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Pre-clinical studies have suggested sex hormone signalling pathways may influence tumorigenesis in neuroendocrine neoplasia (NEN). We conducted a retrospective, population-based study to compare overall survival (OS) between males and females with NEN. A total of 14,834 cases of NEN diagnosed between 2012 and 2018, recorded in England’s National Cancer Registry and Analysis Service (NCRAS), were analysed. The primary outcome was OS with 5 years maximum follow-up. Multivariable analysis, restricted mean survival time and mediation analysis were performed. Appendiceal, pulmonary and early-stage NEN were most commonly diagnosed in females; stomach, pancreatic, small intestinal, colonic, rectal and later-stage NEN were more often diagnosed in males. Females displayed increased survival irrespective of the stage, morphology or level of deprivation. On average, they survived 3.62 (95% CI 1.73–5.90) to 10.26 (6.6–14.45) months longer than males; this was statistically significant in NEN of the lung, pancreas, rectum and stomach (p < 0.001). The stage mediated improved survival in stomach, lung, and pancreatic NEN but not in rectal NEN. The reasons underlying these differences are not yet understood. Overall, females diagnosed with NEN tend to survive longer than males, and the stage at presentation only partially explains this. Future research, as well as prognostication and treatment, should consider sex as an important factor.

Somatostatin receptor (SST) PET/CT is the gold standard for well-differentiated neuroendocrine tumours (NET) imaging. Higher grades of neuroendocrine neoplasms (NEN) show preferential [18F]FDG (FDG) uptake, and even low-grade NET may de-differentiate over time. FDG PET/CT's prognostic role is widely accepted; however, its impact on clinical decision-making remains controversial and its use varies widely. A questionnaire-based survey on FDG PET/CT use and perceived decision-making utility in NEN was submitted to the ENETS Advisory Board Meeting attendees (November 2022, response rate = 70%). In 3/15 statements, agreement was higher than 75%: (i) FDG was considered useful in NET, irrespective of grade, in case of mis-matched lesions (detectable on diagnostic CT but negative/faintly positive on SST PET/CT), especially if PRRT is contemplated (80%); (ii) in NET G3 if curative surgery is considered (82%); and (iii) in NEC prior to surgery with curative intent (98%). FDG use in NET G3, even in the presence of matched lesions, as a baseline for response assessment was favoured by 74%. Four statements obtained more than 60% consensus: (i) FDG use in NET G3 if locoregional therapy is considered (65%); (ii) in neuroendocrine carcinoma before initiating active therapy as a baseline for response assessment (61%); (iii) biopsy to re-assess tumour grade prior to a change in therapeutic management (68%) upon detection of FDG-positivity on the background of a prior G1-2 NET; (iv) 67% were in favour to reconsider PRRT to treat residual SST-positive lesions after achieving complete remission on FDG of the SST-negative disease component. Multidisciplinary opinion broadly supports the use of FDG PET/CT for characterisation of disease biology and to guide treatment selection across a range of indications, despite the lack of full consensus in many situations. This may reflect existing clinical access due to lack of reimbursement or experience with this investigation, which should be

Background: This European Neuroendocrine Tumor Society (ENETS) Expert Consensus document aims to provide practical guidance and standardization for echocardiography in the screening and follow-up of carcinoid heart disease (CHD) in patients with a neuroendocrine tumour (NET) and carcinoid syndrome. Methods: NET experts within the ENETS Carcinoid Heart Disease Task Force reviewed both general reporting guidelines and specialized scoring systems for transthoracic echocardiography (TTE) in CHD. Based on this review, a dedicated template report was designed by the multidisciplinary working group of cardiologists, oncologists, endocrinologists, gastroenterologists, surgeons and radiologists. Results: We propose a Synoptic Reporting of Echocardiography in Carcinoid Heart Disease which represents an agreed peer reviewed proforma to capture information at the time of referral and enable a detailed outcome of CHD assessment. This includes a systematic and detailed list of structures to evaluate data to capture at the time of reporting of TTE. Conclusions: Adherence to these reporting guidelines aims to promote homogeneous and detailed evaluation of CHD to secure accurate assessment and allow comparison of studies performed intra- and inter-individually. These guidelines could also facilitate CHD assessment as part of prospective clinical trials to enable standardization of the findings seen in response to therapy.

