{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T04:03:08Z","timestamp":1788235388992,"version":"build-2803163510"},"reference-count":34,"publisher":"American Medical Association (AMA)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Surg"],"published-print":{"date-parts":[[2026,2,1]]},"abstract":"\n Importance<\/jats:title>\n Lymph node (LN) metastasis is a strong predictor of tumor recurrence following pancreatectomy for localized pancreatic neuroendocrine tumors (PanNETs). However, most patients lack LN metastasis and many tumors recur. Tools to guide risk-adapted surveillance in this group are lacking.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To develop and validate a tumor recurrence and survival risk score for patients with LN-negative PanNETs.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This retrospective, case-control study of patients with localized PanNETs took place at 5 high-volume US institutions from 2000 to 2023. Inclusion required 8 or more evaluated LNs and negative nodal status. Median follow-up was 50.6 months. These data were analyzed from March 2025 to May 2025.<\/jats:p>\n <\/jats:sec>\n \n Exposure<\/jats:title>\n Surgical resection of localized PanNETs per clinical guidelines.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary outcome was tumor recurrence. Independent predictors were identified using multivariable logistic regression and used to construct a 13-point composite risk score. Performance was assessed using C statistics. Kaplan-Meier and log-rank methods evaluated disease-free survival (DFS). Genomic profiling was conducted in an external validation cohort to identify and validate recurrence-associated mutational risk scores.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Of 2024 patients, 770 met inclusion criteria. Median age was 58.7 (IQR, 18.4) years; 405 were male (52.6%) and 365 were female (47.4%). Most tumors were sporadic (94.1%), nonfunctional (90.4%), and located in the body\/neck (50.9%). Recurrence occurred in 82 patients (10.6%) at a median of 32.4 (IQR, 16.3-82.0) months after surgery. Independent predictors included male sex (odds ratio [OR], 2.2; 95% CI, 1.3-3.9), tumor size 3 cm or larger (OR, 2.64; 95% CI, 1.5-4.6), World Health Organization grade 2 or higher (OR, 3.70; 95% CI, 1.4-10.0), and lymphovascular invasion (OR, 3.84; 95% CI, 2.1-6.9). The risk score showed strong performance (area under the receiver operating characteristic, 0.83 internally; 0.95 externally). Recurrence rates by risk group were 2.4%, 9.0%, and 27.7% (\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001), and 10-year DFS rates of 96.1%, 83.6%, and 51.3%, for low-risk, moderate-risk, and high-risk groups, respectively (\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001). Genomic analyses revealed higher tumor mutational burden, somatic mutation count, and somatic mutations in\n CDC42BPB<\/jats:italic>\n ,\n DAXX<\/jats:italic>\n ,\n ERI2<\/jats:italic>\n ,\n GALNT9<\/jats:italic>\n ,\n MTOR<\/jats:italic>\n ,\n NUMA1<\/jats:italic>\n , and\n TRPC7<\/jats:italic>\n genes among recurrent tumors.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n Despite LN-negative status, a subset of patients with PanNETs remained at high risk for recurrence. This validated risk score stratifies recurrence and survival risk showing biological relevance. These findings provide a framework for refining postoperative surveillance and risk-adapted therapeutic strategies.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamasurg.2025.5401","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T17:30:26Z","timestamp":1765992626000},"page":"142","source":"Crossref","is-referenced-by-count":6,"title":["Recurrence in Patients With Lymph Node-Negative Pancreatic Neuroendocrine Tumors"],"prefix":"10.1001","volume":"161","author":[{"given":"Marco","family":"Ventin","sequence":"first","affiliation":[{"name":"Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahrzad","family":"Arya","sequence":"additional","affiliation":[{"name":"Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, 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