{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:56:36Z","timestamp":1791262596148,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>To evaluate the significance of persistent arterial\u2010phase hyperenhancement (APHE) on contrast\u2010enhanced CT\/MRI at 6 and 12\u2009months after proton beam therapy (PBT) for hepatocellular carcinoma (HCC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively analyzed 108 patients with solitary HCC without vascular invasion who underwent definitive PBT as initial treatment between January 2008 and December 2020. APHE was assessed on contrast\u2010enhanced CT\/MRI at approximately 6 and 12\u2009months. Overall survival (OS), local control (LC), and progression\u2010free survival (PFS) were estimated using the Kaplan\u2013Meier method. Associations between APHE and outcomes were evaluated using landmark analyses and Cox models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The median follow\u2010up time was 4.64\u2009years. APHE assessment was available in 87 patients at 6\u2009months and 89 patients at 12\u2009months; APHE was observed in 28 (32.2%) and 26 (29.2%), respectively. At the 6\u2010month landmark, APHE was associated with worse subsequent OS and PFS, whereas LC did not differ significantly. At the 12\u2010month landmark, APHE was associated with worse subsequent LC and PFS and borderline worse OS. The 3\u2010year LC and PFS rates from the 12\u2010month landmark were 69.1% and 25.3% in patients with APHE versus 89.6% and 54.3% in those without APHE (LC:\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.015; PFS:\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.025). However, after adjustment for clinical and treatment\u2010related factors, APHE status was not independently associated with OS, LC, or PFS in the multivariate landmark analyses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Persistent intratumoral APHE at 12\u2009months after PBT was associated with an increased subsequent risk of local failure in landmark analysis, but was not an independent prognostic factor. Persistent APHE may warrant careful imaging follow\u2010up and clinical reassessment but should not be regarded as definitive evidence of viable tumor.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.72242","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T05:05:27Z","timestamp":1788239127000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prognostic Impact of Arterial Phase Hyperenhancement After Proton Beam Therapy for Untreated Solitary Hepatocellular Carcinoma"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8127-254X","authenticated-orcid":false,"given":"Hikaru","family":"Niitsu","sequence":"first","affiliation":[{"name":"Proton Medical Research Center, Department of Radiation Oncology University of Tsukuba Hospital  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7837-1301","authenticated-orcid":false,"given":"Masashi","family":"Mizumoto","sequence":"additional","affiliation":[{"name":"Proton Medical Research Center, Department of Radiation Oncology University of Tsukuba Hospital  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0423-2541","authenticated-orcid":false,"given":"Yinuo","family":"Li","sequence":"additional","affiliation":[{"name":"Proton Medical Research Center, Department of Radiation Oncology University of Tsukuba Hospital  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiko","family":"Harada","sequence":"additional","affiliation":[{"name":"Proton Medical Research Center, Department of Radiation Oncology University of Tsukuba Hospital  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7670-6629","authenticated-orcid":false,"given":"Takuya","family":"Sawada","sequence":"additional","affiliation":[{"name":"Proton Medical Research Center, Department of Radiation Oncology University of Tsukuba Hospital  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3840-6527","authenticated-orcid":false,"given":"Masaaki","family":"Goto","sequence":"additional","affiliation":[{"name":"Proton Medical Research Center, Department of Radiation Oncology University of Tsukuba Hospital  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taisuke","family":"Sumiya","sequence":"additional","affiliation":[{"name":"Proton Medical Research Center, Department of Radiation Oncology University of Tsukuba Hospital  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiichiro","family":"Baba","sequence":"additional","affiliation":[{"name":"Proton Medical Research Center, Department of Radiation Oncology University of Tsukuba Hospital  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Fujisawa","sequence":"additional","affiliation":[{"name":"Proton Medical Research Center, Department of Radiation Oncology University of Tsukuba Hospital  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3329-5999","authenticated-orcid":false,"given":"Masatoshi","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Proton Medical Research Center, Department of Radiation Oncology University of Tsukuba Hospital  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiki","family":"Ishida","sequence":"additional","affiliation":[{"name":"Proton Medical Research Center, Department of Radiation Oncology University of Tsukuba Hospital  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6632-4356","authenticated-orcid":false,"given":"Takashi","family":"Iizumi","sequence":"additional","affiliation":[{"name":"Proton Medical Research Center, Department of Radiation Oncology University of Tsukuba Hospital  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4663-5580","authenticated-orcid":false,"given":"Takashi","family":"Saito","sequence":"additional","affiliation":[{"name":"Proton Medical Research Center, Department of Radiation Oncology University of Tsukuba Hospital  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruko","family":"Numajiri","sequence":"additional","affiliation":[{"name":"Proton Medical Research Center, Department of Radiation Oncology University of Tsukuba Hospital  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0702-2304","authenticated-orcid":false,"given":"Kei","family":"Nakai","sequence":"additional","affiliation":[{"name":"Proton Medical Research Center, Department of Radiation Oncology University of Tsukuba Hospital  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1603-7495","authenticated-orcid":false,"given":"Yoshiko","family":"Oshiro","sequence":"additional","affiliation":[{"name":"Proton Medical Research Center, Department of Radiation Oncology University of Tsukuba Hospital  Tsukuba Ibaraki Japan"},{"name":"Department of Radiation Oncology Tsukuba Medical Center Hospital  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideyuki","family":"Sakurai","sequence":"additional","affiliation":[{"name":"Proton Medical Research Center, Department of Radiation Oncology University of Tsukuba Hospital  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2024.08.028"},{"key":"e_1_2_13_4_1","unstructured":"National Comprehensive Cancer Network \u201cNCCN Clinical Practice Guidelines in Oncology: Hepatocellular Carcinoma Version 1 \u201d(2026) https:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/hcc.pdf."},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/hepr.13892"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.71639"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2023.09.047"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1159\/000520277"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2024.10.040"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1148\/rg.220084"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00261\u2010022\u201003526\u20100"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20100030\u20101247132"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.232408"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2017.08.022"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1259\/bjr.20190375"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16020357"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00261\u2010016\u20100768\u2010x"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1148\/rg.332125119"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/HP.0000000000001601"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13277\u2010010\u20100042\u20108"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00261\u2010020\u201002821\u2010y"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00270\u2010009\u20109766\u20105"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00261\u2010023\u201003827\u2010y"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2022.100498"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2018.09.004"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00261\u2010020\u201002532\u20104"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2021.10.006"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.2214\/AJR.12.10169"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885\u2010016\u20102512\u2010x"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000009249"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctro.2022.03.010"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.23428"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0249003"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201023\u20101044"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1159\/000548347"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1148\/rg.250067"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00330\u2010025\u201011659\u20101"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.72242","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cam4.72242","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.72242","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:48:34Z","timestamp":1791262114000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.72242"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,31]]},"references-count":36,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/cam4.72242"],"URL":"https:\/\/doi.org\/10.1002\/cam4.72242","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,31]]},"assertion":[{"value":"2026-07-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e72242"}}