Compton Camera for Online Range Monitoring of Laser-Accelerated Proton Beams via Prompt-Gamma Detection. EPJ Web of Conferences 66(11036) [4] Hueso-González F, Golnik C, Berthel M, Dreyer A, Enghardt W, Fiedler F, Heidel K, Kormoll T, Rohling H, Schoene S, Schwengner R, Wagner A and Pausch G 2014 Test of Compton camera components for prompt gamma imaging at the ELBE bremsstrahlung beam. J. Instrum. 9 P05002 [5] Polf JC, Avery S, Mackin D and Beddar S 2015 Imaging of prompt gamma rays emitted during delivery of clinical proton beams with a Compton camera: feasibility studies for range verification. Phys Med Biol. 60(18) 7085-7099 [6] McCleskey M, Kaye W, Mackin DS, Beddar S, He Z and Polf JC 2015 Evaluation of a multistage CdZnTe Compton camera for prompt imaging for proton therapy. Nucl. Instrum. Methods Phys. Res. A 785 163-169 [7] Schoene S, Enghardt W, Fiedler F, Golnik C, Pausch G, Rohling H and Kormoll T 2015 An Evaluation System for Compton Camera Imaging for In-vivo Dosimetry of Therapeutic Ion Beams. Submitted to Trans. Nucl. Sci. 186 Design of electronic data processing system for radiotherapy study: lessons learned from VoxTox M. Romanchikova1, K. Harrison2, S.J. Thomas1, A. Bates3, M.P. Sutcliffe4, M.A. Parker2, N.G. Burnet4 1 Medical Physics and Clinical Engineering, Cambridge University Hospitals NHS Foundation Trust, United Kingdom 2 Cavendish Laboratory, University of Cambridge, United Kingdom 3 Cambridge Cancer Trials Centre, Cambridge University Hospitals NHS Foundation Trust, United Kingdom 4 Department of Engineering, University of Cambridge, United Kingdom 5 Department of Oncology, University of Cambridge, United Kingdom
S91 Radiotherapy (RT) research studies operate with vast amounts of imaging and planning data. A purpose-built electronic data processing system helps to eliminate errors, prevent data losses and achieve high data quality. This work presents methods and tools used in data processing pipeline for the VoxTox study. The study will include over 1000 patient data sets comprised of TomoTherapy® imaging and planning data. Data is collected at hospital site, anonymised, tested and transferred to Cavendish Laboratory for processing and storage. A pseudo-anonymisation system was designed, in which each patient identifier was substituted by a token that can be decrypted at the hospital site to re-identify the patient. A token is auto-generated upon adding patient details to the study master file and saved in a dedicated database. Patient imaging and planning data are extracted and converted to Digital Imaging and Communications in Medicine (DICOM) format by in-house developed software. The software tokenises data on-the-fly and makes use of DICOM private tags to add auxiliary data. Testing is performed before and after transfer between sites using MD5 hashes and file lists. As the time gap between RT completion and data collection is small, missing data are identified early and can be recovered. Daily doses are calculated using a modification of CheckTomo application distributed on a computer cluster with 228 job slots via GANGA job management tool originally developed for ATLAS project. The images are outlined using purpose-built Matlab software based on Chan-Vese segmentation algorithm. Both tools are user-interface (UI) free and configurable via text input files that can be auto-generated. Root framework is used for data analysis and visualisation. Toxicity data is collected in the clinic using MOSAIQ® oncology information system and collated with the patient reported outcomes in KeyPoint® software. The electroniconly data acquisition guarantees consistency of format and freedom from transcription errors. On average, VoxTox toolkit outperforms conventional tools used in the clinic by factor 6 (Table 1). Data retrieval is conventionally done via UI on TomoTherapy planning station. There is no tool to obtain TomoTherapy daily doses. Conventional contouring is performed by an experienced oncologist. Toxicity questionnaires are usually entered on paper forms and transcribed to electronic documents. Conventional data testing is a manual check of all files and folders in patient data set.
