ESMO guidelines GEP NET

 Reference: ESMO guidelines

Localized or locoregional

1. G1/G2 NET if local or locoregional-- surgery

2. Functional NET- need symptom control before resection.

3. Pancreatic NET:

    a. If functional, needs resection even if small

    b. If non functional and less than 2 cm, if no symptoms, ok to observe.

    c. If resectable, even if liver Mets, or if primary is resectable , the aim should be to resect. If on the other hand, Ki 67 is > 10% and tumor growth is quick, do medical treatment first, then reassess if resectable.

    d. If pancreatic NET < 2 cm, enucleation may suffice but if > 2 cm pancreato-duodenectomy +LN dissection or splenectomy depending on location is appropriate.

    e. The presence of other high-risk features (e.g. large tumour size and/or high-grade Pan-NEC G3) should discourage an upfront surgical approach. Despite the lack of evidence, in selected patients with high-risk features, a neoadjuvant treatment may be considered. The role of surgery for localised Pan-NEC G3 is still controversial, as upfront surgery may not have a clear benefit in terms of survival.

4. SI NET- resect when possible, palpate for multiple primaries, remove at least 8 LN. Surgery should be considered in all situations except in widely metastatic ( outside liver) and fast growing ie Ki 67 > 10%.

5. Adjuvant therapy only if respected G3 NEC with platinum doublet.

Management of advanced disease

1. Surgery is indicated in stage IV GEP-NETs who have exclusive or predominant liver involvement, after having carefully evaluated the tumour grading, distribution of LMs and primary site 

2. No upfront surgery if extra abdominal Mets, and G3 NEC.

3.  curative resection (R0, R1) of GEP-NETs with liver mets is associated with a 5-year overall survival (OS) rate of around 85%.

4. If pt has advanced SI-NET, the role of prophylactic resection of the primary small intestinal tumor is controversial. No role in survival but may prevent bowel obstruction and or ischemia.

Medical therapy

1.  Octreotide, Lanreotide standard dose q 4 weeks, change to q 2-3 weeks if symptoms not controlled. Can use short acting octreotide for breakthrough symptoms.

2.  Pasireotide LAR off label ( approved for acromegaly) and IFN alpha can be used.

3. Telotristat ethyl (250 mg t.i.d.) is approved for treatment of diarrhoea associated with CS in patients insufficiently controlled with SSA and can be recommended for this indication as an add-on treatment to SSA 

5. Role of Debulking surgery is also not clear- can be undertaken in carcinoid with symptoms (after SSA to control symptoms) and also in NF SI NET if symptoms due to the disease bulk.

6. Liver transplantation may be a valid option in very selected patients with unresectable LMs when the following criteria are met: absence of extrahepatic disease, histological confirmation of a well-differentiated (G1/G2, Ki-67 <10%) NET, previous removal of primary tumour, metastatic diffusion <50% of the total liver volume, stable disease in response to therapy for at least 6 months before transplant consideration and age <60 years [IV, B].20 In these selected patients with good baseline prognostic factors, a 5-year OS of 69%–97.2% has been reported.46 Liver transplantation is preferably considered in patients with functioning tumours (CS refractory to systemic therapies due to high liver tumour burden and in those affected by SI-NETs who usually exhibit a more favourable prognosis). Liver transplantation should be thoroughly discussed within a NET-dedicated multidisciplinary team, carefully considering all the alternative therapeutic options.