{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T04:59:35Z","timestamp":1785473975633,"version":"3.56.0"},"reference-count":93,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["IC230100036"],"award-info":[{"award-number":["IC230100036"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]},{"award":["IC230100036"],"award-info":[{"award-number":["IC230100036"]}],"id":[{"id":"https:\/\/ror.org\/05mmh0f86","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015539","name":"Australian Government","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100015539","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/0314h5y94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Particle arc therapy (PArc) is an emerging radiotherapy technique with the potential to improve dose conformity and organ-at-risk (OAR) sparing, while also enhancing biological effectiveness through favourable dose-averaged linear energy transfer (LETd) distributions. This scoping review aimed to evaluate the current evidence on PArc, including dosimetric, biological, and delivery-related outcomes, and to identify key limitations and future research directions. Methods: Following the PRISMA-ScR 2018 guidelines, a systematic search was conducted across MEDLINE, Scopus, and Google Scholar in December 2025, identifying 74 relevant studies. Eligible studies included peer-reviewed articles reporting treatment planning, dosimetric, biological, or delivery outcomes, with comparisons to conventional particle therapy techniques. Data were extracted and synthesised qualitatively due to heterogeneity in study designs, reported metrics, and outcome definitions. Results: Relative to conventional particle therapy techniques, PArc generally demonstrated maintained target coverage, enhanced conformity (median relative improvement in conformity index: 6.3%), and more variable dose homogeneity. Improved OAR sparing and reduced integral dose (median relative reduction in integral dose: 10.5%) were commonly observed, although these benefits were sometimes accompanied by an increased low-dose bath, reflecting a trade-off between low-dose and intermediate\u2013high-dose regions. Reductions in intermediate-to-high dose volumes were often associated with improved modelled biological outcomes, including reduced predicted normal tissue complication probabilities and secondary cancer risk. Enhanced LETd distributions were reported, with redistribution of high LETd from surrounding healthy tissue to the tumour volume, particularly in studies of carbon-ion arc therapy and radioresistant tumours. Robustness findings were mixed, with trade-offs among conformity, homogeneity, delivery efficiency, and LETd enhancement, and strong dependence on tumour site, delivery strategy, and evaluation method. Delivery efficiency was also variable, depending on machine capabilities and optimisation strategies. Conclusions: PArc shows significant potential to improve radiotherapy outcomes; however, the current evidence is largely limited to in silico studies. Further research is required to establish standardised methodologies and evaluation frameworks, integrate biological optimisation, and validate findings through prospective clinical studies before routine clinical implementation can be achieved.<\/jats:p>","DOI":"10.3390\/cancers18152443","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T17:01:46Z","timestamp":1785344506000},"page":"2443","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Particle Arc Therapy in Cancer Radiotherapy: A Scoping Review of Feasibility and Dosimetric Evidence"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7492-5079","authenticated-orcid":false,"given":"Indiana","family":"Neumann","sequence":"first","affiliation":[{"name":"School of Allied Health & Human Performance, Adelaide University, Adelaide, SA 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1315-1735","authenticated-orcid":false,"given":"Eva","family":"Bezak","sequence":"additional","affiliation":[{"name":"School of Allied Health & Human Performance, Adelaide University, Adelaide, SA 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2322-9775","authenticated-orcid":false,"given":"Shahraam","family":"Afshar Vahid","sequence":"additional","affiliation":[{"name":"School of Physics, Chemistry and Earth Sciences, Adelaide University, Adelaide, SA 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9364-0768","authenticated-orcid":false,"given":"Edward","family":"Simpson","sequence":"additional","affiliation":[{"name":"Department of Nuclear Physics and Accelerator Applications, Australian National University, Canberra, ACT 2601, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3422-9108","authenticated-orcid":false,"given":"Scott","family":"Penfold","sequence":"additional","affiliation":[{"name":"School of Physics, Chemistry and Earth Sciences, Adelaide University, Adelaide, SA 5000, Australia"},{"name":"Australian Bragg Centre for Proton Therapy and Research, Adelaide, SA 5000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"ref_1","unstructured":"Engwall, E., and Fracchiolla, F. (2025, April 28). RaySearch Laboratories Webinars: Proton Arc Therapy in RayStation\u00ae. Available online: https:\/\/www.youtube.com\/watch?v=mI6wFYfM7YE."