Treatment Response and Outcomes of Grade 3 Pancreatic Neuroendocrine Neoplasms Based on Morphology: Well Differentiated Versus Poorly Differentiated

Abstract

Objectives: Emerging data suggest that not all grade 3 (G3) pancreatic neuroendocrine neoplasms (panNENs) behave the same; tumor differentiation may predict outcome.

Methods: Patients with G3 panNENs treated at our institution between 1999 and 2014 were identified. Demographics, response to therapy, and overall survival were determined.

Results: Forty-five patients were identified, 16 with G3 well differentiated pancreatic neuroendocrine tumors (WD-panNETs) and 29 with poorly differentiated neuroendocrine carcinomas (PDNEC). Median overall survival in G3 WD-panNET patients was 52.2 months (95% confidence interval, 19.3-86.9 months) compared with 10.1 months (95% confidence interval, 6.9-12.4 months) in PDNEC patients (P = 0.0009). Response rate to platinum agents was 10% in G3 WD-panNETs and 37% in PDNEC. Response rate to alkylating agents was 50% in G3 WD-panNETs and 50% in PDNEC.

Conclusions: Both G3 WD-panNETs and PDNEC responded to platinum and alkylating agents. Overall survival was significantly greater in G3 WD-panNETs compared with PDNEC. These findings challenge current classification and suggest that G3 panNENs should be classified by morphology.

Conflict of interest statement

Conflicts of Interest: Dr. Diane Reidy-Lagunes has received honoraria and research funding from Novartis. In addition, Dr. Reidy-Lagunes does consulting/advising for Novartis, Ipsen, and Pfizer. Dr. Peter Allen does consulting/advising for Sanofi. In addition, Dr. Allen has received research funding from Novartis.

Figures

Figure 1

Kaplan-Meier overall survival by tumor differentiation, G3 WD-panNETs versus PDNEC. Abbreviations: G3 WD-panNETs, grade 3 well differentiated pancreatic neuroendocrine tumors; PDNEC, poorly differentiated neuroendocrine carcinomas.