In vitro measurement of proton RBE: A multi-centric comparison using a harmonized setup

Background and purpose: This study presents a multi-center comparison of in vitro cell survival measurements and RBE calculations following proton irradiations conducted under harmonized experimental conditions across six European institutions participating in the INSPIRE framework. Materials and me...

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Main Authors: Olga Sokol, Anders Tobias Frederiksen, Mateusz Sitarz, Brita Singers Sørensen, Elham Santina, Christopher Smith, John-William Warmenhoven, Marie Davídková, Anna Jelínek Michaelidesová, Irina Danilová, Oldřich Zahradníček, Amélia Maia Leite, Ludovic de Marzi, Frederic Pouzoulet, Paweł Olko, Justyna Miszczyk, Barbara Orzechowska, Eleftherios Papalanis, Mehran Hariri, Diana Spiegelberg, Bo Stenerlöw, Alexandru Dasu, Elisabeth Bodenstein, Elke Beyreuther, Jörg Pawelke, Dorothee Pfitzmann, Karen Kirkby, Nicholas Henthorn, Marco Durante
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Language:English
Published: Elsevier 2025-07-01
Series:Clinical and Translational Radiation Oncology
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Online Access:http://www.sciencedirect.com/science/article/pii/S2405630825000709
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author Olga Sokol
Anders Tobias Frederiksen
Mateusz Sitarz
Brita Singers Sørensen
Elham Santina
Christopher Smith
John-William Warmenhoven
Marie Davídková
Anna Jelínek Michaelidesová
Irina Danilová
Oldřich Zahradníček
Amélia Maia Leite
Ludovic de Marzi
Frederic Pouzoulet
Paweł Olko
Justyna Miszczyk
Barbara Orzechowska
Eleftherios Papalanis
Mehran Hariri
Diana Spiegelberg
Bo Stenerlöw
Alexandru Dasu
Elisabeth Bodenstein
Elke Beyreuther
Jörg Pawelke
Dorothee Pfitzmann
Karen Kirkby
Nicholas Henthorn
Marco Durante
author_facet Olga Sokol
Anders Tobias Frederiksen
Mateusz Sitarz
Brita Singers Sørensen
Elham Santina
Christopher Smith
John-William Warmenhoven
Marie Davídková
Anna Jelínek Michaelidesová
Irina Danilová
Oldřich Zahradníček
Amélia Maia Leite
Ludovic de Marzi
Frederic Pouzoulet
Paweł Olko
Justyna Miszczyk
Barbara Orzechowska
Eleftherios Papalanis
Mehran Hariri
Diana Spiegelberg
Bo Stenerlöw
Alexandru Dasu
Elisabeth Bodenstein
Elke Beyreuther
Jörg Pawelke
Dorothee Pfitzmann
Karen Kirkby
Nicholas Henthorn
Marco Durante
author_sort Olga Sokol
collection DOAJ
description Background and purpose: This study presents a multi-center comparison of in vitro cell survival measurements and RBE calculations following proton irradiations conducted under harmonized experimental conditions across six European institutions participating in the INSPIRE framework. Materials and methods: V79-4 cells were irradiated using spread-out Bragg peak (SOBP) proton fields of two configurations delivering 6 and 8 Gy with widths of 6 and 4 cm, respectively. Each center adhered to a standardized protocol, utilizing the same phantom design to minimize uncertainties related to sample positioning. X-ray reference irradiations were also performed to assess cell radiosensitivity across the participating centers. Results: Despite the consistent protocol, significant inter-institutional variability was observed in the survival measurements. For both treatment plans, the largest variation was detected in the most distal points of the SOBP (coefficients of variation of 43 % and 60 % for the 6 Gy and 8 Gy plans, respectively). Kruskal-Wallis statistical test confirmed the significant differences between the centers for each of the measured position in the proton field for both SOBP configurations. Discrepancies were observed in calculated RBE data as well, albeit preserving the expected trend for the values to slightly increase towards the distal edge of the SOBP (up to 1.5 and 1.3 for the 6 Gy and 8 Gy plans, respectively). Conclusion: The results of the study highlight the minimal biological variation one could expect performing proton RBE measurements in well-aligned experimental conditions and challenges in conducting large-scale, multi-center radiobiological experiments and inter-comparisons between literature data sets.
