Abstract 224P
Background
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) constitute a diverse group of cancers with a rising global incidence. Despite this, the role of tumor genomic profiling in their clinical management remains unclear. Limited studies have explored their molecular landscape due to rarity, diverse anatomical distribution, and clinical heterogeneity. Therapeutic development for rare cancers like GEP-NENs faces significant challenges. Thus, there's a pressing need to investigate how genomic insights from advanced technologies can improve patient care.
Methods
A multi-institutional cohort of GEP-NEN patients for analysis from January 1, 2017, to March 31, 2024. Data were sourced from comprehensive databases including the Princess Margaret Cancer Centre, AACR Project Genie, and cBioPortal for Cancer Genomics. Any overlapping cases were excluded. The primary endpoint examined was the median overall survival (mOS), determined through Kaplan-Meier methodology. Genomic profiling was characterized using descriptive statistics.
Results
In total, 2,381 GEP-NENs sequenced: 2,149 neuroendocrine tumours (NETs) and 232 neuroendocrine carcinomas (NECs). Predominantly altered genes in GEP-NETs: MEN1 (n=553, 26%), DAXX (n=304, 14%), TP53 (n=259, 12%), ATRX (n=235, 12%), and TSC2 (n=208, 11%), with pancreatic (n=1247, 58%) and small bowel (n=360, 17%) origins prevalent. GEP-NECs exhibited a different mutational profile: TP53 (n=176, 77%), APC (n=160, 69%), KRAS (n=70, 30%), RB1 (n=55, 24%), and BRAF (n=42, 18%), primarily originating from colorectal sites (n=221, 95%). In GEP-NETs survival analyses, the mOS in descending order: MEN1 & ATRX (73 months each), DAXX (59 months), TSC2 (44 months), and TP53 (20 months) (p<0.01). For GEP-NECs, mOS in descending order: BRAF, TP53, APC, KRAS, & RB1 at 13, 10, 9, 5, and 5 months (p<0.01). Current investigations include ct-DNA, MMR, and MSI testing.
Conclusions
This study highlights the genomic landscape of a large cohort of GEP-NENs, revealing distinct mutation profiles and survival patterns between NETs and NECs. These findings emphasize the crucial integration of genomic insights into clinical management, shaping personalized treatment strategies, and guiding future studies.
Legal entity responsible for the study
Princess Margaret Cancer Centre.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.