{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:52:46Z","timestamp":1791237166090,"version":"4.1.0"},"reference-count":75,"publisher":"Radiation Research Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Radiation Research"],"published-print":{"date-parts":[[2026,4,28]]},"abstract":"<jats:p>Proton therapy (PT) and carbon-ion therapy (CIT) differ not only in their physical dose characteristics but also in their biological effects, attributable to variations in fractionation protocols and linear energy transfer (LET). These differences make direct comparisons challenging. This study aims to comprehensively compare the treatment planning of protons and carbon ions for head and neck cancer by incorporating LET-dependent variable \u03b1\/\u03b2 ratios into the calculations of equivalent dose in 2 Gy fractions (EQD2) and normal tissue complication probability (NTCP). We retrospectively created treatment plans for nine head and neck cancer patients using proton therapy and carbon-ion therapy. Variable \u03b1\/\u03b2 ratios, calculated via the microdosimetric kinetic model, were integrated into EQD2 calculations. NTCP assessments for both late and acute toxicities utilized the Lyman-Kutcher-Burman model. In addition to comparing EQD2 and NTCP outcomes between protons and carbon ions, we conducted robustness evaluations that considered a 2 mm positioning error and a 3.5% range uncertainty. The \u03b1\/\u03b2 ratio for protons remained consistent at approximately 3 Gy across all tissues. In contrast, the \u03b1\/\u03b2 ratio for carbon ions varied significantly, reaching up to 20 Gy along the beam path. This variability in \u03b1\/\u03b2 ratios showed that carbon ions achieved lower EQD2 values for organs at risk (OARs) such as the brain, skin, and oral mucosa compared to protons. Furthermore, NTCP analysis revealed a significant reduction in acute toxicities, particularly dermatitis, with carbon-ion therapy. Both treatment modalities effectively minimized the probability of late toxicities. No significant differences in robustness were observed between proton therapy and carbon-ion therapy. EQD2 calculations incorporating variable \u03b1\/\u03b2 ratios revealed that carbon ions offer a dosimetric advantage over protons for certain OARs. However, this difference was relatively minor and did not suggest a clinically significant impact beyond acute toxicities.<\/jats:p>","DOI":"10.1667\/rade-25-00183.1","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:59:18Z","timestamp":1791233958000},"page":"597-606","source":"Crossref","is-referenced-by-count":0,"title":["Comparative Analysis of Proton and Carbon-Ion Therapy for Head and Neck Cancer: LET-Dependent \u03b1\/\u03b2 Ratios in EQD2 and NTCP"],"prefix":"10.1667","volume":"205","author":[{"given":"Yushi","family":"Wakisaka","sequence":"first","affiliation":[{"name":"Department of Radiotherapy, Medical Co. Hakuhokai, Osaka Proton Therapy Clinic, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuya","family":"Miyasaka","sequence":"additional","affiliation":[{"name":"Department of Heavy Particle Medical Science, Yamagata University Graduate School of Medical Science, Yamagata, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Tominaga","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy, Medical Co. Hakuhokai, Osaka Proton Therapy Clinic, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robabeh","family":"Rahimi","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeo","family":"Iwai","sequence":"additional","affiliation":[{"name":"Department of Heavy Particle Medical Science, Yamagata University Graduate School of Medical Science, Yamagata, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teiji","family":"Nishio","sequence":"additional","affiliation":[{"name":"Department of Radiotherapy, Medical Physics Laboratory, Division of Health Science, Graduate School of Medicine, The University of Osaka, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1243","reference":[{"key":"73","doi-asserted-by":"crossref","unstructured":"T Inaniwa, N Kanematsu, M Shinoto, et al.  \"Phys Med Biol.\"  66, \"Adaptation of stochastic microdosimetric kinetic model to hypoxia for hypo-fractionated multi-ion therapy treatment planning.\" 205007 (2021)","DOI":"10.1088\/1361-6560\/ac29cc"},{"key":"1","doi-asserted-by":"crossref","unstructured":"F Bray, M Laversanne, H Sung, et al.  \"CA Cancer J Clin.\"  74, \"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.\" 229 (2024)","DOI":"10.3322\/caac.21834"},{"key":"2","doi-asserted-by":"crossref","unstructured":"JE Leeman, gao Li J, X Pei, et al.  \"JAMA Oncol.\"  3, \"Patterns of treatment failure and postrecurrence outcomes among patients with locally advanced head and neck squamous cell carcinoma after chemoradiotherapy using modern radiation techniques.\" 1487 (2017)","DOI":"10.1001\/jamaoncol.2017.0973"},{"key":"3","doi-asserted-by":"crossref","unstructured":"SA Bhide, KL Newbold, KJ Harrington, et al.  \"Br J Radiol.\"  85, \"Clinical evaluation of intensity-modulated radiotherapy for head and neck cancers.\" 487 (2012)","DOI":"10.1259\/bjr\/85942136"},{"key":"4","doi-asserted-by":"crossref","unstructured":"M Takagi, Y Demizu, N Hashimoto, et al.  \"Radiother Oncol.\"  113, \"Treatment outcomes of particle radiotherapy using protons or carbon ions as a single-modality therapy for adenoid cystic carcinoma of the head and neck.\" 364 (2014)","DOI":"10.1016\/j.radonc.2014.11.031"},{"key":"5","doi-asserted-by":"crossref","unstructured":"A Lin, JHC Chang, RS Grover, et al.  \"Int J Part Ther.\"  8, \"PTCOG head and neck subcommittee consensus guidelines on particle therapy for the management of head and neck tumors.\" 84 (2021)","DOI":"10.14338\/IJPT-20-00071.1"},{"key":"6","doi-asserted-by":"crossref","unstructured":"HK Byun, MC Han, K Yang, et al.  \"Cancer Res Treat.\"  53, \"Physical and Biological Characteristics of Particle Therapy for Oncologists.\" 611 (2021)","DOI":"10.4143\/crt.2021.066"},{"key":"7","doi-asserted-by":"crossref","unstructured":"D Schulz-Ertner  and H Tsujii  \"J Clinical Oncology.\"  25, \"Particle radiation therapy using proton and heavier ion beams.\" 953 (2007)","DOI":"10.1200\/JCO.2006.09.7816"},{"key":"8","doi-asserted-by":"crossref","unstructured":"T Kanai, Y Furusawa, K Fukutsu, et al.  \"Radiat Res.\"  147, \"Irradiation of Mixed Beam and Design of Spread-Out Bragg Peak for Heavy-Ion Radiotherapy.\" 78 (1997)","DOI":"10.2307\/3579446"},{"key":"9","doi-asserted-by":"crossref","unstructured":"M Chuong, SN Badiyan, M Yam, et al.  \"J Gastrointest Oncol.\"  9, \"Pencil beam scanning versus passively scattered proton therapy for unresectable pancreatic cancer.\" 687 (2018)","DOI":"10.21037\/jgo.2018.03.14"},{"key":"10","doi-asserted-by":"crossref","unstructured":"M V. 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\"Front Oncol.\"  5, \"The role of hypofractionated radiation therapy with photons, protons, and heavy ions for treating extracranial lesions.\" 302 (2016)","DOI":"10.3389\/fonc.2015.00302"},{"key":"33","doi-asserted-by":"crossref","unstructured":"R Ahmad, A Barcellini, K Baumann, et al.  \"Int J Part Ther.\"  13, \"Particle Beam Radiobiology Status and Challenges: A PTCOG Radiobiology Subcommittee Report.\" 100626 (2024)","DOI":"10.1016\/j.ijpt.2024.100626"},{"key":"35","doi-asserted-by":"crossref","unstructured":"D Georg, J Hopfgartner, J G\u00f2ra, et al.  \"Int J Radiat Oncol Biol Phys.\"  88, \"Dosimetric considerations to determine the optimal technique for localized prostate cancer among external photon, proton, or carbon-ion therapy and high-dose-rate or low-dose-rate brachytherapy.\" 715 (2014)","DOI":"10.1016\/j.ijrobp.2013.11.241"},{"key":"36","doi-asserted-by":"crossref","unstructured":"M Ton, M Deng, E Meixner, et al.  \"Radiat Oncol.