Endocrine Abstracts

Bladder Paragangliomas (PGLs) are a rare manifestation of sympathetic chain PGLs and occur in prone patients with SDH mutation.They often display an aggressive phenotype with metastatic disease and require long-term follow up. SDHB immunostaining plays a significant role in initial risk stratification and facilitating appropriate genetic testing. We report four cases illustrating diagnostic management and outcome issues in this rare neuroendocrine pathology; two with SDHB muta...

Background: There is currently no effective blood biomarker for lung neuroendocrine neoplasia diagnosis and management. We describe the clinical utility of a 51 neuroendocrine-specific gene expression set in blood to diagnose bronchopulmonary neuroendocrine tumors (BPNETs) and define their clinical status.Methods: The discovery set included BPNETs (n=154) and controls (n=90), randomly assigned (1:1) to a test and validation set. Specifi...

Background: Peptide receptor radionuclide therapy (PRRT) is based on tumor somatostatin receptor (SSR) overexpression to deliver targeted isotope therapy. Functional imaging of SSR expression (SRE) is used as a predictor of efficacy, but there is no method to objectively predict PRRT efficacy. We report the efficacy of Predictive Quotient Index (PQI) to predict the utility of PPRT. PQI is derived from circulating NET transcript analysis (NETest) integrated with the tu...

Background: No effective blood biomarker exists to detect and clinically manage bronchopulmonary (BP) neuroendocrine tumors. We developed a blood-based 51 neuroendocrine tumor (NET)-specific transcript set to diagnose and monitor gastroenteropancreatic NETs. In this study, we examined whether the signature functioned in lung NETs. Thereafter, we examined performance metrics to assess clinical utility. The multianalyte gene signature accurately diagnosed the tumor and in additi...

SDH mutations that contribute 15%–20% of PCC/PGL syndromes predispose to the development of tumours that originate from Adrenal, Parasympathetic and extra-adrenal sympathetic-associated chromaffin tissues. We conducted a retrospective analysis to identify the prevalence of PCC/PGL and elevated biomarkers during initial screening in patients newly identified as carrying a pathogenic SDH mutation.Method: Data collection from our random cohort of patie...

Introduction: Neuroendocrine tumours (NETs) have diverse natural history and clinical syndromes. As a result of the disease or related to management, patients may have altered gut or pancreatic function that can cause nutritional deficiencies. There is a lack of consistent evidence-based dietetic guidance for patients with NETs.Aim: This study evaluated whether nutritional status and nutritional deficiencies had been assessed in patients with NETs in an ...

Background: The median survival for patients with metastatic neuroendocrine tumours is greater than 5 years. Despite a heavy burden of metastatic disease and an incurable diagnosis many patients continue with a relatively normal lifestyle. Vast amounts of time and money is spent on diagnosing and treating the physical aspects of cancer but little is currently available to help with the psychological wellbeing of our patients. As NET nurses we spend large amounts of our time ta...

The number of people diagnosed and living with cancer in the UK continues to rise and this also places increasing demands on specialist cancer care services (NHS England 2015). Neuroendocrine Tumours (NETs) incidence and prevalence increases alongside this demand (PHE 2016). NETs still remain a rare cancer with specialist needs and the clinical nurse specialist (CNS) team are ideally placed to support these patients. Oncology clinics are becoming increasingly pressured and the...

The South Wales regional NET Multidisciplinary Meeting (MDT) discusses patients on a monthly basis. The European Neuroendocrine Tumour Society (ENETS) have guidance on expected pathology input into a NET MDT service. We assessed pathology reports submitted and discussed in 2016 for compliance with ENETS criteria, and determined the time from pathology reporting to MDT discussion. 117 patients had pathology submitted for review in 2016 and were assessed by one specialist NET pa...

Background: Neuroendocrine tumours (NETs) and carcinomas (NECs) are a heterogenous group of malignancies, with no common clinical pathway, but previous study has highlighted a common need for effective, well-timed support. There is geographic variation in the availability and provision of specialist NET cancer services across the UK and this is reflected in the diverse patient experiences reported.Service improvement: To improve the patients journey, the...

