{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T06:38:12Z","timestamp":1792737492656,"version":"4.5.0"},"reference-count":33,"publisher":"IOP Publishing","issue":"20","license":[{"start":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:00:00Z","timestamp":1792713600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:00:00Z","timestamp":1792713600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/iopscience.iop.org\/info\/page\/text-and-data-mining"}],"funder":[{"name":"DFG","award":["441208898"],"award-info":[{"award-number":["441208898"]}]}],"content-domain":{"domain":["iopscience.iop.org"],"crossmark-restriction":false},"short-container-title":["Phys. Med. Biol."],"published-print":{"date-parts":[[2026,10,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Objective.<\/jats:italic>\n                    Prompt gamma (PG) detection enables beam range verification and margin reduction in proton therapy, but its effectiveness is limited by counting statistics. Spot boosting has been proposed to enhance the signal-to-noise ratio by increasing the number of protons in selected spots of a pencil beam scanning treatment plan. This work integrates PG monitoring into an multi-criteria optimization (MCO) framework to investigate trade-offs between proton counts in boosted spots and dosimetric metrics.\n                    <jats:italic>Approach.<\/jats:italic>\n                    Intensity modulated proton therapy plans for a prostate-tumor and a brain-tumor patient were optimized in OpenTPS. Dose, LET weighted dose (LETxdose) and PG distributions were simulated for each pencil beam using the fast Monte Carlo (MC) engine MCSquare. For each field, ten candidate spots were selected based on three metrics quantifying the quality of PG monitoring and an even spatial distribution across the clinical target volume. Initial pencil beam weights and corresponding dose and LETxdose distributions were imported into an MCO framework for re-optimization, simultaneously considering both dosimetric goals and boosting objectives.\n                    <jats:italic>Main results.<\/jats:italic>\n                    Boosting up to\n                    <jats:inline-formula>\n                      <jats:tex-math>\n                        \n                      <\/jats:tex-math>\n                      <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" overflow=\"scroll\">\n                        <mml:mrow>\n                          <mml:mn>5<\/mml:mn>\n                          <mml:mo>\u22c5<\/mml:mo>\n                          <mml:msup>\n                            <mml:mn>10<\/mml:mn>\n                            <mml:mn>8<\/mml:mn>\n                          <\/mml:msup>\n                        <\/mml:mrow>\n                      <\/mml:math>\n                    <\/jats:inline-formula>\n                    protons\/spot maintained the plan quality without violating constraints in the prostate case. In the brain case, spot boosting required moderate deviations from the initial target dose constraints. For both cases, only minor boosting gains were obtained by relaxing dose metrics for organs at risk.\n                    <jats:italic>Significance.<\/jats:italic>\n                    This study is the first to visualize spot boosting trade-offs via Pareto fronts to support an informed decision, integrating verification quality aspects into the treatment planning stage. The approach enables selection of plans that preserve dose and LETxdose objectives while enhancing PG signal in targeted spots for reliable\n                    <jats:italic>in-vivo<\/jats:italic>\n                    range verification. The framework is broadly applicable and can provide a strategy for embedding verification-driven objectives into treatment optimization beyond PG monitoring.\n                  <\/jats:p>","DOI":"10.1088\/1361-6560\/aeb223","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:53:22Z","timestamp":1791500002000},"page":"205024","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi-criteria proton treatment planning incorporating spot boosting for prompt gamma\n                    <i>in-vivo<\/i>\n                    range verification"],"prefix":"10.1088","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-8469-7901","authenticated-orcid":true,"family":"Mara Schubert","sequence":"first","affiliation":[{"name":"Fraunhofer Institute for Industrial Mathematics (ITWM)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1533-8851","authenticated-orcid":true,"given":"Ze","family":"Huang","sequence":"additional","affiliation":[{"name":"Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6835-2561","authenticated-orcid":true,"given":"Marco","family":"Pinto","sequence":"additional","affiliation":[{"name":"Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Thieke","sequence":"additional","affiliation":[{"name":"Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen"},{"name":"Bavarian Cancer Research Center (BZKF)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl-Heinz","family":"K\u00fcfer","sequence":"additional","affiliation":[{"name":"Fraunhofer Institute for Industrial Mathematics (ITWM)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2293-407X","authenticated-orcid":true,"given":"Katrin","family":"Teichert","sequence":"additional","affiliation":[{"name":"Fraunhofer Institute for Industrial Mathematics (ITWM)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7779-6690","authenticated-orcid":true,"given":"Katia","family":"Parodi","sequence":"additional","affiliation":[{"name":"Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2026,10,23]]},"reference":[{"key":"pmbaeb223bib1","doi-asserted-by":"publisher","first-page":"4399","DOI":"10.1088\/0031-9155\/56\/14\/011","type":"journal-article","article-title":"Is it necessary to plan with safety margins for actively scanned proton therapy?","volume":"56","author":"Albertini","year":"2011","journal-title":"Phys. Med. Biol."},{"key":"pmbaeb223bib2","doi-asserted-by":"publisher","first-page":"25","DOI":"10.3109\/0284186X.2013.832835","type":"journal-article","article-title":"LET-painting increases tumour control probability in hypoxic tumours","volume":"53","author":"Bassler","year":"2014","journal-title":"Acta. Oncol."},{"key":"pmbaeb223bib3","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1016\/j.ijrobp.2023.05.002","type":"journal-article","article-title":"Detectability of anatomical changes with prompt-gamma imaging: first systematic evaluation of clinical application during prostate-cancer proton therapy","volume":"117","author":"Berthold","year":"2023","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"pmbaeb223bib4","doi-asserted-by":"publisher","DOI":"10.1016\/j.phro.2023.100447","type":"journal-article","article-title":"Potential margin reduction in prostate cancer proton therapy with prompt gamma imaging for online treatment verification","volume":"26","author":"Bertschi","year":"2023","journal-title":"Phys. Imaging Radiat. Oncol."},{"key":"pmbaeb223bib5","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1287\/ijoc.1120.0508","type":"journal-article","article-title":"An algorithm for approximating convex Pareto surfaces based on dual techniques","volume":"25","author":"Bokrantz","year":"2012","journal-title":"Inf. J. Comput."},{"key":"pmbaeb223bib6","first-page":"pp 35","author":"Byrd","year":"2006","type":"book"},{"key":"pmbaeb223bib7","doi-asserted-by":"publisher","DOI":"10.1088\/1361-6560\/aaa203","type":"journal-article","article-title":"3d prompt gamma imaging for proton beam range verification","volume":"63","author":"Draeger","year":"2018","journal-title":"Phys. Med. Biol."},{"key":"pmbaeb223bib8","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1002\/pro6.70020","type":"journal-article","article-title":"Clinical advances and challenges in dose constraints for organs at risk in proton therapy: a systematic review of the last decade\u2019s literature","volume":"9","author":"Duan","year":"2025","journal-title":"Precis. Radiat. Oncol."},{"key":"pmbaeb223bib9","doi-asserted-by":"publisher","DOI":"10.1088\/1361-6560\/ad6116","type":"journal-article","article-title":"An experimental validation of a filtering approach for prompt gamma prediction in a research proton treatment planning system","volume":"69","author":"Huang","year":"2024","journal-title":"Phys. Med. Biol."},{"key":"pmbaeb223bib10","doi-asserted-by":"publisher","first-page":"4427","DOI":"10.1088\/0031-9155\/59\/15\/4427","type":"journal-article","article-title":"Factors influencing the accuracy of beam range estimation in proton therapy using prompt gamma emission","volume":"59","author":"Janssen","year":"2014","journal-title":"Phys. Med. Biol."},{"key":"pmbaeb223bib11","doi-asserted-by":"publisher","first-page":"5102","DOI":"10.1002\/mp.14393","type":"journal-article","article-title":"Classification of the source of treatment deviation in proton therapy using prompt-gamma imaging information","volume":"47","author":"Khamfongkhruea","year":"2020","journal-title":"Med. Phys."