},{"key":"ref_2","unstructured":"(2026, April 09). Particle Therapy Co-Operative Group. PTCOG-Start-Page. Available online: https:\/\/www.ptcog.site\/index.php\/facilities-in-operation-public."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S43","DOI":"10.1016\/0167-8140(96)80599-8","article-title":"Conformal proton tomotherapy using distal-edge tracking","volume":"37","author":"Deasy","year":"1995","journal-title":"Radiother. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/S0360-3016(97)00059-X","article-title":"Phantom assessment of lung dose from proton arc therapy","volume":"38","author":"Sandison","year":"1997","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1016\/j.ijrobp.2016.08.049","article-title":"Spot-Scanning Proton Arc (SPArc) Therapy: The First Robust and Delivery-Efficient Spot-Scanning Proton Arc Therapy","volume":"96","author":"Ding","year":"2016","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3191","DOI":"10.1002\/mp.17669","article-title":"Static proton arc therapy: Comprehensive plan quality evaluation and first clinical treatments in patients with complex head and neck targets","volume":"52","author":"Fracchiolla","year":"2025","journal-title":"Med. Phys."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"100749","DOI":"10.1016\/j.ijpt.2025.100749","article-title":"First Clinical Implementation of Step-and-Shoot Proton Arc Therapy for Head and Neck Cancer Treatment","volume":"16","author":"Liu","year":"2025","journal-title":"Int. J. Part. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"110434","DOI":"10.1016\/j.radonc.2024.110434","article-title":"Particle arc therapy: Status and potential","volume":"199","author":"Mein","year":"2024","journal-title":"Radiother. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"20190469","DOI":"10.1259\/bjr.20190469","article-title":"Is there a role for arcing techniques in proton therapy?","volume":"93","author":"Karagounis","year":"2020","journal-title":"Br. J. Radiol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"McIntyre, M., Wilson, P., Gorayski, P., and Bezak, E. (2023). A Systematic Review of LET-Guided Treatment Plan Optimisation in Proton Therapy: Identifying the Current State and Future Needs. Cancers, 15.","DOI":"10.3390\/cancers15174268"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"165006","DOI":"10.1088\/1361-6560\/ab9455","article-title":"Proton monoenergetic arc therapy (PMAT) to enhance LETd within the target","volume":"65","author":"Bertolet","year":"2020","journal-title":"Phys. Med. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Li, X., Ding, X., Zheng, W., Liu, G., Janssens, G., Souris, K., Barragan-Montero, A.M., Yan, D., Stevens, C., and Kabolizadeh, P. (2021). Linear Energy Transfer Incorporated Spot-Scanning Proton Arc Therapy Optimization: A Feasibility Study. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.698537"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"065010","DOI":"10.1088\/1361-6560\/ac55a6","article-title":"Fast robust optimization of proton PBS arc therapy plans using early energy layer selection and spot assignment","volume":"67","author":"Engwall","year":"2022","journal-title":"Phys. Med. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"105609","DOI":"10.1016\/j.compbiomed.2022.105609","article-title":"Treatment planning in arc proton therapy: Comparison of several optimization problem statements and their corresponding solvers","volume":"148","author":"Wuyckens","year":"2022","journal-title":"Comput. Biol. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1080\/0284186X.2023.2214320","article-title":"Robustness of multifield pseudo-arc proton therapy for sinonasal cancer","volume":"62","author":"Elstrom","year":"2023","journal-title":"Acta Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5723","DOI":"10.1002\/mp.16617","article-title":"Partitioning of discrete proton arcs into interlaced subplans can bring proton arc advances to existing proton facilities","volume":"50","author":"Engwall","year":"2023","journal-title":"Med. Phys."