Clinical-pathological Evaluation of Pit-NETs

NCT06607198 | Not Yet Recruiting

• 1 other identifier: 6859
• Study Type: observational
• Target: 940
• Locations: 1 country
• Sites: 1

Brief Summary

Pituitary adenomas, namely pituitary neuroendocrine tumors (PitNETs), are recognized as rare neoplasia by national and international institutions. Albeit most PitNETs are slow-growing with an indolent behavior, about one-third do not achieve biochemical control, recur, re-grow, and resist conventional treatments. The predictors of aggressive behavior have not been identified for PitNETs. In 2013 Trouillas and coworkers developed a five tiered clinicopathological score by mixing histopathological data and clinico-radiological evidence of invasion. This system proved of prognostic value. Nonetheless, unlike for NET of gut and lung, no formal grading and/or staging tools were developed. In addition, PitNETs have not been thoroughly investigated by radiomics to predict clinical behavior, nor have druggable pathways been elucidated in PitNET cells to unveil new potential therapeutic approaches. The first aim of this project is to define grading and staging tools for PitNETs based on: i) lineage-specific transcription factors ; ii) cell type specification by hormone production (prolactin, TSH, LH, FSH, ACTH, GH or none); iii) integration of standard radiological measures with recognized tools for clinical and pathological staging. The second aim of this project is to investigate radiomics features as predictors of PitNETs behavior, prognosis, and treatment outcome. The third aim of this project is to investigate whether the expression of molecular biomarkers \[Vascular Endothelial Growth Factor (VEGF), Epithelial Growth Factor Receptor (EGFR), somatostatin receptors 1-5 (SSTRs), Fibroblast Growth Factor (FGF), mTOR (mammalian target of rapamycin), Programmed cells Death 1 (PD1) and its ligands (PD-L1), and Cytotoxic T Lymphocyte Associated protein 4 (CTLA4)\] may impact on patients prognosis. Identifying new molecular pathways may help fine-tune and schedule the emerging targeted therapies for aggressive PitNETs, including mTOR inhibitors, VEGF, EGFR, and immune check-point inhibitors. This study will investigate a large multicenter retrospective series of 740 PitNET patients and a prospective cohort of 200 patients to reach these objectives.

Conditions

Pituitary; Cancer; Neuroendocrine Tumors

Outcome Measures

Primary Outcomes (1)

• Grating and staging

  To investigate the following pathological features of PitNET cell lineage-specific transcription factors, cell type specification by hormone production, proliferative index, p53, mitotic count, expression of somatostatin receptors, through immunohistochemistry analysis on formalin-fixed paraffin-embedded samples of PitNETs

  2 years

Secondary Outcomes (3)

• PitNET morphology analysis

  2 years

• Radiomics

  2 years

• Molecular test: proteomics

  2 years

Interventions

grading & staging DIAGNOSTIC_TEST

To investigate the following pathological features of PitNET cell lineage-specific transcription factors, cell type specification by hormone production, proliferative index, p53, mitotic count, expression of somatostatin receptors

PitNET morphology analysis DIAGNOSTIC_TEST

Revision of the pre-surgical magnetic resonance images (MRIs): tumor maximum diameter, volume, sites of tumor extensions and invasion, and grading of cavernous sinus invasion

Radiomics DIAGNOSTIC_TEST

To investigate radiomics features of PitNETs

Molecular test: proteomics DIAGNOSTIC_TEST

To investigate on PitNets of molecular biomarkers Vascular Endothelial Growth Factor (VEGF), Epithelial Growth Factor Receptor (EGFR), somatostatin receptors 1-5 (SSTRs), Fibroblast Growth Factor (FGF), mTOR (mammalian target of rapamycin), Programmed cells Death 1 (PD1) and its ligands (PD-L1), and Cytotoxic T Lymphocyte Associated protein 4 (CTLA4)\]

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

This study will investigate a large multicenter retrospective series of 740 PitNET patients and a prospective cohort of 200 patients

You may qualify if:

• Consecutive patients older than 18 years;
• availability of tumor samples for the required pathology analyses;
• clinico-radiological follow-up of at least 5-10 years

You may not qualify if:

• \- Not applicable for this study

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Study Sites (1)

Fondazione Policlinico Universitario A. Gemelli IRCCS, UOC ANATOMIA PATOLOGICA

Rome, Lazio, 00168, Italy

Location

MeSH Terms

Conditions

Pituitary Diseases; Neoplasms; Neuroendocrine Tumors

Interventions

Radiomics

Condition Hierarchy (Ancestors)

Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• Guido Rindi

  Fondazione Policlinico Universitario A. Gemelli, IRCCS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Guido Rindi

CONTACT

+390630154433; guido.rindi@policlinicogemelli.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2024
• First Posted: September 23, 2024
• Study Start: October 1, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: September 23, 2024

Record last verified: 2024-09

Locations

IT (1)