Well-differentiated gastroenteropancreatic G3 NET: findings from a large single centre cohort

Area of Science:

• Oncology
• Gastroenterology
• Endocrinology

Background:

• Neuroendocrine neoplasms exhibit diverse biological behaviors.
• G3 neuroendocrine tumours (NET G3) are defined by well-differentiated morphology and Ki67 > 20%, with intermediate prognosis between NET G2 and neuroendocrine carcinoma (NEC).
• Clinical management of NET G3 is challenging due to limited treatment strategy data.

Purpose of the Study:

• To describe clinical characteristics, treatment, and outcomes in a large single-center cohort of patients with gastroenteropancreatic NET G3.
• To analyze the efficacy of various treatment modalities for NET G3.
• To provide insights into the prognosis of NET G3.

Main Methods:

• Retrospective review of 26 gastroenteropancreatic NET G3 cases managed at Queen Elizabeth Hospital, Birmingham, UK (2012-2019).
• Analysis of primary tumor site, somatostatin receptor avidity, Ki67 index, and disease stage at diagnosis.
• Evaluation of treatment outcomes including progression-free survival (PFS) and overall survival (OS) for surgery, somatostatin analogs (SSA), and chemotherapy (platinum-based or temozolomide-based).

Main Results:

• Most primary tumors were of unknown origin or originated in the GI tract.
• Median Ki67 was 30%, with most patients diagnosed at stage IV.
• Estimated PFS was 4 months with SSA and 3 months with chemotherapy. Median survival was 19 months, with 1-year and 2-year survival rates of 60% and 13%, respectively. Disease control was observed in 5/11 patients treated with chemotherapy.

Conclusions:

• Gastroenteropancreatic NET G3 represents a heterogeneous group with commonly advanced disease at presentation and typically poor prognosis.
• Select NET G3 patients may show response to SSA and/or chemotherapy.
• Further research is required to compare the efficacy of different treatment strategies for NET G3.