{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:36:57Z","timestamp":1791848217844,"version":"4.3.4"},"reference-count":36,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2019,10,16]],"date-time":"2019-10-16T00:00:00Z","timestamp":1571184000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>This study aimed to evaluate the efficacy of carbon\u2010ion radiotherapy in combination with chemotherapy using dacarbazine, nimustine, and vincristine (DAV therapy) in mucosal melanoma. Twenty\u2010one patients with clinically localized mucosal melanoma of the head and neck were enrolled. The primary endpoint was 3\u2010year overall survival (OS). Secondary endpoints included local control, progression\u2010free survival (PFS), and adverse event occurrence. Carbon\u2010ion radiotherapy with a dose of 57.6\u201064.0 Gy (relative biological effectiveness) in 16 fractions was delivered concurrently with DAV therapy, and 2 cycles of adjuvant DAV therapy were administered every 6\u00a0weeks. The median follow\u2010up periods were 15.5\u00a0months for all patients, and 31.2\u00a0months for 12 surviving patients. All patients had locally advanced T4a or T4b disease in the rhino\u2010sinus area. In 16 patients (76.2%), 3 cycles of planned DAV therapy were completed. The 3\u2010year OS and PFS rates were 49.2% and 37.0% respectively. The 3\u2010year local control rate was 92.3%. Eleven patients (52%) developed distant metastasis, which was the most frequent pattern of the first failure. Commonly presenting acute grade 2\u20103 toxicities associated with radiotherapy and chemotherapy were mucositis (11 patients [53%]) and leukopenia (9 patients [43%]), which improved with conservative therapy. None of the patients developed grade 3 or greater late toxicities. Carbon\u2010ion radiotherapy in combination with DAV therapy led to excellent local control for advanced mucosal melanoma within acceptable toxicities. The efficacy of additional DAV therapy in improving survival was weaker than expected as distant metastases still occurred frequently. Trial registration no. UMIN000007939.<\/jats:p>","DOI":"10.1002\/cam4.2614","type":"journal-article","created":{"date-parts":[[2019,10,17]],"date-time":"2019-10-17T02:04:21Z","timestamp":1571277861000},"page":"7227-7235","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Carbon\u2010ion radiotherapy combined with chemotherapy for head and neck mucosal melanoma: Prospective observational study"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6291-5025","authenticated-orcid":false,"given":"Yukihiro","family":"Takayasu","sequence":"first","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery Gunma University Graduate School of Medicine Maebashi Gunma Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuteru","family":"Kubo","sequence":"additional","affiliation":[{"name":"Gunma University Heavy Ion Medical Center Maebashi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Shino","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery Gunma University Graduate School of Medicine Maebashi Gunma Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Nikkuni","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery Gunma University Graduate School of Medicine Maebashi Gunma Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shota","family":"Ida","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery Gunma University Graduate School of Medicine Maebashi Gunma Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Musha","sequence":"additional","affiliation":[{"name":"Gunma University Heavy Ion Medical Center Maebashi Japan"},{"name":"Department of Oral and Maxillofacial Surgery, Plastic Surgery Gunma University Graduate School of Medicine Maebashi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsumasa","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Takasaki General Medical Center National Hospital Organization Takasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junko","family":"Hirato","sequence":"additional","affiliation":[{"name":"Department of Pathology Gunma University Hospital Maebashi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuyuki","family":"Shirai","sequence":"additional","affiliation":[{"name":"Department of Radiology Jichi Medical University Saitama Center Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7863-6023","authenticated-orcid":false,"given":"Jun\u2010ichi","family":"Saitoh","sequence":"additional","affiliation":[{"name":"Department of Radiology Graduate School of Medicine and Pharmaceutical Sciences University of Toyama Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Yokoo","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Plastic Surgery Gunma University Graduate School of Medicine Maebashi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuaki","family":"Chikamatsu","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head and Neck Surgery Gunma University Graduate School of Medicine Maebashi Gunma Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Ohno","sequence":"additional","affiliation":[{"name":"Gunma University Heavy Ion Medical Center Maebashi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Nakano","sequence":"additional","affiliation":[{"name":"Gunma University Heavy Ion Medical Center Maebashi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Working Group on Head and Neck Tumors","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,10,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2017.01.019"},{"key":"e_1_2_7_3_1","unstructured":"Japan Society of Head and Neck Cancer.Report of head and neck cancer registry of Japan: clinical statistics of registered patients 2002 Available from:http:\/\/www.jshnc.umin.ne.jp\/pdf\/2002syourei_houkoku.pdf."},{"key":"e_1_2_7_4_1","unstructured":"Japan Society of Head and Neck Cancer.Report of Head and Neck Cancer Registry of Japan: Clinical Statistics of Registered Patients 2015 Available from:http:\/\/www.jshnc.umin.ne.jp\/pdf\/2015syourei_houkoku_1027.pdf."},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2003.11.013"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-011-1685-4"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.20775"},{"issue":"4","key":"e_1_2_7_8_1","first-page":"385","article-title":"Mucosal melanoma of the head and neck: radiotherapy or surgery?","volume":"39","author":"Douglas CM","year":"2010","journal-title":"J Otolaryngol Head Neck Surg"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/CMR.0b013e3283470ffd"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2014.03.042"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1269\/jrr.10016"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2008.07.056"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2010.09.017"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.5227\/skincancer.4.349"},{"key":"e_1_2_7_15_1","first-page":"73","article-title":"Clinical study of DAV+IFN\u2010beta therapy (combination adjuvant therapy with intravenous DTIC, ACNU and VCR, and local injection of IFN\u2010beta) for malignant melanoma","volume":"12","author":"Yamamoto A","year":"1996","journal-title":"Int J Immunother"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2014.09.009"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2005.07.298"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2009.08.041"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2016.12.028"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.4.12.2205"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.04.165"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.12040"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198210073071503"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/jso.2930360404"},{"issue":"2","key":"e_1_2_7_25_1","first-page":"93","article-title":"DTIC vs. IFN\u2010alpha plus DTIC in the treatment of patients with metastatic malignant melanoma","volume":"43","author":"Rudolf Z","year":"1996","journal-title":"Neoplasma"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1684\/ejd.2016.2949"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)31601-X"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30700-9"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1708539"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1709030"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1802357"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2017.08.014"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1259\/0007-1285-64-768-1147"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00066-013-0489-9"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/1748-717X-9-162"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2015.10.025"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.24256"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcam4.2614","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.2614","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cam4.2614","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.2614","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T12:04:21Z","timestamp":1694174661000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.2614"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,16]]},"references-count":36,"journal-issue":{"issue":"17","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["10.1002\/cam4.2614"],"URL":"https:\/\/doi.org\/10.1002\/cam4.2614","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,16]]},"assertion":[{"value":"2019-07-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-10-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-10-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}