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"109973","DOI":"10.1016\/j.radonc.2023.109973","article-title":"Treatment planning comparison for head and neck cancer between photon, proton, and combined proton-photon therapy\u2014From a fixed beam line to an arc","volume":"190","author":"Amstutz","year":"2024","journal-title":"Radiother. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"105007","DOI":"10.1088\/1361-6560\/add103","article-title":"Potential Toxicity Benefit and Inter-Fraction Robustness of Proton Arc Therapy Compared to IMPT and VMAT for Nasopharyngeal Cancer Patients","volume":"70","author":"Maring","year":"2025","journal-title":"Phys. Med. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"467","DOI":"10.7326\/M18-0850","article-title":"PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation","volume":"169","author":"Tricco","year":"2018","journal-title":"Ann. Intern. Med."},{"key":"ref_20","unstructured":"Veritas Health Innovation (2025, December 18). Covidence Systematic Review Software. Melbourne, Australia. Available online: https:\/\/www.covidence.org."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4710","DOI":"10.1002\/mp.16577","article-title":"An orthogonal matching pursuit optimization method for solving minimum-monitor-unit problems: Applications to proton IMPT, ARC and FLASH","volume":"50","author":"Zhu","year":"2023","journal-title":"Med. Phys."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"015009","DOI":"10.1088\/1361-6560\/ac4212","article-title":"Minimum-monitor-unit optimization via a stochastic coordinate descent method","volume":"67","author":"Cai","year":"2022","journal-title":"Phys. Med. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e18089","DOI":"10.1002\/mp.18089","article-title":"A multi-arc and constant-energy-per-arc treatment planning method for efficient proton arc therapy","volume":"52","author":"Ma","year":"2025","journal-title":"Med. Phys."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"245017","DOI":"10.1088\/1361-6560\/aca5e9","article-title":"Bi-criteria Pareto optimization to balance irradiation time and dosimetric objectives in proton arc therapy","volume":"67","author":"Wuyckens","year":"2022","journal-title":"Phys. Med. Biol."},{"key":"ref_25","unstructured":"Battinelli, C. (2019). Proton Arc Therapy Optimization. [Master\u2019s Thesis, KTH Royal Institute of Technology]. Available online: https:\/\/kth.diva-portal.org\/smash\/get\/diva2:1326105\/FULLTEXT01.pdf."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2072","DOI":"10.1002\/mp.14083","article-title":"A novel energy layer optimization framework for spot-scanning proton arc therapy","volume":"47","author":"Gu","year":"2020","journal-title":"Med. Phys."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"100661","DOI":"10.1016\/j.adro.2021.100661","article-title":"Spot-Scanning Hadron Arc (SHArc) Therapy: A Study with Light and Heavy Ions","volume":"6","author":"Mein","year":"2021","journal-title":"Adv. Radiat. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1088\/0031-9155\/44\/1\/014","article-title":"Intensity Modulation Methods for Proton Radiotherapy","volume":"44","author":"Lomax","year":"1999","journal-title":"Phys. Med. Biol."},{"key":"ref_29","unstructured":"Sarrut, D., and Rit, S. (2024). Mid-Range Proton Arc Therapy. Proceedings of the XX-th International Conference on the Use of Computers in Radiation Therapy (ICCR), HAL Open Science. Available online: https:\/\/hal.science\/hal-04720234."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.3109\/0284186X.2016.1170199","article-title":"Dosimetric feasibility of single-energy proton modulated arc therapy for treatment of chordoma at the skull base","volume":"55","author":"White","year":"2016","journal-title":"Acta Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"N565","DOI":"10.1088\/0031-9155\/61\/21\/N565","article-title":"Range optimization for mono- and bi-energetic proton modulated arc therapy with pencil beam scanning","volume":"61","author":"Kirk","year":"2016","journal-title":"Phys. Med. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"104829","DOI":"10.1016\/j.ejmp.2024.104829","article-title":"Sectored single-energy volumetric-modulated proton arc therapy (VPAT): A preliminary multi-disease-site concept study","volume":"127","author":"Modiri","year":"2024","journal-title":"Phys. Medica"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/s44172-025-00460-z","article-title":"Range-compensated pencil beam scanning proton Arc therapy: A feasibility study","volume":"4","author":"Smith","year":"2025","journal-title":"Commun. Eng."