What is the initial treatment approach for a patient with a Grade 2 neuroendocrine tumor (NET) of the pancreas with whole-body involvement on positron emission tomography (PET) scan?

From the Guidelines

The initial treatment approach for a patient with a Grade 2 pancreatic neuroendocrine tumor (NET) with whole-body involvement on PET scan typically involves systemic therapy with somatostatin analogs (SSAs) as first-line treatment, as recommended by the most recent study 1.

Key Considerations

• The patient's tumor is classified as a Grade 2 NET, which is well-differentiated with a Ki67 index of 3-20% 1.
• The tumor has whole-body involvement on PET scan, indicating metastatic disease.
• The treatment approach should prioritize controlling tumor growth, managing hormonal symptoms, and providing disease control with manageable side effects.

Treatment Options

• Somatostatin analogs (SSAs): Octreotide LAR (20-30 mg intramuscularly every 4 weeks) or lanreotide (120 mg subcutaneously every 4 weeks) are recommended as first-line treatment to control tumor growth and manage hormonal symptoms 1.
• Targeted therapies: Everolimus (10 mg orally daily) or sunitinib (37.5 mg orally daily) may be added to the regimen for patients with progressive or high-volume disease 1.
• Chemotherapy: Capecitabine (750-1000 mg/m² twice daily on days 1-14) and temozolomide (150-200 mg/m² on days 10-14) in 28-day cycles is another option, particularly for pancreatic NETs with higher proliferation rates 1.

Diagnostic Considerations

• Somatostatin receptor imaging: Gallium-68 DOTATATE PET should be performed to assess somatostatin receptor expression, which helps predict response to SSAs and determine eligibility for peptide receptor radionuclide therapy (PRRT) if the disease progresses 1.

From the FDA Drug Label

SOMATULINE DEPOT is a somatostatin analog indicated for: the treatment of adult patients with unresectable, well- or moderately-differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) to improve progression-free survival. (1.2)

The initial treatment approach for a patient with a Grade 2 neuroendocrine tumor (NET) of the pancreas with whole-body involvement on positron emission tomography (PET) scan is lanreotide (SQ), a somatostatin analog, at a recommended dosage of 120 mg every 4 weeks 2.

• Key points:
  • Indication: Treatment of adult patients with unresectable, well- or moderately-differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs)
  • Dosage: 120 mg every 4 weeks
  • Administration: Deep subcutaneous injection only, intended for administration by a healthcare provider.

From the Research

Initial Treatment Approach for Grade 2 Neuroendocrine Tumor of the Pancreas

• The initial treatment approach for a patient with a Grade 2 neuroendocrine tumor (NET) of the pancreas with whole-body involvement on positron emission tomography (PET) scan may involve peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE 3, 4.
• PRRT has shown promising activity in non-comparative studies in advanced neuroendocrine tumors, with significant improvements in progression-free survival, overall survival, and quality of life 3, 4.
• Patient selection for PRRT is based on specific factors, including somatostatin receptor positivity, and should be sequenced carefully with respect to other available therapies, ideally in multidisciplinary cancer conferences 4.

Role of PET/CT in Therapy Management

• Molecular imaging with PET/CT has become indispensable for the management of pancreatic neuroendocrine tumors (panNETs), with [68Ga]Ga-DOTA-peptide PET/CT (SSA-PET/CT) recommended for staging and restaging of non-insulinoma well-differentiated panNEN cases 5.
• SSA-PET/CT has high sensitivity, specificity, and accuracy, and is used to evaluate in vivo somatostatin receptors expression (SRE) to select patient candidates for PRRT with 90Y or 177Lu and/or cold analogs 5.

Other Treatment Options

• Other treatment options for advanced neuroendocrine tumors include surgical resection of the primary and metastases, somatostatin analogues, and cytotoxic agents such as streptozotocin, dacarbazine, temozolomide, and oxaliplatin 6.
• Liver-directed therapies, including embolization, are also effective in both pancreatic and gastrointestinal tract neuroendocrine tumors 6.