We report the impact of 177Lu-DOTATATE treatment on abdominal pain, diarrhea, and flushing, symptoms that patients with advanced midgut neuroendocrine tumors often find burdensome. Methods: All patients enrolled in the international randomized phase 3 Neuroendocrine Tumors Therapy (NETTER-1) trial (177Lu-DOTATATE plus standard-dose octreotide long-acting repeatable [LAR], n = 117; high-dose octreotide LAR, n = 114) were asked to record the occurrence of predefined symptoms in a daily diary. Change from baseline in symptom scores (mean number of days with a symptom) was analyzed using a mixed model for repeated measures. Results: Patients (intent-to-treat) who received 177Lu-DOTATATE experienced a significantly greater decline from baseline in symptom scores than patients who received high-dose octreotide LAR. For 177Lu-DOTATATE, the mean decline in days with abdominal pain, diarrhea, and flushing was 4.10, 4.55, and 4.52 d per 4 wk, respectively, compared with 0.99, 1.44, and 2.54 d for high-dose octreotide LAR. The mean differences were 3.11 d (95% CI, 1.35–4.88; P = 0.0007) for abdominal pain, 3.11 d (1.18–5.04; P = 0.0017) for diarrhea, and 1.98 d (0.08–3.88; P = 0.0413) for flushing, favoring 177Lu-DOTATATE. A positive repeated-measures correlation was found between diary-recorded symptom scores and questionnaire-recorded pain, diarrhea, and flushing. Conclusion: In addition to efficacy and quality-of-life benefits, symptom diaries from NETTER-1 demonstrated that treatment with 177Lu-DOTATATE was associated with statistically significant reductions in abdominal pain, diarrhea, and flushing, constituting the core symptoms of patients with progressive midgut neuroendocrine tumors, compared with high-dose octreotide LAR, supporting a beneficial effect of 177Lu-DOTATATE on health-related quality of life., Title in Web of Science: Symptom Diaries of Patients with Midgut Neuroendocrine Tumors Treated with Lu-177-DOTATATE

We report the impact of 177Lu DOTATATE treatment on abdominal pain, diarrhea, and flushing, symptoms that patients with advanced midgut neuroendocrine tumors (NETs) often find burdensome. Methods: All patients enrolled in the international randomized phase 3 Neuroendocrine Tumors Therapy (NETTER-1) trial (177Lu-DOTATATE plus standard-dose octreotide long-acting repeatable [LAR], n = 117; high-dose octreotide LAR, n = 114) were asked to record the occurrence of predefined symptoms in a daily diary. Change from baseline in symptom scores (mean number of days with a symptom) was analyzed using a mixed model for repeated measures. Results: Patients (intent-to-treat) who received 177Lu-DOTATATE experienced a significantly greater decline from baseline in symptom scores than patients who received high-dose octreotide LAR. For 177Lu-DOTATATE, the mean decline in days with abdominal pain, diarrhea, and flushing was 4.10, 4.55, and 4.52 days per 4 weeks, respectively, compared with 0.99, 1.44, and 2.54 days for high-dose octreotide LAR. The mean differences were 3.11 days (95% confidence interval, 1.35-4.88; P = 0.0007) for abdominal pain, 3.11 days (1.18-5.04; P = 0.0017) for diarrhea, and 1.98 days (0.08-3.88; P = 0.0413) for flushing, favoring 177Lu-DOTATATE. A positive repeated measures correlation was found between diary-recorded symptom scores and questionnaire-recorded pain, diarrhea, and flushing. Conclusion: In addition to efficacy and quality of life benefits, symptom diaries from NETTER-1 demonstrated that treatment with 177Lu DOTATATE was associated with statistically significant reductions in abdominal pain, diarrhea, and flushing, constituting the core symptoms of patients with progressive midgut NETs, compared with high-dose octreotide LAR, supporting a beneficial effect of 177Lu DOTATATE on HRQoL.

Purpose To assess the impact of baseline liver tumour burden, alkaline phosphatase (ALP) elevation, and target lesion size on treatment outcomes with Lu-177-Dotatate. Methods In the phase 3 NETTER-1 trial, patients with advanced, progressive midgut neuroendocrine tumours (NET) were randomised to 177Lu-Dotatate (every 8 weeks, four cycles) plus octreotide long-acting release (LAR) or to octreotide LAR 60 mg. Primary endpoint was progression-free survival (PFS). Analyses of PFS by baseline factors, including liver tumour burden, ALP elevation, and target lesion size, were performed using Kaplan-Meier estimates; hazard ratios (HRs) with corresponding 95% CIs were estimated using Cox regression. Results Significantly prolonged median PFS occurred with Lu-177-Dotatate versus octreotide LAR 60 mg in patients with low (< 25%), moderate (25-50%), and high (> 50%) liver tumour burden (HR 0.187, 0.216, 0.145), and normal or elevated ALP (HR 0.153, 0.177), and in the presence or absence of a large target lesion (diameter > 30 mm; HR, 0.213, 0.063). Within the Lu-177-Dotatate arm, no significant difference in PFS was observed amongst patients with low/moderate/high liver tumour burden (P = 0.7225) or with normal/elevated baseline ALP (P = 0.3532), but absence of a large target lesion was associated with improved PFS (P = 0.0222). Grade 3 and 4 liver function abnormalities were rare and did not appear to be associated with high baseline liver tumour burden. Conclusions Lu-177-Dotatate demonstrated significant prolongation in PFS versus high-dose octreotide LAR in patients with advanced, progressive midgut NET, regardless of baseline liver tumour burden, elevated ALP, or the presence of a large target lesion. : NCT01578239, EudraCT: 2011-005049-11

