LECTURES

Diagnostic and Therapeutic Aspects of Handling GPNETs

Partner	Topic of the training	Training description	Proposed duration of the training	Planned date
NKUA	Diagnostic and therapeutic aspects of handling GPNETs	Online course for medical students related to Training in treating patients with GI tumours and Training in surgical operational procedures aiming to treat patients with GI	Online - 1 day / 20-30 persons	2.6.2021 at 15:00 (CET)

Agenda: Download

Introduction to GPNETs – Prof. Georgios Mastorakos

Gastroenteropancreatic neuroendocrine neoplasms (GPNENs) are rare neoplasms arising from the neuroendocrine cells that secrete bioactive substances, in the blood stream causing distinct clinical syndromes. This group of NENs is denoted as functioning NENs; however, the majority of NENs is non-functioning. According to the most recent 2019 WHO classification, the diagnosis of a NEN is based on both its differentiation and proliferative activity, ranging from the well-differentiated neuroendocrine tumours (NETs) of grade G1, G2, or G3, to the poorly differentiated neuroendocrine carcinomas (NECs) G3. The grade in various tumour entities has been categorised based on their Ki-67 level of expression. Their prognosis depends mainly on grading and staging systems but also on the tissue of origin of the primary tumor. Well-differentiated NETs have a prolonged survival in the absence of metastatic disease; however, a subset may display a truly aggressive behavior exhibiting a poor prognosis.

Surgery as a Treatment for GP-NETs - Prof. Christos Dervenis

GEP – Net’s are classified in relation to:
     • Primary Site
     • Functional or Non-Functional
     • Grade
     • TNM Stage
     • Carcinoid Syndrome = in 30% of cases

The role of surgery has as follows:
     • Intention to Treat – Prolong OS
     • Improve QoL – alleviate symptoms from Functional NETs and also sometimes improve OS
     • Prevent or Treat Local Complications

Different types of surgery could be offered:
     • Radical Oncologic Resection
     • Conservative Resection – Enucleations – Organ Preserving
     • Palliative Resection
     • Resection for Local Complications like Bleeding, Obstruction, Pain, Ischaemia (often in Small Bowel NETs)

Metastatic GEP – NETs

      ✔ Liver is almost the only site for a surgical approach in the metastatic disease from GEP NETs.
      ✔ The indications should be taken following a stepwise algorithm which would take into account both the aggressiveness of the disease and the pattern of diffusion into the liver.
      ✔ Since the low level of scientific evidence any decision should be taken only after MDTs discussion.

Therapeutic Spectrum in GPNETs – Dr. Krystallenia Alexandraki

Neuroendocrine neoplasms (NENs) are rare neoplasms and arise mainly in the gastrointestinal or pulmonary system. Most gastroenteropancreatic NENs (GPNENs) are well-differentiated neuroendocrine tumours (GPNETs) with prolonged survival in the absence of metastatic disease; however, a subset may display a truly aggressive behaviour exhibiting a poor prognosis. The grade of differentiation defining tumour’ classification along with advances in immunohistochemistry and functional imaging help to the choice of the treatment. Surgery is the mainstay of treatment of NENs for localized disease with intention to treat or for cytoreduction. In case of locally or regionally advanced or metastatic disease medical treatment is followed. Long-acting somatostatin analogues are the first line treatment for functioning GPNETs in order to control the secretive syndrome but also for non-functioning GPNETs in order to achieve tumour growth stabilization. Other systemic treatments include interferon-α for functioning small bowel NETs, molecular and peptide receptor radionuclide targeted treatments for less aggressive neoplasms, while chemotherapy, and recently immunotherapy, are both reserved for more aggressive neoplasms. New agents such as telotristat are used to control carcinoid syndrome. The appropriate sequence of therapeutic agents is still to be defined, and the choice of monotherapy or combination therapy should be individualized in the context of the site of origin, TNM staging and grading, extension of liver disease, presence of clinical syndrome, patients’ performance status, availability of therapeutic techniques and patient’ choice. Advances in the molecular pathogenesis of NENs and larger prospective studies will shed light on biomolecular tumour markers that may suggest the appropriate sequence of treatment in each individual patient.