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.radonc.2019.04.032","article-title":"The first prototype of spot-scanning proton arc treatment delivery","volume":"137","author":"Li","year":"2019","journal-title":"Radiother. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1016\/j.ijrobp.2023.05.012","article-title":"A Novel Ultrahigh-Dose-Rate Proton Therapy Technology: Spot-Scanning Proton Arc Therapy + FLASH (SPLASH)","volume":"117","author":"Liu","year":"2023","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"110623","DOI":"10.1016\/j.radonc.2024.110623","article-title":"Proton FLASH-arc therapy (PFAT): A feasibility study for meeting FLASH dose-rate requirements in the clinic","volume":"202","author":"Rothwell","year":"2025","journal-title":"Radiother. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"101632","DOI":"10.1016\/j.adro.2024.101632","article-title":"Rotationally Intensified Proton Lattice: A Novel Lattice Technique Using Spot-Scanning Proton Arc Therapy","volume":"9","author":"Lee","year":"2024","journal-title":"Adv. Radiat. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"215027","DOI":"10.1088\/1361-6560\/ad8855","article-title":"Proton ARC based LATTICE radiation therapy: Feasibility study, energy layer optimization and LET optimization","volume":"69","author":"Zhu","year":"2024","journal-title":"Phys. Med. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1002\/jmrs.769","article-title":"Single high-energy arc proton therapy with Bragg peak boost (SHARP)","volume":"71","author":"Penfold","year":"2024","journal-title":"J. Med. Radiat. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e18051","DOI":"10.1002\/mp.18051","article-title":"Shoot-through layers in upright proton arcs unlock advantages in plan quality and range verification","volume":"52","author":"Engwall","year":"2025","journal-title":"Med. Phys."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"21731","DOI":"10.1038\/s41598-022-25774-2","article-title":"A novel optimization algorithm for enabling dynamically collimated proton arc therapy","volume":"12","author":"Smith","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e17889","DOI":"10.1002\/mp.17889","article-title":"The Cut-Sort-Group algorithm for efficient delivery of collimated step-and-shoot proton arc therapy","volume":"52","author":"Wake","year":"2025","journal-title":"Med. Phys."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e17916","DOI":"10.1002\/mp.17916","article-title":"Early generation dynamic and static proton arc treatment planning algorithms assessment in oropharyngeal cancer patients","volume":"52","author":"Zhao","year":"2025","journal-title":"Med. Phys."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1080\/0284186X.2018.1555374","article-title":"Improving dosimetric outcome for hippocampus and cochlea sparing whole brain radiotherapy using spot-scanning proton arc therapy","volume":"58","author":"Ding","year":"2019","journal-title":"Acta Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1080\/0284186X.2019.1639823","article-title":"Towards proton arc therapy: Physical and biologically equivalent doses with increasing number of beams in pediatric brain irradiation","volume":"58","author":"Toussaint","year":"2019","journal-title":"Acta Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Chang, S., Liu, G., Zhao, L., Zheng, W., Yan, D., Chen, P., Li, X., Yang, K., Deraniyagala, R., and Stevens, C. (2022). Redefine the Role of Spot-Scanning Proton Beam Therapy for the Single Brain Metastasis Stereotactic Radiosurgery. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.804036"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6082","DOI":"10.1002\/mp.15800","article-title":"Spot-scanning hadron arc (SHArc) therapy: A proof of concept using single- and multi-ion strategies with helium, carbon, oxygen, and neon ions","volume":"49","author":"Mein","year":"2022","journal-title":"Med. Phys."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.ijrobp.2022.04.025","article-title":"Biological Dose Optimization for Particle Arc Therapy Using Helium and Carbon Ions","volume":"114","author":"Mein","year":"2022","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e13954","DOI":"10.1002\/acm2.13954","article-title":"Intensity modulated proton arc therapy via geometry-based energy selection for ependymoma","volume":"24","author":"Cao","year":"2023","journal-title":"J. Appl. Clin. Med. Phys."