{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T13:18:56Z","timestamp":1787663936413,"version":"build-2736575974"},"reference-count":20,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100015689","name":"GIST Cancer Research Fund","doi-asserted-by":"publisher","award":["3661"],"award-info":[{"award-number":["3661"]}],"id":[{"id":"10.13039\/100015689","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30 CA023100"],"award-info":[{"award-number":["P30 CA023100"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 CA292590"],"award-info":[{"award-number":["R01 CA292590"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32 CA121398"],"award-info":[{"award-number":["T32 CA121398"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01 CA278470"],"award-info":[{"award-number":["U01 CA278470"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Avapritinib is a selective tyrosine kinase inhibitor approved for advanced\n                      <jats:italic>PDGFRA<\/jats:italic>\n                      exon 18\u2013mutant gastrointestinal stromal tumors (GIST), including the imatinib\u2010resistant\n                      <jats:italic>D842V<\/jats:italic>\n                      variant. However, its role in the preoperative setting for localized, resectable disease has not been defined.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted a retrospective two\u2010center exploratory case series of eight patients with localized, resectable\n                      <jats:italic>PDGFRA<\/jats:italic>\n                      \u2010mutant gastric GIST who received preoperative avapritinib between 2020 and 2025. Radiographic and pathologic responses, treatment duration, adverse events (AEs), and surgical outcomes were evaluated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>All patients initiated avapritinib at 300\u2009mg daily. Median treatment duration was 2\u2009months (range, &lt;\u20091\u201321\u2009months). Tumor size decreased in seven patients (88%), with a median reduction of 25% and an overall range from \u221251% to +29%. Three patients (38%) met RECIST\u2010based thresholds for partial response (\u2265\u200930% reduction). Five patients underwent surgical resection, all achieving complete (0% viable tumor) or near\u2010complete (\u2264\u20095% viable tumor) pathologic response. Dose reductions were required in three patients due to toxicity; however, tumor regression continued in all. Treatment\u2010related grade \u2265\u20093 AEs occurred in 50% of patients, including one fatal intracranial hemorrhage. Most toxicities emerged within two months, and most nonfatal toxicities improved with dose adjustment or discontinuation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      In this exploratory two\u2010center case series, preoperative avapritinib demonstrated marked pathologic activity in localized\n                      <jats:italic>PDGFRA<\/jats:italic>\n                      \u2010mutant GIST, including after dose reduction in some patients. However, early toxicity at the standard 300\u2009mg dose was frequent and, in several cases, prevented patients from reaching planned surgery. These findings argue against routine preoperative avapritinib use and support limiting this approach to clinical trials or highly selected patients with a compelling surgical rationale until prospective data are available.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.72100","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T05:15:35Z","timestamp":1785388535000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Preoperative Avapritinib for Localized\n                    <i>PDGFRA<\/i>\n                    \u2010Mutant\n                    <scp>GIST<\/scp>\n                    : Marked Pathologic Response, but Limited Feasibility at Standard Dosing"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9404-7823","authenticated-orcid":false,"given":"Tannaz","family":"Ranjbarian","sequence":"first","affiliation":[{"name":"Division of Surgical Oncology, Department of Surgery University of California San Diego  San Diego California USA"},{"name":"Moores Cancer Center University of California San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Antkowiak","sequence":"additional","affiliation":[{"name":"Division of Surgical Oncology, Department of Surgery University of California San Diego  San Diego California USA"},{"name":"Moores Cancer Center University of California San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirley","family":"Sarno","sequence":"additional","affiliation":[{"name":"Division of Surgical Oncology, Department of Surgery University of California San Diego  San Diego California USA"},{"name":"Moores Cancer Center University of California San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shumei","family":"Kato","sequence":"additional","affiliation":[{"name":"Moores Cancer Center University of California San Diego  La Jolla California USA"},{"name":"Division of Hematology\u2010Oncology, Department of Medicine University of California San Diego  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam M.","family":"Burgoyne","sequence":"additional","affiliation":[{"name":"Moores Cancer Center University of California San Diego  La Jolla California USA"},{"name":"Division of Hematology\u2010Oncology, Department of Medicine University of California San Diego  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Skye C.","family":"Mayo","sequence":"additional","affiliation":[{"name":"Division of Surgical Oncology, Department of Surgery Oregon Health &amp; Science University (OHSU)  Portland Oregon USA"},{"name":"OHSU Knight Cancer Institute  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Heinrich","sequence":"additional","affiliation":[{"name":"OHSU Knight Cancer Institute  Portland Oregon USA"},{"name":"Portland VA Health Care System  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul T.","family":"Fanta","sequence":"additional","affiliation":[{"name":"Moores Cancer Center University of California San Diego  La Jolla California USA"},{"name":"Division of Hematology\u2010Oncology, Department of Medicine University of California San Diego  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4403-0271","authenticated-orcid":false,"given":"Jason K.","family":"Sicklick","sequence":"additional","affiliation":[{"name":"Division of Surgical Oncology, Department of Surgery University of California San Diego  San Diego California USA"},{"name":"Moores Cancer Center University of California San Diego  La Jolla California USA"},{"name":"Department of Pharmacology University of California San Diego  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3143"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20100463.2007.apm_587.x"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12325\u2010022\u201002115\u20103"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1079666"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265\u2010020\u201001275\u20102"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2020.12.008"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(20)30269\u20102"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2021.100159"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1245\/s10434\u2010013\u20103013\u20107"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.2144\/fsoa\u20102020\u20100178"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/onco.13674"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.5603\/OCP.2023.0036"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201053821\u20101"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010019\u20100407\u20105"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0b013e3181b13ca2"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2008.10.026"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2017.144"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.927587"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2003.04.190"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.07.3411"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.72100","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cam4.72100","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.72100","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T12:24:52Z","timestamp":1787660692000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.72100"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,29]]},"references-count":20,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/cam4.72100"],"URL":"https:\/\/doi.org\/10.1002\/cam4.72100","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,29]]},"assertion":[{"value":"2026-01-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e72100"}}