{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T12:20:12Z","timestamp":1785327612745,"version":"3.55.0"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,8]],"date-time":"2022-06-08T00:00:00Z","timestamp":1654646400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010687","name":"H2020 Euratom","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010687","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Proton therapy enables to deliver highly conformed dose distributions owing to the characteristic Bragg peak and the finite range of protons. However, during proton therapy, secondary neutrons are created, which can travel long distances and deposit dose in out-of-field volumes. This out-of-field absorbed dose needs to be considered for radiation-induced secondary cancers, which are particularly relevant in the case of pediatric treatments. Unfortunately, no method exists in clinics for the computation of the out-of-field dose distributions in proton therapy. To help overcome this limitation, a computational tool has been developed based on the Monte Carlo code TOPAS. The purpose of this work is to evaluate the accuracy of this tool in comparison to experimental data obtained from an anthropomorphic phantom irradiation. An anthropomorphic phantom of a 5-year-old child (ATOM, CIRS) was irradiated for a brain tumor treatment in an IBA Proteus Plus facility using a pencil beam dedicated nozzle. The treatment consisted of three pencil beam scanning fields employing a lucite range shifter. Proton energies ranged from 100 to 165 MeV. A median dose of 50.4 Gy(RBE) with 1.8 Gy(RBE) per fraction was prescribed to the initial planning target volume (PTV), which was located in the cerebellum. Thermoluminescent detectors (TLDs), namely, Li-7-enriched LiF : Mg, Ti (MTS-7) type, were used to detect gamma radiation, which is produced by nuclear reactions, and secondary as well as recoil protons created out-of-field by secondary neutrons. Li-6-enriched LiF : Mg,Cu,P (MCP-6) was combined with Li-7-enriched MCP-7 to measure thermal neutrons. TLDs were calibrated in Co-60 and reported on absorbed dose in water per target dose (\u03bcGy\/Gy) as well as thermal neutron dose equivalent per target dose (\u03bcSv\/Gy). Additionally, bubble detectors for personal neutron dosimetry (BD-PND) were used for measuring neutrons (&amp;gt;50 keV), which were calibrated in a Cf-252 neutron beam to report on neutron dose equivalent dose data. The Monte Carlo code TOPAS (version 3.6) was run using a phase-space file containing 10<jats:sup>10<\/jats:sup> histories reaching an average standard statistical uncertainty of less than 0.2% (coverage factor <jats:italic>k<\/jats:italic> = 1) on all voxels scoring more than 50% of the maximum dose. The primary beam was modeled following a Fermi\u2013Eyges description of the spot envelope fitted to measurements. For the Monte Carlo simulation, the chemical composition of the tissues represented in ATOM was employed. The dose was tallied as dose-to-water, and data were normalized to the target dose (physical dose) to report on absorbed doses per target dose (mSv\/Gy) or neutron dose equivalent per target dose (\u03bcSv\/Gy), while also an estimate of the total organ dose was provided for a target dose of 50.4 Gy(RBE). Out-of-field doses showed absorbed doses that were 5 to 6 orders of magnitude lower than the target dose. The discrepancy between TLD data and the corresponding scored values in the Monte Carlo calculations involving proton and gamma contributions was on average 18%. The comparison between the neutron equivalent doses between the Monte Carlo simulation and the measured neutron doses was on average 8%. Organ dose calculations revealed the highest dose for the thyroid, which was 120 mSv, while other organ doses ranged from 18 mSv in the lungs to 0.6 mSv in the testes. The proposed computational method for routine calculation of the out-of-the-field dose in proton therapy produces results that are compatible with the experimental data and allow to calculate out-of-field organ doses during proton therapy.