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Henjum, H., Tjelta, J., Fjaera, L.F., Pilskog, S., Stokkevag, C.H., Lyngholm, E., Handeland, A.H., and Ytre-Hauge, K.S. (2023). Influence of beam pruning techniques on LET and RBE in proton arc therapy. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1155310"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"100480","DOI":"10.1016\/j.phro.2023.100480","article-title":"Risk of second primary cancer from proton arc therapy of pediatric brain tumors","volume":"27","author":"Toussaint","year":"2023","journal-title":"Phys. Imaging Radiat. Oncol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"110421","DOI":"10.1016\/j.radonc.2024.110421","article-title":"Secondary cancer risk in six anatomical sites when using PAT, IMPT, and VMAT\/IMRT radiotherapy","volume":"199","author":"Johnson","year":"2024","journal-title":"Radiother. Oncol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1007\/s12553-024-00842-x","article-title":"Innovative approaches to enhance high-LETd tumor targeting in carbon ion radiotherapy","volume":"14","author":"Mairani","year":"2024","journal-title":"Health Technol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"101611","DOI":"10.1016\/j.adro.2024.101611","article-title":"First Dosimetric and Biological Verification for Spot-Scanning Hadron Arc Radiation Therapy with Carbon Ions","volume":"9","author":"Tessonnier","year":"2024","journal-title":"Adv. Radiat. Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e14526","DOI":"10.1002\/acm2.14526","article-title":"Explore the feasibility of using spot-scanning proton arc therapy for a synchrotron accelerator-based proton therapy system\u2014A simulation study","volume":"26","author":"Cong","year":"2025","journal-title":"J. Appl. Clin. Med. Phys."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"654","DOI":"10.2340\/1651-226X.2025.42001","article-title":"Dosimetric comparison of intensity-modulated proton therapy and proton arc therapy for pediatric ependymoma","volume":"64","author":"Henjum","year":"2025","journal-title":"Acta Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"101763","DOI":"10.1016\/j.adro.2025.101763","article-title":"HyperSHArc: Single-Isocenter Stereotactic Radiosurgery of Multiple Brain Metastases Using Proton, Helium, and Carbon Ion Arc Therapy","volume":"10","author":"Volz","year":"2025","journal-title":"Adv. Radiat. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"045003","DOI":"10.1088\/1361-6560\/adad2d","article-title":"Proton arc therapy plan optimization with energy layer pre-selection driven by organ at risk sparing and delivery time","volume":"70","author":"Wuyckens","year":"2025","journal-title":"Phys. Med. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s13014-020-1476-9","article-title":"Improve the dosimetric outcome in bilateral head and neck cancer (HNC) treatment using spot-scanning proton arc (SPArc) therapy: A feasibility study","volume":"15","author":"Liu","year":"2020","journal-title":"Radiat. Oncol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1002\/mp.16098","article-title":"Spot scanning proton arc therapy reduces toxicity in oropharyngeal cancer patients","volume":"50","author":"Battinelli","year":"2023","journal-title":"Med. Phys."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"109670","DOI":"10.1016\/j.radonc.2023.109670","article-title":"Proton arc therapy increases the benefit of proton therapy for oropharyngeal cancer patients in the model based clinic","volume":"184","author":"Korevaar","year":"2023","journal-title":"Radiother. Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"055015","DOI":"10.1088\/1361-6560\/ad2718","article-title":"Impact of and interplay between proton arc therapy and range uncertainties in proton therapy for head-and-neck cancer","volume":"69","author":"Tattenberg","year":"2024","journal-title":"Phys. Med. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1007\/s12553-024-00877-0","article-title":"Exploring energy selection methods for robust biologically optimized carbon ion arc for head&neck cancer patients","volume":"14","author":"Volz","year":"2024","journal-title":"Health Technol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"4982","DOI":"10.1002\/mp.17127","article-title":"Efficient proton arc optimization and delivery through energy layer pre-selection and post-filtering","volume":"51","author":"Wuyckens","year":"2024","journal-title":"Med. Phys."},{"key":"ref_65","first-page":"9","article-title":"Automated Planning for Bias-Free Validation of Discrete Proton Arc Therapy for Oropharyngeal Cancer","volume":"18","author":"Kong","year":"2025","journal-title":"Int. J. Part. Ther."