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      Efficacy of immune checkpoint inhibitor treatment for head and neck mucosal melanoma recurrence in patients treated with carbon‐ion radiotherapy

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          Abstract

          Background

          Carbon‐ion radiotherapy (C‐ion RT) is effective for head and neck mucosal melanoma (HN‐MM), including radioresistant mucosal melanoma. Melanoma also responds effectively to immune checkpoint inhibitors (ICIs). Data on the efficacy and safety of ICIs for HN‐MM are insufficient.

          Aims

          To analyze the efficacy and safety of ICI salvage therapy in patients with HN‐MM recurrence after C‐ion RT.

          Methods and Results

          This retrospective study analyzed the medical records of 52 patients with HN‐MM treated with C‐ion RT between 2012 and 2020. A dose of 57.6 or 64.0 Gy (relative biological effectiveness) was provided in 16 fractions. The primary endpoint was 3‐year overall survival (OS) rate. The median follow‐up time was 26.8 months for all patients. A total of 29 patients had local recurrence or distant metastasis, and 16 patients who received ICI therapy. The 3‐year OS rate in the ICI group ( n = 16) and best supportive care group ( n = 13) were 53.8% and 0.0%, respectively ( p = 0.837); the difference was not statistically significant. There were no deaths after 1 year among patients who underwent ICI therapy. No adverse events associated with C‐ion RT were related to or exacerbated by ICI.

          Conclusion

          ICI salvage therapy is effective and safe for patients with HN‐MM recurrence after C‐ion RT.

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          Most cited references28

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          Signatures of mutational processes in human cancer

          All cancers are caused by somatic mutations. However, understanding of the biological processes generating these mutations is limited. The catalogue of somatic mutations from a cancer genome bears the signatures of the mutational processes that have been operative. Here, we analysed 4,938,362 mutations from 7,042 cancers and extracted more than 20 distinct mutational signatures. Some are present in many cancer types, notably a signature attributed to the APOBEC family of cytidine deaminases, whereas others are confined to a single class. Certain signatures are associated with age of the patient at cancer diagnosis, known mutagenic exposures or defects in DNA maintenance, but many are of cryptic origin. In addition to these genome-wide mutational signatures, hypermutation localized to small genomic regions, kataegis, is found in many cancer types. The results reveal the diversity of mutational processes underlying the development of cancer with potential implications for understanding of cancer etiology, prevention and therapy.
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            Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.

            Blockade of programmed death 1 (PD-1), an inhibitory receptor expressed by T cells, can overcome immune resistance. We assessed the antitumor activity and safety of BMS-936558, an antibody that specifically blocks PD-1. We enrolled patients with advanced melanoma, non-small-cell lung cancer, castration-resistant prostate cancer, or renal-cell or colorectal cancer to receive anti-PD-1 antibody at a dose of 0.1 to 10.0 mg per kilogram of body weight every 2 weeks. Response was assessed after each 8-week treatment cycle. Patients received up to 12 cycles until disease progression or a complete response occurred. A total of 296 patients received treatment through February 24, 2012. Grade 3 or 4 drug-related adverse events occurred in 14% of patients; there were three deaths from pulmonary toxicity. No maximum tolerated dose was defined. Adverse events consistent with immune-related causes were observed. Among 236 patients in whom response could be evaluated, objective responses (complete or partial responses) were observed in those with non-small-cell lung cancer, melanoma, or renal-cell cancer. Cumulative response rates (all doses) were 18% among patients with non-small-cell lung cancer (14 of 76 patients), 28% among patients with melanoma (26 of 94 patients), and 27% among patients with renal-cell cancer (9 of 33 patients). Responses were durable; 20 of 31 responses lasted 1 year or more in patients with 1 year or more of follow-up. To assess the role of intratumoral PD-1 ligand (PD-L1) expression in the modulation of the PD-1-PD-L1 pathway, immunohistochemical analysis was performed on pretreatment tumor specimens obtained from 42 patients. Of 17 patients with PD-L1-negative tumors, none had an objective response; 9 of 25 patients (36%) with PD-L1-positive tumors had an objective response (P=0.006). Anti-PD-1 antibody produced objective responses in approximately one in four to one in five patients with non-small-cell lung cancer, melanoma, or renal-cell cancer; the adverse-event profile does not appear to preclude its use. Preliminary data suggest a relationship between PD-L1 expression on tumor cells and objective response. (Funded by Bristol-Myers Squibb and others; ClinicalTrials.gov number, NCT00730639.).
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              Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma

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                Author and article information

                Contributors
                musha@gunma-u.ac.jp
                Journal
                Cancer Rep (Hoboken)
                Cancer Rep (Hoboken)
                10.1002/(ISSN)2573-8348
                CNR2
                Cancer Reports
                John Wiley and Sons Inc. (Hoboken )
                2573-8348
                28 April 2023
                July 2023
                : 6
                : 7 ( doiID: 10.1002/cnr2.v6.7 )
                : e1825
                Affiliations
                [ 1 ] Gunma University Heavy Ion Medical Center Maebashi Japan
                [ 2 ] Department of Oral and Maxillofacial Surgery and Plastic Surgery Gunma University Graduate School of Medicine, Maebashi Maebashi Japan
                [ 3 ] Department of Otolaryngology‐Head and Neck Surgery Gunma University Graduate School of Medicine Maebashi Japan
                [ 4 ] Department of Radiology Jichi Medical University Hospital Tochigi Japan
                [ 5 ] Division of Radiation Oncology, Department of Radiology Faculty of Medicine, University of Toyama Toyama Japan
                Author notes
                [*] [* ] Correspondence

                Atsushi Musha, Gunma University Heavy Ion Medical Center, Maebashi, Japan, 3‐39‐22, Showa‐machi, Maebashi, Gunma, 371‐8511, Japan.

                Email: musha@ 123456gunma-u.ac.jp

                Author information
                https://orcid.org/0000-0002-5210-8764
                https://orcid.org/0000-0002-0626-8142
                https://orcid.org/0000-0003-4899-1715
                https://orcid.org/0000-0001-7669-6110
                https://orcid.org/0000-0001-8267-6917
                https://orcid.org/0000-0001-7863-6023
                Article
                CNR21825
                10.1002/cnr2.1825
                10363791
                37115713
                8be3f0be-b727-49fe-889a-c4280f36a6dc
                © 2023 The Authors. Cancer Reports published by Wiley Periodicals LLC.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 15 March 2023
                : 02 February 2023
                : 10 April 2023
                Page count
                Figures: 3, Tables: 3, Pages: 10, Words: 5566
                Funding
                Funded by: Japan Society for the Promotion of Science , doi 10.13039/501100001691;
                Award ID: 21K07693
                Funded by: Takeda Science Foundation , doi 10.13039/100007449;
                Funded by: Uehara Memorial Foundation , doi 10.13039/100008732;
                Categories
                Clinical Research Article
                Clinical Research Article
                Custom metadata
                2.0
                July 2023
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.3.2 mode:remove_FC converted:24.07.2023

                chemotherapy,melanoma,radiotherapy,survival
                chemotherapy, melanoma, radiotherapy, survival

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