{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T21:05:33Z","timestamp":1777928733402,"version":"3.51.4"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,8]],"date-time":"2023-11-08T00:00:00Z","timestamp":1699401600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Background and purpose<\/jats:title><jats:p>This study aimed to investigate the feasibility of safe-dose escalation to dominant intraprostatic lesions (DILs) and assess the clinical impact using dose-volume (DV) and biological metrics in photon and proton therapy. Biological parameters defined as late grade \u2265 2 gastrointestinal (GI) and genitourinary (GU) derived from planned (<jats:italic>D<\/jats:italic><jats:sub>P<\/jats:sub>) and accumulated dose (<jats:italic>D<\/jats:italic><jats:sub>A<\/jats:sub>) were utilized.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>In total, 10 patients with high-risk prostate cancer with multiparametric MRI-defined DILs were investigated. Each patient had two plans with a focal boost to the DILs using intensity-modulated proton therapy (IMPT) and volumetric-modulated arc therapy (VMAT). Plans were optimized to obtain DIL coverage while respecting the mandatory organ-at-risk constraints. For the planning evaluation, DV metrics, tumor control probability (TCP) for the DILs and whole prostate excluding the DILs (prostate-DILs), and normal tissue complication probability (NTCP) for the rectum and bladder were calculated. Wilcoxon signed-rank test was used for analyzing TCP and NTCP data.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>IMPT achieved a higher <jats:italic>D<\/jats:italic>mean for the DILs compared to VMAT (IMPT: 68.1 GyRBE vs. VMAT: 66.6 Gy, <jats:italic>p<\/jats:italic> &amp;lt; 0.05). Intermediate\u2013high rectal and bladder doses were lower for IMPT (<jats:italic>p<\/jats:italic> &amp;lt; 0.05), while the high-dose region (V60 Gy) remained comparable. IMPT-TCP for prostate-DIL were higher compared to VMAT (IMPT: 86%; \u03b1\/\u03b2 = 3, 94.3%; \u03b1\/\u03b2 = 1.5 vs. VMAT: 84.7%; \u03b1\/\u03b2 = 3, 93.9%; \u03b1\/\u03b2 = 1.5, <jats:italic>p<\/jats:italic> &amp;lt; 0.05). Likewise, IMPT obtained a moderately higher DIL TCP (IMPT: 97%; \u03b1\/\u03b2 = 3, 99.3%; \u03b1\/\u03b2 = 1.5 vs. VMAT: 95.9%; \u03b1\/\u03b2 = 3, 98.9%; \u03b1\/\u03b2 = 1.5, <jats:italic>p<\/jats:italic> &amp;lt; 0.05). Rectal <jats:italic>D<\/jats:italic><jats:sub>A<\/jats:sub>-NTCP displayed the highest GI toxicity risk at 5.6%, and IMPT has a lower GI toxicity risk compared to VMAT-predicted Quantec-NTCP (<jats:italic>p<\/jats:italic> &amp;lt; 0.05). Bladder <jats:italic>D<\/jats:italic><jats:sub>P<\/jats:sub>-NTCP projected a higher GU toxicity than <jats:italic>D<\/jats:italic><jats:sub>A<\/jats:sub>-NTCP, with VMAT having the highest risk (<jats:italic>p<\/jats:italic> &amp;lt; 0.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Dose escalation using IMPT is able to achieve a high TCP for the DILs, with the lowest rectal and bladder DV doses at the intermediate\u2013high-dose range. The reduction in physical dose was translated into a lower NTCP (<jats:italic>p<\/jats:italic> &amp;lt; 0.05) for the bladder, although rectal toxicity remained equivalent.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2023.1241711","type":"journal-article","created":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T16:15:30Z","timestamp":1699546530000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Proton versus photon therapy for high-risk prostate cancer with dose escalation of dominant intraprostatic lesions: a preliminary planning study"],"prefix":"10.3389","volume":"13","author":[{"given":"Ashley Li Kuan","family":"Ong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kellie","family":"Knight","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanessa","family":"Panettieri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathew","family":"Dimmock","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey Kit Loong","family":"Tuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong Qi","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Wright","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,11,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2011.05.035","article-title":"Pathological predictors for site of local recurrence after radiotherapy for prostate cancer","volume":"82","author":"Chopra","year":"2012","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"B2","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/s41747-019-0088-3","article-title":"Evolution of prostate MRI: from multiparametric standard to less-is-better and different-is better strategies","volume":"3","author":"Girometti","year":"2019","journal-title":"Eur Radiol Exp"},{"key":"B3","doi-asserted-by":"publisher","first-page":"88","DOI":"10.3109\/0284186X.2013.837581","article-title":"Accurate prostate tumour detection with multiparametric magnetic resonance imaging: Dependence on histological properties","volume":"53","author":"Borren","year":"2014","journal-title":"Acta Oncol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/bju.14925","article-title":"Ultra-hypofractionated radiation therapy for unfavourable intermediate-risk and high-risk prostate cancer is safe and effective: 5-year outcomes of a phase II trial","volume":"125","author":"Macias","year":"2020","journal-title":"BJU Int"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2017.01.008","article-title":"ASCENDE-RT: an analysis of treatment-related morbidity for a randomized trial comparing a low-dose-rate brachytherapy boost with