{
  "abstract": "Background/Objectives: The efficacy of somatostatin analogues (SSA) in Grade 3 (G3) neuroendocrine neoplasms (NEN) remains controversial, and registry data rarely permit a formal separation of NET G3 from neuroendocrine carcinoma (NEC). Methods: We analyzed 519 patients with G3 gastroenteropancreatic (GEP) NEN recorded in a national neuroendocrine tumor registry (data export 3 April 2025; 464 de novo G3, 55 transformed G3); bronchopulmonary primaries were excluded. A Ki-67 > 55%, entered as a time-varying indicator, served as a surrogate for NEC. Outcomes were compared using Kaplan–Meier and Cox proportional hazards models with all treatments and the Ki-67 > 55% indicator entered as time-varying covariates. Results: Among 410 patients with classifiable Ki-67, 256 (62.4%) ever had a Ki-67 > 55%. Ki-67 > 55% was associated with worse progression-free survival (PFS; HR 1.40, 95% CI 1.06–1.84; p = 0.016) and overall survival (OS; HR 1.65, 95% CI 1.15–2.37; p = 0.006). SSA use was not significantly associated with PFS (HR 1.32, 95% CI 0.85–2.04; p = 0.215) or OS (HR 0.91, 95% CI 0.54–1.56; p = 0.744). After adjustment for Ki-67, transformed G3 was associated with worse OS (HR 1.60, 95% CI 1.02–2.51; p = 0.040). Conclusions: SSA therapy was not associated with improved survival in G3 GEP-NEN. As this is an observational analysis subject to confounding by indication, these estimates do not establish a lack of biological efficacy of SSA. A Ki-67 threshold of 55% identified a prognostically distinct subgroup and explains why transformed G3 appears indolent: after adjustment, it was associated with worse overall survival. This finding rests on 55 patients with 29 deaths and is hypothesis-generating.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland",
    "Department of Hematology and Oncology, Hirslanden Klinik Zurich, 8032 Zurich, Switzerland",
    "Department of Clinical Research, University of Bern, 3010 Bern, Switzerland",
    "Clinic for Radiology and Nuclear Medicine, Center for Neuroendocrine and Endocrine Tumors, University Hospital Basel, 4031 Basel, Switzerland",
    "ENETS Center of Excellence, University Hospital Basel, 4031 Basel, Switzerland",
    "Center of Endocrine and Neuroendocrine Tumors, Department of Endocrinology, Diabetes and Metabolism, University Hospital Basel, University of Basel, 4031 Basel, Switzerland",
    "Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 4,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Alexander R. Siebenhüner"
    },
    {
      "affs": [
        2
      ],
      "name": "Jean-Benoît Rossel",
      "orcid": "0000-0001-5803-3233"
    },
    {
      "affs": [
        3,
        4,
        5
      ],
      "name": "Emanuel Christ"
    },
    {
      "affs": [
        6
      ],
      "name": "Attila Kollár",
      "orcid": "0000-0001-7955-3406"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4zwb451w0rxk7.bib",
  "cited_by": 0,
  "doi": "10.3390/cancers18203357",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13702314/?tool=EBI",
  "id": "4zwb451w0rxk7",
  "issns": [
    "2072-6694"
  ],
  "landing_url": "https://www.mdpi.com/2072-6694/18/20/3357",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2713|Neuroendocrine Tumor Research Advances"
    ]
  ],
  "openalex": "W7222922414",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13702314/pdf/?tool=EBI",
  "pmcid": "PMC13702314",
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/4zwb451w0rxk7.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:58Z",
      "native_id": "10.3390/cancers18203357",
      "source": "crossref",
      "url": "https://www.mdpi.com/2072-6694/18/20/3357"
    },
    {
      "first_seen": "2026-10-30T12:21:45Z",
      "native_id": "PMC:PMC13702314",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13702314"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Neuroendocrine Tumor Research Advances",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Somatostatin Analogues Do Not Improve Survival in Grade 3 Gastroenteropancreatic Neuroendocrine Neoplasms: A Registry-Based Analysis with Ki-67 Stratification",
  "title_text": "Somatostatin Analogues Do Not Improve Survival in Grade 3 Gastroenteropancreatic Neuroendocrine Neoplasms: A Registry-Based Analysis with Ki-67 Stratification",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:21:45Z",
  "url": "https://research.draconitic.com/paper/4zwb451w0rxk7",
  "venue": "Cancers",
  "versions": []
}