E256: Characterization and Natural Evolution of Mixed Adeno-neuroendocrine Carcinoma of the Pancreas

ePoster Abstract Author(s)

Sayed Imtiaz, MD

Fellow- Hepatobiliary Surgery
University of Southern California, California, United States

Submitter(s)

Sayed Imtiaz, MD

Fellow- Hepatobiliary Surgery
University of Southern California, California, United States

Author(s)

ZK

Zain Kashif, BS

Medical Student
University of Southern California, California, United States
GM

Gautam Malhotra, MD, PhD

Assistant Professor Clinical Surgery
University of Southern California, California, United States
RS

Rick Selby, MD

Professor
University of Southern California, United States
SK

Sujit Kulkarni, MD

Associate Professor
University of Southern California, United States

Introduction: Pancreatic neuroendocrine carcinomas are rare tumors with an evolving nomenclature. The prevalence of pancreatic neuroendocrine neoplasms (PanNEN) is 0.48 per 100,000 and further division into new subtypes diminishes their presence in the literature. Here we report on PanNENs with a focus on Mixed Adeno-neuroendocrine Carcinomas (MANECs) to better understand their biology and therapeutic approaches.

Methods: We performed a retrospective cohort study using cases of PanNENs from 2004-2017 from the NCDB (National Cancer Database) according to the WHO (World Health Organization). We report patient demographics, choice and sequence of therapy, grade, stage, and survival. We performed a Kruskal-Wallis rank sum test for continuous variables, Pearson’s Chi-squared test for categorical variables, and Kaplan Meier analysis using R Studio.

Results: Most PanNETs presented with early stage (1-2) (60.8%), while PanNECs & MANETs presented with >50% late stage (3-4). MANECs were more rare and presented in early and late stages with equal percentage (p < 0.001). Surgical resection was most common in grades 1 and 2 PanNETs (67%) and least common in Small Cell PanNECs (6.2%) (p < 0.001). MANECs received chemotherapy with the most frequency at 62% while both Large and Small Cell PanNECs received chemotherapy in 57% of cases (p < 0.001). The exact sequence between neoadjuvant and adjuvant chemotherapy was not always clear but the majority of chemotherapy was in the adjuvant setting across all histologic types. In Kaplan-Meier Analysis, Small Cell PanNECs had the shortest median survival of 6 months (95%CI: 5.3-7.0) while Large Cell PanNECs had relatively longer median survival at 10 months (95%CI: 8.1-13). Grades 1 and 2 PanNETs had the best median survival time (146 months; 95%CI: 135-154) (p<0.001).

Conclusions: PanNENs with high grade, neuroendocrine carcinoma, or mixed adenoneuroendocrine pathologies can be deadly with an especially poor prognosis for MANECs. Here we present a large-scale characterization of the natural history of these rare tumors. Given their poor prognosis, biomarkers and targeted therapies will be essential to improve clinical outcomes.

Learning Objectives:
How to classify neuroendocrine carcinomas according to new 2022 WHO Guidelines
What type of mixed NECs have the lowest survival and receive the least amount of chemotherapy and why?
Which patients should undergo resection and whom should undergo a trial of neoadjuvant therapy in PanNENs? Does it improve outcomes?