ATRX/DAXX in EUS-FNB Specimens of Pan-NETs

Recruiting

• Conditions: Pancreatic Neuroendocrine Tumor
• Interventions: Diagnostic Test: ATRX/DAXX immunohistochemistry

• Registration Number: NCT06406387
• Lead Sponsor: Azienda Ospedaliera Universitaria Integrata Verona

Brief Summary

P-NENs are classified as functional (F-) or non-functional (NF-) depending on the presence or absence of a clinical hormonal hypersecretion syndrome. Moreover, the WHO 2017 classification of pNENs distinguishes between well-differentiated pancreatic neuroendocrine tumors (pNETs) and poorly differentiated pancreatic neuroendocrine carcinomas (pNECs). pNETs are then divided according to a grading scheme based on Ki67 index in pNETs-G1 (Ki67 index ≤3%) and pNETs-G2 (Ki67 index between 4% and 20%). pNECs are all G3, with a Ki67 index \>20%. Endoscopic ultrasound with fine-needle biopsy (EUS-FNB) demonstrated safe and effective preoperative grading based on the Ki-67 proliferative index. However, downstaging rate is not neglectable, reaching 15% in a recent metanalysis. Moreover, recent whole-exome and whole genome sequencing studies revealed that the mutually exclusive inactivating mutations in death domain-associated protein (DAXX) and/or in α-thalassemia/mental retardation X-linked (ATRX) chromatin remodeling genes are associated with more aggressive disease. In a retrospective study, the investigators recently evaluated the correspondence of DAXX/ATRX expression on 41 EUS-FNB samples with corresponding surgical specimens demonstrating a 95.1% (almost perfect agreement, κ = 0.828; p \< 0.001) and 92.7% (substantial agreement, κ = 0.626; p \< 0.001) concordance for DAXX and ATRX expression, respectively. This study aims to evaluate the potential clinical/prognostic role of DAXX/ATRX expression as implementation of the currently used Ki67-based grading, evaluated on EUS-FNB samples in a prospective cohort of patients with NF-pNETs

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-05-06
• Study First Submitted QC: 2024-05-06
• Study First Posted: 2024-05-09
• Study Start: 2024-06-01
• Status Verified: 2024-12
• Last Update Submitted: 2025-02-06
• Last Update Posted: 2025-02-07
• Primary Completion: 2025-03-30
• Study Completion: 2029-11-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Age ≥18 years
• Cyto/histologic diagnosis of pNETs
• Signed informed consent

Exclusion Criteria

• Functional pNETs
• Multiple pancreatic nodules
• Diagnosis of MEN-1 or Von-Hippel Lindau
• Mixed types (e.g., mixed neuroendocrine-acinar/adenocarcinoma) or neuroendocrine carcinomas
• Predominantly cystic lesions (more than 50% of the volume).
• Metastatic tumors at the time of diagnosis
• Known bleeding disorder that cannot be sufficiently corrected with co-fact or fresh frozen plasma
• Use of anticoagulants that cannot be discontinued
• INR >1.5 or platelet count <50.000
• Pregnancy or breastfeeding
• Failure to sign the patient's or closest relative's informed consent

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
ATRX/DAXX preserved	ATRX/DAXX immunohistochemistry	The "negative" group including those with preserved DAXX and ATRX expression evaluated on immunohistochemistry on endoscopic ultrasound biopsy specimens
ATRX/DAXX loss	ATRX/DAXX immunohistochemistry	The "positive" group including patients with loss of DAXX or ATRX expression evaluated on immunohistochemistry on endoscopic ultrasound biopsy specimens

Primary Outcome Measures

Name	Time	Method
ATRX/DAXX loss-tumor aggressiveness association	18 months	To assess the association between ATRX/DAXX loss of expression assessed on endoscopic ultrasound biopsy specimens and pathological features indicative of tumor aggressiveness evaluated on surgical pathology

Secondary Outcome Measures

Name	Time	Method
DAXX/ATRX concordance	18 months	To evaluate the concordance rate of DAXX/ATRX expression between endoscopic ultrasound biopsy samples and surgical specimens
Preoperative prognosis assessment	60 months	To evaluate the association between DAXX/ATRX expression on endoscopic ultrasound biopsy samples, Ki67-based grade 2/3 on endoscopic ultrasound biopsy samples, and tumor size on endoscopic ultrasound and progression-free survival and relapse-free survival.
Ki-67 concordance	18 months	To evaluate the concordance rate of Ki67-based tumor grade between endoscopic ultrasound biopsy samples and surgical specimens.
Ki-67-tumor aggressiveness association	18 months	To assess the association between preoperative Ki67-based grade 2/3 on endoscopic ultrasound samples and pathological features indicative of tumor aggressiveness evaluated on surgical pathology

Trial Locations

Locations (1)

University Hospital of Verona; 🇮🇹 Verona, Italy