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spelling doaj-art-de9cc3907ea04a38bcc2dec55148532b2025-08-20T02:36:59ZengElsevierClinical and Translational Radiation Oncology2405-63082025-07-015310097810.1016/j.ctro.2025.100978In vitro measurement of proton RBE: A multi-centric comparison using a harmonized setupOlga Sokol0Anders Tobias Frederiksen1Mateusz Sitarz2Brita Singers Sørensen3Elham Santina4Christopher Smith5John-William Warmenhoven6Marie Davídková7Anna Jelínek Michaelidesová8Irina Danilová9Oldřich Zahradníček10Amélia Maia Leite11Ludovic de Marzi12Frederic Pouzoulet13Paweł Olko14Justyna Miszczyk15Barbara Orzechowska16Eleftherios Papalanis17Mehran Hariri18Diana Spiegelberg19Bo Stenerlöw20Alexandru Dasu21Elisabeth Bodenstein22Elke Beyreuther23Jörg Pawelke24Dorothee Pfitzmann25Karen Kirkby26Nicholas Henthorn27Marco Durante28GSI Helmholtz Centre for Heavy Ion Research, Darmstadt, GermanyDepartment of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark; Danish Centre for Particle Therapy (DCPT), Aarhus University Hospital, Aarhus DenmarkDanish Centre for Particle Therapy (DCPT), Aarhus University Hospital, Aarhus Denmark; CIMAP, CEA-CNRS-ENSICAEN-UNICAEN, Normandie Université, Caen, FranceDepartment of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark; Danish Centre for Particle Therapy (DCPT), Aarhus University Hospital, Aarhus DenmarkDivision of Cancer Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK; Manchester Academic Health Science Centre, The Christie NHS Foundation Trust, Manchester, UKDivision of Cancer Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK; Manchester Academic Health Science Centre, The Christie NHS Foundation Trust, Manchester, UKDivision of Cancer Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK; Manchester Academic Health Science Centre, The Christie NHS Foundation Trust, Manchester, UKNuclear Physics Institute of the Czech Academy of Sciences, Řež, Czech RepublicNuclear Physics Institute of the Czech Academy of Sciences, Řež, Czech RepublicNuclear Physics Institute of the Czech Academy of Sciences, Řež, Czech RepublicNuclear Physics Institute of the Czech Academy of Sciences, Řež, Czech RepublicInserm U1021 - CNRS UMR 3347, Institut Curie, PSL Research University, University Paris Saclay, Orsay, France; Institut Curie, PSL Research University, Radiation Oncology Department, Proton Therapy Centre, Centre universitaire, Orsay, FranceInstitut Curie, PSL Research University, Radiation Oncology Department, Proton Therapy Centre, Centre universitaire, Orsay, France; Inserm U1288, Laboratory of Translational Imaging in Oncology (LITO), Institut Curie, PSL Research University, University Paris Saclay, Orsay, FranceInserm U1288, Laboratory of Translational Imaging in Oncology (LITO), Institut Curie, PSL Research University, University Paris Saclay, Orsay, France; Translational Research Department, Institut Curie, Experimental Radiotherapy Platform, University Paris Saclay, Orsay, FranceInstitute of Nuclear Physics Polish Academy of Sciences, Krakow, PolandInstitute of Nuclear Physics Polish Academy of Sciences, Krakow, PolandInstitute of Nuclear Physics Polish Academy of Sciences, Krakow, PolandDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala, SwedenDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala, SwedenDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala, SwedenDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala, SwedenDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; The Skandion Clinic, Uppsala, SwedenHelmholtz-Zentrum Dresden – Rossendorf (HZDR), Institute of Radiooncology - OncoRay, Dresden, Germany; OncoRay – National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden – Rossendorf, Dresden, GermanyOncoRay – National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden – Rossendorf, Dresden, Germany; Helmholtz-Zentrum Dresden – Rossendorf, Institute of Radiation Physics, Dresden, GermanyHelmholtz-Zentrum Dresden – Rossendorf (HZDR), Institute of Radiooncology - OncoRay, Dresden, Germany; OncoRay – National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden – Rossendorf, Dresden, GermanyDepartment