Treatment Approach for Neuroendocrine Tumors Associated with the INSM1 Gene

Diagnostic Approach

The National Comprehensive Cancer Network recommends that for proper diagnosis, synaptophysin and/or INSM1 staining should be performed in tumors with solid, trabecular, gyriform or regular glandular growth pattern, uniform nuclei and coarsely stippled ('salt and pepper') chromatin 3, 4
Multiphase contrast-enhanced CT or MRI should be performed to identify the primary tumor and assess for metastatic disease, as recommended by the National Comprehensive Cancer Network 1, 5
Somatostatin receptor scintigraphy (Octreoscan) should be considered for tumor localization, except in insulinomas which are less consistently octreotide-avid, according to the National Comprehensive Cancer Network 2

The National Comprehensive Cancer Network recommends that before surgical excision, any symptoms of hormonal excess must be treated 2, 5
For insulinomas, glucose levels should be stabilized with diet and/or medication, as recommended by the National Comprehensive Cancer Network 1, 2
For gastrinomas, gastrin hypersecretion should be treated with proton pump inhibitors, according to the National Comprehensive Cancer Network 1, 2
Octreotide or lanreotide can be considered for symptom control in most pancreatic NET subtypes, but should be used with caution in patients with insulinoma, as recommended by the National Comprehensive Cancer Network 2

The National Comprehensive Cancer Network recommends that for nonfunctioning pancreatic NETs >2 cm, complete resection with negative margins and regional lymph node dissection should be performed 1, 2
For nonfunctioning pancreatic NETs 1-2 cm, resection with lymph node dissection should be considered due to small but real risk of lymph node metastases, according to the National Comprehensive Cancer Network 2, 7
For insulinomas, enucleation for peripheral tumors or distal pancreatectomy or pancreatoduodenectomy for deeper tumors should be performed, as recommended by the National Comprehensive Cancer Network 7
For gastrinomas, duodenotomy with local resection or enucleation of tumors and periduodenal node dissection, or pancreatoduodenectomy for tumors in the head of the pancreas should be performed, according to the National Comprehensive Cancer Network 7

Surgical resection should be considered in selected patients with liver metastases and potentially resectable disease, as recommended by the European Society for Medical Oncology 5, 8
Macroscopic radical resection can be achieved in 80% of cases if carried out by experienced surgeons, according to the European Society for Medical Oncology 5
Cholecystectomy is recommended when performing surgery for advanced NETs in patients anticipated to receive long-term octreotide therapy, as recommended by the National Comprehensive Cancer Network 6

Treatment options include somatostatin analogues, biotherapy, radionuclides, ablation therapies, and chemotherapy, as recommended by the European Society for Medical Oncology 8
Chemotherapy may be used for inoperable or metastatic pancreatic and bronchial tumors, or poorly differentiated NETs, according to the European Society for Medical Oncology 8
External beam radiotherapy may relieve bone pain from metastases, as recommended by the European Society for Medical Oncology 8

Using octreotide in insulinoma patients without confirming octreotide-avidity can precipitously worsen hypoglycemia and result in fatal complications, as warned by the National Comprehensive Cancer Network 1, 2
Failure to perform adequate lymph node dissection during surgery can lead to recurrence, as NETs often have lymph node metastases, according to the National Comprehensive Cancer Network 7
Planned cytoreductive, incomplete (R2) resection of advanced disease in patients with asymptomatic or nonfunctional disease remains controversial, as noted by the National Comprehensive Cancer Network 6
Liver-directed therapies following pancreatoduodenectomy are associated with increased risk for perihepatic sepsis and liver abscess, as warned by the National Comprehensive Cancer Network 6