Michael J. Levy

Aims Small nonfunctioning pancreas neuroendocrine tumors (pNETS) are thought to be biologically indolent. The 2020 North American Neuroendocrine Tumor Society consensus paper recommends that a decision to observe or resect an asymptomatic 11-19mm pNET may be individualized. Routine prognostic marker clinical testing with DAXX/ATRX and telomere-specific FISH are not routinely available. In the absence of such biomarkers, we sought to identify tumor size and Ki-67% thresholds associated with disease progression, and disease progression within the <10mm and 11-19mm pNET population. Methods A single center 20-year retrospective review of 180 consecutive primary pancreas pNET endoscopic ultrasound fine needle aspiration or core biopsy [FNA:115 (63.9%) /FNB: 65 (36%)] examinations (2001-2021) were identified and followed over 36.9 (12.2-73.1) months. Genetic pNET syndromes and non-primary NETS were excluded from evaluation. Results Disease progression (25; 14%) was associated with pNET size [34mm (19-51.5) vs. 15mm (10-26); p<0.0001] and predicted with 52% sensitivity and 86.5% specificity using a lesion size ≥32 mm. It was also predicted with 71.4% sensitivity and 70.5% specificity using a Ki-67% of ≥3.9% mm ([Fig. 1]). Disease progression was evident in 3 (6.4%), 3 (5.8%) and 19 (23.5%) of ≤10mm, 11-19mm, and ≥20mm pNETs, respectively. Conclusions In our 20-year experience with non-genetic pNET EUS FNA/FNB lesions, in the absence of DAXX/ATRX immunohistochemistry and telomere-specific FISH, disease progression was associated with lesion size ≥32mm and Ki-67%≥3.9%. Importantly, almost 6% of <20mm pNETS had disease progression and would benefit from advanced prognostic markers. Article published online: 14 April 2023 © 2023. European Society of Gastrointestinal Endoscopy. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

BACKGROUND: A patient-derived organoid (PDO) platform may serve as a promising tool for translational cancer research. In this study, we evaluated PDO’s ability to predict clinical response to gastrointestinal (GI) cancers. METHODS: We generated PDOs from primary and metastatic lesions of patients with GI cancers, including pancreatic ductal adenocarcinoma, colorectal adenocarcinoma, and cholangiocarcinoma. We compared PDO response with the observed clinical response for donor patients to the same treatments. RESULTS: We report an approximately 80% concordance rate between PDO and donor tumor response. Importantly, we found a profound influence of culture media on PDO phenotype, where we showed a significant difference in response to standard-of-care chemotherapies, distinct morphologies, and transcriptomes between media within the same PDO cultures. CONCLUSION: While we demonstrate a high concordance rate between donor tumor and PDO, these studies also showed the important role of culture media when using PDOs to inform treatment selection and predict response across a spectrum of GI cancers. TRIAL REGISTRATION: Not applicable. FUNDING: The Joan F. & Richard A. Abdoo Family Fund in Colorectal Cancer Research, GI Cancer program of the Mayo Clinic Cancer Center, Mayo Clinic SPORE in Pancreatic Cancer, Center of Individualized Medicine (Mayo Clinic), Department of Laboratory Medicine and Pathology (Mayo Clinic), Incyte Pharmaceuticals and Mayo Clinic Hepatobiliary SPORE, University of Minnesota-Mayo Clinic Partnership, and the Early Therapeutic program (Department of Oncology, Mayo Clinic).

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