{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T07:06:35Z","timestamp":1782975995695,"version":"3.54.5"},"reference-count":24,"publisher":"IOP Publishing","issue":"13","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/iopscience.iop.org\/info\/page\/text-and-data-mining"},{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/publishingsupport.iopscience.iop.org\/questions\/alternative-author-rights-policies\/"},{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/publishingsupport.iopscience.iop.org\/questions\/alternative-author-rights-policies\/"}],"funder":[{"name":"European Research Council","award":["817908"],"award-info":[{"award-number":["817908"]}]},{"name":"Grand Equipement National de Calcul Intensif","award":["A0170314559"],"award-info":[{"award-number":["A0170314559"]}]}],"content-domain":{"domain":["iopscience.iop.org"],"crossmark-restriction":false},"short-container-title":["Phys. Med. Biol."],"published-print":{"date-parts":[[2026,7,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Objective<\/jats:italic>\n                    . Partial tumor irradiation (PTI) targeting hypoxic\/hypovascularized\/hypometabolic tumor segment (PATHY) while sparing the peritumoral immune microenvironment has emerged as an innovative radiotherapy (RT) strategy designed to exploit non-targeted and immune-mediated effects. Although promising clinical responses have been reported, the limited availability and technical complexity of preclinical PATHY implementations have constrained mechanistic investigation and rational optimization of treatment parameters. Here, we establish a PATHY-inspired PTI workflow on a Small Animal Radiation Research Platform and evaluate its therapeutic efficacy in a rat glioma model.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:italic>Approach.<\/jats:italic>\n                    A protocol was developed integrating magnetic resonance imaging-based target delineation, millimetric small-field dosimetry, and\n                    <jats:italic>in vivo<\/jats:italic>\n                    quality assurance to selectively irradiate the tumor core using orthovoltage photons. Tumor-bearing rats were assigned to one of three PTI regimens differing in temporal fractionation\u2014conventional fractionation (15 Gy \u00d7 3, \u0394\n                    <jats:italic>t<\/jats:italic>\n                    = 24 h), accelerated fractionation (15 Gy \u00d7 3, \u0394\n                    <jats:italic>t<\/jats:italic>\n                    = 8 h), or single-fraction PTI (30 Gy \u00d7 1)\u2014or to a non-irradiated control group.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:italic>Main results.<\/jats:italic>\n                    All PTI regimens significantly prolonged overall survival compared with controls, yielding median survival increases ranging from 32% to 62%. No statistically significant differences were observed among the irradiated groups, indicating that, under the investigated dose and fractionation conditions, interfraction timing did not significantly influence survival outcome in this highly radioresistant and immunosuppressive glioma model.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:italic>Significance.<\/jats:italic>\n                    This study establishes a robust and reproducible preclinical framework for PTI and provides the first\n                    <jats:italic>in vivo<\/jats:italic>\n                    evidence of its therapeutic potential in glioma. By enabling systematic investigation of partial tumor high-dose irradiation, this platform lays the groundwork for future studies incorporating hypoxia-guided targeting and immune mechanistic endpoints to refine and translate PATHY-based RT strategies.\n                  <\/jats:p>","DOI":"10.1088\/1361-6560\/ae7232","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T22:55:16Z","timestamp":1779490516000},"page":"135016","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["PATHY-inspired partial tumor irradiation on a small-animal irradiator: workflow development and first therapeutic evaluation in glioma"],"prefix":"10.1088","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3198-2934","authenticated-orcid":true,"given":"Angela","family":"Corvino","sequence":"first","affiliation":[{"name":"Signalisation Radiobiologie et Cancer"},{"name":"Signalisation Radiobiologie et Cancer"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjorie","family":"Juchaux","sequence":"additional","affiliation":[{"name":"Signalisation Radiobiologie et Cancer"},{"name":"Signalisation Radiobiologie et Cancer"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristele","family":"Gilbert","sequence":"additional","affiliation":[{"name":"Signalisation Radiobiologie et Cancer"},{"name":"Signalisation Radiobiologie et Cancer"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Espenon","sequence":"additional","affiliation":[{"name":"Signalisation Radiobiologie et Cancer"},{"name":"Signalisation Radiobiologie et Cancer"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Sebrie","sequence":"additional","affiliation":[{"name":"BIOMAPS Universit\u00e9 