• Humans
• France
• Neoplasms/radiotherapy
• Hospitals
• Risk Management
• Trust
• Health Personnel/psychology

• ERA Permed

• DOTA-Tyr(3)-octreotate
• NETest
• Neuroendocrine neoplasms
• PPQ
• Peptide receptor radionucleotide therapies
• Response

• Humans
• Female
• Middle Aged
• Aged
• Male
• Neuroendocrine Tumors/complications
• Neuroendocrine Tumors/diagnosis
• Neuroendocrine Tumors/drug therapy
• Malignant Carcinoid Syndrome/diagnosis
• Malignant Carcinoid Syndrome/drug therapy
• Carcinoid Tumor/diagnosis
• Carcinoid Tumor/therapy
• Somatostatin/therapeutic use
• Intestinal Neoplasms

• Diarrhea
• HRQoL
• Neuroendocrine tumor
• Quality of life
• Surufatinib
• Time until definitive deterioration

• Diarrhea/chemically induced
• Double-Blind Method
• Humans
• Indoles
• Neuroendocrine Tumors/drug therapy
• Neuroendocrine Tumors/pathology
• Pyrimidines/therapeutic use
• Quality of Life
• Sulfonamides

• Carcinoid syndrome
• Carcinoid tumour
• Health economic evaluation
• Neuroendocrine neoplasia
• Neuroendocrine tumour

• Cost-Benefit Analysis
• Humans
• Neuroendocrine Tumors/therapy
• Positron-Emission Tomography
• Radionuclide Imaging
• Technology Assessment, Biomedical

• King's College London

• hyperinsulinism
• hypoglycaemia
• insulin
• insulinoma
• neuroendocrine tumors
• pancreas
• quality of life

• Adult
• Delayed Diagnosis
• Finland
• Humans
• Insulinoma/surgery
• Quality of Life
• Surveys and Questionnaires

• Carcinoid syndrome
• Measure development
• Priority symptoms
• Qualitative methods
• Symptom index

• Aged
• Female
• Humans
• Male
• Malignant Carcinoid Syndrome/diagnosis
• Malignant Carcinoid Syndrome/therapy
• Middle Aged
• Psychometrics/instrumentation
• Severity of Illness Index

• 18F-FDG
• 68Ga-labeled somatostatin analogue
• NET
• PRRT
• RECIST
• SWOG
• WHO
• neuroendocrine tumors
• peptide receptor radionuclide therapy
• response assessment

• cachexia
• clinical decisions
• home care
• intestinal obstruction
• prognosis
• quality of life

Approximately 20% of patients with neuroendocrine tumours (NETs) develop carcinoid syndrome (CS), characterised by flushing and diarrhoea. Somatostatin analogues or telotristat can be used to control symptoms of CS through inhibition of serotonin secretion. Although CS is often the cause of diarrhoea among patients with gastroenteropancreatic NETs (GEP-NETs), other causes to consider include pancreatic enzyme insufficiency (PEI), bile acid malabsorption and small intestinal bacterial overgrowth. If other causes of diarrhoea unrelated to serotonin secretion are mistaken for CS diarrhoea, these treatments may be ineffective against the diarrhoea, risking detrimental effects to patient quality of life.

To identify and synthesise qualitative and quantitative evidence relating to the differential diagnosis of diarrhoea in patients with GEP-NETs.

Electronic databases (MEDLINE, Embase and the Cochrane Library) were searched from inception to September 12, 2018 using terms for NETs and diarrhoea. Congresses, systematic literature review bibliographies and included articles were also hand-searched. Any study designs and publication types were eligible for inclusion if relevant data on a cause(s) of diarrhoea in patients with GEP-NETs were reported. Studies were screened by two independent reviewers at abstract and full-text stages. Framework synthesis was adapted to synthesise quantitative and qualitative data. The definition of qualitative data was expanded to include all textual data in any section of relevant publications.

Forty-seven publications (44 studies) were included, comprising a variety of publication types, including observational studies, reviews, guidelines, case reports, interventional studies, and opinion pieces. Most reported on PEI on/after treatment with somatostatin analogs; 9.5%-84% of patients with GEP-NETs had experienced steatorrhoea or confirmed PEI. Where reported, 14.3%–50.7% of patients received pancreatic enzyme replacement therapy. Other causes of diarrhoea reported in patients with GEP-NETs included bile acid malabsorption (80%), small intestinal bacterial overgrowth (23.6%-62%), colitis (20%) and infection (7.1%). Diagnostic approaches included faecal elastase, breath tests, tauroselcholic (selenium-75) acid (SeHCAT) scan and stool culture, although evidence on the effectiveness or diagnostic accuracy of these approaches was limited. Assessment of patient history or diarrhoea characteristics was also reported as initial approaches for investigation. From the identified evidence, if diarrhoea is assumed to be CS diarrhoea, consequences include uncontrolled diarrhoea, malnutrition, and perceived ineffectiveness of CS treatment. Approaches for facilitating differential diagnosis of diarrhoea include improving patient and clinician awareness of non-CS causes and involvement of a multidisciplinary clinical team, including gastroenterologists.

