{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:30:20Z","timestamp":1760146220643,"version":"build-2065373602"},"reference-count":41,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2024,10,5]],"date-time":"2024-10-05T00:00:00Z","timestamp":1728086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NRF","award":["2021R1F1A1047378"],"award-info":[{"award-number":["2021R1F1A1047378"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Proton therapy requires caution when treating patients with targets near neural structures. Intuitive and quantitative guidelines are needed to support decision-making concerning the treatment modality. This study compared dosimetric profiles of intensity-modulated proton therapy (IMPT) and intensity-modulated radiation therapy (IMRT) using helical tomotherapy (HT) for adaptive re-planning in cT3-4 nasopharyngeal cancer (NPCa) patients, aiming to establish criteria for selecting appropriate treatment modalities. Methods: HT and IMPT plans were generated for 28 cT3-4 NPCa patients undergoing definitive radiotherapy. Dosimetric comparisons were performed for target coverage and high-priority organs at risk (OARs). The correlation between dosimetric parameters and RT modality selection was analyzed with the target OAR distances. Results: Target coverages were similar, while IMPT achieved better dose spillage. HT was more favorable for brainstem D1, optic chiasm Dmax, optic nerves Dmax, and p-cord D1. IMPT showed advantages for oral cavity Dmean. Actually, 14 IMPT and 14 HT plans were selected as adaptive plans, with IMPT allocated to most cT3 patients (92.9% vs. 42.9%, p = 0.013). The shortest distances from the target to neural structures were negatively correlated with OAR doses. Receiver operating characteristic curve analyses were carried out to discover the optimal cut-off values of the shortest distances between the target and the OARs (temporal lobes and brainstem), which were 0.75 cm (AUC = 0.908, specificity = 1.00) and 0.85 cm (AUC = 0.857, specificity = 0.929), respectively. Conclusions: NPCa patients with cT4 tumor or with the shortest distance between the target and critical neural structures &lt; 0.8 cm were suboptimal candidates for IMPT adaptive re-planning. These criteria may improve resource utilization and clinical outcomes.<\/jats:p>","DOI":"10.3390\/cancers16193402","type":"journal-article","created":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T07:08:18Z","timestamp":1728284898000},"page":"3402","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Dosimetric Comparison and Selection Criteria of Intensity-Modulated Proton Therapy and Intensity-Modulated Radiation Therapy for Adaptive Re-Plan in T3-4 Nasopharynx Cancer Patients"],"prefix":"10.3390","volume":"16","author":[{"given":"Mincheol","family":"Ko","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul 06351, Republic of Korea"},{"name":"Department of Bio-Convergence Engineering, Korea University, Seoul 02841, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2262-997X","authenticated-orcid":false,"given":"Kyungmi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul 06351, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1971-8472","authenticated-orcid":false,"given":"Yong Chan","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul 06351, Republic of Korea"},{"name":"Department of Digital Health, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul 06355, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang Gyu","family":"Ju","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul 06351, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5643-5519","authenticated-orcid":false,"given":"Dongryul","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul 06351, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yeong-bi","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Digital Health, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul 06355, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong Yeol","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul 06351, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seyjoon","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul 06351, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7517-3967","authenticated-orcid":false,"given":"Kisung","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Bio-Convergence Engineering, Korea University, Seoul 02841, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e49968","DOI":"10.2196\/49968","article-title":"Nasopharyngeal Cancer Incidence and Mortality in 185 Countries in 2020 and the Projected Burden in 2040: Population-Based Global Epidemiological Profiling","volume":"9","author":"Zhang","year":"2023","journal-title":"JMIR Public Health Surveill."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1016\/j.hoc.2008.08.014","article-title":"New advances in high-technology radiotherapy for head and neck cancer","volume":"22","author":"Kubicek","year":"2008","journal-title":"Hematol. Oncol. Clin. North. Am."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.oraloncology.2010.03.005","article-title":"Advances in radiotherapy for head and neck cancer","volume":"46","author":"Bhide","year":"2010","journal-title":"Oral. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3277","DOI":"10.1200\/JCO.2015.61.2994","article-title":"Advances in radiotherapy for head and neck cancer","volume":"33","author":"Gregoire","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.radonc.2012.08.013","article-title":"A prospective, randomized study comparing outcomes and toxicities of intensity-modulated radiotherapy vs. conventional two-dimensional radiotherapy for the treatment of nasopharyngeal carcinoma","volume":"104","author":"Peng","year":"2012","journal-title":"Radiother. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.radonc.2013.10.020","article-title":"Long-term outcomes of intensity-modulated radiotherapy for 868 patients with nasopharyngeal carcinoma: An analysis of survival and treatment toxicities","volume":"110","author":"Sun","year":"2014","journal-title":"Radiother. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1177\/107327481602300304","article-title":"Clinical Benefits of Proton Beam Therapy for Tumors of the Skull Base","volume":"23","author":"Ahmed","year":"2016","journal-title":"Cancer Control."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1002\/jso.25502","article-title":"A prospective clinical trial of proton therapy for chordoma and chondrosarcoma: Feasibility assessment","volume":"120","author":"Baumann","year":"2019","journal-title":"J. Surg. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"96","DOI":"10.25259\/SNI-213-2019","article-title":"Skull base chordoma treated with proton therapy: A systematic review","volume":"10","author":"Alahmari","year":"2019","journal-title":"Surg. Neurol. Int."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"28","DOI":"10.14338\/IJPT-20-00057.1","article-title":"Intensity-Modulated Proton Therapy for Nasopharynx Cancer: 2-year Outcomes from a Single Institution","volume":"8","author":"Williams","year":"2021","journal-title":"Int. J. Part. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"537","DOI":"10.4143\/crt.2015.081","article-title":"Tumor volume reduction rate during adaptive radiation therapy as a prognosticator for nasopharyngeal cancer","volume":"48","author":"Lee","year":"2016","journal-title":"Cancer Res. Treat."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"603","DOI":"10.4143\/crt.2018.240","article-title":"Feasibility of Selective Neck Irradiation with Lower Elective Radiation Dose in Treating Nasopharynx Cancer Patients","volume":"51","author":"Cho","year":"2019","journal-title":"Cancer Res. Treat."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1016\/j.ijrobp.2021.02.018","article-title":"Brain-Specific Relative Biological Effectiveness of Protons Based on Long-term Outcome of Patients with Nasopharyngeal Carcinoma","volume":"110","author":"Zhang","year":"2021","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Vai, A., Molinelli, S., Rossi, E., Iacovelli, N.A., Magro, G., Cavallo, A., Pignoli, E., Rancati, T., Mirandola, A., and Russo, S. (2022). Proton radiation therapy for nasopharyngeal cancer patients: Dosimetric and NTCP evaluation supporting clinical decision. Cancers., 14.","DOI":"10.3390\/cancers14051109"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e586","DOI":"10.1016\/j.ijrobp.2021.07.1572","article-title":"NTCP Modelling for High Grade Temporal Radio-Necrosis in a Large Cohort of Patients Receiving PBS Proton Therapy for Skull Base and Head and Neck Tumors","volume":"111","author":"Schroeder","year":"2021","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s13014-014-0326-z","article-title":"Analysis of late toxicity in nasopharyngeal carcinoma patients treated with intensity modulated radiation therapy","volume":"10","author":"Zheng","year":"2015","journal-title":"Radiat. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1007\/s11912-019-0799-x","article-title":"Changes in the 8th Edition of the American Joint Committee on Cancer (AJCC) Staging of Head and Neck Cancer: Rationale and Implications","volume":"21","author":"Zanoni","year":"2019","journal-title":"Curr. Oncol. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.radonc.2017.10.032","article-title":"International guideline for the delineation of the clinical target volumes (CTV) for nasopharyngeal carcinoma","volume":"126","author":"Lee","year":"2018","journal-title":"Radiother. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.radonc.2015.07.041","article-title":"CT-based delineation of organs at risk in the head and neck region: DAHANCA, EORTC, GORTEC, HKNPCSG, NCIC CTG, NCRI, NRG Oncology and TROG consensus guidelines","volume":"117","author":"Brouwer","year":"2015","journal-title":"Radiother. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1016\/j.tranon.2017.06.011","article-title":"Oral mucosa dose parameters predicting grade\u2265 3 acute toxicity in locally advanced nasopharyngeal carcinoma patients treated with concurrent intensity-modulated radiation therapy and chemotherapy: An independent validation study comparing oral cavity versus mucosal surface contouring techniques","volume":"10","author":"Li","year":"2017","journal-title":"Trans. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3013","DOI":"10.1118\/1.3584198","article-title":"Dynamic tomotherapy delivery","volume":"38","author":"Chen","year":"2011","journal-title":"Med. Phys."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Chang, L., Shaaban, S.G., Gogineni, E., Page, B., Quon, H., Li, H., and Ger, R. (2023). Daily Head and Neck Treatment Assessment for Optimal Proton Therapy Planning Robustness. Cancers., 15.","DOI":"10.3390\/cancers15143719"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"109729","DOI":"10.1016\/j.radonc.2023.109729","article-title":"PTV-based VMAT vs. robust IMPT for head-and-neck cancer: A probabilistic uncertainty analysis of clinical plan evaluation with the Dutch model-based selection","volume":"186","author":"Korevaar","year":"2023","journal-title":"Radiother. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/j.ijrobp.2009.09.040","article-title":"Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC): An introduction to the scientific issues","volume":"76","author":"Bentzen","year":"2010","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Wu, Q., Mohan, R., Morris, M., Lauve, A., and Schmidt-Ullrich, R. (2003). Simultaneous integrated boost intensity-modulated radiotherapy for locally advanced head-and-neck squamous cell carcinomas. I: Dosimetric results. Int. J. Radiat. Oncol. Biol. Phys., 56.","DOI":"10.1016\/S0360-3016(02)04617-5"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"219","DOI":"10.3171\/jns.2000.93.supplement_3.0219","article-title":"A simple scoring ratio to index the conformity of radiosurgical treatment plans. Technical note","volume":"93","author":"Paddick","year":"2000","journal-title":"J. Neurosurg."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1200\/JCO.2006.09.7469","article-title":"Stereotactic body radiation therapy in multiple organ sites","volume":"25","author":"Timmerman","year":"2007","journal-title":"J. Clin. Oncol."},{"key":"ref_28","first-page":"152","article-title":"A measure tool for evaluating dose falloff outside the target volume in high precision radiotherapy","volume":"15","author":"Zhang","year":"2022","journal-title":"J. Radiat. Res. Appl. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5497","DOI":"10.1118\/1.3253464","article-title":"Patient geometry-driven information retrieval for IMRT treatment plan quality control","volume":"36","author":"Wu","year":"2009","journal-title":"Med. Phys."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1002\/acm2.13128","article-title":"Potential benefits of adaptive intensity-modulated proton therapy in nasopharyngeal carcinomas","volume":"22","author":"Minatogawa","year":"2021","journal-title":"J. Appl. Clin. Med. Phys."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1080\/0284186X.2020.1730001","article-title":"Mixed-beam approach in locally advanced nasopharyngeal carcinoma: IMRT followed by proton therapy boost versus IMRT-only. Evaluation of toxicity and efficacy","volume":"59","author":"Alterio","year":"2020","journal-title":"Acta Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"135","DOI":"10.3857\/roj.2011.29.3.135","article-title":"Basics of particle therapy I: Physics","volume":"29","author":"Park","year":"2011","journal-title":"Radiat. Oncol. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2867","DOI":"10.1111\/cas.14115","article-title":"Early clinical outcomes of helical tomotherapy\/intensity-modulated proton therapy combination in nasopharynx cancer","volume":"110","author":"Park","year":"2019","journal-title":"Cancer Sci."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Newhauser, W. (2009). International Commission on Radiation Units and Measurements Report 78: Prescribing, Recording and Reporting Proton-Beam Therapy, Oxford University Press.","DOI":"10.1093\/rpd\/ncp005"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Safai, S., Bortfeld, T., and Engelsman, M. (2008). Comparison between the lateral penumbra of a collimated double-scattered beam and uncollimated scanning beam in proton radiotherapy. Phys. Med. Biol., 53.","DOI":"10.1088\/0031-9155\/53\/6\/016"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.3938\/jkps.60.1973","article-title":"Study of the penumbra for high-energy photon beams with Gafchromic\u2122 EBT2 films","volume":"60","author":"Oh","year":"2012","journal-title":"J. Korean Phys. Soc."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1007\/s41365-019-0687-y","article-title":"Quantifying lateral penumbra advantages of collimated spot-scanning beam for intensity-modulated proton therapy","volume":"30","author":"Liu","year":"2019","journal-title":"Nucl. Sci. Tech."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1186\/s13014-019-1405-y","article-title":"Dose distribution of intensity-modulated proton therapy with and without a multi-leaf collimator for the treatment of maxillary sinus cancer: A comparative effectiveness study","volume":"14","author":"Sugiyama","year":"2019","journal-title":"Radiat. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"P\u00e9rez-And\u00fajar, A., Newhauser, W.D., and DeLuca, P.M. (2009). Neutron production from beam-modifying devices in a modern double scattering proton therapy beam delivery system. Phys. Med. Biol., 54.","DOI":"10.1088\/0031-9155\/54\/4\/012"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1093\/rpd\/nci259","article-title":"Therapeutic step and shoot proton beam spot-scanning with a multi-leaf collimator: A Monte Carlo study","volume":"115","author":"Bues","year":"2005","journal-title":"Radiat. Prot. Dosimetry."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1118\/1.3116382","article-title":"Characterization of a mini-multileaf collimator in a proton beamline","volume":"36","author":"Daartz","year":"2009","journal-title":"Med Phys."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/19\/3402\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:11:18Z","timestamp":1760112678000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/19\/3402"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,5]]},"references-count":41,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["cancers16193402"],"URL":"https:\/\/doi.org\/10.3390\/cancers16193402","relation":{},"ISSN":["2072-6694"],"issn-type":[{"type":"electronic","value":"2072-6694"}],"subject":[],"published":{"date-parts":[[2024,10,5]]}}}