{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T11:21:20Z","timestamp":1782991280158,"version":"3.54.5"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T00:00:00Z","timestamp":1666224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Science Foundation of Peking University Cancer Hospital","award":["2022-18"],"award-info":[{"award-number":["2022-18"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81972566"],"award-info":[{"award-number":["81972566"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82073011"],"award-info":[{"award-number":["82073011"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81972562"],"award-info":[{"award-number":["81972562"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Beijing Natural Science Foundation","award":["7202024"],"award-info":[{"award-number":["7202024"]}]},{"DOI":"10.13039\/501100009601","name":"Beijing Municipal Administration of Hospitals\u2019 Ascent Plan","doi-asserted-by":"crossref","award":["DFL20181101"],"award-info":[{"award-number":["DFL20181101"]}],"id":[{"id":"10.13039\/501100009601","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Clinical Medicine Plus X-Young Scholars Project, Peking University","award":["PKU2019LCXQ017"],"award-info":[{"award-number":["PKU2019LCXQ017"]}]},{"name":"Beijing Medical Award Foundation","award":["YXJL-2020-0889-0106"],"award-info":[{"award-number":["YXJL-2020-0889-0106"]}]},{"name":"Beijing Hospitals Authority\u2019s Ascent Plan","award":["DFL20220901"],"award-info":[{"award-number":["DFL20220901"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Acral melanoma (AM) is less responsive to immunotherapy than nonacral cutaneous melanoma. Variable responses are seen during immunotherapy, including pseudoprogression, hyperprogressive disease (HPD) and heterogeneous responses. There are currently no studies on the response patterns of patients with AM treated with immunotherapy and the impact on the outcome.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To evaluate the response patterns and prognosis of patients with AM treated with anti-programmed death (PD)-1 antibodies.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Patients with advanced AM treated prospectively in five clinical trials of anti-PD-1 monotherapy at Peking University Cancer Hospital were included. Responses of individual metastases and heterogeneous responses were evaluated during immunotherapy. Cox proportional hazards regression analysis was conducted to identify the possible predictive factors and generate a nomogram to predict the risk of 1-year and 2-year mortality.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The overall response rate was 18\u00b70%, the disease control rate was 36\u00b71%, median progression-free survival was 3\u00b75 months [95% confidence interval (CI) 1\u00b77\u20135\u00b73] and median overall survival was 17\u00b75 months (95% CI 15\u00b71\u201319\u00b79) for anti-PD-1 monotherapy. Overall, 9\u00b78% of patients met the criteria of HPD, and displayed a dramatically worse outcome than patients without HPD. In total, 369 metastatic lesions were assessed, with the highest response rate in lymph nodes (20\u00b74%) and the lowest in the liver (5\u00b76%). Homogeneous response, heterogeneous response and heterogeneous or homogeneous progression had different prognoses from the best to the worst. A predictive model was constructed and achieved good accuracy with a C-index of 0\u00b773 (95% CI 0\u00b763\u20130\u00b784) in the training set and 0\u00b774 (95% CI 0\u00b761\u20130\u00b786) in the validation set.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>HPD during immunotherapy serves as an essential biomarker of poor prognosis in advanced AM. Metastases in different sites respond distinctively to immunotherapy. Clinically heterogeneous responses to immunotherapy affect the outcome of patients. A predictive model was built to distinguish the prognosis of acral melanoma under immunotherapy.