PurposeTo assess the impact of baseline liver tumour burden, alkaline phosphatase (ALP) elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate.MethodsIn the phase 3 NETTER-1 trial, patients with advanced, progressive midgut neuroendocrine tumours (NET) were randomised to 177Lu-Dotatate (every 8 weeks, four cycles) plus octreotide long-acting release (LAR) or to octreotide LAR 60 mg. Primary endpoint was progression-free survival (PFS). Analyses of PFS by baseline factors, including liver tumour burden, ALP elevation, and target lesion size, were performed using Kaplan-Meier estimates; hazard ratios (HRs) with corresponding 95% CIs were estimated using Cox regression.ResultsSignificantly prolonged median PFS occurred with 177Lu-Dotatate versus octreotide LAR 60 mg in patients with low (< 25%), moderate (25-50%), and high (> 50%) liver tumour burden (HR 0.187, 0.216, 0.145), and normal or elevated ALP (HR 0.153, 0.177), and in the presence or absence of a large target lesion (diameter > 30 mm; HR, 0.213, 0.063). Within the 177Lu-Dotatate arm, no significant difference in PFS was observed amongst patients with low/moderate/high liver tumour burden (P = 0.7225) or with normal/elevated baseline ALP (P = 0.3532), but absence of a large target lesion was associated with improved PFS (P = 0.0222). Grade 3 and 4 liver function abnormalities were rare and did not appear to be associated with high baseline liver tumour burden.Conclusions177Lu-Dotatate demonstrated significant prolongation in PFS versus high-dose octreotide LAR in patients with advanced, progressive midgut NET, regardless of baseline liver tumour burden, elevated ALP, or the presence of a large target lesion. Clinicaltrials.gov : NCT01578239, EudraCT: 2011-005049-11.

BACKGROUND/AIMS: Long-term outcomes are understudied in patients with well-differentiated appendiceal neuroendocrine neoplasms (WD-ANENs). We aimed to evaluate the validity of currently applied criteria for completion prophylactic right hemicolectomy (pRHC) and determine its association with patient outcomes, including health-related quality of life (HRQoL). METHODS: Eligible patients from five European referral centers were divided between those who underwent appendectomy alone and those who underwent completion pRHC. HRQoL EORTC-QLC-C30 questionnaires and cross-sectional imaging data were prospectively collected. Age- and sex-matched healthy controls were recruited for HRQoL analysis' validation. RESULTS: We included 166 patients (119 women [71.2%]: mean age at baseline: 31 ± 16 years). Mean follow-up was 50.9 ± 54 months. Most patients (152 [92%]) had tumors ≤20 mm in size. Fifty-eight patients (34.9%) underwent pRHC that in final analysis was regarded as an overtreatment in 38/58 (65.5%). In multivariable analysis, tumor size >20 mm was the only independent predictor for lymph node (LN) involvement (p = 0.002). No mortality was reported, whereas 2-, 5- and 10-year recurrence-free survival in patients subjected to postoperative cross-sectional imaging (n = 136) was 98.5%, 97.8%, and 97.8%, respectively. Global HRQoL was not significantly impaired in patients with WD-ANEN compared with age- and sex-matched healthy individuals (median scores 0.83[0.08-1] vs 0.83[0.4-1], respectively; p = 0.929). Among patients with WD-ANEN impaired social functioning (p = 0.016), diarrhea (p = 0.003) and financial difficulties (0.024) were more frequently reported in the pRHC group. CONCLUSIONS: WD-ANEN is a low-malignant neoplasm with unconfirmed associated mortality, low recurrence rate, and overall preserved HRQoL. pRHC comes at a price of excessive surgery, functional HRQoL issues, and diarrhea. The value per se of a prophylactic surgical approach to patients with WD-ANENs &