{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T10:14:19Z","timestamp":1785147259923,"version":"3.55.0"},"reference-count":47,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T00:00:00Z","timestamp":1716508800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Helium ion therapy (HRT) is a promising modality for the treatment of pediatric tumors and those located close to critical structures due to the favorable biophysical properties of helium ions. This in silico study aimed to explore the potential benefits of HRT in advanced juvenile nasopharyngeal angiofibroma (JNA) compared to proton therapy (PRT). We assessed 11 consecutive patients previously treated with PRT for JNA in a definitive or postoperative setting with a relative biological effectiveness (RBE) weighted dose of 45 Gy (RBE) in 25 fractions at the Heidelberg Ion-Beam Therapy Center. HRT plans were designed retrospectively for dosimetric comparisons and risk assessments of radiation-induced complications. HRT led to enhanced target coverage in all patients, along with sparing of critical organs at risk, including a reduction in the brain integral dose by approximately 27%. In terms of estimated risks of radiation-induced complications, HRT led to a reduction in ocular toxicity, cataract development, xerostomia, tinnitus, alopecia and delayed recall. Similarly, HRT led to reduced estimated risks of radiation-induced secondary neoplasms, with a mean excess absolute risk reduction of approximately 30% for secondary CNS malignancies. HRT is a promising modality for advanced JNA, with the potential for enhanced sparing of healthy tissue and thus reduced radiation-induced acute and long-term complications.<\/jats:p>","DOI":"10.3390\/cancers16111993","type":"journal-article","created":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T05:36:06Z","timestamp":1716528966000},"page":"1993","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Helium Ion Therapy for Advanced Juvenile Nasopharyngeal Angiofibroma"],"prefix":"10.3390","volume":"16","author":[{"given":"Line","family":"Hoeltgen","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7087-9581","authenticated-orcid":false,"given":"Eva","family":"Meixner","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Hoegen-Sa\u00dfmannshausen","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany"},{"name":"Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0775-8565","authenticated-orcid":false,"given":"Ji-Young","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Seidensaal","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3913-4693","authenticated-orcid":false,"given":"Thomas","family":"Held","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Herfarth","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Haberer","sequence":"additional","affiliation":[{"name":"Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg University Hospital, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Debus","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany"},{"name":"Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"},{"name":"Heidelberg Institute of Radiation Oncology (HIRO), 69120 Heidelberg, Germany"},{"name":"Partner Site, German Cancer Consortium (DKTK), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Mairani","sequence":"additional","affiliation":[{"name":"Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany"},{"name":"Centro Nazionale di Adroterapia Oncologica (CNAO), Medical Physics Department, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1195-7150","authenticated-orcid":false,"given":"Semi","family":"Harrabi","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Tessonnier","sequence":"additional","affiliation":[{"name":"Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg University Hospital, 69120 Heidelberg, Germany"},{"name":"Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1002\/hed.24696","article-title":"Nasal juvenile angiofibroma: Current perspectives with emphasis on management","volume":"39","author":"Lopez","year":"2017","journal-title":"Head Neck"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1055\/s-0037-1615810","article-title":"Juvenile Angiofibroma: Current Management Strategies","volume":"79","author":"Safadi","year":"2018","journal-title":"J. Neurol. Surg. B Skull Base"},{"key":"ref_3","first-page":"75","article-title":"Long-term treatment outcomes of juvenile nasopharyngeal angiofibroma treated with radiotherapy","volume":"35","author":"Mallick","year":"2015","journal-title":"Acta Otorhinolaryngol. Ital."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1016\/j.ijrobp.2010.04.048","article-title":"Conformal radiotherapy in the treatment of advanced juvenile nasopharyngeal angiofibroma with intracranial extension: An institutional experience","volume":"80","author":"Chakraborty","year":"2011","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2855","DOI":"10.1200\/JCO.2014.55.1945","article-title":"Promise and pitfalls of heavy-particle therapy","volume":"32","author":"Mitin","year":"2014","journal-title":"J. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.canrad.2015.05.028","article-title":"Paediatric brain tumours: A review of radiotherapy, state of the art and challenges for the future regarding protontherapy and carbontherapy","volume":"19","author":"Laprie","year":"2015","journal-title":"Cancer Radiother."