and low grade typical carcinoids, as well as from pre-invasive lesions diffuse idiopathic neuroendocrine cell hyperplasia (DIPNECH). In 1972, Arrigoni et al described aggressive lung NETs, which they termed leading to the categories of typical versus atypical NETs. This definition ‘atypical’, is still used to describe low grade and intermediate grade lung NETs respectively (8). The prognosis for metastatic NETs is 24-37 months (2). Over the last decade, treatment options have been evolving in an effort to improve patient outcomes including further exploration into targeted therapies such as everolimus, a mammalian target of rapamycin (mTOR) inhibitor. This review will aim to discuss the treatment options for neuroendocrine tumors of the respiratory and gastroenteropancreatic systems, particularly focusing on the therapeutic role of everolimus in this disease group. Treatment of GEP NETs: where does everolimus fit into current guidance The ESMO Clinical Practice Guidelines advise on diagnosis, treatment, and follow up of GEP NET tumors (9). Management of local or locoregional disease should be evaluated in a multidisciplinary team (MDT) setting including an experienced surgeon, and these patients should be considered as candidates for curative surgery. It is generally agreed that grade 3 pancreatic NET patients are not surgical candidates as these tumors are widely metastasized at diagnosis. Cytoreductive surgery may be considered for patients with a diagnosis of metastatic well-differentiated NET if the metastatic disease is localized or if >70% of tumor load is thought to be resectable, although in clinical practice and other studies, surgery is advised against if <90% of the tumor is thought resectable (10). Follow up of trial patients should include biochemical parameters and conventional imaging. options for management of non-resectable or symptomatic gastro-enteric NETs include somatostatin analogues (SSA), chemotherapy, interferon, peptide receptor radiotargeted therapy
and low grade typical carcinoids, as well as from pre-invasive lesions diffuse idiopathic neuroendocrine cell hyperplasia (DIPNECH). In 1972, Arrigoni et al described aggressive lung NETs, which they termed ‘atypical’, leading to the categories of typical versus atypical NETs. This definition is still used to describe low grade and intermediate grade lung NETs respectively (8). The prognosis for metastatic NETs is 24-37 months (2). Over the last decade, treatment options have been evolving in an effort to improve patient outcomes including further exploration into targeted therapies such as everolimus, a mammalian target of rapamycin (mTOR) inhibitor. This review will aim to discuss the treatment options for neuroendocrine tumors of the respiratory and gastroenteropancreatic systems, particularly focusing on the therapeutic role of everolimus in this disease group. Treatment of GEP NETs: where does everolimus fit into current guidance The ESMO Clinical Practice Guidelines advise on diagnosis, treatment, and follow up of GEP NET tumors (9). Management of local or locoregional disease should be evaluated in a multidisciplinary team (MDT) setting including an experienced surgeon, and these patients should be considered as candidates for curative surgery. It is generally agreed that grade 3 pancreatic NET patients are not surgical candidates as these tumors are widely metastasized at diagnosis. Cytoreductive surgery may be considered for patients with a diagnosis of metastatic well-differentiated NET if the metastatic disease is localized or if >70% of tumor load is thought to be resectable, although in clinical practice and other studies, surgery is advised against if <90% of the tumor is thought resectable (10). Follow up of patients should include biochemical parameters and conventional imaging. options for management of non-resectable or symptomatic gastro-enteric NETs include somatostatin analogues (SSA), chemotherapy, interferon, peptide receptor radiotargeted therapy trial
2016_07_29_Future_Oncology_Everolimus_review_manuscript.docx