Advanced small-bowel well-differentiated neuroendocrine tumours:An international survey of practice on 3rd-line treatment

BACKGROUND Somatostatin analogues are an established first-line therapy for well differentiated small bowel neuroendocrine tumours(Wd-SBNETs),while and peptide receptor radionuclide therapy(PRRT)is frequently used as a second-line therapy.Adequate treatment selection of third-line treatment remains challenging due to the limited prospective data currently available on the best therapeutic sequence.AIM To understand current practice and rationale for decision-making by physicians in the 3rd-line setting by building an online survey.METHODS Weighted average(WA)of likelihood of usage between responders(1 very unlikely;4 very likely)was used to reflect the relevance of factors explored.RESULTS Replies from representatives of 28 centers were received(5/8/2020-21/9/2020);medical oncologist(53.6%),gastroenterologist(17.9%);United Kingdom(21.4%),Spain(17.9%),Italy(14.3%).Majority from European Neuroendocrine Tumor Society(ENETS)Centres of Excellence(57.1%),who followed ENETS guidelines(82.1%).Generally speaking,3rd-line treatment for Wd-SBNETs was:everolimus(EVE)(66.7%),PRRT(18.5%),liver embolization(LE)(7.4%)and interferon-alpha(IFN)(3.7%);chemotherapy(0%);decision was based on clinical trial data(59.3%),or personal experience(22.2%).EVE was most likely used if Ki-67<10%(WA 3.27/4)or age<70 years(WA 3.23/4),in the 3rd-line setting(WA 3.23/4);regardless of presence/absence of carcinoid syndrome(CS),rate of progression or extent of disease.Chemotherapy was mainly utilised only if rapid progression(within 6 mo)(WA 3.35/4),Ki-6710%-20%(WA 2.77/4),negative somatostatin receptor imaging(WA 2.65/4)or high tumour burden(WA 2.77/4);temozolomide or streptozocin was used with capecitabine or 5-fluorouracil(5-FU)(57.7%),FOLFOX(5-FU combined with oxaliplatin)(23.1%).LE was selected if presence of CS(WA 3.24/4)or Ki-67<10%(WA 2.8/4),after progression to other treatments(WA 2.8/4).IFN was rarely used(WA 1.3/4).CONCLUSION Everolimus was the most frequently used therapeutic option in the third-line setting.The most important factors for decision-making included Ki-67,rate of progression,functionality and tumour burden;since this decision is based on multiple factors,it highlights the need for a multidisciplinary assessment.

Review of recent advances in medical treatment for neuroendocrine neoplasms:somatostatin analogs and chemotherapy

Neuroendocrine neoplasms(NENs)are a heterogeneous group of rare tumours often producing high levels of hormones and causing symptoms.There are a number of different types of NENs.They usually arise as advanced and low/intermediate grade only in a minority of cases,as high grade.Treatment depends on which type and may include surgery,interventional radiology,and systemic treatment,including chemotherapy,somatostatin analogs,interferonα2b,peptide receptor radionuclide therapy,and only for pancreatic neuroendocrine tumors,molecular targeted agents,including everolimus and sunitinib.The aim of the article is to review the medical approaches with somatostatin analogs and chemotherapy.The treatment of NENs is mainly based on their biological characteristics of aggressiveness and functional features,such as symptoms and endocrine markers.