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e70176","DOI":"10.1002\/mp.70176","article-title":"Combining IMPT and spot-scanning hadron arc to efficiently boost dose and LET in hypoxic target volumes","volume":"52","author":"Li","year":"2025","journal-title":"Med. Phys."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s13014-025-02621-y","article-title":"Gantry-based pencil beam scanning proton therapy for uveal melanoma: IMPT versus proton arc therapy","volume":"20","author":"Qi","year":"2025","journal-title":"Radiat. Oncol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e14611","DOI":"10.1002\/acm2.14611","article-title":"Partial and full arc with DynamicARC technique in pencil beam scanning proton therapy for bilateral head and neck cancer: A feasibility and dosimetric study","volume":"26","author":"Rana","year":"2025","journal-title":"J. Appl. Clin. Med. Phys."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Reiners, K., Artz, M., Bryant, C.M., Dagan, R., Grewal, H.S., Johnson, P.B., Li, Z., Park, J., Vieceli, M., and Zhang, Y. (2025). RBE-Guided Treatment Planning, LET Optimization, and Implications of Proton Arc Therapy for the Sparing of Nervous Tissue in Head and Neck Proton Therapy. Cancers, 17.","DOI":"10.3390\/cancers17233724"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"245020","DOI":"10.1088\/1361-6560\/ae2739","article-title":"Proton arc therapy and associated improvements in quality-adjusted life expectancy for head-and-neck cancer patients compared to volumetric modulated arc therapy and intensity-modulated proton therapy","volume":"70","author":"Tattenberg","year":"2025","journal-title":"Phys. Med. Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"100837","DOI":"10.1016\/j.phro.2025.100837","article-title":"Dynamic proton arc treatment planning study for oesophageal cancer","volume":"36","author":"Wera","year":"2025","journal-title":"Phys. Imaging Radiat. Oncol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1186\/s13014-020-01676-3","article-title":"Feasibility study: Spot-scanning proton arc therapy (SPArc) for left-sided whole breast radiotherapy","volume":"15","author":"Chang","year":"2020","journal-title":"Radiat. Oncol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.ijrobp.2013.04.048","article-title":"Proton arc reduces range uncertainty effects and improves conformality compared with photon volumetric modulated arc therapy in stereotactic body radiation therapy for non-small cell lung cancer","volume":"87","author":"Seco","year":"2013","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s13014-018-0981-6","article-title":"Improve dosimetric outcome in stage III non-small-cell lung cancer treatment using spot-scanning proton arc (SPArc) therapy","volume":"13","author":"Li","year":"2018","journal-title":"Radiat. Oncol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1080\/0284186X.2021.1892183","article-title":"Is proton beam therapy ready for single fraction spine SBRS?\u2014A feasibility study to use spot-scanning proton arc (SPArc) therapy to improve the robustness and dosimetric plan quality","volume":"60","author":"Liu","year":"2021","journal-title":"Acta Oncol."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Liu, G., Zhao, L., Qin, A., Grills, I., Deraniyagala, R., Stevens, C., Zhang, S., Yan, D., Li, X., and Ding, X. (2021). Lung Stereotactic Body Radiotherapy (SBRT) Using Spot-Scanning Proton Arc (SPArc) Therapy: A Feasibility Study. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.664455"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"805","DOI":"10.2340\/1651-226X.2024.40549","article-title":"A dosimetric and robustness analysis of proton arc therapy with early energy layer and spot assignment for lung cancer versus conventional intensity modulated proton therapy","volume":"63","author":"Chocan","year":"2024","journal-title":"Acta Oncol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"100876","DOI":"10.1016\/j.phro.2025.100876","article-title":"Integrating spot-scanning proton arc therapy with functional avoidance strategies to reduce pulmonary toxicity","volume":"36","author":"Chen","year":"2025","journal-title":"Phys. Imaging Radiat. Oncol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"100750","DOI":"10.1016\/j.ijpt.2025.100750","article-title":"Feasibility of Utilizing Spot-Scanning Proton Arc (SPArc) for Whole-Lung Irradiation: A Case Report","volume":"16","author":"Liu","year":"2025","journal-title":"Int. J. Part. Ther."