Diarrhoea in GEP-NETs can be multifactorial with misdiagnosis leading to delayed patient recovery and inefficient resource use. This systematic literature review highlights gaps for further research on prevalence of non-CS diarrhoea and suitability of diagnostic approaches, to determine an effective algorithm for differential diagnosis of GEP-NET diarrhoea.

• Carcinoid syndrome
• Diarrhea
• Differential diagnosis
• Neuroendocrine tumours
• Serotonin
• Systematic review

• Diagnosis, Differential
• Diarrhea/diagnosis
• Diarrhea/etiology
• Humans
• Intestinal Neoplasms/diagnosis
• Neuroendocrine Tumors/complications
• Neuroendocrine Tumors/diagnosis
• Pancreatic Neoplasms/complications
• Pancreatic Neoplasms/diagnosis
• Quality of Life

To understand the quality of life (QoL) for patients with neuroendocrine tumors (NETs) through comparison of QoL questionnaires and symptom tracking as well as journaling via the Carcinoid NETs Health Storylines mobile application (app).

This was a 12-week prospective, observational study of US patients with NET who were taking long-acting somatostatin analogs. National Institutes of Health Patient-Reported Outcomes Measurement Information System (PROMIS) and European Organisation for Research and Treatment of Cancer (EORTC) questionnaires were administered three times. Patients also monitored symptoms, mood, bowel movements, food, activity, and sleep, and they journaled in their app, which was coded by theme and sentiment for qualitative analysis.

Of the 120 patients with NET, 78% were women (mean age, 57 years); 76% had gastroenteropancreatic NETs, and 88% had metastases. Lanreotide depot and octreotide long-acting release (LAR) were used by 41% and 59%, respectively. The most common symptoms at baseline were fatigue (76.7%), diarrhea (62.5%), abdominal discomfort (64.1%), and trouble sleeping (57.5%). The majority completed five of six survey assessments (median, 5; mean, 5.1) and tracked four symptoms in the app (median, 4; mean, 5.5); the average frequency was 41.6 days for each symptom (median, 43; mean, 41.6; range, 1 to 84 days [12 weeks]). Without treatment change, most EORTC-assessed physical symptoms decreased from baseline to midpoint (eg, 59.3% at baseline v 33% at midpoint reported “quite a bit” or “very much” diarrhea; P = .002). App-based symptom tracking revealed large day-to-day variation, but weekly averages correlated well with survey scores. Journal entries showed that more patients made predominantly negative unsolicited entries about their injection experience with octreotide LAR compared with lanreotide (13 of 17 v two of 13; P < .001).

Patients with NET experience a large symptom burden that varies daily. A decrease in physical symptoms on QoL surveys suggests an effect from daily app-based monitoring or journaling, which may reduce recall bias and benefit the patient’s experience of symptoms.

Neuroendocrine tumours (NETs) are rare malignancies characterised by its capacity to synthesise and secrete monoamines, due to its neuroendocrine origin. Its varied locations and symptoms have traditionally been responsible for extended delays in their diagnosis. The interest of this study was to characterise the patient population diagnosed with NETs in Spain and to revise how the disease is managed, together with the hospitalisation costs of these patients.

The database included records of all patients diagnosed with a NET between 2010 and 2015. Admission records were used to evaluate hospitalisation, disease management data and costs, and single-patient files were used to characterise the population.

Nine Thousand One Hundred Twenty patients were diagnosed with a neuroendocrine tumour between 2010 and 2015, with a 2 fold increase in the diagnosis rate over the study period. 42.25% of the patients were females, while 57.75% were males, and mean diagnosis age was 62.58 years (SD = 14.65). Considering all the registered neuroendocrine neoplasms, 46.86% of the patients had malignant well-differentiated NETs, 32.02% had a malignant poorly differentiated neuroendocrine carcinoma and 42.93% of patients developed metastatic NETs. In addition, 18.59% of patients were diagnosed with benign well-differentiated NETs. The most common tumour sites were the bronchus, lung and other sites, including pancreatic tumours; metastasis was found in the liver and distant lymph nodes. Pancreatic resection was the most common surgical procedure utilised in these patients, summing 19% of total expenses, the injection of an unspecified therapeutic substance (including targeted therapies) was registered in 11.40% of admissions, while chemotherapy was registered in only 6.85% of admissions. The annual healthcare cost of NETs was €15,373,961, corresponding to €9092 per patient.

The implementation of standard diagnosis procedures should be prioritised, with a focus on the pancreas and lung, and taking into account that 42.93% of the patients develop a metastatic tumour. The presence of comorbidities and multimorbidities should be considered in order to develop more efficient disease management protocols.