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bjd\/ljac005","type":"journal-article","created":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T14:13:28Z","timestamp":1674224008000},"page":"112-121","source":"Crossref","is-referenced-by-count":13,"title":["Impact of response patterns for patients with advanced acral melanoma treated with anti-programmed death-1 monotherapy"],"prefix":"10.1093","volume":"188","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9331-0600","authenticated-orcid":false,"given":"Li","family":"Zhou","sequence":"first","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute , 52 Fucheng Road, Haidian District, Beijing 100142 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lizhi","family":"Shao","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Molecular Imaging, Institute of Automation , Beijing 100190 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunyu","family":"Gao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Department of Radiology, Peking University Cancer Hospital & Institute , 52 Fucheng Road, Haidian District, Beijing 100142 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanliang","family":"Cui","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute , 52 Fucheng Road, Haidian District, Beijing 100142 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihong","family":"Chi","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute , 52 Fucheng Road, Haidian District, Beijing 100142 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinan","family":"Sheng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute , 52 Fucheng Road, Haidian District, Beijing 100142 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bixia","family":"Tang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute , 52 Fucheng Road, Haidian District, Beijing 100142 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Mao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute , 52 Fucheng Road, Haidian District, Beijing 100142 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Lian","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute , 52 Fucheng Road, Haidian District, Beijing 100142 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xieqiao","family":"Yan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute , 52 Fucheng Road, Haidian District, Beijing 100142 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute , 52 Fucheng Road, Haidian District, Beijing 100142 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5203-4080","authenticated-orcid":false,"given":"Xue","family":"Bai","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute , 52 Fucheng Road, Haidian District, Beijing 100142 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siming","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Guo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute , 52 Fucheng Road, Haidian District, Beijing 100142 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Si","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute , 52 Fucheng Road, Haidian District, Beijing 100142 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,10,20]]},"reference":[{"key":"2023100516131219900_ljac005-B1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/1471-2407-11-85","article-title":"Clinical presentation, histology, and prognoses of malignant melanoma in ethnic Chinese: a study of 522 consecutive cases","volume":"11","author":"Chi","year":"2011","journal-title":"BMC Cancer"},{"key":"2023100516131219900_ljac005-B2","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1038\/s41467-022-28566-4","article-title":"Integrative \u00admolecular and clinical profiling of acral melanoma links focal amplification of 22q11.21 to metastasis","volume":"13","author":"Farshidfar","year":"2022","journal-title":"Nat Commun"},{"key":"2023100516131219900_ljac005-B3","doi-asserted-by":"crossref","first-page":"6946","DOI":"10.1158\/1078-0432.CCR-17-0070","article-title":"Frequent genetic aberrations in the CDK4 pathway in acral melanoma indicate the potential for CDK4\/6 inhibitors in targeted therapy","volume":"23","author":"Kong","year":"2017","journal-title":"Clin Cancer Res"},{"key":"2023100516131219900_ljac005-B4","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1016\/j.annonc.2020.05.031","article-title":"Anti-PD1 checkpoint inhibitor therapy in acral melanoma: a multicenter study of 193 Japanese patients","volume":"31","author":"Nakamura","year":"2020","journal-title":"Ann Oncol"},{"key":"2023100516131219900_ljac005-B5","doi-asserted-by":"crossref","first-page":"3354","DOI":"10.1002\/cncr.30259","article-title":"The efficacy of anti-PD-1 agents in acral and mucosal melanoma","volume":"122","author":"Shoushtari","year":"2016","journal-title":"Cancer"},{"key":"2023100516131219900_ljac005-B6","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2020.602705","article-title":"Immune checkpoint inhibitors in