<\/jats:p>","DOI":"10.3389\/fonc.2022.882489","type":"journal-article","created":{"date-parts":[[2022,6,8]],"date-time":"2022-06-08T05:00:13Z","timestamp":1654664413000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":34,"title":["Validation of a Monte Carlo Framework for Out-of-Field Dose Calculations in Proton Therapy"],"prefix":"10.3389","volume":"12","author":[{"given":"Marijke","family":"De Saint-Hubert","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nico","family":"Verbeek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"B\u00e4umer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Esser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg","family":"Wulff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Racell","family":"Nabha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Van Hoey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00e9mie","family":"Dabin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Stuckmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiano","family":"Vasi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Radonic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Boissonnat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Rodriguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beate","family":"Timmermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Thierry-Chef","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Brualla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"085017","DOI":"10.1088\/1361-6560\/aab469","article-title":"Dose Distribution of Secondary Radiation in a Water Phantom for a Proton Pencil Beam\u2014EURADOS WG9 Intercomparison Exercise","volume":"63","author":"Stolarczyk","year":"2018","journal-title":"Phys Med Biol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1093\/rpd\/ncv158","article-title":"The Andante Project: A Multidisciplinary Approach to Neutron Rbe","volume":"166","author":"Ottolenghi","year":"2015","journal-title":"Radiat Prot Dosim"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.radmeas.2021.106693","article-title":"The Influence of Nuclear Models and Monte Carlo Radiation Transport Codes on Stray Neutron Dose Estimations in Proton Therapy","volume":"150","author":"De Saint-Hubert","year":"2022","journal-title":"Radiat Meas"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3069","article-title":"Assessing the Risk of Second Malignancies After Modern Radiotherapy","volume":"11","author":"Newhauser","year":"2011","journal-title":"Nat Rev Cancer"},{"key":"B5","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1093\/rpd\/ncab063","article-title":"EURADOS Strategic Research Agenda 2020: Vision for the Dosimetry of Ionising Radiation","volume":"194","author":"Harrison","year":"2021","journal-title":"Radiat Prot Dosim"},{"key":"B6","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1118\/1.4894702","article-title":"The ANACONDA Algorithm for Deformable Image Registration in Radiotherapy","volume":"42","author":"Weistrand","year":"2015","journal-title":"Med Phys"},{"key":"B7","volume-title":"SMS. NIST Standard Reference Database","author":"Hubbell","year":"2004"},{"key":"B8","doi-asserted-by":"publisher","first-page":"109688","DOI":"10.1016\/j.radphyschem.2021.109688","article-title":"Development and Validation of a Model for Assessing Neutron Fluence With Lithium Fluoride Thermoluminescent Detectors","volume":"188","author":"Van Hoey","year":"2021","journal-title":"Radiat Phys Chem"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmp.2021.01.073","article-title":"Characterization of Passive Dosimeters in Proton Pencil Beam Scanning - A EURADOS Intercomparison for Mailed Dosimetry Audits in Proton Therapy Centres","volume":"82","author":"De Saint-Hubert","year":"2021","journal-title":"Phys Med"},{"key":"B10","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.radphyschem.2019.05.021","article-title":"Photon Energy Response of LiF : Mg,Ti (MTS) and LiF : Mg,Cu,P (MCP) Thermoluminescent Detectors: Experimental Measurements and Microdosimetric Modeling","volume":"163","author":"Parisi","year":"2019","journal-title":"Radiat Phys Chem"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1093\/rpd\/ncx188","article-title":"Microdosimetric Modeling of the Relative Luminescence Efficiency of LiF : Mg,Ti (MTS) Detectors Exposed to Charged Particles","volume":"180","author":"Parisi","year":"2018","journal-title":"Radiat Prot Dosim"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.rpor.2014.04.008","article-title":"Evaluation of Energy Deposition and Secondary Particle Production in Proton Therapy of Brain Using a Slab Head Phantom","volume":"19","author":"Jia","year":"2014","journal-title":"Rep Pract Oncol Radiother"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.zemedi.2014.03.010","article-title":"Correction Factors kE and kQ for LiF-TLDs for Dosimetry in Megavoltage Electron and Photon Beams","volume":"25","author":"Bruggmoser","year":"2015","journal-title":"Z Med Phys"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1118\/1.4938578","article-title":"Experimental Evaluation of Neutron Dose in Radiotherapy Patients: Which Dose","volume":"43","author":"Romero-Exp\u00f3sito","year":"2016","journal-title":"Med Phys"},{"key":"B15","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1016\/S0168-9002(03)01368-8","article-title":"Geant4\u2014a Simulation Toolkit","volume":"506","author":"Agostinelli","year":"2003","journal-title":"Nucl Instrum Meth