{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:47:01Z","timestamp":1782434821575,"version":"3.54.5"},"reference-count":15,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"vor","delay-in-days":9,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Pancreatic neuroendocrine tumors (PanNETs) are typically characterized by low tumor mutational burden and limited responsiveness to immune checkpoint inhibitors. Emerging evidence suggests that prior exposure to alkylating chemotherapeutic agents may be associated with a hypermutated phenotype (along with DNA mismatch repair dysfunction or DNA damage response gene alterations), potentially sensitizing tumors to immunotherapy. We present a case of a 68-year-old woman with metastatic functional PanNET (VIPoma) who developed a treatment-associated hypermutated, microsatellite instability-high phenotype following capecitabine-temozolomide therapy. Treatment with pembrolizumab resulted in a robust clinical, biochemical, and radiographic response. This case highlights dynamic genomic evolution in PanNETs and underscores the importance of serial molecular profiling in guiding therapeutic decisions.<\/jats:p>","DOI":"10.1093\/oncolo\/oyag229","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T19:07:37Z","timestamp":1781550457000},"source":"Crossref","is-referenced-by-count":0,"title":["Robust response to pembrolizumab in temozolomide-associated hypermutated and microsatellite instability-high functional pancreatic neuroendocrine tumor"],"prefix":"10.1093","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9638-3629","authenticated-orcid":false,"given":"Udhayvir S","family":"Grewal","sequence":"first","affiliation":[{"name":"Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University , Atlanta, GA 30308,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles W","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Emory University School of Medicine , Atlanta, GA 30308,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saima","family":"Muzahir","sequence":"additional","affiliation":[{"name":"Department of Radiology and Imaging Sciences, Emory University School of Medicine , Atlanta, GA 30308,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po H","family":"Ear","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University , Atlanta, GA 30308,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth J","family":"Concors","sequence":"additional","affiliation":[{"name":"Division of Surgical Oncology, Winship Cancer Institute of Emory University , Atlanta, GA 30308,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel M","family":"Halperin","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University , Atlanta, GA 30308,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,15]]},"reference":[{"key":"2026062519565071500_oyag229-B1","doi-asserted-by":"crossref","first-page":"7035","DOI":"10.1158\/1078-0432.CCR-19-1324","article-title":"Validation of microsatellite instability detection using a comprehensive Plasma-Based genotyping panel","volume":"25","author":"Willis","year":"2019","journal-title":"Clin Cancer Res"},{"key":"2026062519565071500_oyag229-B2","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1007\/s12022-025-09887-8","article-title":"Immunotherapy for metastatic pancreatic neuroendocrine tumors with high mutational burden and mismatch 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gliomas","volume":"6","author":"Ahmad","year":"2019","journal-title":"Neurooncol Pract"},{"key":"2026062519565071500_oyag229-B15","doi-asserted-by":"crossref","first-page":"100897","DOI":"10.1016\/j.medj.2025.100897","article-title":"Neuroendocrine neoplasm classification: the missing piece of the puzzle","volume":"6","author":"Grewal","year":"2025","journal-title":"Med"}],"container-title":["The 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