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"103757","DOI":"10.1016\/j.clon.2025.103757","article-title":"Comparing the Robustness of Intensity-modulated Proton Therapy and Proton-arc Therapy Against Interplay Effects of 4D Robust-optimised Plans for Lung Stereotactic Body Radiotherapy","volume":"39","author":"Wei","year":"2025","journal-title":"Clin. Oncol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"100971","DOI":"10.1016\/j.phro.2026.100971","article-title":"Necessity of Energy Layer Repainting for Proton Radiotherapy in Breast Cancer Patients","volume":"39","author":"Andersen","year":"2026","journal-title":"Phys. Imaging Radiat. Oncol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"104816","DOI":"10.1016\/j.ejmp.2024.104816","article-title":"Investigate potential clinical benefits and linear energy transfer sparing utilizing proton arc therapy for hepatocellular carcinoma","volume":"126","author":"Liu","year":"2024","journal-title":"Phys. Medica"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e70055","DOI":"10.1002\/mp.70055","article-title":"Development and dosimetric verification of static SHArc: Step-and-shoot carbon ion arc therapy for LETd escalation in pancreatic tumors","volume":"52","author":"Baltazar","year":"2025","journal-title":"Med. Phys."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.1002\/mp.17569","article-title":"Investigating LETd optimization strategies in carbon ion radiotherapy for pancreatic cancer: A dosimetric study using an anthropomorphic phantom","volume":"52","author":"Baltazar","year":"2025","journal-title":"Med. Phys."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1080\/0284186X.2017.1358463","article-title":"Have we reached proton beam therapy dosimetric limitations?\u2014A novel robust, delivery-efficient and continuous spot-scanning proton arc (SPArc) therapy is to improve the dosimetric outcome in treating prostate cancer","volume":"57","author":"Ding","year":"2018","journal-title":"Acta Oncol."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Moteabbed, M., Bobic, M., Paganetti, H., and Efstathiou, J.A. (2024). The Role of Proton Therapy for Prostate Cancer in the Setting of Hip Prosthesis. Cancers, 16.","DOI":"10.3390\/cancers16020330"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.ijrobp.2005.09.028","article-title":"Conformity index: A review","volume":"64","author":"Feuvret","year":"2006","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"4078","DOI":"10.1118\/1.3438081","article-title":"Stereotactic body radiation therapy: The report of AAPM Task Group 101","volume":"37","author":"Benedict","year":"2010","journal-title":"Med. Phys."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.radonc.2018.06.039","article-title":"Inhomogeneous tumor dose distribution provides better local control than homogeneous distribution in stereotactic radiotherapy for brain metastases","volume":"130","author":"Lucia","year":"2019","journal-title":"Radiother. Oncol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"7338","DOI":"10.1002\/mp.16771","article-title":"The LET trilemma: Conflicts between robust target coverage, uniform dose, and dose-averaged LET in carbon therapy","volume":"50","author":"Fredriksson","year":"2023","journal-title":"Med. Phys."},{"key":"ref_91","unstructured":"Azienda Provinciale per i Servizi Sanitari (APSS) (2026, May 15). La Protonterapia di Trento al Centro delle Rivoluzioni della Fisica Applicata. Available online: https:\/\/www.asuit.tn.it\/notizie\/la-protonterapia-di-trento-al-centro-delle-rivoluzioni-della-fisica-applicata."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1016\/j.ijrobp.2021.07.1695","article-title":"The Influence of Severe Radiation-Induced Lymphopenia on Overall Survival in Solid Tumors: A Systematic Review and Meta-Analysis","volume":"111","author":"Damen","year":"2021","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/j.ijrobp.2025.03.080","article-title":"Radiation-Induced Lymphopenia: In Silico Replications of Preclinical Studies Suggest Importance of Dose to Lymphoid Organs","volume":"123","author":"Beekman","year":"2025","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/15\/2443\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T04:28:03Z","timestamp":1785472083000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/15\/2443"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,29]]},"references-count":93,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["cancers18152443"],"URL":"https:\/\/doi.org\/10.3390\/cancers18152443","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,29]]}}}