{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T02:07:25Z","timestamp":1789697245976,"version":"4.0.1"},"reference-count":10,"publisher":"American Medical Association (AMA)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2026,4,1]]},"abstract":"<jats:sec id=\"ab-cbr260001-4\">\n                    <jats:title>Importance<\/jats:title>\n                    <jats:p>\n                      Gastrointestinal stromal tumors (GISTs) harboring\n                      <jats:italic toggle=\"yes\">KIT<\/jats:italic>\n                      exon 9 mutations represent a biologically distinct subgroup with reduced sensitivity to standard-dose imatinib in the advanced setting. The benefit of adjuvant imatinib in this population remains uncertain.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-cbr260001-5\">\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      To evaluate the association between adjuvant imatinib and recurrence-free survival (RFS) and overall survival (OS) in patients with resected GISTs with\n                      <jats:italic toggle=\"yes\">KIT<\/jats:italic>\n                      exon 9 mutations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-cbr260001-6\">\n                    <jats:title>Design, Setting, and Participants<\/jats:title>\n                    <jats:p>\n                      This international, multicenter cohort study included patients with localized, molecularly confirmed GISTs with\n                      <jats:italic toggle=\"yes\">KIT<\/jats:italic>\n                      exon 9 mutations who underwent curative-intent surgery between January 1990 and July 2022 at 35 referral centers in Europe, the US, and Japan, or were registered in the Life Raft Group database. The analysis took place between January 2025 and November 2025.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-cbr260001-7\">\n                    <jats:title>Exposures<\/jats:title>\n                    <jats:p>Adjuvant imatinib initiated after curative surgery, modeled as a time-dependent covariate to account for immortal time bias.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-cbr260001-8\">\n                    <jats:title>Main Outcomes and Measures<\/jats:title>\n                    <jats:p>The primary end points were RFS (time from surgery to recurrence or death) and OS (time from surgery to death) in the full cohort and in the high-risk subgroup defined by modified National Institutes of Health (mNIH) criteria. Multivariable Cox regression models included established prognostic covariates and cluster-robust standard errors. Overlap weighting (OW) based on propensity scores was used as a causal inference model. Secondary analyses evaluated 400 mg\/d vs 800 mg\/d dosing in the mNIH high-risk subgroup.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-cbr260001-9\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 367 patients were included, 187 (51.0%) male and 180 (49%) female, with a mean (SD) age of 56 (13) years. Among these, 91 (24.8%) were observed and 276 (75.2%) received adjuvant imatinib (median [IQR] duration, 27.3 [13.5-36.0] months; 116 [42.0%] treated \u22653 years). Consistent with a cytostatic activity, adjuvant imatinib in the full cohort was associated with a reduced early hazard of recurrence or death (HR, 0.19; 95% CI, 0.10-0.36), with attenuation over time (time-interaction hazard ratio [HR], 1.85 per log-year). Treatment was also associated with improved OS (HR, 0.37; 95% CI, 0.17-0.83). Similar results were obtained when limiting the analysis to patients with mNIH high-risk disease. OW models and sensitivity analyses confirmed similar associations with RFS and OS. Among 257 patients with mNIH high-risk disease receiving imatinib, no significant difference was observed between 400 mg\/d and 800 mg\/d dosing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"ab-cbr260001-10\">\n                    <jats:title>Conclusion and relevance<\/jats:title>\n                    <jats:p>\n                      In this large international cohort study of resected GISTs with\n                      <jats:italic toggle=\"yes\">KIT<\/jats:italic>\n                      exon 9 mutations, adjuvant imatinib was independently associated with delayed recurrence and improved survival. These findings support the use of adjuvant imatinib in mNIH high-risk GISTs with\n                      <jats:italic toggle=\"yes\">KIT<\/jats:italic>\n                      exon 9 mutations and underscore the need for prospective studies to define optimal dosing and treatment duration.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1001\/jamaoncol.2026.0007","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T16:30:35Z","timestamp":1772123435000},"page":"407","source":"Crossref","is-referenced-by-count":3,"title":["Adjuvant Imatinib or Observation in Patients With Gastrointestinal Stromal Tumors With\n                    <i>KIT<\/i>\n                    Exon 9 Mutations"],"prefix":"10.1001","volume":"12","author":[{"given":"Andrea","family":"Napolitano","sequence":"first","affiliation":[{"name":"The Royal Marsden Hospital and The Institute for Cancer Research, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heikki","family":"Joensuu","sequence":"additional","affiliation":[{"name":"Helsinki University Hospital and University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Rothschild","sequence":"additional","affiliation":[{"name":"The Life Raft Group, Wayne, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denisse","family":"Evans","sequence":"additional","affiliation":[{"name":"The Life Raft Group, Wayne, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Heinrich","sequence":"additional","affiliation":[{"name":"Portland VA Health Care System and Oregon Health and Science University, Knight Cancer Institute, Portland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas L.","family":"Sutton","sequence":"additional","affiliation":[{"name":"Oregon Health and Science University, Knight Cancer Institute, Portland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Skye C.","family":"Mayo","sequence":"additional","affiliation":[{"name":"Oregon Health and Science University, Knight Cancer Institute, Portland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kjetil","family":"Boye","sequence":"additional","affiliation":[{"name":"Oslo University Hospital, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Falkenhorst","sequence":"additional","affiliation":[{"name":"Essen University Hospital, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Le Cesne","sequence":"additional","affiliation":[{"name":"Gustave Roussy, Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Hohenberger","sequence":"additional","affiliation":[{"name":"University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Rutkowski","sequence":"additional","affiliation":[{"name":"Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Winan J.","family":"van Houdt","sequence":"additional","affiliation":[{"name":"the Netherlands Cancer Institute, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neeltje","family":"Steeghs","sequence":"additional","affiliation":[{"name":"the Netherlands Cancer Institute, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Gelderblom","sequence":"additional","affiliation":[{"name":"Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid M. 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