advanced acral melanoma: a systematic review","volume":"10","author":"Zheng","year":"2020","journal-title":"Front Oncol"},{"key":"2023100516131219900_ljac005-B7","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1007\/s40259-020-00425-y","article-title":"Pseudoprogression and hyperprogression as new forms of response to immunotherapy","volume":"34","author":"Frelaut","year":"2020","journal-title":"BioDrugs"},{"key":"2023100516131219900_ljac005-B8","doi-asserted-by":"crossref","first-page":"3541","DOI":"10.1200\/JCO.2015.61.6870","article-title":"Pseudoprogression and immune-related response in solid tumors","volume":"33","author":"Chiou","year":"2015","journal-title":"J Clin Oncol"},{"key":"2023100516131219900_ljac005-B9","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.ctrv.2018.07.006","article-title":"Hyperprogression as a distinct outcome after immunotherapy","volume":"70","author":"Fuentes-Antras","year":"2018","journal-title":"Cancer Treat Rev"},{"key":"2023100516131219900_ljac005-B10","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.1158\/1078-0432.CCR-16-1741","article-title":"Hyperprogressive disease is a new pattern of progression in cancer patients treated by anti-PD-1\/PD-L1","volume":"23","author":"Champiat","year":"2017","journal-title":"Clin Cancer Res"},{"key":"2023100516131219900_ljac005-B11","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1002\/cncr.32522","article-title":"Site-specific response patterns, pseudoprogression, and acquired resistance in patients with melanoma treated with ipilimumab combined with anti-PD-1 therapy","volume":"126","author":"Pires da Silva","year":"2020","journal-title":"Cancer"},{"key":"2023100516131219900_ljac005-B12","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1016\/j.tranon.2019.02.007","article-title":"A phase Ib study of pembrolizumab as second-line therapy for Chinese patients with advanced or \u00admetastatic melanoma (KEYNOTE-151)","volume":"12","author":"Si","year":"2019","journal-title":"Transl Oncol"},{"key":"2023100516131219900_ljac005-B13","doi-asserted-by":"crossref","first-page":"4250","DOI":"10.1158\/1078-0432.CCR-19-3922","article-title":"Safety, efficacy, and biomarker analysis of toripalimab in previously treated advanced melanoma: results of the POLARIS-01 multicenter phase II trial","volume":"26","author":"Tang","year":"2020","journal-title":"Clin Cancer Res"},{"issue":"7","key":"2023100516131219900_ljac005-B14","article-title":"Safety and clinical activity with an anti-PD-1 antibody JS001 in advanced melanoma or urologic cancer patients","volume":"12","author":"Tang","year":"2019","journal-title":"J Hematol Oncol"},{"key":"2023100516131219900_ljac005-B15","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2019-000437","article-title":"Tislelizumab in Chinese patients with advanced solid tumors: an open-label, non-comparative, phase 1\/2 study","volume":"8","author":"Shen","year":"2020","journal-title":"J Immunother Cancer"},{"key":"2023100516131219900_ljac005-B16","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1186\/s12885-022-09663-5","article-title":"Safety, activity, and pharmacokinetics of camrelizumab in advanced Asian melanoma patients: a phase I study","volume":"22","author":"Zhou","year":"2022","journal-title":"BMC Cancer"},{"key":"2023100516131219900_ljac005-B17","doi-asserted-by":"crossref","first-page":"4242","DOI":"10.1158\/1078-0432.CCR-16-3133","article-title":"Hyperprogressors after immunotherapy: analysis of genomic alterations associated with accelerated growth rate","volume":"23","author":"Kato","year":"2017","journal-title":"Clin Cancer Res"},{"key":"2023100516131219900_ljac005-B18","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1001\/jamaoncol.2019.0138","article-title":"Hyperprogression-immunotherapy-related phenomenon versus intrinsic natural history of cancer \u2013 in reply","volume":"5","author":"Ferrara","year":"2019","journal-title":"JAMA Oncol"},{"key":"2023100516131219900_ljac005-B19","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1093\/annonc\/mdx178","article-title":"Hyperprogression during anti-PD-1\/PD-L1 therapy in patients with recurrent and\/or metastatic head and neck squamous cell carcinoma","volume":"28","author":"Saada-Bouzid","year":"2017","journal-title":"Ann Oncol"},{"key":"2023100516131219900_ljac005-B20","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1158\/1078-0432.CCR-19-2226","article-title":"Capturing