We created a system that is modular, robust and efficient. All processing tools can run on a single computer or be deployed in a job management system on a cluster. Utilization of existing tools and staff skills minimizes project costs and accelerates the development. Key design elements such as pseudo-anonymisation, text-based inputs, batch processing and electronic data entry can be applied to any RT study. Keywords: DICOM, automated processing, TomoTherapy 187 A model for the relative biological effectiveness of protons based on the linear energy transfer spectrum E. Rørvik1, K.S. Ytre-Hauge1 1 Department of Physics and Technology, University of Bergen, Norway
S92 Purpose: In proton therapy a generic relative biological effectiveness (RBE) of 1.1 has traditionally been clinically applied, implying that protons are slightly more effective than photons. However, there exist large amounts of data, mainly from in vitro studies, demonstrating that the RBE is variable and dependent on a set of factors, including the radiation quality of the beam. Most of the phenomenological models made for estimating the RBE use the dose average Linear Energy Transfer (LETd) as a parameter for the radiation quality. However, such a simplified description of the quality might lead to inaccurate RBE. In this work a new RBE model for proton therapy has been developed, utilizing the dose weighted LET spectrum (d(L)) to describe the radiation quality. Materials/methods: A new formalism for RBE calculation is introduced, based on the concept of RBEmax and the usage of biological weighting functions. RBEmax is found by weighting the LET spectrum by rmax(L), a smooth continuous function for the full LET range of protons (0-83 keV/μm). We assumed that rmax(L) is nonlinear and symmetric around a turnover point (LETu). A quantitative description of rmax(L) was found by making a regression fit to the α/αx of 96 data points, where the α and αx are coefficients of the linear-quadratic model, for proton and photon irradiation respectively. These points were extracted from experiments with semimonoenergetic proton beams found in literature. In our model we have assumed that β = βx and thus RBEmin = 1. A Fluka Monte Carlo simulation was done to check the new calculation method was benchmarked against a constant RBE of 1.1 and an existing LETd based model for variable RBE (McNamara et al., 2015). Results: By fitting rmax(L) to the data, we found a peak at LETu=34.5 keV/μm. The fit had a R2 value of 0.634. In the simulated example, the new model estimated a RBE of 1.001.02 in the entrance region. The RBE rises from 1.05 to 1.6 along the SOBP. This indicates that a constant RBE of 1.1 leads to an overestimate of the dose to the normal tissue, as well to the proximal part of the tumour. Compared to the LETd based model, the RBE is approximately 9-11% lower at all depths. Conclusions: A dose and tissue dependent RBE model, based on the LET spectrum has been developed for application in proton therapy. Compared to LETd–based model, this approach might give a better estimation of the biological dose in a mixed radiation field. The model could be further optimized, by adjusting the definition of rmax(L) and introducing a term for rmin(L), taking into account a variable LET dependent β parameter. Keywords: RBE, dose average LET, LET spectrum References: [1] A.L. McNamara et al, Phys. Med. Biol. 60, 8399. (2015) 188 DoPET: an in-treatment monitoring system for particle therapy V.Rosso1*,G. Battistoni2, N. Belcari1, N. Camarlinghi1, G.A.P. Cirrone3, F. Collini4, G. Cuttone3, M.Ciocca5, A. Del Guerra1, A. Ferrari6, S. Ferretti1, A.C. Kraan1, A. Mairani5, M. Pullia5, S. Molinelli5, F. Romano3, P. Sala6, G. Sportelli1, E. Zaccaro1 1 Department of Physics, University of Pisa and INFN, Pisa, Italy. 2 INFN Milano, Milano, Italy 3 INFN - Laboratori Nazionali del Sud, Catania, Italy 4 Department of Physical Sciences, Earth and Environment, University of Siena and INFN, Pisa, Italy 5 CNAO Foundation, Pavia, Italy 6 CERN, Geneva, Switzerland Purpose: The growing interest in charged particle therapy has led to the development of dedicated systems able to monitor the dose delivered to the patient. Positron Emission Tomography (PET) is a non-invasive way for in-vivo verification of the dose delivery. In fact, during particle + irradiation, various ß -emitting isotopes (15O, 11C etc.) are
ICTR-PHE 2016 generated in the patient and this activity distribution can be related to the delivered dose. Materials/methods: A compact PET system was developed to be installed close to the patient. The PET system, DoPET, is based on two planar heads. Over the years the dimension of the heads was increased, from 5cm x 5cm, to 10cm x10cm and finally to the dimension of 15cm x 15cm per head. The heads result from the assembly of several detecting modules: in the present prototype there are 9 modules (3x3) per head. Each detecting module, (5cm x 5cm) consists of a segmented LYSO crystal matrix (2 mm pitch) coupled to a PSPMT. The readout is performed by custom electronics, and the data acquisition was designed to cope with the high fluxes present during the treatment plan (TP) delivery. The + data reconstruction of the measured 3-D ß -activity distribution, based on a MLEM-OSEM 3D algorithm takes less than one minute. The system was mostly characterized for proton therapy applications: at CATANA, a cyclotron-based center(LNSINFN Catania, Italy), and at CNAO a synchrotron-based center (Pavia, Italy). Preliminary characterization for carbon irradiations were also performed. Results: The DoPET spatial resolution guarantees the reconstruction of the distal fall activity profile with a sensibility of 1 mm, operating in-treatment [1, 2]. The intreatment data were useful. In fact, DoPET provided information on a whole protonTP and on its very early phases [3]. A study was done delivering only the proton TP Highest Energy Layer: thanks to the sharp shape of the mono-energetic activity fall- off profile, the shift due to the presence of a small air cavity was evident. + The experimental ß -activity profiles were also compared to calculated data obtained with FLUKA Monte Carlo, with very satisfactory agreement [3]. Conclusions: DoPET represents a reliable and fast intreatment monitoring system that could act as an image guidance in the case of hypo-fractionation scheme. The present head dimension allows studies with anthropomorphic phantoms that will be done before moving onto patients. Keywords: Particle therapy monitoring, on-line PET References: [1] N. Camarlinghi et al. An In-beam PET System For Monitoring Ion-beam Therapy: Test On Phantoms Using Clinical 62 MeV Protons; JINST 9 C04005 (2014) 1-12 [2] G. Sportelli et al. First full-beam PET acquisitions in proton therapy with a modular dual-head dedicated system; Phys. Med. Biol. 59 (2014) 43–60; [3] A.C. Kraan et al. First tests for an on line treatment monitoring system with in-beam PET for proton therapy; JINST, 10, C01010 (2015) 1-11
189 Design of an innovative beam monitor for particle therapy for the simultaneous measurement of beam fluence and energy R. Sacchi1,2, N.Cartiglia1, F. Cenna1, L. Fanola1,2, M. Ferrero2, S. Giordanengo1, F. Marchetto1, V. Monaco1,2, A. Vignati1, M. Varasteh Anvar1,2, R. Cirio1,2 1 Istituto Nazionale di Fisica Nucleare (INFN), division of Torino, Torino, Italy 2 Department of Physics, University of Torino, Torino, Italy