A"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1109\/TNS.2006.869826","article-title":"Geant4 Developments and Applications","volume":"53","author":"Allison","year":"2006","journal-title":"IEEE T Nucl Sci"},{"key":"B17","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1016\/j.nima.2016.06.125","article-title":"Recent Developments in Geant4","volume":"835","author":"Allison","year":"2016","journal-title":"Nucl Instrum Meth A"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1118\/1.4758060","article-title":"TOPAS: An Innovative Proton Monte Carlo Platform for Research and Clinical Applications","volume":"39","author":"Perl","year":"2012","journal-title":"Med Phys"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1002\/mp.12251","article-title":"Development of the Open-Source Dose Calculation and Optimization Toolkit Matrad","volume":"44","author":"Wieser","year":"2017","journal-title":"Med Phys"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1118\/1.598116","article-title":"An Analytical Approximation of the Bragg Curve for Therapeutic Proton Beams","volume":"4","author":"Bortfeld","year":"1997","journal-title":"Med Phys"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1088\/0031-9155\/57\/5\/1147","article-title":"Golden Beam Data for Proton Pencil-Beam Scanning","volume":"57","author":"Clasie","year":"2012","journal-title":"Phys Med Biol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1088\/0031-9155\/60\/2\/633","article-title":"Characterizing a Proton Beam Scanning System for Monte Carlo Dose Calculation in Patients","volume":"60","author":"Grassberger","year":"2015","journal-title":"Phys Med Biol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1120\/jacmp.v16i6.5577","article-title":"Evaluation of Detectors for Acquisition of Pristine Depth-Dose Curves in Pencil Beam Scanning","volume":"16","author":"B\u00e4umer","year":"2015","journal-title":"Med Phys"},{"key":"B24","first-page":"4470","article-title":"Techniques of Proton Radiotherapy: Transport Theory","volume":"1204","author":"Gottschalk","year":"2012","journal-title":"arXiv"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1002\/mp.14598","article-title":"Single Pencil Beam Benchmark of a Module for Monte Carlo Simulation of Proton Transport in the PENELOPE Code","volume":"48","author":"Verbeek","year":"2021","journal-title":"Med Phys"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1002\/mp.14860","article-title":"Experiments and Monte Carlo Simulations on Multiple Coulomb Scattering of Protons","volume":"48","author":"Verbeek","year":"2021","journal-title":"Med Phys"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1088\/0031-9155\/52\/11\/015","article-title":"A Beam Source Model for Scanned Proton Beams","volume":"52","author":"Kimstrand","year":"2007","journal-title":"Phys Med Biol"},{"key":"B28","first-page":"140\u2013141","article-title":"Absorbed Dose Determination in External Beam Radiotherapy: An International Code of Practice for Dosimetry Based on Standards of Absorbed Dose to Water","author":"Andreo","year":"2006","journal-title":"IAEA Tech Rep Ser"},{"key":"B29","volume-title":"Procedures of Dosimetry With Probe-Type Detectors for Proton and Ion Radiation - Part 1: Ionization Chambers. DIN 6801-1","year":"2019"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1109\/TNS.2008.922816","article-title":"Physics Settings for Using the Geant4Toolkit in Proton Therapy","volume":"55","author":"Jarlskog","year":"2008","journal-title":"IEEE Trans Nucl Sci"},{"key":"B31","article-title":"ICRU Report 90. Key Data for Ionizing-Radiation Dosimetry: Measurement Standards and Applications","volume-title":"Reports of the International Commission on Radiation Units and Measurements","year":""},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1088\/0031-9155\/41\/1\/009","article-title":"The Calibration of CT Hounsfield Units for Radiotherapy Treatment Planning","volume":"41","author":"Schneider","year":"1996","journal-title":"Phys Med Biol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1002\/mp.12206","article-title":"Systematic Out-of-Field Secondary Neutron Spectrometry and Dosimetry in Pencil Beam Scanning Proton Therapy","volume":"44","author":"Trinkl","year":"2017","journal-title":"Med Phys"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.zemedi.2021.01.001","article-title":"A Comprehensive Monte Carlo Study of Out-of-Field Secondary Neutron Spectra in a Scanned-Beam Proton Therapy Gantry Room","volume":"31","author":"Englbrecht","year":"2021","journal-title":"Z Med Phys"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1088\/0031-9155\/60\/14\/5627","article-title":"On the Nuclear Halo of a Proton Pencil Beam Stopping in Water","volume":"60","author":"Gottschalk","year":"2015","journal-title":"Phys Med Biol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1118\/1.3575419","article-title":"Variations