},{"key":"pmbaeb223bib12","doi-asserted-by":"publisher","first-page":"R131","DOI":"10.1088\/0031-9155\/58\/15\/R131","type":"journal-article","article-title":"In vivo proton range verification: a review","volume":"58","author":"Knopf","year":"2013","journal-title":"Phys. Med. Biol."},{"key":"pmbaeb223bib13","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1007\/s10957-024-02570-8","type":"journal-article","article-title":"Efficient approximation quality computation for sandwiching algorithms for convex multicriteria optimization","volume":"204","author":"Lammel","year":"2025","journal-title":"J. Optim. Theory Appl."},{"key":"pmbaeb223bib14","doi-asserted-by":"publisher","DOI":"10.1118\/1.4801899","type":"journal-article","article-title":"Effectiveness of robust optimization in intensity-modulated proton therapy planning for head and neck cancers","volume":"40","author":"Liu","year":"2013","journal-title":"Med. Phys."},{"key":"pmbaeb223bib15","doi-asserted-by":"publisher","DOI":"10.1016\/j.phro.2024.100692","type":"journal-article","article-title":"Recommendations for reporting and evaluating proton therapy beyond dose and constant relative biological effectiveness","volume":"33","author":"L\u00fchr","year":"2025","journal-title":"Phys. Imaging Radiat. Oncol."},{"key":"pmbaeb223bib16","doi-asserted-by":"publisher","DOI":"10.1259\/bjr.20120288","type":"journal-article","article-title":"Treatment planning optimisation in proton therapy","volume":"86","author":"McGowan","year":"2014","journal-title":"Br. J. Radiol."},{"key":"pmbaeb223bib17","doi-asserted-by":"publisher","first-page":"4268","DOI":"10.3390\/cancers15174268","type":"journal-article","article-title":"A systematic review of LET-guided treatment plan optimisation in proton therapy: identifying the current state and future needs","volume":"15","author":"McIntyre","year":"2023","journal-title":"Cancers"},{"key":"pmbaeb223bib18","doi-asserted-by":"publisher","DOI":"10.1063\/1.2378561","type":"journal-article","article-title":"Prompt gamma measurements for locating the dose falloff region in the proton therapy","volume":"89","author":"Min","year":"2006","journal-title":"Appl. Phys. Lett."},{"key":"pmbaeb223bib19","doi-asserted-by":"publisher","first-page":"R99","DOI":"10.1088\/0031-9155\/57\/11\/R99","type":"journal-article","article-title":"Range uncertainties in proton therapy and the role of Monte Carlo simulations","volume":"57","author":"Paganetti","year":"2012","journal-title":"Phys. Med. Biol."},{"key":"pmbaeb223bib20","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1002\/mp.15975","type":"journal-article","article-title":"Automatic detection and classification of treatment deviations in proton therapy from realistically simulated prompt gamma imaging data","volume":"50","author":"Pietsch","year":"2022","journal-title":"Med. Phys."},{"key":"pmbaeb223bib21","doi-asserted-by":"publisher","DOI":"10.1002\/mcda.70021","type":"journal-article","article-title":"Bi-level multi-criteria optimization to include linear energy transfer into proton treatment planning","volume":"32","author":"Schubert","year":"2025","journal-title":"J. Multi-Criteria Decis. Anal."},{"key":"pmbaeb223bib22","article-title":"Multi-objective optimization in mixed integer problems with application to the beam angle optimization problem in IMRT","author":"Serna","year":"2012","type":"other"},{"key":"pmbaeb223bib23","doi-asserted-by":"publisher","first-page":"1700","DOI":"10.1118\/1.4943377","type":"journal-article","article-title":"Fast multipurpose Monte Carlo simulation for proton therapy using multi- and many-core CPU architectures","volume":"43","author":"Souris","year":"2016","journal-title":"Med. Phys."},{"key":"pmbaeb223bib24","doi-asserted-by":"publisher","first-page":"4915","DOI":"10.1088\/0031-9155\/60\/12\/4915","type":"journal-article","article-title":"Analytical computation of prompt gamma ray emission and detection for proton range verification","volume":"60","author":"Sterpin","year":"2015","journal-title":"Phys. Med. Biol."},{"key":"pmbaeb223bib25","doi-asserted-by":"publisher","first-page":"5356","DOI":"10.1002\/mp.15097","type":"journal-article","article-title":"Proton range uncertainty reduction benefits for skull base tumors in terms of normal tissue complication probability (NTCP) and healthy tissue doses","volume":"48","author":"Tattenberg","year":"2021","journal-title":"Med. Phys."