a dose-escalated external beam boost for high- and intermediate-risk prostate cancer","volume":"98","author":"Rodda","year":"2017","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.921465","article-title":"Long-term outcomes of prostate intensity-modulated radiation therapy incorporating a simultaneous intra-prostatic MRI-directed boost","volume":"12","author":"Laughlin","year":"2022","journal-title":"Front Oncol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1200\/jco.20.02873","article-title":"Focal boost to the intraprostatic tumor in external beam radiotherapy for patients with localized prostate cancer: results from the FLAME randomized phase III trial","volume":"39","author":"Kerkmeijer","year":"2021","journal-title":"J Clin Oncol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2018.11.012","article-title":"Proton therapy for prostate cancer: A review of the rationale, evidence, and current state","volume":"37","author":"Royce","year":"2019","journal-title":"Urol Oncol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1002\/pro6.1149","article-title":"A review of proton therapy \u2013 Current status and future directions","volume":"6","author":"Mohan","year":"2022","journal-title":"Precis Radiat Oncol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.3390\/cancers10040116","article-title":"Proton beam therapy alone for intermediate- or high-risk prostate cancer: an institutional prospective cohort study","volume":"10","author":"Arimura","year":"2018","journal-title":"Cancers (Basel)"},{"key":"B11","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1016\/j.ijrobp.2013.11.007","article-title":"Five-year outcomes from 3 prospective trials of image-guided proton therapy for prostate cancer","volume":"88","author":"Mendenhall","year":"2014","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2022.11.027","article-title":"Late toxicity of moderately hypofractionated intensity modulated proton therapy treating the prostate and pelvic lymph nodes for high-risk prostate cancer","volume":"115","author":"Choo","year":"2023","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1080\/0284186X.2021.1947523","article-title":"Proton vs. photon radiotherapy for MR-guided dose escalation of intraprostatic lesions","volume":"60","author":"Moteabbed","year":"2021","journal-title":"Acta Oncol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctro.2020.08.003","article-title":"PIVOTALboost: A phase III randomised controlled trial of prostate and pelvis versus prostate alone radiotherapy with or without prostate boost (CRUK\/16\/018)","volume":"25","author":"Syndikus","year":"2020","journal-title":"Clin Transl Radiat Oncol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2016.71.7397","article-title":"Randomized trial of a hypofractionated radiation regimen for the treatment of localized prostate cancer","volume":"35","author":"Catton","year":"2017","journal-title":"J Clin Oncol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/s40644-016-0068-2","article-title":"Prostate MRI based on PI-RADS version 2: how we review and report","volume":"16","author":"Steiger","year":"2016","journal-title":"Cancer Imaging"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.26933","article-title":"Histopathological features of MRI-invisible regions of prostate cancer lesions","volume":"51","author":"Van Houdt","year":"2020","journal-title":"J Magn Reson Imaging"},{"key":"B18","doi-asserted-by":"publisher","first-page":"193","DOI":"10.3348\/kjr.2018.19.2.193","article-title":"Prostate imaging-reporting and data system version 2: beyond prostate cancer detection","volume":"19","author":"Park","year":"2018","journal-title":"Korean J Radiol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2008.08.002","article-title":"RTOG GU Radiation oncology specialists reach consensus on pelvic lymph node volumes for high-risk prostate cancer","volume":"74","author":"Lawton","year":"2009","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"B20","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.clon.2016.09.009","article-title":"Twenty fraction prostate radiotherapy with intra-prostatic boost: results of a pilot study","volume":"29","author":"Onjukka","year":"2017","journal-title":"Clin Oncol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1259\/bjr.20190359","article-title":"Proton therapy delivery: what is needed in the next ten years","volume":"93","author":"Schreuder","year":"2020","journal-title":"Br J Radiol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1186\/s13014-020-01683-4","article-title":"Prostate cancer tumour control probability modelling for external beam radiotherapy based on multi-parametric MRI-GTV definition","volume":"15","author":"Sachpazidis","year":"2020","journal-title":"Radiat Oncol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-015-3257-5","article-title":"MRI versus (6)(8)Ga-PSMA PET\/CT for gross tumour volume delineation in radiation treatment planning of primary prostate cancer","volume":"43","author":"Zamboglou","year":"2016","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"B24","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1186\/s13014-018-1040-z","article-title":"The alfa and beta of tumours: a review of parameters of the linear-quadratic model, derived from clinical radiotherapy studies","volume":"13","author":"Van Leeuwen","year":"2018","journal-title":"Radiat Oncol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.meddos.2021.09.004","article-title":"Application of an automated dose accumulation workflow in high-risk prostate cancer - validation