{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T19:09:39Z","timestamp":1772996979949,"version":"3.50.1"},"reference-count":28,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"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 Reports"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pembrolizumab is approved for treating patients with advanced solid tumors exhibiting high tumor mutation burden (TMB), including pancreatic cancer. However, owing to the rarity of TMB\u2010high pancreatic cancer, its genetic and clinical characteristics, alongside the therapeutic effectiveness of pembrolizumab, remain unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To investigate the characteristics and assess the effectiveness of pembrolizumab in this patient population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p>\n                      We retrospectively reviewed data of 293 patients with unresectable or recurrent pancreatic cancer who underwent comprehensive genomic profiling at our hospital between December 2019 and April 2023. TMB\u2010high was observed in 13 cases (4.4%), including four patients with microsatellite instability\u2010high (MSI\u2010H) (1.4%). Two patients exhibited germline\n                      <jats:italic>BRCA2<\/jats:italic>\n                      mutations: one with adenocarcinoma and the other with acinar cell carcinoma. Germline mutations in\n                      <jats:italic>MLH1<\/jats:italic>\n                      and\n                      <jats:italic>MSH6<\/jats:italic>\n                      were each identified in one case, both exhibiting MSI\u2010H plus TMB\u2010high. The frequency of pathogenic mutations in\n                      <jats:italic>KRAS<\/jats:italic>\n                      ,\n                      <jats:italic>TP53<\/jats:italic>\n                      ,\n                      <jats:italic>CDKN2A<\/jats:italic>\n                      , and\n                      <jats:italic>SMAD4<\/jats:italic>\n                      was notably high.\n                      <jats:italic>KRAS<\/jats:italic>\n                      mutations were detected in 12 of the 13 patients (92.3%). Pembrolizumab was administered to six patients, yielding an objective response rate of 33.3% and a disease control rate of 66.7%. Among the three patients with MSI\u2010H plus TMB\u2010high, two achieved partial response, and the median progression\u2010free survival for all three patients was 227\u2009days. Among the three microsatellite stable (MSS) plus TMB\u2010high cases, two exhibited stable disease, and the median progression\u2010free survival for all three patients was 90\u2009days.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The frequency of TMB\u2010high was 4.4%, which is slightly higher than that previously reported. Pembrolizumab demonstrated greater efficacy in patients with MSI\u2010H plus TMB\u2010high while also exhibiting some efficacy in patients with MSS plus TMB\u2010high.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cnr2.70492","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T08:51:36Z","timestamp":1770799896000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic and Clinical Characteristics of Patients With Tumor Mutation Burden\u2010High Unresectable Pancreatic Cancer and the Efficacy of Pembrolizumab Treatment"],"prefix":"10.1002","volume":"9","author":[{"given":"Yugo","family":"Kai","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Oncology Osaka International Cancer Institute  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7517-8960","authenticated-orcid":false,"given":"Kenji","family":"Ikezawa","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Oncology Osaka International Cancer Institute  Osaka Japan"},{"name":"Department of Gastroenterology and Hepatology Kansai Rosai Hospital  Amagasaki Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuhiro","family":"Kozumi","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Oncology Osaka International Cancer Institute  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makiko","family":"Urabe","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Oncology Osaka International Cancer Institute  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6568-8091","authenticated-orcid":false,"given":"Ryoji","family":"Takada","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Oncology Osaka International Cancer Institute  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takumi","family":"Kinomoto","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Oncology Osaka International Cancer Institute  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takanori","family":"Masumoto","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Oncology Osaka International Cancer Institute  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaki","family":"Kawabata","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Oncology Osaka International Cancer Institute  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroki","family":"Kishimoto","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Oncology Osaka International Cancer Institute  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kana","family":"Hosokawa","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Oncology Osaka International Cancer Institute  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaori","family":"Mukai","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Oncology Osaka International Cancer Institute  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9486-850X","authenticated-orcid":false,"given":"Tasuku","family":"Nakabori","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Oncology Osaka International Cancer Institute  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuko","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Department of Genetic Oncology Osaka International Cancer Institute  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naotoshi","family":"Sugimoto","sequence":"additional","affiliation":[{"name":"Department of Genetic Oncology Osaka International Cancer Institute  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuyoshi","family":"Ohkawa","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Oncology Osaka International Cancer Institute  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,2,11]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30974-0"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21820"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10147-023-02317-x"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1011923"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1304369"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)01366-1"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)00986-1"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-023-11205-6"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10147-023-02432-9"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.22733"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-019-0647-4"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01679"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdy495"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/d41586-018-05312-9"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan6733"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.02105"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(20)30445-9"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2017.4182"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.07.002"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1200\/PO.23.00092"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-023-02058-8"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.70249"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-017-0424-2"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/jjco\/hyad176"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-019-0109-y"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15030970"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0312-8"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2020.7684"}],"container-title":["Cancer Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cnr2.70492","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cnr2.70492","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cnr2.70492","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T16:16:14Z","timestamp":1772986574000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cnr2.70492"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2]]},"references-count":28,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1002\/cnr2.70492"],"URL":"https:\/\/doi.org\/10.1002\/cnr2.70492","archive":["Portico"],"relation":{},"ISSN":["2573-8348","2573-8348"],"issn-type":[{"value":"2573-8348","type":"print"},{"value":"2573-8348","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2]]},"assertion":[{"value":"2025-05-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70492"}}