Neuroendocrine Tumor

 Neuroendocrine tumor

• Site of origin
• Ki 67
• Mitoses
• Stage
• Differentiation

Pearls:

1. NETs are well differentiated, NEC are poorly differentiated.
2. All poorly differentiated NECs are grade 3, but not all Grade 3 are poorly differentiated. Therefore 2017 update included a more indolent Grade 3 tumor that is classified under NET rather than NEC.
3. Prognostic factors in survival-- LN and distant Mets, but not the T size.
4. The classification for lung and thymus NET differ from GI-Panc. The former includes necrosis but not Ki 67
5. Pancreatic NET metastatic 5 yr OS < 20%
6. No single biomarker as yet diagnostic, predictive or prognostic
7. Bronchial and thymic NET may cause Cushing's
8. NET in small intestine and appendix when metastatic to the liver or retroperitoneum can cause carcinoid syndrome
9. Genetic testing if lung, thymic NET, adrenal, paraganglioma, pheochromocytomas, parathyroid adenoma before age 30
10. 24 hr urine HIAA for carcinoid screening in symptomatic individuals.

Management of Loco regional disease: 

Resection is the mainstay. Although hormone hypersecretion is more common with mets, it can be seen in localized disease and can use octreotide and lanreotide

Grade 1 NET Less than 1 cm

• Gastric: observation, endoscopic FU
• Pancreatic NF- observation, 
• Rectal: endoscopic resection

Grade 1 NET 1-2 cm

• Gastric: Endoscopic resection
• Colon: Curative resection, polypectomy
• Rectal-curative local resection

Grade 2/3, > 2 cm

• Gastric: Total gastrectomy, LN dissection
• Colon: resection and hemicolectomy+ LN dissection
• Pancreatic NF:  pancreatic-duodenectomy+ splenectomy
• Pancreatic functional- Debulking surgery
• Rectal: TME+ LN dissection
• Small bowel - resection +LN dissection, if terminal ileum hemicolectomy

Gastric NET if > 2cm, angioinvasion,higher grade 2/3--> gastrectomy+LN

Type 2 Gastric NET associated with ZE syndrome, high gastrin levels. Antrectomy not useful. Need PPI.  Remove the gastrinoma, likely in the duodenum.

Thymic NET- stage I, II, III A/B --resection if neg margins, no adjuvant therapy.

• Somatostatin analogs are the typical first systemic therapy for GEP-NETs and primarily lead to disease stabilization. ¹⁷⁷Lu-dotatate combined with a somatostatin analog is an option for patients with somatostatin receptor (SSTR)–positive higher-grade GEP-NETs (Ki-67 >10%).
• ¹⁷⁷Lu-dotatate is a second-line option for patients with SSTR-positive GEP-NETs and is the preferred second-line systemic option for most patients with a history of carcinoid syndrome/small bowel primary tumors. Contraindicated if significant peritoneal disease.
• Everolimus can be used as a second-line therapy, particularly in patients who do not qualify for ¹⁷⁷Lu-dotatate. This is approved in pancreatic NET, non functional mid gut and lung NET.
• Capecitabine/temozolomide (CAPTEM) is an active regimen for progressive pancreatic NETs and can be used in grade 3 NETs of different primary sites. This is not useful in small bowel NET except as a last resort.