Clinical trial NCT06406387: ATRX/DAXX in EUS-FNB Specimens of Pan-NETs
Official title: Association Between Endoscopic Ultrasound Based Preoperative ATRX/DAXX Immunohistochemistry Expression and Prognosis of Sporadic, Non-FunctiOnal PancREatic Neuroendocrine TumorS: a ProspEctivE Cohort Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Pancreatic Neuroendocrine Tumor
Lead sponsor: Azienda Ospedaliera Universitaria Integrata Verona
Sponsor class: OTHER
First posted: 2024-05-09
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with a diagnosis of pancreatic neuroendocrine tumors

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


Eligibility criteria: 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

Primary outcomes:
measure: ATRX/DAXX loss-tumor aggressiveness association
timeFrame: 18 months
Secondary outcomes:
measure: Ki-67 concordance
timeFrame: 18 months
measure: DAXX/ATRX concordance
timeFrame: 18 months
measure: Ki-67-tumor aggressiveness association
timeFrame: 18 months
measure: Preoperative prognosis assessment
timeFrame: 60 months
Other outcomes:
Locations:
city: Verona
country: Italy
facility: University Hospital of Verona
Study officials:
References: