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RECIST 1.1 criteria are commonly used with computed tomography (CT) to evaluate the efficacy of systemic treatments in patients with neuroendocrine tumors (NETs) and liver metastases (LMs), but their relevance is questioned in this setting. We aimed to explore alternative criteria using different numbers of measured LMs and thresholds of size and density variation. We retrospectively studied patients with advanced pancreatic or small intestine NETs with LMs, treated with systemic treatment in the first-and/or second-line, without early progression, in 14 European expert centers. We compared time to treatment failure (TTF) between responders and non-responders according to various criteria defined by 0%, 10%, 20% or 30% decrease in the sum of LM size, and/or by 10%, 15% or 20% decrease in LM density, measured on two, three or five LMs, on baseline (≤1 month before treatment initiation) and first revaluation (≤6 months) contrast-enhanced CT scans. Multivariable Cox proportional hazard models were performed to adjust the association between response criteria and TTF on prognostic factors. We included 129 systemic treatments (long-acting somatostatin analogs 41.9%, chemotherapy 26.4%, targeted therapies 31.8%), administered as first-line (53.5%) or second-line therapies (46.5%) in 91 patients. A decrease ≥10% in the size of three LMs was the response criterion that best predicted prolonged TTF, with significance at multivariable analysis (HR 1.90; 95% CI: 1.06–3.40; p =.03). Conversely, response defined by RECIST 1.1 did not predict prolonged TTF (p =.91), and neither did criteria based on changes in LM density. A ≥10% decrease in size of three LMs could be a more clinically relevant criterion than the current 30% threshold utilized by RECIST 1.1 for the evaluation of treatment efficacy in patients with advanced NETs. Its implementation in clinical trials is mandatory for prospective validation. Criteria based on changes in LM density were not predictive of treatment

This ENETS guidance paper for well-differentiated nonfunctioning pancreatic neuroendocrine tumours (NF-Pan-NET) has been developed by a multidisciplinary working group, and provides up-to-date and practical advice on the management of these tumours. Using the extensive experience of centres treating patients with NF-Pan-NEN, the authors of this guidance paper discuss 10 troublesome questions in everyday clinical practice. Our many years of experience in this field are still being verified in the light of the results of new clinical, which set new ways of proceeding in NEN. The treatment of NF-Pan-NEN still requires a decision of a multidisciplinary team of specialists in the field of neuroendocrine neoplasms.

Objective: To evaluate the impact of multidisciplinary team (MDT) meetings on the management of patients with neuroendocrine neoplasms (NENs). Methods: All newly referred gastro-entero-pancreatic (GEP)-NEN patients discussed from 1 April to 1 October 2017 in the MDT of seven European expert centres were prospectively included. The impact on patients' management was defined as a change in diagnosis, grade, stage or treatment. Results: A total of 292 patients were included, mainly small intestinal (siNENs) (32%) and pancreatic NENs (28%), with distant metastases in 51%. Patients had received prior surgery in 43% of cases and prior medical treatment in 32%. A significant change occurred in 61% of NENs: 7% changes in diagnosis, 8% in grade and 16% in stage. The MDT recommended a new treatment for 51% of patients, mainly surgery (9%) or somatostatin analogues (20%). A significant change was most frequently observed in patients with Stage IV disease (hazard ratio [HR] 3.6, 95% confidence interval [CI]: 1.9–6.9 vs. Stage I) and G2 NENs (vs. G1, HR 2.1 95% CI: 1.2–3.8). Conclusion: NEN-dedicated MDT discussion in expert centres yields significant management changes in over 60% of patients and thus represents the gold standard for the management of these patients.

INTRODUCTION: Tumor growth rate (TGR), percentage of change in tumor volume/month, has been previously identified as an early radiological biomarker for treatment monitoring in neuroendocrine tumors (NETs) patients. We assessed the performance and reproducibility of TGR 3 months (TGR3m) as a predictor factor of progression-free survival (PFS), including the impact of imaging method and reader variability. METHODS: Baseline and 3-months (±1month) CT/MRI images from patients with advanced, grade 1-2 NETs were retrospectively reviewed by 2 readers. Influence of number of targets, tumor burden and location of lesion on the performance of TGR3m to predict PFS was assessed by uni/multivariable Cox regression analysis. Agreement between readers was assessed by the Lin's concordance coefficient (LCC) and Kappa (KC). RESULTS: A total of 790 lesions were measured in 222 patients. Median PFS was 22.9 months. On univariable analysis, number of lesions (

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 3(rd)-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, 3(rd)-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 3(rd)-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-67 10%-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 wa

Background: Long-acting somatostatin analogs (SSAs) are the primary first-line treatment of well-differentiated advanced gastroenteropancreatic neuroendocrine tumors (NETs), but data about their efficacy in pancreatic NETs (panNETs) with Ki-67 ≥10% are still limited. Materials and Methods: To assess the clinical outcomes of advanced, nonfunctioning, well-differentiated panNETs with Ki-67 ≥10% receiving first-line long-acting SSAs in a real-world setting, we carried out a retrospective, multicenter study including patients treated between 2014–2018 across 10 centers of the NET CONNECT Network. The primary endpoints were time to next treatment (TNT) and progression-free survival (PFS), whereas overall survival (OS) and treatment safety were secondary endpoints. Results: A total of 73 patients were included (68 grade [G]2, 5 G3), with liver metastases in 61 cases (84%). After a median follow-up of 36.4 months (range, 6–173), the median TNT and PFS were 14.2 months (95% confidence interval [CI], 11.6–16.2) and 11.9 months (95% CI, 8.6–14.1) respectively. No statistically significant difference was observed according to the somatostatin analog used (octreotide vs. lanreotide), whereas increased tumor grade (hazard ratio [HR], 4.4; 95% CI, 1.2–16.6; p =.04) and hepatic tumor load (HR, 2; 95% CI, 1–4; p =.03) were independently associated with shortened PFS. The median OS recorded was 86 months (95% CI, 56.8–86 months), with poor outcomes observed when the hepatic tumor burden was >25% (HR, 3.4; 95% CI, 1.2–10; p =.01). Treatment-related adverse events were reported in 14 patients, most frequently diarrhea. Conclusion: SSAs exert antiproliferative activity in panNETs with Ki-67 ≥10%, particularly in G2 tumors, as well as when hepatic tumor load is ≤25%. Implications for Practice: The results of the study call into question the antiproliferative activity of somatostatin analogs (SSAs) in pancreatic neuroendocrine tumors with Ki-67 ≥10%. Patients with grade 2 tumors an