Paris-Saclay"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4543-5863","authenticated-orcid":false,"given":"Slavisa","family":"Tubin","sequence":"additional","affiliation":[{"name":"Division of Radiotherapy\u2014Radiation Oncology (University Hospital Krems)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5957-2327","authenticated-orcid":true,"given":"Yolanda","family":"Prezado","sequence":"additional","affiliation":[{"name":"University of Santiago de Compostela"},{"name":"Xunta de Galicia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"266","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"pmbae7232bib1","author":"Ashland (USA)","type":"report"},{"key":"pmbae7232bib2","doi-asserted-by":"publisher","first-page":"4161","DOI":"10.1118\/1.2969065","type":"journal-article","article-title":"Some implications of linear\u2010quadratic\u2010linear radiation dose\u2010response with regard to hypofractionation","volume":"35","author":"Astrahan","year":"2008","journal-title":"Med. Phys."},{"key":"pmbae7232bib3","doi-asserted-by":"publisher","first-page":"4865","DOI":"10.3390\/cancers13194865","type":"journal-article","article-title":"First evaluation of temporal and spatial fractionation in proton minibeam radiation therapy of glioma-bearing rats","volume":"13","author":"Bertho","year":"2021","journal-title":"Cancers"},{"key":"pmbae7232bib4","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1016\/j.ijrobp.2022.08.011","type":"journal-article","article-title":"Evaluation of the role of the immune system response after minibeam radiation therapy","volume":"115","author":"Bertho","year":"2023","journal-title":"IJROBP"},{"key":"pmbae7232bib5","doi-asserted-by":"publisher","DOI":"10.5281\/zenodo.19717603","type":"dataset","article-title":"Data for :PATHY-inspired partial tumor irradiation on a small-animal irradiator: workflow development and first therapeutic evaluation in glioma","author":"Corvino","year":"2026","unstructured":"Corvino A et al 2026 Data for :PATHY-inspired partial tumor irradiation on a small-animal irradiator: workflow development and first therapeutic evaluation in glioma https:\/\/doi.org\/10.5281\/zenodo.19717603"},{"key":"pmbae7232bib6","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/j.jrras.2015.03.003","type":"journal-article","article-title":"Targeted and non-targeted effects of ionizing radiation","volume":"8","author":"Desouky","year":"2015","journal-title":"J. Radiat. Res. Appl. Sci."},{"key":"pmbae7232bib7","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.597702","type":"journal-article","article-title":"Biological guided carbon-ion microporous radiation to tumor hypoxia area triggers robust abscopal effects as open field radiation","volume":"10","author":"Huang","year":"2020","journal-title":"Front. Oncol."},{"key":"pmbae7232bib8","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2025.1493436","type":"journal-article","article-title":"Optimal fractionation scheme for lymphocyte infiltration in glioblastoma multiforme radiotherapy","volume":"15","author":"Iturri","year":"2025","journal-title":"Front. Oncol."},{"key":"pmbae7232bib9","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1016\/j.semradonc.2008.04.005","type":"journal-article","article-title":"The linear-quadratic model is inappropriate to model high dose per fraction effects in radiosurgery","volume":"18","author":"Kirkpatrick","year":"2008","journal-title":"Semin. Radiat. Oncol."},{"key":"pmbae7232bib10","doi-asserted-by":"publisher","first-page":"S302","DOI":"10.1016\/j.jtho.2023.09.519","type":"journal-article","article-title":"P2.03-02 hybrid immuno-RT (EclipseRT) for bulky tumors: low-dose radiotherapy with partial tumor SBRT in mice and patients","volume":"18","author":"Luo","year":"2023","journal-title":"J. Thoracic Oncol."},{"key":"pmbae7232bib11","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1016\/j.ijrobp.2018.10.009","type":"journal-article","article-title":"An antitumor immune response is evoked by partial-volume single-dose radiation in 2 murine models","volume":"103","author":"Markovsky","year":"2019","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"pmbae7232bib12","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.3390\/cancers11091236","type":"journal-article","article-title":"Relevance of non-targeted effects for radiotherapy and diagnostic radiology; a historical and conceptual analysis of key players","volume":"11","author":"Mothersill","year":"2019","journal-title":"Cancers"},{"key":"pmbae7232bib13","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1007\/s00066-014-0638-9","type":"journal-article","article-title":"Clinical radiobiology of glioblastoma multiforme: estimation of tumor control probability from various radiotherapy fractionation schemes","volume":"190","author":"Pedicini","year":"2014","journal-title":"Strahlenther. Onkol."},{"key":"pmbae7232bib14","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2025.118107","type":"journal-article","article-title":"Partial versus whole tumor-volume irradiation in combination with immunotherapy: comparable outcomes in immunosuppressed mouse models of oral squamous cell carcinoma","volume":"187","author":"Pisljar","year":"2025","journal-title":"Biomed. Pharmacother."