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Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

5878 - The Prognostic Role of Morphology and Ki67 in Grade 3 Gastroenteropancreatic (GEP) Neuroendocrine Neoplasms (NEN)

Date

21 Oct 2018

Session

Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

Presenters

Aimee Hayes

Citation

Annals of Oncology (2018) 29 (suppl_8): viii467-viii478. 10.1093/annonc/mdy293

Authors

A.R. Hayes1, M. Furnace1, C. Rundell2, R. Shah2, G. Muller2, C. Thirlwell1, T.V. Luong1, C. Toumpanakis1, M. Caplin1, D. Mandair1

Author affiliations

  • 1 Neuroendocrine Tumour Unit, Royal Free Hospital, NW3 2QG - London/GB
  • 2 School Of Medicine, University College of London, London/GB
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Resources

Abstract 5878

Background

GEP NEN are classified according to morphology and proliferation index. According to the WHO 2010 classification, grade 3 (G3) GEP NEN are defined as having a Ki67 >20%. However, G3 well-differentiated NETs (WD-NETs) and poorly-differentiated neuroendocrine carcinomas (PD-NECs) may overlap in their proliferation index leading to prognostic and therapeutic uncertainties. Recently, WHO 2017, defined a new subgroup of G3 pancreatic NETs (PNET); G3a for WD-NETs and G3b for PD-NECs.

Methods

We retrospectively identified patients with G3 GEP NEN and divided them into WD-NETs and PD-NECs according to histological reports. The relationship between baseline characteristics and OS was analysed using the Kaplan Meier logrank test. Univariate and multivariate analyses were performed using the Cox proportional hazards model. Optimal Ki67 cut-points were explored using R version 2.15.0.

Results

145 patients with G3 GEP NENs had median follow-up 17 mo (59% male, 50% PD-NEC, 37% PNEN). There was a trend in improved survival in the WD-NET cohort (median Ki67 30%) compared to PD-NECs (median Ki67 60%); 29 vs 22 months (p = 0.1) more marked in the non-PNET cohort (median OS WD-NET 44 mo vs PD-NEC 20 mo; p = 0.1). Of the entire cohort, an independent effect of Ki67 was demonstrated on risk of mortality (p = 0.02). A Ki67 cutoff of 50% was found to have the highest logrank statistic. Ki67 ≥50% was associated with poorer OS compared to lower Ki67 index (median OS 38 mo vs 20 mo; p = 0.005). Somatostatin receptor imaging (SRI) was positive in 81% of WD-NETs compared to 45% of PD-NECs.

Conclusions

Our findings suggest that morphology and proliferative index are important factors in the prognostic evaluation of G3 GEP NEN of pancreatic and non-pancreatic origin. Ki67 remains the most reliable prognostic factor and further work is required to refine optimal Ki67 cutoffs in the G3 GEP NEN cohort to guide prognosis and treatment.

Clinical trial identification

Legal entity responsible for the study

Aimee Hayes.

Funding

Has not received any funding.

Editorial Acknowledgement

Not applicable

Disclosure

C. Thirlwell: Advisory board, Speaker honoraria: Ipsen. C. Toumpanakis: Speaker honoraria: Ipsen, Novartis and AAA. M. Caplin: Advisory Board, Speaker honoraria: Novartis, Ipsen, AAA, Lexicon. All other authors have declared no conflicts of interest.

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