Neuroendocrine Tumor GEP Grade 1-3

Neuroendocrine tumours (NETs), better defined as neoplasms (NENs), are a heterogeneous group of neoplasms that range from well-differentiated tumours to more aggressive carcinomas. Peptide receptor radionuclide therapy (PRRT) with Lutetium-177 DOTATATE is the established standard of care for patients with well-differentiated metastatic or locally advanced GEP-NETs. It has demonstrated a significant improvement in outcomes compared to Octreotide LAR, both as a first-line and second-line treatment approach, following the results of NETTER-1 and NETTER-2 trials, respectively. ENETS guidelines recommend the use of Ga-68 labeled DOTANOC/TOC/TATAE imaging only for WHO Grade 1 NET whereas FDG PET is the preferred modality for WHO Grade 3 NEN and NEC. For Grade 2 tumors (Mib index ranging from 3-20%), there are no strong recommendations for the addition of FDG PETCT in existing diagnostic algorithm. FDG PET positivity has been shown to be an independent predictor of shorter progression-free and overall survival in NET patients undergoing peptide receptor radionuclide therapy (PRRT). (8) Consequently, it is imperative to address FDG-avid tumors by integrating PRRT and chemotherapy. There are no strong recommendations for the grade wise management of GEP-NETs particularly grade 2 \& 3. Although recently published NETTER 2 trial substantiated the role of PRRT as a first line treatment for advanced grade GEP-NETs, still there is lack of evidence supporting the addition of chemotherapy in management of GEP-NETs. Given the absence of a prospective study to establish this treatment regimen, we designed a Phase 3 Randomized Controlled Trial to evaluate the combination of PRRT and CAPE-TEM-based chemotherapy in patients with FDG-positive metastatic well-differentiated NETs.

Neuroendocrine tumors (NETs), often seen as "chronic cancer" present a survival paradox with relatively prolonged patient survival despite active disease. Treatment strategies emphasize management over cure, integrating tumor control with quality of life (QOL) considerations. Surgery is a cornerstone of NET management but demands a careful balance between its potential benefits and the morbidity risks. Current literature on post-surgical QOL is limited and non-generalizable, underscoring the need for comprehensive, multi-institutional data to inform surgical decisions. We will study QOL after surgery for NETs in a prospective multi-institutional international cohort study. Specifically, we aim to 1) describe the post-operative QOL of patients with NETs and 2) identify factors associated with QOL measures after surgery for NETs. This project will be led in partnership by the Susan Leslie Clinic for NETs at Sunnybrook Health Sciences Centre in Toronto, Canada, and the IRCCS San Raffaele ENETS Centre of Excellent in Milan, Italy, and enrol adults undergoing surgery for resection of gastro-entero-pancreatic NETs across 12 North-American and European high-volume NETs surgery centres over a 18-month period. Measures of QOL using the SF-12 Survey, the EORTC-QLQ C30 and GEPNET21 tool, and clinical symptoms assessment, will be captured prior to surgery and at 6, 12, 24, and 36 months after surgery. Mixed linear regression models with random intercepts to account for longitudinal data correlation and individual variability will be used to analyze the QOL measures over time. Patient and service users engagement (PSUE) will be integrated throughout the study continuum. This project will fill the knowledge gap in QOL after surgery for NETs, with a view to support better-informed surgical decisions and patient-centred care. The prospective, multi-institutional, and international design promises a comprehensive understanding of the impact of surgery on patient's lives, potentially shaping management pathways globally.