A retrospective study on Mixed Neuroendocrine Non-Neuroendocrine Neoplasms from five European centres

Melissa Frizziero, Xin Wang, Bipasha Chakrabarty, Alexa Childs, Tu V. Luong, Thomas Walter, Mohid S. Khan, Meleri Morgan, Adam Christian, Mona Elshafie, Tahir Shah, Annamaria Minicozzi, Wasat Mansoor, Tim Meyer, Angela Lamarca, Richard Hubner, Juan Valle, Mairead Mcnamara

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BACKGROUND (37 words) Mixed neuroendocrine non-neuroendocrine neoplasm (MiNEN) is a rare diagnosis, mainly encountered in the gastro-entero-pancreatic tract. There is limited knowledge of its epidemiology, prognosis and biology, and the best management for affected patients is still to be defined. AIM (20 words) To investigate clinical-pathological characteristics, treatment modalities and survival outcomes of a retrospective cohort of patients with a diagnosis of MiNEN. METHODS (86 words) Consecutive patients with a histologically proven diagnosis of MiNEN were identified at 5 European centres. Patient data were retrospectively collected from medical records. Pathological samples were reviewed to ascertain compliance with the 2017 World Health Organisation definition of MiNEN. Tumour responses to systemic treatment were assessed according to the Response Evaluation Criteria in Solid Tumours 1.1. Kaplan-Meier analysis was applied to estimate survival outcomes. Associations between clinical-pathological characteristics and survival outcomes were explored using Log-rank test for equality of survivors functions (univariate) and Cox-regression analysis (multivariable). RESULTS (188 words) Sixty-nine consecutive patients identified; Median age at diagnosis: 64 years. Males: 63.8%. Localised disease (curable): 53.6%. Commonest sites of origin: colon-rectum (43.5%) and oesophagus/oesophagogastric junction (15.9%). The neuroendocrine component was; predominant in 58.6%, poorly differentiated in 86.3%, and large cell in 81.25%, of cases analysed. Most distant metastases analysed (73.4%) were occupied only by a poorly differentiated neuroendocrine component. Ninety-four percent of patients with localised disease underwent curative surgery; 53% also received perioperative treatment, most often in line with protocols for adenocarcinomas from the same sites of origin. Chemotherapy was offered to most patients (68.1%) with advanced disease, and followed protocols for pure neuroendocrine carcinomas or adenocarcinomas in equal proportion. In localised cases, median recurrence free survival (RFS); 14.0 months (mo) (95%-CI; 9.2–24.4), and median overall survival (OS): 28.6mo (95%-CI; 18.3–41.1). On univariate analysis, receipt of perioperative treatment (versus surgery alone) did not improve RFS (p=0.375), or OS (p=0.240). In advanced cases, median progression free survival (PFS); 5.6mo (95%-CI; 4.4–7.4), and median OS; 9.0mo (95%-CI; 5.2–13.4). On univariate analysis, receipt of palliative active treatment (versus best supportive care) prolonged PFS and OS (both, p<0.001). CONCLUSION (30 words) MiNEN is most commonly driven by a poorly differentiated neuroendocrine component, and has poor prognosis. Advances in its biological understanding are needed to identify effective treatments and improve patient outcomes.
Original languageEnglish
JournalWorld Journal of Gastroenterology
Publication statusAccepted/In press - 10 Sept 2019


  • mixed neuroendcorine non-neuroendocrine neoplasm
  • 2017 World Health Organisation classification
  • Mixed adeno-neuroendocrine carcinoma
  • gastroentero-pancreatic tract
  • digestive system
  • neuroendocrine neoplasms
  • survival outcomes


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