in Photon Energy Spectra of a 6 MV Beam and Their Impact on TLD Response","volume":"38","author":"Scarboro","year":"2011","journal-title":"Med Phys"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1002\/mp.12462","article-title":"AAPM TG 158: Measurement and Calculation of Doses Outside the Treated Volume From External-Beam Radiation Therapy","volume":"44","author":"Kry","year":"2017","journal-title":"Med Phys"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.radmeas.2007.10.029","article-title":"TL-Efficiency\u2014Overview and Experimental Results Over the Years","volume":"43","author":"Berger","year":"2008","journal-title":"Radiat Meas"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1093\/rpd\/ncv458","article-title":"Secondary Neutron Doses in a Proton Therapy Centre","volume":"170","author":"De Saint-Hubert","year":"2016","journal-title":"Radiat Prot Dosim"},{"key":"B40","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1002\/mp.14226","article-title":"Report on G4-Med, a Geant4 Benchmarking System for Medical Physics Applications Developed by the Geant4 Medical Simulation Benchmarking Group","volume":"48","author":"Arce","year":"2021","journal-title":"Med Phys"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-583X(01)00748-0","article-title":"Space Radiation Dosimetry in Low-Earth Orbit and Beyond","volume":"184","author":"Benton","year":"2001","journal-title":"Nucl Instrum Meth B"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1093\/rpd\/ncx254","article-title":"Comparison of Response of Passive Dosimetry Systems in Scanning Proton Radiotherapy-a Study Using Paediatric Anthropomorphic Phantoms","volume":"180","author":"Kne\u017eevic","year":"2018","journal-title":"Radiat Prot Dosim"},{"key":"B43","doi-asserted-by":"publisher","first-page":"035012","DOI":"10.1088\/1361-6560\/abcb1f","article-title":"Out-Of-Field Doses for Scanning Proton Radiotherapy of Shallowly Located Paediatric Tumours-a Comparison of Range Shifter and 3D Printed Compensator","volume":"66","author":"Wochnik","year":"2021","journal-title":"Phys Med Biol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1088\/0031-9155\/59\/10\/2457","article-title":"Measurements of the Neutron Dose Equivalent for Various Radiation Qualities, Treatment Machines and Delivery Techniques in Radiation Therapy","volume":"59","author":"H\u00e4lg","year":"2014","journal-title":"Phys Med Biol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1088\/0031-9155\/54\/8\/001","article-title":"Stray Radiation Dose and Second Cancer Risk for a Pediatric Patient Receiving Craniospinal Irradiation With Proton Beams","volume":"54","author":"Taddei","year":"2009","journal-title":"Phys Med Biol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1088\/0031-9155\/61\/2\/683","article-title":"Dose Assessment for the Fetus Considering Scattered and Secondary Radiation From Photon and Proton Therapy When Treating a Brain Tumor of the Mother","volume":"61","author":"Geng","year":"2015","journal-title":"Phys Med Biol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.radmeas.2021.106665","article-title":"Fetus Dose Calculation During Proton Therapy of Pregnant Phantoms Using Mcnpx and Mcnp6.2 Codes","volume":"149","author":"De Saint-Hubert","year":"2021","journal-title":"Radiat Meas"},{"key":"B48","doi-asserted-by":"publisher","first-page":"225010","DOI":"10.1088\/1361-6560\/ac3209","article-title":"Secondary Neutron Dose Contribution From Pencil Beam Scanning, Scattered and Spatially Fractionated Proton Therapy","volume":"66","author":"Leite","year":"2021","journal-title":"Phys Med Biol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1093\/rpd\/ncx015","article-title":"Out-Of-Field Dose Measurements for 3d Conformal and Intensity Modulated Radiotherapy of a Paediatric Brain Tumour","volume":"176","author":"Majer","year":"2017","journal-title":"Radiat Prot Dosim"},{"key":"B50","volume-title":"Health Risks From Exposure to Low Levels of Ionizing Radiation: BEIR VII Phase 2","year":"2006"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.3109\/0284186X.2015.1008648","article-title":"Childhood Cancer Survivor Cohorts in Europe","volume":"54","author":"Winther","year":"2015","journal-title":"Acta Oncol"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2022.882489\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,8]],"date-time":"2022-06-08T05:00:22Z","timestamp":1654664422000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2022.882489\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,8]]},"references-count":51,"alternative-id":["10.3389\/fonc.2022.882489"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2022.882489","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,8]]},"article-number":"882489"}}