P33. Recurrent Pancreatic Neuroendocrine Tumors in Lymph Node Negative Patients: A Multi-Institutional Risk-Score of Recurrence and Survival

Thursday, March 5, 2026

11:28 AM - 11:35 AM MST

Location: 301D

Co-Author(s)

Shahrzad Arya, MD

Postdoctoral research fellow
Cedars Sinai Medical Center
Los Angeles, California, United States
Liti Zhang, MD (she/her/hers)

Resident
Cedars-Sinai Medical Center
Los Angeles, California, United States
AG

Alexandra Gangi, MD

Attending
Cedars Sinai Medical Centre
Los Angeles, California, United States
CF

Carlos Fernandez-del Castillo, MD

Professor of Surgery
Massacheussets General Hospital
Boston, Massachusetts, United States
Motaz Qadan, MD PhD

Surgeon-in-Chief
Mass General Brigham Cancer Institute
Boston, Massachusetts, United States
AH

Andrew Hendifar, MD

Hematologist/Oncologist - Associate Professor of Medicine
Cedars Sinai Medical Center
Los Angeles, California, United States
GC

Giulia Cattaneo, PhD

Cedars-Sinai Medical Center
Los Angeles, California, United States
LL

Luigi Liguori, MD

Cedars-Sinai Medical Center
Los Angeles, California, United States
AO

Arsen Osipov, MD

Cedars-Sinai Medical Center
Los Angeles, California, United States
FS

Francesco Sabbatino, MD PhD

University of Salerno
Salerno, Campania, Italy
Nicholas Nissen, MD

Director of Hepatobiliary and Pancreatic Surgery
Cedars Sinai Medical Center
Los Angeles, California, United States
Kambiz Kosari, MD (he/him/his)

Associate Professor, Surgery
Cedars Sinai Medical Center
Los Angeles, California, United States
KL

Keith D. Lillemoe, MD

Surgeon-in-Chief and Chief of Surgery, Professor of Surgery
Massachusetts General Hospital
Boston, Massachusetts, United States
Alice C. Wei, MD (she/her/hers)

Attending Surgeon
MEMORIAL SLOAN KETTERING CANCER CENTER
New York, New York, United States
Jin He, MD PhD

Associate Professor
Johns Hopkins University School of Medicine
Baltimore, Maryland, United States
Amer H. Zureikat, MD

Professor and Chief, Division of Surgical Oncology
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States
Cristina R. Ferrone, MD (she/her/hers)

Chair of Surgery
Cedars-Sinai Medical Center
Los Angeles, California, United States

Primary Presenter(s)

Marco Ventin, MD

General Surgery Resident
Cedars-Sinai Medical Center
Los Angeles, California, United States

Slides

Introduction:
Lymph node (LN) metastasis is a known predictor of recurrence in pancreatic neuroendocrine tumors (PanNETs). However, many patients without LN involvement still recur, and risk-adapted tools to guide surveillance and therapy are lacking. This study aimed to define clinicopathologic predictors of recurrence in LN-negative PanNETs and develop a validated risk score for recurrence and survival.

Methods:
A multi-institutional, retrospective case-control study was conducted across five high-volume U.S. centers between 2000 and 2023. Patients with localized, surgically resected PanNETs and ≥8 examined LNs with negative nodal status were included. Multivariable logistic regression identified independent predictors of recurrence. A 13-point composite risk score was constructed and validated internally and externally. C-statistics assessed model discrimination. Kaplan-Meier and log-rank tests evaluated disease-free survival (DFS). In an external cohort, whole genome sequencing was analyzed to identify recurrence-associated somatic mutations.

Results:
Among 2024 patients, 770 met inclusion criteria. Median age was 58.7 years; 52.6% were male. Most tumors were sporadic (94.1%), non-functional (90.4%), and located in the body/neck (50.9%). Tumor recurrence occurred in 82 patients (10.6%) at a median of 32.4 months postoperatively. Independent predictors of recurrence included male sex (OR 2.2), tumor size >3 cm (OR 2.64), WHO grade ≥2 (OR 3.70), and lymphovascular invasion (OR 3.84). The risk score stratified patients into low- (2.4%), moderate- (9.0%), and high-risk (27.7%) recurrence groups (P< 0.001), with corresponding 10-year DFS rates of 96.1%, 83.6%, and 51.3% (P< 0.001). The model showed excellent discrimination (AUROC 0.83 internal; 0.95 external). Recurrent tumors harbored higher tumor mutational burden and recurrent mutations in CDC42BPB, DAXX, ERI2, GALNT9, MTOR, NUMA1, and TRPC7.

Conclusions:
Despite negative LN status, a significant subset of PanNET patients remain at risk for recurrence. This validated clinical-genomic risk score provides a framework for personalized surveillance: annual imaging for low-risk patients (discontinued after 5 years), 10-year annual surveillance for moderate-risk, and intensified surveillance every 6 months for 3 years, then annually for 10 years in high-risk cases.

Learning Objectives:

Prediction of tumor recurrence in lymph node negative PanNETs after surgery
Surveillance protocol recommendations