hyperprogressive disease with immune-checkpoint inhibitors using RECIST 1.1 criteria","volume":"26","author":"Matos","year":"2020","journal-title":"Clin Cancer Res"},{"issue":"5","key":"2023100516131219900_ljac005-B21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v039.i05","article-title":"Regularization paths for Cox\u2019s proportional hazards model via coordinate descent","volume":"39","author":"Simon","year":"2011","journal-title":"J Stat Softw"},{"key":"2023100516131219900_ljac005-B22","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.jhep.2020.08.010","article-title":"Hyperprogressive disease during PD-1 blockade in patients with advanced hepatocellular carcinoma","volume":"74","author":"Kim","year":"2021","journal-title":"J Hepatol"},{"key":"2023100516131219900_ljac005-B23","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1038\/s41571-018-0111-2","article-title":"Hyperprogressive disease: recognizing a novel pattern to improve patient management","volume":"15","author":"Champiat","year":"2018","journal-title":"Nat Rev Clin Oncol"},{"key":"2023100516131219900_ljac005-B24","article-title":"The impact of liver metastasis on anti-PD-1 monoclonal antibody monotherapy in advanced melanoma: analysis of five clinical studies","volume":"10","author":"Wang","year":"2020","journal-title":"Front Oncol"},{"issue":"15 Suppl.","key":"2023100516131219900_ljac005-B25","doi-asserted-by":"crossref","first-page":"e21013","DOI":"10.1200\/JCO.2017.35.15_suppl.e21013","article-title":"OrienX010 oncolytic viral therapy in phase Ic trial of intralesional injection in liver metastases among patients with stage IV melanoma after standard treatment","volume":"35","author":"Cui","year":"2017","journal-title":"J Clin Oncol"},{"issue":"16 Suppl.","key":"2023100516131219900_ljac005-B26","doi-asserted-by":"crossref","first-page":"9551","DOI":"10.1200\/JCO.2022.40.16_suppl.9551","article-title":"Analysis of overall survival (OS) and relapse-free survival (RFS) in the phase 1b clinical trial of anti-PD-1 ab (toripalimab) plus intralesional injection of OrienX010 in stage IV melanoma with liver metastases","volume":"40","author":"Cui","year":"2022","journal-title":"J Clin Oncol"},{"key":"2023100516131219900_ljac005-B27","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1038\/s41591-021-01233-9","article-title":"Intratumoral heterogeneity in cancer progression and response to immunotherapy","volume":"27","author":"Vitale","year":"2021","journal-title":"Nat Med"},{"key":"2023100516131219900_ljac005-B28","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1158\/1078-0432.CCR-21-1688","article-title":"Association of neutrophil-to-lymphocyte ratio with efficacy of first-line avelumab plus axitinib vs. sunitinib in patients with advanced renal cell carcinoma enrolled in the phase 3 JAVELIN renal 101 trial","volume":"28","author":"Bilen","year":"2022","journal-title":"Clin Cancer Res"},{"key":"2023100516131219900_ljac005-B29","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1093\/annonc\/mdz123","article-title":"Hyperprogressive disease during PD-1\/PD-L1 blockade in patients with non-small-cell lung cancer","volume":"30","author":"Kim","year":"2019","journal-title":"Ann Oncol"},{"key":"2023100516131219900_ljac005-B30","doi-asserted-by":"crossref","DOI":"10.1093\/jnci\/dju124","article-title":"Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis","volume":"106","author":"Templeton","year":"2014","journal-title":"J Natl Cancer Inst"}],"container-title":["British Journal of Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bjd\/advance-article-pdf\/doi\/10.1093\/bjd\/ljac005\/48426147\/ljac005.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bjd\/article-pdf\/188\/1\/112\/51888881\/ljac005.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bjd\/article-pdf\/188\/1\/112\/51888881\/ljac005.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T16:13:32Z","timestamp":1696522412000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bjd\/article\/188\/1\/112\/6763703"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,20]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,10,20]]},"published-print":{"date-parts":[[2023,1,23]]}},"URL":"https:\/\/doi.org\/10.1093\/bjd\/ljac005","relation":{},"ISSN":["0007-0963","1365-2133"],"issn-type":[{"value":"0007-0963","type":"print"},{"value":"1365-2133","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,1]]},"published":{"date-parts":[[2022,10,20]]}}}