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1186\/1748-717X-7-170","article-title":"Treatment of pediatric patients and young adults with particle therapy at the Heidelberg Ion Therapy Center (HIT): Establishment of workflow and initial clinical data","volume":"7","author":"Combs","year":"2012","journal-title":"Radiat. Oncol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Hoeltgen, L., Tessonnier, T., Meixner, E., Hoegen, P., Kim, J.Y., Deng, M., Seidensaal, K., Held, T., Herfarth, K., and Debus, J. (2023). Proton Therapy for Advanced Juvenile Nasopharyngeal Angiofibroma. Cancers, 15.","DOI":"10.3390\/cancers15205022"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3958","DOI":"10.1088\/1361-6560\/aa6516","article-title":"Experimental dosimetric comparison of (1)H, (4)He, (12)C and (16)O scanned ion beams","volume":"62","author":"Tessonnier","year":"2017","journal-title":"Phys. Med. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"751","DOI":"10.3109\/0284186X.2015.1125016","article-title":"Can particle beam therapy be improved using helium ions?\u2014A planning study focusing on pediatric patients","volume":"55","author":"Knausl","year":"2016","journal-title":"Acta Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Mairani, A., Mein, S., Blakely, E., Debus, J., Durante, M., Ferrari, A., Fuchs, H., Georg, D., Grosshans, D.R., and Guan, F. (2022). Roadmap: Helium ion therapy. Phys. Med. Biol., 67.","DOI":"10.1088\/1361-6560\/ac65d3"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Wickert, R., Tessonnier, T., Deng, M., Adeberg, S., Seidensaal, K., Hoeltgen, L., Debus, J., Herfarth, K., and Harrabi, S.B. (2022). Radiotherapy with Helium Ions Has the Potential to Improve Both Endocrine and Neurocognitive Outcome in Pediatric Patients with Ependymoma. Cancers, 14.","DOI":"10.3390\/cancers14235865"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Bonaccorsi, S.G., Tessonnier, T., Hoeltgen, L., Meixner, E., Harrabi, S., Horner-Rieber, J., Haberer, T., Abdollahi, A., Debus, J., and Mairani, A. (2024). Exploring Helium Ions\u2019 Potential for Post-Mastectomy Left-Sided Breast Cancer Radiotherapy. Cancers, 16.","DOI":"10.3390\/cancers16020410"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/j.ijrobp.2023.01.015","article-title":"Commissioning of Helium Ion Therapy and the First Patient Treatment with Active Beam Delivery","volume":"116","author":"Tessonnier","year":"2023","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.radonc.2017.12.013","article-title":"The EPTN consensus-based atlas for CT- and MR-based contouring in neuro-oncology","volume":"128","author":"Eekers","year":"2018","journal-title":"Radiother. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1097\/COC.0b013e318178e4e8","article-title":"A radiation oncologist\u2019s guide to contouring the hippocampus","volume":"32","author":"Chera","year":"2009","journal-title":"Am. J. Clin. Oncol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e53","DOI":"10.1002\/mp.13390","article-title":"Report of the AAPM TG-256 on the relative biological effectiveness of proton beams in radiation therapy","volume":"46","author":"Paganetti","year":"2019","journal-title":"Med. Phys."},{"key":"ref_18","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_19","doi-asserted-by":"crossref","first-page":"N244","DOI":"10.1088\/1361-6560\/aa6be9","article-title":"Optimizing the modified microdosimetric kinetic model input parameters for proton and (4)He ion beam therapy application","volume":"62","author":"Mairani","year":"2017","journal-title":"Phys. Med. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1118\/1.1591991","article-title":"Nontumor integral dose variation in conventional radiotherapy treatment planning","volume":"30","author":"Rosen","year":"2003","journal-title":"Med. Phys."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.ijrobp.2005.10.038","article-title":"Modeling radiation dosimetry to predict cognitive outcomes in pediatric patients with CNS embryonal tumors including medulloblastoma","volume":"65","author":"Merchant","year":"2006","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.ijrobp.2020.11.073","article-title":"Neurocognitive Effects and Necrosis in Childhood Cancer Survivors Treated with Radiation Therapy: A PENTEC Comprehensive Review","volume":"119","author":"Mahajan","year":"2021","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1016\/j.ijrobp.2012.11.031","article-title":"Hippocampal dosimetry predicts neurocognitive function impairment after fractionated stereotactic radiotherapy for benign or low-grade adult brain tumors","volume":"85","author":"Gondi","year":"2013","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.ijrobp.2023.04.024","article-title":"Central Endocrine Complications among Childhood Cancer Survivors Treated with Radiation Therapy: A PENTEC Comprehensive Review","volume":"119","author":"Wheeler","year":"2023","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1002\/mp.15360","article-title":"Normal tissue complication probability modeling to guide individual treatment planning in pediatric cranial proton and photon radiotherapy","volume":"49","author":"Wilson","year":"2022","journal-title":"Med. Phys."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"20130459","DOI":"10.1259\/bjr.20130459","article-title":"Clinical-dosimetric relationship between lacrimal gland dose and ocular toxicity after intensity-modulated radiotherapy for sinonasal tumours","volume":"86","author":"Batth","year":"2013","journal-title":"Br. J. Radiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.radonc.2018.06.036","article-title":"Development and validation of NTCP models for acute side-effects resulting from proton beam therapy of brain tumours","volume":"130","author":"Dutz","year":"2019","journal-title":"Radiother. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1016\/j.ijrobp.2009.07.1685","article-title":"A comparison of dose-response models for the parotid gland in a large group of head-and-neck cancer patients","volume":"76","author":"Houweling","year":"2010","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1186\/s13014-015-0501-x","article-title":"Normal tissue complication probability modeling for cochlea constraints to avoid causing tinnitus after head-and-neck intensity-modulated radiation therapy","volume":"10","author":"Lee","year":"2015","journal-title":"Radiat. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"20140413","DOI":"10.1259\/bjr.20140413","article-title":"Use of gEUD for predicting ear and pituitary gland damage following proton and photon radiation therapy","volume":"88","author":"Feuvret","year":"2015","journal-title":"Br. J. Radiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/0360-3016(91)90172-Z","article-title":"Fitting of normal tissue tolerance data to an analytic function","volume":"21","author":"Burman","year":"1991","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2883","DOI":"10.1088\/0031-9155\/59\/12\/2883","article-title":"The risk of radiation-induced second cancers in the high to medium dose region: A comparison between passive and scanned proton therapy, IMRT and VMAT for pediatric patients with brain tumors","volume":"59","author":"Moteabbed","year":"2014","journal-title":"Phys. Med. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s00411-005-0016-1","article-title":"Radiation risk estimates after radiotherapy: Application of the organ equivalent dose concept to plateau dose-response relationships","volume":"44","author":"Schneider","year":"2005","journal-title":"Radiat. Environ. Biophys."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1016\/j.cell.2016.10.021","article-title":"Adult Neurogenesis in the Hippocampus: From Stem Cells to Behavior","volume":"167","author":"Goncalves","year":"2016","journal-title":"Cell"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Pazzaglia, S., Briganti, G., Mancuso, M., and Saran, A. (2020). Neurocognitive Decline Following Radiotherapy: Mechanisms and Therapeutic Implications. Cancers, 12.","DOI":"10.3390\/cancers12010146"},{"key":"ref_36","first-page":"vdaa057","article-title":"Radiation-induced brain injury: Current concepts and therapeutic strategies targeting neuroinflammation","volume":"2","author":"Turnquist","year":"2020","journal-title":"Neurooncol. Adv."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Rube, C.E., Raid, S., Palm, J., and Rube, C. (2023). Radiation-Induced Brain Injury: Age Dependency of Neurocognitive Dysfunction Following Radiotherapy. Cancers, 15.","DOI":"10.3390\/cancers15112999"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1111\/jre.12183","article-title":"Relationship between xerostomia and gingival condition in young adults","volume":"50","author":"Mizutani","year":"2015","journal-title":"J. Periodontal Res."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Stolze, J., Teepen, J.C., Raber-Durlacher, J.E., Loonen, J.J., Kok, J.L., Tissing, W.J.E., de Vries, A.C.H., Neggers, S., van Dulmen-den Broeder, E., and van den Heuvel-Eibrink, M.M. (2022). Prevalence and Risk Factors for Hyposalivation and Xerostomia in Childhood Cancer Survivors Following Different Treatment Modalities\u2014A Dutch Childhood Cancer Survivor Study Late Effects 2 Clinical Study (DCCSS LATER 2). Cancers, 14.","DOI":"10.3390\/cancers14143379"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"4091","DOI":"10.1002\/cncr.33775","article-title":"Clinical and genetic risk factors for radiation-associated ototoxicity: A report from the Childhood Cancer Survivor Study and the St. Jude Lifetime Cohort","volume":"127","author":"Trendowski","year":"2021","journal-title":"Cancer"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.ijrobp.2024.01.206","article-title":"Radiation Therapy Technology Advances and Mitigation of Subsequent Neoplasms in Childhood Cancer Survivors","volume":"119","author":"Stokkevag","year":"2024","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1016\/j.ijrobp.2015.11.046","article-title":"Radiation-Related New Primary Solid Cancers in the Childhood Cancer Survivor Study: Comparative Radiation Dose Response and Modification of Treatment Effects","volume":"94","author":"Inskip","year":"2016","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1001\/jamaoncol.2022.4425","article-title":"Pooled Analysis of Meningioma Risk Following Treatment for Childhood Cancer","volume":"8","author":"Withrow","year":"2022","journal-title":"JAMA Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4782","DOI":"10.1118\/1.2989019","article-title":"Measurement of neutron ambient dose equivalent in passive carbon-ion and proton radiotherapies","volume":"35","author":"Yonai","year":"2008","journal-title":"Med. Phys."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.ijrobp.2006.12.059","article-title":"Effectiveness of carbon ion radiotherapy in the treatment of skull-base chordomas","volume":"68","author":"Karger","year":"2007","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_46","first-page":"264","article-title":"Status on NHa C400 cyclotron for hadrontherapy","volume":"2022","author":"Mandrillon","year":"2022","journal-title":"JACoW"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"168312","DOI":"10.1016\/j.nima.2023.168312","article-title":"Design of a compact superconducting accelerator for advanced heavy-ion therapy","volume":"1053","author":"Iwata","year":"2023","journal-title":"Nucl. Instrum. Methods Phys. Res. Sect. A Accel. Spectrometers Detect. Assoc. Equip."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/11\/1993\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:47:52Z","timestamp":1760107672000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/16\/11\/1993"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,24]]},"references-count":47,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,6]]}},"alternative-id":["cancers16111993"],"URL":"https:\/\/doi.org\/10.3390\/cancers16111993","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,24]]}}}