Introduction: Close long-term follow-up of patients with pulmonary carcinoid (PC) tumours is important for detection of recurrence, which can occur many years after primary surgery. Expert consensus guidelines for management of PC were published in 2015 (European Neuroendocrine Tumor Society (ENETS)) and provide recommendations for follow-up type, frequency and duration. The LEAP Project aimed to describe current follow-up practices in the UK following publication of the guida...

Introduction: Accurate survival data for patients with neuroendocrine tumours (NETs) across the UK has been difficult to capture. Individual centres often report good survival rates, however, national data has not previously been available.Materials and methods: NET patient survival was calculated for England using the Public Health England (PHE) National Cancer Registration and Analysis Service (NCRAS) dataset which captures tumour stage using TNM stagi...

Introduction: Historically there has been an association with neuroendocrine tumours (NETs) and other cancers. However, this has not previously been well characterised. We aimed to determine the incidence of second malignancies in patients with NETs and investigate any association of the anatomical site of NETs with other malignancies.Materials and methods: 12,844 patients were diagnosed with a NET between 2013 and 2015 and captured by the National Cance...

Background: The phase III, placebo-controlled, randomized TELESTAR study evaluated efficacy and safety of telotristat ethyl (TE) in patients (pts) with diarrhoea (≥4 bowel movements (BMs)/day) due to carcinoid syndrome (CS) inadequately controlled by somatostatin analogs (SSAs). TE, a tryptophan hydroxylase inhibitor, decreases peripheral serotonin levels. As add-on treatment to SSAs, TE 250 mg 3x/day (tid) and TE 500 mg tid significantly reduced BM frequency (P...

Introduction: Platinum-etoposide chemotherapy is a globally established chemotherapy combination for EP-G3-NEC. However, there are many different schedules for such chemotherapy, and the preferred one for EP-G3-NEC has not been established.Methods: An international survey was created, and completed by colleagues with an expertise in the field of neuroendocrine neoplasms. The aim was to explore which schedules of platinum-etoposide chemotherapy are used a...

Background: The safety and efficacy of telotristat ethyl (TE) in patients (pts) with metastatic neuroendocrine tumors (NETs) and carcinoid syndrome (CS) not adequately controlled with somatostatin analogs (SSAs) have been demonstrated. TE-treated pts showed significantly greater reductions in bowel movement (BM) frequency and more presented with durable response than placebo (PBO)-treated pts. These post-hoc analyses examined the relationship between improvements in symptoms a...

Background: Neuroendocrine tumours of the appendix (ANET) are relatively indolent tumours typically identified incidentally at surgery for suspected appendicitis. The role of right hemicolectomy (RH) for tumours with ‘high risk’ features is debated. We compared the management of ANET at three centres against ENETS criteria for therapy selection.Methods: Retrospective review of all patients diagnosed with ANET at three tertiary centres. Patients...

Background: Bone metastases have been described in up to 15% of patients with NETs and are associated with a worse clinical outcome. Here we investigate the role of CTCs as a marker of bone metastases in a large cohort of patients with gastroenteropancreatic NETs.Methods: To be eligible for the study, patients were required to be ≥ 18 years old, have histologically confirmed midgut or pancreatic NET (pNET) and metastatic disease measurable by RECIS...

Introduction: MANEC is a rare diagnosis and little is known on its epidemiology/prognosis/management.Methods: Demographic/clinical-pathological/survival data of patients with a diagnosis of MANEC (2010 WHO criteria) from five European centres were retrospectively reviewed.Results: Sixty-six patients were identified (09/80–07/17); median age: 62.5 years (range 34–89); male: 66.7%; ECOG-PS 0-1: 59%; primary tumours from: sm...

Introduction: To prevent loco-regional recurrence and subsequent development of distant metastases in Appendiceal Neuro-Endocrine Neoplasms (ANEN), the existing Guidelines have suggested several criteria for a prophylactic right hemicolectomy, following the initial appendectomy. However, some of those criteria seem rather arbitrary and have not been validated by large studies.Aim: To assess the outcomes of prophylactic right hemicolectomy (RHC), focusing...