and dose-volume analysis between planned and delivered dose","volume":"47","author":"Ong","year":"2022","journal-title":"Med Dosim"},{"key":"B26","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.phro.2022.07.001","article-title":"Dose-volume analysis of planned versus accumulated dose as a predictor for late gastrointestinal toxicity in men receiving radiotherapy for high-risk prostate cancer","volume":"23","author":"Ong","year":"2022","journal-title":"Phys Imaging Radiat Oncol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.1084311","article-title":"Predictive modelling for late rectal and urinary toxicities after prostate radiotherapy using planned and delivered dose","volume":"12","author":"Ong","year":"2022","journal-title":"Front Oncol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2009.03.078","article-title":"Radiation dose-volume effects in radiation-induced rectal injury","volume":"76","author":"Michalski","year":"2010","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/0360-3016(91)90171-y","article-title":"Tolerance of normal tissue to therapeutic irradiation","volume":"21","author":"Emami","year":"1991","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.00910","article-title":"External validation of a predictive model of urethral strictures for prostate patients treated with HDR brachytherapy boost","volume":"10","author":"Panettieri","year":"2020","journal-title":"Front Oncol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1016\/j.ijrobp.2022.09.058","article-title":"Standard and hypofractionated dose escalation to intraprostatic tumor nodules in localized prostate cancer: 5-year efficacy and toxicity in the DELINEATE trial","volume":"15","author":"Tree","year":"2022","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1259\/bjr.20190845","article-title":"A planning study of focal dose escalations to multiparametric MRI-defined dominant intraprostatic lesions in prostate proton radiation therapy","volume":"93","author":"Wang","year":"2020","journal-title":"Br J Radiol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.clon.2015.09.006","article-title":"Prostate dose-painting radiotherapy and radiobiological guided optimisation enhances the therapeutic ratio","volume":"28","author":"Uzan","year":"2016","journal-title":"Clin Oncol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2015.10.006","article-title":"Variable proton relative biological effectiveness: how do we move forward","volume":"95","author":"Underwood","year":"2016","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"B35","doi-asserted-by":"publisher","first-page":"115027","DOI":"10.1088\/1361-6560\/ab2144","article-title":"Applying a variable relative biological effectiveness (RBE) might affect the analysis of clinical trials comparing photon and proton therapy for prostate cancer","volume":"64","author":"Marteinsdottir","year":"2019","journal-title":"Phys Med Biol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1080\/0284186x.2017.1388539","article-title":"Minimal toxicity after proton beam therapy for prostate and pelvic nodal irradiation: results from the proton collaborative group REG001-09 trial","volume":"57","author":"Chuong","year":"2018","journal-title":"Acta Oncol"},{"key":"B37","doi-asserted-by":"publisher","first-page":"109628","DOI":"10.1016\/j.radonc.2023.109628","article-title":"Validation of prediction models for radiation-induced late rectal bleeding: evidence from a large pooled population of prostate cancer patients","volume":"183","author":"Cicchetti","year":"2023","journal-title":"Radiother Oncol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"11","DOI":"10.14338\/IJPT-18-00048.1","article-title":"IMPT versus VMAT for pelvic nodal irradiation in prostate cancer: A dosimetric comparison","volume":"5","author":"Whitaker","year":"2019","journal-title":"Int J Part Ther"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1080\/0284186X.2020.1762928","article-title":"Clinical implications of variable relative biological effectiveness in proton therapy for prostate cancer","volume":"59","author":"Bertolet","year":"2020","journal-title":"Acta Oncol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.31661\/jbpe.v9i3Jun.655","article-title":"Comparison of radiobiological models for radiation therapy plans of prostate cancer: three-dimensional conformal versus intensity modulated radiation therapy","volume":"9","author":"Mesbahi","year":"2019","journal-title":"J BioMed Phys Eng"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2021.08.016","article-title":"Does the uncertainty in relative biological effectiveness affect patient treatment in proton therapy","volume":"163","author":"S\u00f8rensen","year":"2021","journal-title":"Radiother Oncol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1088\/0031-9155\/59\/22\/r419","article-title":"Relative biological effectiveness (RBE) values for proton beam therapy. Variations as a function of biological endpoint, dose, and linear energy transfer","volume":"59","author":"Paganetti","year":"2014","journal-title":"Phys Med Biol"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2023.1241711\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T16:15:32Z","timestamp":1699546532000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2023.1241711\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,8]]},"references-count":42,"alternative-id":["10.3389\/fonc.2023.1241711"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2023.1241711","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,8]]},"article-number":"1241711"}}