\"  19, \"Efficacy and toxicity of photon, proton, and carbon ion radiotherapy in the treatment of intracranial solitary fibrous tumor\/hemangiopericytoma.\" 42 (2024)","DOI":"10.1186\/s13014-024-02434-5"},{"key":"37","doi-asserted-by":"crossref","unstructured":"A Niemierko  and M Goitein  \"Int J Radiat Oncol Biol Phys.\"  25, \"Modeling of normal tissue response to radiation: the critical volume model.\" 135 (1993)","DOI":"10.1016\/0360-3016(93)90156-P"},{"key":"38","doi-asserted-by":"crossref","unstructured":"K Miki, S Mori, A Hasegawa, et al.  \"Br J Radiol.\"  89, \"Single-energy metal artefact reduction with CT for carbonion radiation therapy treatment planning.\" 20150988 (2016)","DOI":"10.1259\/bjr.20150988"},{"key":"42","doi-asserted-by":"crossref","unstructured":"S Hong, N Laack, A Mahajan, et al.  \"World Neurosurg.\"  171, \"Analysis of Early Outcomes of Pencil Beam Proton Therapy Compared with Passive Scattering Proton Therapy for Clival Chordoma.\" e644 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Janson, L Glimelius, A Fredriksson, et al.  \"Med Dosimet.\"  49, \"Treatment planning of scanned proton beams in RayStation.\" 2 (2024)","DOI":"10.1016\/j.meddos.2023.10.009"},{"key":"48","doi-asserted-by":"crossref","unstructured":"A Mcnamara  and H Paganetti  \"Br J Radiol.\"  93, \"Proton therapy special feature: review article modelling variable proton relative biological effectiveness for treatment planning.\" 20190334 (2020)","DOI":"10.1259\/bjr.20190334"},{"key":"49","doi-asserted-by":"crossref","unstructured":"NM Padannayil, DS Sharma, S Nangia, et al.  \"Radiat Oncol.\"  18, \"IMPT of head and neck cancer: unsupervised machine learning treatment planning strategy for reducing radiation dermatitis.\" 11 (2023)","DOI":"10.1186\/s13014-023-02201-y"},{"key":"50","doi-asserted-by":"crossref","unstructured":"JT. Lyman,  \"Radiat Res Suppl.\"  8, \"Complication probability as assessed from dose-volume histograms.\" S13 (1985)","DOI":"10.2307\/3583506"},{"key":"51","doi-asserted-by":"crossref","unstructured":"GJ Kutcher  and C Burman  \"Int J Radiat Oncol Biol Phys.\"  16, \"Calculation of complication probability factors for non-uniform normal tissue irradiation: the effective volume method.\" 1623 (1989)","DOI":"10.1016\/0360-3016(89)90972-3"},{"key":"52","doi-asserted-by":"crossref","unstructured":"B Emami, J Lyman, A Brown, et al.  \"Int J Radiat Oncol Phys.\"  21, \"Tolerance of normal tissue to therapeutic irradiation.\" 109 (1991)","DOI":"10.1016\/0360-3016(91)90171-Y"},{"key":"54","doi-asserted-by":"crossref","unstructured":"T Cao, Q Yuan, Z Dai,  \"Precis Radiat Oncol.\"  8, \"A new formula for calculating normal tissue complication probability.\" 126 (2024)","DOI":"10.1002\/pro6.1240"},{"key":"55","doi-asserted-by":"crossref","unstructured":"C Burman, GJ Kijtcher, B Emami, et al.  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carbon-ion therapy.\" e0288545 (2023)","DOI":"10.1371\/journal.pone.0288545"},{"key":"59","doi-asserted-by":"crossref","unstructured":"T Tsubouchi, H Shiomi, O Suzuki, et al.  \"J Appl Clin Med Phys.\"  26, \"Assessing the robustness of dose distributions in carbon ion prostate radiotherapy using a fast dose evaluation system.\" e14528 (2025)","DOI":"10.1002\/acm2.14528"},{"key":"60","doi-asserted-by":"crossref","unstructured":"W Deng, Y Yang, C Liu, et al.  \"Int J Part Ther.\"  8, \"A critical review of LET-based intensity-modulated proton therapy plan evaluation and optimization for head and neck cancer management.\" 36 (2021)","DOI":"10.14338\/IJPT-20-00049.1"},{"key":"61","doi-asserted-by":"crossref","unstructured":"Y Demizu, O Fujii, K Terashima, et al.  \"Strahlentherapie und Onkologie.\"  190, \"Particle therapy for mucosal melanoma of the head and neck: A single-institution retrospective comparison of proton and carbon ion therapy.\" 186 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