Poorly differentiated gastro-entero-pancreatic neuroendocrine carcinomas: Are they really heterogeneous? Insights from the FFCD-GTE national cohort

Eur J Cancer. 2017 Jul:79:158-165. doi: 10.1016/j.ejca.2017.04.009. Epub 2017 May 11.

Abstract

Background: Diagnosis and management of poorly differentiated gastro-entero-pancreatic (GEP) neuroendocrine carcinomas (NECs) remain challenging. Recent studies suggest prognostic heterogeneity. We designed within the French Group of Endocrine Tumours a prospective cohort to gain insight in the prognostic stratification and treatment of GEP-NEC.

Patients and methods: All patients with a diagnosis of GEP-NEC between 1st January 2010 and 31st December 2013 could be included in this national cohort. Adenoneuroendocrine tumours were excluded.

Results: 253 patients from 49 centres were included. Median age was 66 years. Main primary locations were pancreas (21%), colorectal (27%), oesophagus-stomach (18%); primary location was unknown in 20%. Tumours were metastatic at diagnosis in 78% of cases. Performance status (PS) at diagnosis was 0-1 in 79% of patients. Among the 147 (58%) cases reviewed by an expert pathological network, 39% were classified as small cell NEC and 61% as large cell NEC. Median Ki67 index was 75% (range, 20-100). Median overall survival was 15.6 (13.6-17.0) months. Significant adverse prognostic factors in univariate analysis were PS > 1 (hazard ratio [HR] = 2.5), metastatic disease (HR = 1.6), NSE>2 upper limit of normal [ULN]; HR = 3.2), CgA>2 ULN (HR = 1.7) and lactate dehydrogenase >2 ULN (HR = 2.1). After first-line palliative chemotherapy (CT1) with platinum-etoposide (n = 152), objective response, progression-free survival and overall survival were 50%, 6.2 and 11.6 months; they were 24%, 2.9 and 5.9, respectively, after post-CT1 FOLFIRI regimen (n = 72).

Conclusions: We report a large prospective series of GEP-NEC which show the predominance of large cell type and advanced stage at diagnosis. Prognosis was found more homogeneous than previously reported, mainly impacted by PS and tumour burden.

Keywords: Gastrointestinal cancer; Ki67 index; Neuroendocrine carcinoma; Prognosis; Treatment.

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carboplatin / administration & dosage
  • Carcinoma, Neuroendocrine / mortality
  • Carcinoma, Neuroendocrine / pathology*
  • Cell Transformation, Neoplastic / pathology
  • Cisplatin / administration & dosage
  • Cohort Studies
  • Etoposide / administration & dosage
  • Female
  • Gastrointestinal Neoplasms / mortality
  • Gastrointestinal Neoplasms / pathology*
  • Humans
  • Male
  • Neoplasm Metastasis
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology*
  • Prognosis

Substances

  • Etoposide
  • Carboplatin
  • Cisplatin