},{"key":"pmbaeb223bib26","doi-asserted-by":"publisher","DOI":"10.1088\/1361-6560\/abc939","type":"journal-article","article-title":"Accounting for prompt gamma emission and detection for range verification in proton therapy treatment planning","volume":"66","author":"Tian","year":"2021","journal-title":"Phys. Med. Biol."},{"key":"pmbaeb223bib27","doi-asserted-by":"publisher","DOI":"10.1088\/1361-6560\/aae749","type":"journal-article","article-title":"Toward a new treatment planning approach accounting for in vivo proton range verification","volume":"63","author":"Tian","year":"2018","journal-title":"Phys. Med. Biol."},{"key":"pmbaeb223bib28","doi-asserted-by":"publisher","DOI":"10.1088\/1361-6560\/ab7d15","type":"journal-article","article-title":"A new treatment planning approach accounting for prompt gamma range verification and interfractional anatomical changes","volume":"65","author":"Tian","year":"2020","journal-title":"Phys. Med. Biol."},{"key":"pmbaeb223bib29","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1016\/j.ijrobp.2016.08.038","type":"journal-article","article-title":"Reoptimization of intensity modulated proton therapy plans based on linear energy transfer","volume":"96","author":"Unkelbach","year":"2016","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"pmbaeb223bib30","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/j.semradonc.2017.11.005","type":"journal-article","article-title":"Robust proton treatment planning: physical and biological optimization","volume":"28","author":"Unkelbach","year":"2018","journal-title":"Semin. Radiat. Oncol."},{"key":"pmbaeb223bib31","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1148\/47.5.487","type":"journal-article","article-title":"Radiological use of fast protons","volume":"47","author":"Wilson","year":"1946","journal-title":"Radiology"},{"key":"pmbaeb223bib32","article-title":"OpenTPS - open-source treatment planning system for research in proton therapy","author":"Wuyckens","year":"2023","type":"other"},{"key":"pmbaeb223bib33","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.ijrobp.2017.04.027","type":"journal-article","article-title":"Prompt gamma imaging for in vivo range verification of pencil beam scanning proton therapy","volume":"99","author":"Xie","year":"2017","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."}],"container-title":["Physics in Medicine &amp; Biology"],"original-title":[],"link":[{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6560\/aeb223","content-type":"text\/html","content-version":"am","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6560\/aeb223\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6560\/aeb223","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6560\/aeb223\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6560\/aeb223\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6560\/aeb223\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6560\/aeb223\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"similarity-checking"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6560\/aeb223\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T05:53:08Z","timestamp":1792734788000},"score":1,"resource":{"primary":{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6560\/aeb223"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,23]]},"references-count":33,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2026,10,23]]},"published-print":{"date-parts":[[2026,10,28]]}},"URL":"https:\/\/doi.org\/10.1088\/1361-6560\/aeb223","relation":{},"ISSN":["0031-9155","1361-6560"],"issn-type":[{"value":"0031-9155","type":"print"},{"value":"1361-6560","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,23]]},"assertion":[{"value":"Multi-criteria proton treatment planning incorporating spot boosting for prompt gamma\n                      in-vivo\n                      range verification","name":"article_title","label":"Article Title"},{"value":"Physics in Medicine & Biology","name":"journal_title","label":"Journal Title"},{"value":"paper","name":"article_type","label":"Article Type"},{"value":"\u00a9 2026 The Author(s). Published on behalf of Institute of Physics and Engineering in Medicine by IOP Publishing Ltd","name":"copyright_information","label":"Copyright Information"},{"value":"2026-05-12","name":"date_received","label":"Date Received","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2026-10-08","name":"date_accepted","label":"Date Accepted","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2026-10-23","name":"date_epub","label":"Online publication date","group":{"name":"publication_dates","label":"Publication dates"}}]}}