Influence of Tumour and Patient's Related Factors on the Response to Medical Treatments in Well Differentiated GEP-NENs

This is an observational retrospective multicentric cohort study. The primary outcome of the study is the global Progression-free survival (PFS) adjusted for the risk factors considered. In a subgroup of patients only previously enrolled in San Raffaele Hospital that were included in the BIO-PANCREAS study (approval number INT/96/2021, a local monocentric protocol in which blood and/or Endoscopic UltraSound-Fine Needle Aspiration (EUS-FNA) derived samples are collected for further molecular analyses), the trascriptome signature will also be investigated as potential biomarker of disease behavior. Retrospective enrolment will be performed from January 2015 to March 2023. As for the primary aim, patients' and tumours' related variables will be investigated as explanatory variables for the outcome "time to progression", hence this analysis will allow a response to the clinical question of whether these factors have an influence on tumour behavior under treatment. As for the subgroup analysis (analysis of trascriptome signatures), again, this will be investigated to test whether there is a signature able to discriminate different responses to treatment.

Inclusion criteria

• Age >= 18
• Well-differentiated, localized (but not suitable for surgical treatment) or advanced (locally or with distant metastasis) GEP-NENs
• availability of data on site of primary tumor, stage of the, date of diagnosis
• treated with one (or more) of the following therapies:

• Somatostatin analogs

• G1 or G2 (Ki67 <10%) GEP-NENs
• Treated for at least 6 months
• first-line therapy (or as second-line after surgery in patients with residual disease or recurrence after surgical resection)
• Sunitinib/Everolimus

• G1/G2 GEP-NENs
• Treated for at least 6 months
• first- or second-line therapy
• Capecitabine-Temozolomide (CAP-TEM)

• G2 or G3 (Ki67 < 55%) GEP-NENs
• first-, second-, or third-line therapy
• Treated for at least 6 months

Exclusion criteria

• Age < 18aa
• Patients concomitantly treated with loco-regional treatments
• Patients previously treated with radioligand therapy
• Patients with need of CAP-TEM dose reduction of more than 33% for at least 3 administrations
• NENs of unknown primitivity (including patients with biopsy on secondary lesion compatible with metastasis from GEP-NEN, but with occult primary neoplasm)
• Patients with Mixed NENs (MiNENs)
• Patients with poorly differentiated neuroendocrine carcinoma
• Pregnancy and breastfeeding