• Disease management
• Economic impact study
• Neuroendocrine tumors
• Population-based study
• Spain

Due to the increasing incidence and prevalence of neuroendocrine tumors (NETs), there is a need to assess any gaps in awareness and care. A survey was undertaken in 2017 to identify perceived unmet needs from the perspectives of patients/families, patient advocates and health care professionals (HCPs). The survey consisted of 33–37 questions (depending on type of respondent) across four areas: information, care, treatments and research. In total, 443 participants from 26 countries responded: 338 patients/families, 35 advocates and 70 HCPs. Perceived unmet needs regarding provision of information at diagnosis differed between groups. While 59% of HCPs believed they provided sufficient information, informational needs were mostly/fully met for only 30% of patients and 18% of advocates. Additionally, 91% of patients and 97% of advocates felt that patients had to search for information themselves. Availability of Gallium‐68‐Dotatate PET/CT scan was limited for the majority of patients (patients: 73%; advocates: 85%; HCP: 86%), as was access to treatments, particularly peptide receptor radionuclide therapy (patients: 42%; advocates: 95%; HCPs: 77%). All groups felt that standards of care, including psychological needs and diagnosis of mental health, were not fully met. Although about two‐thirds of patients were managed by a multidisciplinary team, 14% of patients reportedly did not have enough contact. All groups supported more patient involvement in research; patients and advocates prioritized improvement in diagnosis and HCPs focused on clinical trials. This survey revealed significant unmet needs but differing perceptions regarding these among the groups. There is a need for investigation and collaboration to improve standards of care for NET patients.

What's new?

Even though the incidence of neuroendocrine tumors (NETs) has been rising worldwide, the current management of patients varies considerably, potentially leaving many with suboptimal care. An international survey was carried out in 2017 to investigate unmet needs in the NET patient community. The survey revealed that patients perceive numerous unmet needs in key areas including provision of information, diagnostics and treatment access, care standards, and research involvement. While healthcare professionals were aware of these gaps, they generally underestimated their magnitude. Patients and healthcare professionals need to work together to improve the lives and prospects of the increasing numbers of patients.

• neuroendocrine tumor
• perspective
• standards of care
• survey
• unmet needs

Neuroendocrine tumors (NETs) are rare cancers with an associated prolonged survival in some patients. A proportion of patients diagnosed with NETs will present with carcinoid syndrome symptoms, characterized by diarrhea, flushing and/or wheezing. This review summarizes the current treatment options for carcinoid syndrome, focusing on the latest novel treatment option, telotristat ethyl. In addition, information on patient-reported outcomes and impact of carcinoid syndrome on quality of life (QOL) and improvement of following treatment with telotristat ethyl are reviewed. This article also provides an overview of the current QOL questionnaires for patients with NETs and addresses unmet needs in this field of patient-reported outcomes.

• NET
• carcinoid syndrome
• diarrhea
• telotristat ethyl

• Carcinoid
• Neuroendocrine
• Outcomes
• Patient‐reported
• Quality of life
• Symptoms

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Cohort Studies
• Female
• Humans
• Male
• Middle Aged
• Neuroendocrine Tumors/diagnosis
• Neuroendocrine Tumors/pathology
• Patient Reported Outcome Measures
• Prospective Studies
• Retrospective Studies
• Young Adult

The objective was to estimate the cost‐of‐illness of grades 1 and 2 metastatic gastroenteropancreatic neuroendocrine tumours (GEP‐NETs) in Sweden in 2013 in a population‐based study including all patients diagnosed between 2005 and 2013. Data were obtained from national registers, and patients who utilised healthcare resources due to metastatic GEP‐NETs in 2013 were included. The study included 478 patients (mean age 64 [SD=11] years, 51% men). The majority (80%) had small intestinal NET, 10% had pancreatic NET, and 41% had carcinoid syndrome. The total cost‐of‐illness was €12,189,000 in 2013, of which direct costs constituted 77% and costs from production loss constituted 22%. The largest contributor to the direct medical costs was prescription drugs (54%; primarily somatostatin analogues [91% of the total drug cost]). Production loss due to sickness absence constituted 52% of the total costs of production loss. The total annual cost per patient was €25,500. By patient group, the cost was €24,800 (95% CI €21,600–€28,100) for patients with small intestinal NET, €37,300 (95% CI €23,300–€51,300) for those with pancreatic NET and €18,600 (95% CI €12,600–€24,500) for patients with other GEP‐NETs. To conclude, the total annual cost of grades 1 and 2 metastatic GEP‐NETs in Sweden was €25,500 per patient and year.