of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; OncoRay – National Center for Radiation Research in Oncology, Faculty of Medicine, Dresden, GermanyDivision of Cancer Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK; Manchester Academic Health Science Centre, The Christie NHS Foundation Trust, Manchester, UKDivision of Cancer Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK; Manchester Academic Health Science Centre, The Christie NHS Foundation Trust, Manchester, UKGSI Helmholtz Centre for Heavy Ion Research, Darmstadt, Germany; Institute for Condensed Matter Physics, Technische Universität Darmstadt, Darmstadt, Germany; Corresponding author at: Biophysics Department, GSI Helmholtz Centre for Heavy Ion Research, 64291 Darmstadt, Germany.Background and purpose: This study presents a multi-center comparison of in vitro cell survival measurements and RBE calculations following proton irradiations conducted under harmonized experimental conditions across six European institutions participating in the INSPIRE framework. Materials and methods: V79-4 cells were irradiated using spread-out Bragg peak (SOBP) proton fields of two configurations delivering 6 and 8 Gy with widths of 6 and 4 cm, respectively. Each center adhered to a standardized protocol, utilizing the same phantom design to minimize uncertainties related to sample positioning. X-ray reference irradiations were also performed to assess cell radiosensitivity across the participating centers. Results: Despite the consistent protocol, significant inter-institutional variability was observed in the survival measurements. For both treatment plans, the largest variation was detected in the most distal points of the SOBP (coefficients of variation of 43 % and 60 % for the 6 Gy and 8 Gy plans, respectively). Kruskal-Wallis statistical test confirmed the significant differences between the centers for each of the measured position in the proton field for both SOBP configurations. Discrepancies were observed in calculated RBE data as well, albeit preserving the expected trend for the values to slightly increase towards the distal edge of the SOBP (up to 1.5 and 1.3 for the 6 Gy and 8 Gy plans, respectively). Conclusion: The results of the study highlight the minimal biological variation one could expect performing proton RBE measurements in well-aligned experimental conditions and challenges in conducting large-scale, multi-center radiobiological experiments and inter-comparisons between literature data sets.http://www.sciencedirect.com/science/article/pii/S2405630825000709Relative biological effectivenessProton therapyCell survival
spellingShingle Olga Sokol
Anders Tobias Frederiksen
Mateusz Sitarz
Brita Singers Sørensen
Elham Santina
Christopher Smith
John-William Warmenhoven
Marie Davídková
Anna Jelínek Michaelidesová
Irina Danilová
Oldřich Zahradníček
Amélia Maia Leite
Ludovic de Marzi
Frederic Pouzoulet
Paweł Olko
Justyna Miszczyk
Barbara Orzechowska
Eleftherios Papalanis
Mehran Hariri
Diana Spiegelberg
Bo Stenerlöw
Alexandru Dasu
Elisabeth Bodenstein
Elke Beyreuther
Jörg Pawelke
Dorothee Pfitzmann
Karen Kirkby
Nicholas Henthorn
Marco Durante
In vitro measurement of proton RBE: A multi-centric comparison using a harmonized setup
Clinical and Translational Radiation Oncology
Relative biological effectiveness
Proton therapy
Cell survival
title In vitro measurement of proton RBE: A multi-centric comparison using a harmonized setup
title_full In vitro measurement of proton RBE: A multi-centric comparison using a harmonized setup
title_fullStr In vitro measurement of proton RBE: A multi-centric comparison using a harmonized setup
title_full_unstemmed In vitro measurement of proton RBE: A multi-centric comparison using a harmonized setup
title_short In vitro measurement of proton RBE: A multi-centric comparison using a harmonized setup
title_sort in vitro measurement of proton rbe a multi centric comparison using a harmonized setup
topic Relative biological effectiveness
Proton therapy
Cell survival
url http://www.sciencedirect.com/science/article/pii/S2405630825000709
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