Introduction: Platinum-etoposide is considered standard-of-care first-line treatment for patients diagnosed with advanced EP-PD-NECs. The optimal platinum-etoposide schedule remains undefined; carboplatin is often substituted for cisplatin, although quality data is lacking.Methods: Electronic records of patients with advanced EP-PD-NEC treated with carboplatin-etoposide (06/09-02/17) were reviewed retrospectively, with aim to provide real-life efficacy/s...

Introduction: High doses/frequency of somatostatin analogues (SSA) are often used to control refractory functional symptoms and/or tumour progression in patients treated with standard doses of SSAs, but there is limited evidence for the efficacy of this strategy.Methods: Retrospective analysis of 47 NET patients on lanreotide Autogel 120 mg every 3 weeks (as monotherapy). Progression-free survival (PFS) and clinical outcomes were assessed. A 30% change i...

Introduction: Escalated doses of octreotide LAR are commonly used to control functional symptoms and/or tumour growth, but there is limited evidence regarding the efficacy of this approach.Methods: Retrospective analysis of 69 NET patients treated with octreotide LAR 30 mg every 3 weeks (as monotherapy). Progression-free survival (PFS) and clinical outcomes were assessed. A 30% change in symptomatology and biomarker levels was considered significant....

Background: Small-bowel neuroendocrine tumours (SB-NET) commonly metastasise despite most being low grade. The NET nomogram developed, estimates 5- and 10-year survival in SB-NET by allocating scores for 15 clinicopathological parameters. We comparatively evaluated the prognostic power of this nomogram, the WHO/ENETS grading and AJCC/UICC staging systems.Methods: Patients with histologically-confirmed SB-NET were identified from databases at two tertiary...

Vitamin D (vit-D) deficiency is common in patients with gastro-entero-pancreatic neuroendocrine tumours (GEP-NET) and has been linked to reduced survival in these patients. Vit-D status was assessed in 183 patients with GEP-NET, at the time of their first presentation in the ARDEN-NET-Centre; and following simple advice at routine 6-monthly follow-up appointments to increase vit-D intake using over-the-counter vit-D preparations (Colecalciferol (Vit-D3), 1000–2000 units/d...

Background: The presence of liver metastases is a poor prognostic factor in patients with Neuroendocrine tumours (NET). Resection of NET liver metastases (NET mets) has been reported to be associated with good long-term outcomes but must be balanced against the risks of major surgery. Thermal ablation or arterial embolisation offers an alternative to surgery.Objective: To review the outcomes of radical treatment of NET mets.Materia...

Background: Gastrointestinal (GI) neuroendocrine tumours (NETs) are potentially malignant lesions originating from the enterochromaffin cells of the GI tract. These neoplasms often produce characteristic hormonal syndromes and can cause debilitating symptoms. Endoscopic submucosal dissection (ESD) is a well-established, complex, endoscopic technique, which allows for full resection of the mucosal and submucosal lesions without the need for open surgery.M...

Introduction: Duodenal neuro endocrine tumors (d-NETs) comprise about 2% of all NETs. Treatment of d-NETs involves resection of the tumour either by endoscopic or surgical resection. Local resection of the lesion is usually a safer option compared to a more radical pancreaticoduodenectomy. However, inadequate clearance by local resection might result in recurrent disease and reduce the overall survival. There is no current available evidence regarding the extent of resection.<...

Background: Pulmonary-NETs are classified in low-grade typical carcinoid (TC), intermediate-grade atypical carcinoid (AC), and high-grade large cell carcinoma (LCNEC) and small cell carcinoma (SCLC). However, the proportion of pulmonary-NETs with similar histology that behave quite differently is not negligible. Recent studies favour the use of the proliferation marker Ki67.Aim: To evaluate the utility of Ki67 for predicting metastasis in a cohort of pat...

Somatostatin analogues (SSAs) are regularly used in the treatment of neuroendocrine tumours (NETs) to control the symptoms of hormonal hypersecretion. Evidence shows that SSAs can reduce tumour progression, and are therefore also being used in patients with non-functioning tumours. As many NETs present with advanced disease curative therapy is often not possible; therefore, assessing the impact of therapy on quality of life (QoL) is vital to patient management. This is particu...