• GEP-NET
• Sweden
• cost-of-illness
• metastatic
• register study
• treatment

• budget impact
• cost-of-illness
• costs
• economic burden
• economic evaluation
• gastroenteropancreatic neuroendocrine tumors
• resource utilization
• systematic review

• novartis pharmaceuticals canada

• Everolimus
• Health-related quality of life
• Pancreatic neuroendocrine tumours
• Real-world study

• Adult
• Aged
• Antineoplastic Agents/adverse effects
• Antineoplastic Agents/therapeutic use
• Disease Progression
• Disease-Free Survival
• Everolimus/adverse effects
• Everolimus/therapeutic use
• Female
• Humans
• Male
• Middle Aged
• Pancreatic Neoplasms/drug therapy
• Pancreatic Neoplasms/mortality
• Quality of Life
• Surveys and Questionnaires
• Survival Rate

• Fatigue
• Health-related quality of life
• Neuroendocrine tumor
• Octreotide

• Aged
• Delayed-Action Preparations/adverse effects
• Delayed-Action Preparations/therapeutic use
• Disease-Free Survival
• Double-Blind Method
• Female
• Follow-Up Studies
• Germany
• Humans
• Intestinal Neoplasms/drug therapy
• Intestinal Neoplasms/pathology
• Male
• Middle Aged
• Neoplasm Metastasis
• Neuroendocrine Tumors/drug therapy
• Neuroendocrine Tumors/pathology
• Octreotide/adverse effects
• Octreotide/therapeutic use
• Placebos
• Quality of Life
• Surveys and Questionnaires

• Costs
• Insurance claims
• Lung neuroendocrine tumors
• Resource utilization
• Treatment adherence

• Adult
• Aged
• Databases, Factual
• Female
• Health Care Costs/statistics & numerical data
• Hospitalization/statistics & numerical data
• Humans
• Longitudinal Studies
• Lung Neoplasms/drug therapy
• Male
• Middle Aged
• Neuroendocrine Tumors/drug therapy
• Patient Acceptance of Health Care
• Retrospective Studies
• Somatostatin/analogs & derivatives
• Treatment Adherence and Compliance
• United States

• Gastrointestinal neuroendocrine tumors
• I00
• I11
• I19
• I20
• costs
• insurance claims
• resource utilization
• treatment adherence

• Adolescent
• Adult
• Aged
• Antineoplastic Agents/therapeutic use
• Costs and Cost Analysis
• Female
• Gastrointestinal Neoplasms/drug therapy
• Gastrointestinal Neoplasms/economics
• Health Resources/economics
• Health Resources/statistics & numerical data
• Humans
• Insurance Claim Review
• Longitudinal Studies
• Male
• Middle Aged
• Models, Econometric
• Neuroendocrine Tumors/drug therapy
• Neuroendocrine Tumors/economics
• Retrospective Studies
• Treatment Adherence and Compliance/statistics & numerical data
• United States
• Young Adult

• clinical practice
• gastroenteropancreatic neuroendocrine tumors
• health-related quality of life
• peptide receptor radionuclide therapy
• routine monitoring

To compare health-related quality of life (HRQoL), anxiety, depression, and impulsivity scores in patients with and without carcinoid syndrome (CS), and correlated them with serum 5-hydroxyindoleacetic acid (5-HIAA) levels.

Patients with advanced gastroenteropancreatic neuroendocrine tumours (GEPNET), with and without CS completed HRQoL QLQ-C30 and QLQ-GI.NET21, Hospital Anxiety and Depression Scale (HADS) and Barratt Impulsivity Scale (BIS) questionnaires. Two-sample Wilcoxon test was applied to assess differences in serum 5-HIAA levels, two-sample Mann-Whitney U test for HRQoL and BIS, and proportion test for HADS, between those with and without CS.

Fifty patients were included; 25 each with and without CS. Median 5-HIAA in patients with and without CS was 367nmol/L and 86nmol/L, respectively (P = 0.003). Scores related to endocrine symptoms were significantly higher amongst patients with CS (P = 0.04) and scores for disease-related worries approached significance in the group without CS, but no other statistically-significant differences were reported between patients with and without CS in responses on QLQ-C30 or QLQ-GI.NET21. Fifteen patients (26%) scored ≥ 8/21 on anxiety scale, and 6 (12%) scored ≥ 8/21 on depression scale. There was no difference in median 5-HIAA between those scoring < or ≥ 8/21 on anxiety scale (P = 0.53). There were no statistically significant differences between groups in first or second-order factors (BIS) or total sum (P = 0.23).

Excepting endocrine symptoms, there were no significant differences in HRQoL, anxiety, depression or impulsivity between patients with advanced GEPNET, with or without CS. Over one quarter of patients had high anxiety scores, unrelated to peripheral serotonin metabolism.

• Gastroenteropancreatic neuroendocrine tumours
• Carcinoid syndrome
• Quality of life
• Anxiety
• Depression
• Impulsivity

• Aged
• