{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:36:23Z","timestamp":1787027783526,"version":"build-2736575974"},"reference-count":30,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,11,26]],"date-time":"2022-11-26T00:00:00Z","timestamp":1669420800000},"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>We report here the long-term results of marker-less respiratory-gated proton therapy (PT), without fiducial markers for hepatocellular carcinoma (HCC), which was planned using a four-dimensional computed tomography technique. Local tumor control (LTC) and overall survival (OS) were estimated using the Kaplan\u2013Meier method. Toxicity was graded per CTCAE v5.0. Patients (n = 105; median age 73 years, range 38\u201390 years) with 128 lesions were treated. The median radiation dose was 66 gray relative biological effectiveness (GyRBE) (range, 52.8\u201382.5 GyRBE) delivered in 2.0 to 6.6 GyRBE fractions, depending on lesion volume, the involved liver, and the patient\u2019s condition. The median follow-up of surviving patients was 63 months (range, 1\u2013126 months), and the 5-year LTC and OS rates were 93.2% and 40.4%, respectively. Univariate and multivariate analyses identified tumors near the gastrointestinal tract as an independent risk factor for local recurrence and revealed that hepatic reserve, tumor stage, performance status, operability, sex, and portal vein thrombosis were independent risk factors for OS. Acute and late treatment-related grade 3 toxicities were experienced by eight patients (7.6%). Adverse events \u2265 grade 4 were not evident. Marker-less respiratory-gated PT for HCC is a safe and effective treatment without severe complications.<\/jats:p>","DOI":"10.3390\/cancers14235842","type":"journal-article","created":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T07:01:30Z","timestamp":1669618890000},"page":"5842","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Long-Term Results of Proton Therapy for Hepatocellular Carcinoma Using Four-Dimensional Computed Tomography Planning without Fiducial Markers"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2125-3675","authenticated-orcid":false,"given":"Sayuri","family":"Bou","sequence":"first","affiliation":[{"name":"Department of Radiology, Kanazawa University, Kanazawa 920-8641, Japan"},{"name":"Proton Therapy Center, Fukui Prefectural Hospital, Fukui 910-8526, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0743-4413","authenticated-orcid":false,"given":"Shigeyuki","family":"Takamatsu","sequence":"additional","affiliation":[{"name":"Department of Radiology, Kanazawa University, Kanazawa 920-8641, Japan"},{"name":"Proton Therapy Center, Fukui Prefectural Hospital, Fukui 910-8526, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sae","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Proton Therapy Center, Fukui Prefectural Hospital, Fukui 910-8526, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoko","family":"Asahi","sequence":"additional","affiliation":[{"name":"Proton Therapy Center, Fukui Prefectural Hospital, Fukui 910-8526, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Tatebe","sequence":"additional","affiliation":[{"name":"Proton Therapy Center, Fukui Prefectural Hospital, Fukui 910-8526, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshitaka","family":"Sato","sequence":"additional","affiliation":[{"name":"Proton Therapy Center, Fukui Prefectural Hospital, Fukui 910-8526, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9211-4934","authenticated-orcid":false,"given":"Mariko","family":"Kawamura","sequence":"additional","affiliation":[{"name":"Department of Radiology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Shibata","sequence":"additional","affiliation":[{"name":"Department of Radiology, Kanazawa University, Kanazawa 920-8641, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamaki","family":"Kondou","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Therapeutic Radiology, Kanazawa Medical University, Kahoku 920-0293, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Tameshige","sequence":"additional","affiliation":[{"name":"Proton Therapy Center, Fukui Prefectural Hospital, Fukui 910-8526, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3040-5549","authenticated-orcid":false,"given":"Yoshikazu","family":"Maeda","sequence":"additional","affiliation":[{"name":"Proton Therapy Center, Fukui Prefectural Hospital, Fukui 910-8526, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Proton Therapy Center, Fukui Prefectural Hospital, Fukui 910-8526, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazutaka","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Proton Therapy Center, Fukui Prefectural Hospital, Fukui 910-8526, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajime","family":"Sunagozaka","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Fukui Prefectural Hospital, Fukui 910-8526, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Aoyagi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Fukui Prefectural Hospital, Fukui 910-8526, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyasu","family":"Tamamura","sequence":"additional","affiliation":[{"name":"Proton Therapy Center, Fukui Prefectural Hospital, Fukui 910-8526, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7759-399X","authenticated-orcid":false,"given":"Satoshi","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Radiology, Kanazawa University, Kanazawa 920-8641, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshifumi","family":"Gabata","sequence":"additional","affiliation":[{"name":"Department of Radiology, Kanazawa University, Kanazawa 920-8641, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,26]]},"reference":[{"key":"ref_1","unstructured":"(2022, July 13). 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