Background: Although small bowel (SB) neuroendocrine tumours (SBNETs) often present as indolent lesions, late diagnosis may result in poor outcomes. Successful management is therefore dependent on early identification. Double-balloon enteroscopy (DBE) enables direct SB mucosal visualisation, sampling and endotherapy. Our aim was to evaluate the role of DBE for early diagnosis and management of SBNETs.Methods: Retrospective review of all SBNETs diagnosed/...

Objective: To compare 3 methods of generating Ki-67% in gastroenteropancreatic neuroendocrine tumours (GEP-NETs).Methods: Twenty-four slides were used to generate 49 images for analysis. Each image was analysed and 3 different methods were used to calculate Ki-67%.Results: The comparison of Ki-67% from counting and estimating using the diameter (shortcut method) was strongly positively correlated, whereas the Ki-67% from counting a...

Case presentations: Case 1: The index case is a 10 year old girl who presented episodic symptoms of feeling unwell, unexplained headache, seizure, vomiting and dehydration over a period of 8 months. She was subsequently found to have systemic hypertension which led to further investigations revealing raised plasma noradrenaline of 32 and 103.7 (NR 0–5 nmol/). US abdomen suggested bilateral pheochromocytoma but an MIBG showed unilateral left sided increased uptake. She und...

Introduction: Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin receptor (SSTR) agonists is highly effective and has become an integral part of neuroendocrine tumour (NET) treatment. However, tumour uptake and tumour-to-tissue dose ratios may be higher with radiolabelled SSTR antagonists than agonists. OPS201 (DOTA-JR11) is a very promising next-generation SSTR antagonist selective for SSTR2 (expressed by NETs). This phase 1/2, international, single-...

Choroidal metastases were first reported by Perls in 1872. The choroid is the most common ocular site for metastatic disease due to the abundant blood supply. Bilateral lesions are commonly associated with breast carcinoma (40–47%) and unilateral with lung (21–29%). Treatment frequently depends on the patient status but includes observation, systemic chemotherapy, immunotherapy, hormone therapy, radiotherapy, plaque therapy, or photodynamic therapy. Neuroendocrine tu...

Neuroendocrine tumours are rare, with an incidence of 8/100,000 in the UK. They result from excessive proliferation of neuroendocrine cells and are classified based on their site of origin, differentiation and clinical syndrome. Giant cell arteritis (GCA), a systemic vasculitis of unknown aetiology, rarely appears as a paraneoplastic syndrome. It is histologically characterised by granulomatous infiltrates with multinucleated giant cells at the intima media junction. The relat...

Introduction: Carcinoid crisis is a life threatening endocrine emergency. It remains unclear whether there is an optimal dose of prophylactic somatostatin analogue (SSA) therapy in the peri-operative periodCase Study: A 62 year old lady with a new diagnosis of metastatic carcinoid disease was electively admitted for a right hemicolectomy for a well differentiated neuroendocrine tumour in the terminal ileum. A multi-disciplinary decision was made to offer...

A case is reported of a man with stage IV grade 2 pancreatic VIPoma. At diagnosis he had several features which may have expedited the diagnosis including refractory diarrhoea containing undigested foodstuffs, alcohol-related flushing, electrolyte abnormalities and intestinal oedema on imaging. Symptom control was challenging. There was no benefit from creon, loperamide or codeine and escalation to both short and long acting somatostatin analogues was futile. Consistent with a...

Somatostatin analogues (SSA) have an established role in the medical management of patients with neuroendocrine tumours (NETs). They are effective in the symptomatic treatment of some metastatic NETs and may also provide tumour stabilisation or reduction. We report two patients with disease progression who benefited from SSA. Mrs HW, 64-year old woman, was diagnosed with a grade 1 small-bowel NET with lymph node and liver metastasis in 2012: Ki-67 index < 1%. Despite a seg...

Phaeochromocytomas are rare neuroendocrine tumours. Prediction of aggressive tumour behaviour remains a major challenge. We report a 68-year-old female who was found to have a locally arising colonic adenocarcinoma on biopsies. Staging also identified a 10.7 cm right adrenal lesion and work-up revealed markedly raised urinary metanephrines and positive MIBG imaging. The MDT decision was to first remove the colonic cancer with appropriate alpha blockade. It was felt that a comb...