},{"key":"pmbae7232bib15","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2024.110577","type":"journal-article","article-title":"The significance of dose heterogeneity on the anti-tumor response of minibeam radiation therapy","volume":"201","author":"Potiron","year":"2024","journal-title":"Radiother. Oncol."},{"key":"pmbae7232bib16","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1118\/1.3070538","type":"journal-article","article-title":"Biological equivalent dose studies for dose escalation in the stereotactic synchrotron radiation therapy clinical trials","volume":"36","author":"Prezado","year":"2009","journal-title":"Med. Phys."},{"key":"pmbae7232bib17","doi-asserted-by":"publisher","first-page":"1570","DOI":"10.1016\/j.ijrobp.2005.12.022","type":"journal-article","article-title":"An estimation of radiobiologic parameters from clinical outcomes for radiation treatment planning of brain tumor","volume":"64","author":"Qi","year":"2006","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"pmbae7232bib18","doi-asserted-by":"publisher","first-page":"i76","DOI":"10.1093\/jrr\/rrw015","type":"journal-article","article-title":"Radiobiology of hypofractionated stereotactic radiotherapy: what are the optimal fractionation schedules?","volume":"57","author":"Shibamoto","year":"2016","journal-title":"J. Radiat. Res."},{"key":"pmbae7232bib19","doi-asserted-by":"publisher","first-page":"50","DOI":"10.3390\/cancers13010050","type":"journal-article","article-title":"Shifting the immune-suppressive to predominant immune-stimulatory radiation effects by SBRT-partial tumor irradiation targeting hypoxic segment (SBRT-PATHY)","volume":"13","author":"Tubin","year":"2020","journal-title":"Cancers"},{"key":"pmbae7232bib20","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1016\/j.semradonc.2024.04.005","type":"journal-article","article-title":"A partial tumor irradiation approach for complex bulky disease","volume":"34","author":"Tubin","year":"2024","journal-title":"Semin. Radiat. Oncol."},{"key":"pmbae7232bib21","article-title":"Overcoming palliation by single ultra-high dose partial irradiation of complex bulky tumors allied with immune-\/targeted therapy: first-in-human data","author":"Tubin","year":"2026","type":"conference-proceedings"},{"key":"pmbae7232bib22","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1186\/s13014-019-1227-y","type":"journal-article","article-title":"Novel stereotactic body radiation therapy (SBRT)-based partial tumor irradiation targeting hypoxic segment of bulky tumors (SBRT-PATHY): improvement of the radiotherapy outcome by exploiting the bystander and abscopal effects","volume":"14","author":"Tubin","year":"2019","journal-title":"Radiat. Oncol."},{"key":"pmbae7232bib23","doi-asserted-by":"publisher","first-page":"437","DOI":"10.3322\/caac.21689","type":"journal-article","article-title":"Radiation therapy-associated toxicity: etiology, management, and prevention","volume":"71","author":"Wang","year":"2021","journal-title":"CA A Cancer J. Clin."},{"key":"pmbae7232bib24","article-title":"MuriPlan treatment planning demonstration","author":"Xstrahl","year":"2020","type":"report"}],"container-title":["Physics in Medicine &amp; Biology"],"original-title":[],"link":[{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6560\/ae7232","content-type":"text\/html","content-version":"am","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6560\/ae7232\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6560\/ae7232","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6560\/ae7232\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6560\/ae7232\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6560\/ae7232\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6560\/ae7232\/pdf","content-type":"application\/pdf","content-version":"am","intended-application":"similarity-checking"},{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6560\/ae7232\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T06:35:29Z","timestamp":1782974129000},"score":1,"resource":{"primary":{"URL":"https:\/\/iopscience.iop.org\/article\/10.1088\/1361-6560\/ae7232"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,2]]},"references-count":24,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7,2]]},"published-print":{"date-parts":[[2026,7,14]]}},"URL":"https:\/\/doi.org\/10.1088\/1361-6560\/ae7232","relation":{},"ISSN":["0031-9155","1361-6560"],"issn-type":[{"value":"0031-9155","type":"print"},{"value":"1361-6560","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,2]]},"assertion":[{"value":"PATHY-inspired partial tumor irradiation on a small-animal irradiator: workflow development and first therapeutic evaluation in glioma","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":"2026-03-02","name":"date_received","label":"Date Received","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2026-05-22","name":"date_accepted","label":"Date Accepted","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2026-07-02","name":"date_epub","label":"Online publication date","group":{"name":"publication_dates","label":"Publication dates"}}]}}