Analysis of patient selection for germline testing in early-onset gastroenteropancreatic neuroendocrine neoplasms (GEPNENs) at a single institution

Lizeth Estrada; Le Bryan Khuong; Li Zhang; Alan Paciorek; Claire Mulvey; MD, Emily Bergsland,

doi:10.1530/endoabs.116.O2

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Endocrine Abstracts (2025) 116 O2 | DOI: 10.1530/endoabs.116.O2

NANETS2025 18th Annual Multidisciplinary NET Medical Symposium NANETS 2025 Other Section (13 abstracts)

Analysis of patient selection for germline testing in early-onset gastroenteropancreatic neuroendocrine neoplasms (GEPNENs) at a single institution

Lizeth Estrada ¹ , Bryan Khuong Le ² , Li Zhang ^1,3 , Alan Paciorek ^2,3 , Claire Mulvey ^2,4 & Emily Bergsland ⁴

Author affiliations

¹School of Medicine, University of California San Francisco, San Francisco, CA; ²Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA; ³Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA; ⁴Department of Medicine, Division of Hematology/Oncology, University of California San Francisco, San Francisco, CA

Background: In our previous work, we found a high rate of pathogenic/likely pathogenic germline mutations (PGM) in patients with early-onset GEPNENs (EO-GEPNENs) at UCSF, particularly in pancreatic primaries. However, germline testing practices in EO-GEPNENs have not been standardized. Testing has historically been driven by clinical factors, patient preference, and insurance coverage, but the process is prone to bias and relies on subjective provider assessment. This study characterizes the clinicodemographic features of EO-GEPNEN patients who underwent testing versus those who did not.

Methods: In this IRB-approved study, we identified 252 EO-GEPNEN patients (age 18–49 at diagnosis, any stage/grade) from 2011–2023. Group differences in categorical and continuous variables were assessed using the Chi-squared and Wilcoxon tests.

Results: Of 252 patients with EO-GEPNENs, 109 (43%) underwent germline testing. Among them, 29 (27%) had a PGM. Tested patients had a median age of 42 years at diagnosis, 55% female, 47% locoregional disease, and 92% well-differentiated tumors. Additional clinicodemographic features are in Table 1:


Characteristic	Not Tested (n = 143, 56.7%)	Tested (n = 109, 43.3%)	P Value
Age (median [IQR])	42.00 [36.00, 46.00]	43.00 [35.00, 47.00]	0.914
Sex Female Male	78 (54.5) 65 (45.5)	60 (55.0) 49 (45.0)	1
Race White Non-White	86 (66.7) 43 (33.3)	82 (78.1) 23 (21.9)	0.074
Suspected genetic syndrome	10 (9.2)	21 (19.3)	0.052
Other cancers besides NEN	14 (10.3)	18 (17.1)	0.173
Primary Tumor Site GI Pancreas	70 (49.0) 73 (51.0)	50 (45.9)59 (54.1)	0.721
Grade at Diagnosis G1/G2 NET G3 NET G3 NEC Unknown	108 (75.5) 3 (2.1) 8 (5.6) 24 (16.7)	82 (75.2) 12 (11) 6 (5.5) 9 (8.3)	0.036
Metastatic Disease	79 (56.4)	82 (75.2)	0.003

Conclusions: EO-GEPNEN incidence is rising, but its association with PGMs is unclear. At UCSF, 43.3% of patients underwent germline testing, with 26.6% harboring a PGM. The tested population was enriched for G3 and stage IV disease, with no significant differences in age, sex, site, second cancers, or race, though our data suggest more suspected genetic syndromes in tested patients and more non-White patients in the non-tested group. Clinicodemographic features by PGM status will be presented. Further work is needed to define testing indications and assess downstream implications.

Abstract ID #33483