What is the outline for studying Neuroendocrine (NE) tumors?

From the Guidelines

A comprehensive neuroendocrine tumor study should prioritize a multidisciplinary team approach, including specialist physicians, surgeons, radiologists, and nuclear medicine specialists, to ensure accurate diagnosis and effective treatment selection, as recommended by the most recent guidelines 1. The study should include initial imaging with CT or MRI scans, followed by functional imaging such as somatostatin receptor scintigraphy (Octreoscan) or gallium-68 DOTATATE PET/CT for better tumor localization and characterization.

• Laboratory tests should measure specific biomarkers including chromogranin A, 5-HIAA (for carcinoid tumors), gastrin, insulin, and other hormones depending on suspected functionality.
• Pathological assessment requires tissue sampling through biopsy or surgical resection, with immunohistochemical staining for chromogranin A, synaptophysin, and Ki-67 proliferation index to determine tumor grade (G1, G2, or G3) according to WHO classification.
• The study should also include TNM staging to assess tumor extent, lymph node involvement, and metastases.
• Genetic testing may be valuable, particularly for familial syndromes like MEN1 or VHL.
• Treatment response evaluation should use RECIST criteria modified for neuroendocrine tumors, with regular follow-up imaging and biomarker measurements, as suggested by previous studies 1. This comprehensive approach enables accurate diagnosis, appropriate treatment selection, and effective monitoring of disease progression or response to therapy in neuroendocrine tumor patients, ultimately improving morbidity, mortality, and quality of life outcomes.
• Anatomical imaging of NETs should be as detailed and extensive as possible to provide accurate information about site and extent of the primary tumour, and the location and extent of regional and distant metastases, as recommended by 1.
• Functional imaging procedures applying sstr imaging using 111In-pentetreotide (OctreoScan) with SPECT or PET with 68Ga-labelled SSA, combined with morphological imaging procedures, are used to collect essential information for staging, assessing sstr status and making decisions on the most appropriate therapy regimens 1.

From the FDA Drug Label

The primary efficacy outcome measure was disease-free survival (DFS) in patients receiving sunitinib versus placebo as assessed by blinded independent central review (BICR). A clinically significant improvement for sunitinib over placebo in PFS was seen by both investigator and independent assessment.

• Neuroendocrine tumor study outline:
  • Sunitinib (PO):
    • Disease-free survival (DFS): statistically significant improvement in DFS in patients treated with sunitinib compared to placebo 2
    • Progression-free survival (PFS): clinically significant improvement for sunitinib over placebo in PFS 2
  • Lanreotide (SQ):
    • No direct information on neuroendocrine tumor study outline is available in the provided drug label 3

From the Research

Neuroendocrine Tumor Study Outline

• Definition and Classification: Neuroendocrine tumors (NETs) are a heterogeneous group of tumors with diversity in primary tumor sites, functional status, and degrees of aggressiveness 4.
• Clinical Presentation: Clinical presentation of NETs is variable, ranging from incidental lesions to carcinoid syndrome, and can be associated with hormonal function, including eutopic and ectopic hormone production 4, 5.
• Diagnosis: Diagnosis relies on biochemical markers, computed tomography (CT), magnetic resonance imaging (MRI), and somatostatin-receptor based functional imaging 4.
• Treatment: Treatment comprises surgery, somatostatin analogues, peptide receptor radionuclide therapy (PRRT), everolimus, sunitinib, liver-directed therapies, and sometimes chemotherapy 4, 6, 7.
• Somatostatin Analogues: Octreotide and lanreotide are the two somatostatin analogs currently available in clinical practice, approved for controlling clinical syndrome and tumor growth control in advanced low/intermediate grade NET 6.
• Classification and Grading: The 2022 WHO Classification of Neuroendocrine Neoplasms distinguishes between well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs), with NETs graded as G1, G2, and G3 based on proliferation 5.
• Biomarkers: Biomarkers such as Ki67, INSM1, synaptophysin, chromogranins, and somatostatin receptors (SSTRs) are used for accurate classification and diagnosis of NETs 5.
• Treatment Strategies: Treatment strategies for advanced well-differentiated NET include somatostatin analogues, PRRT, everolimus, sunitinib, interferon alpha, and classical cytostatic, with indication and use differing based on primary tumor origin, grading, and symptomatic burden 7.
• Guidelines and Consensus: Consensus guidelines for the management and treatment of neuroendocrine tumors have been published, providing an overview for the treatment of patients with these malignancies 8.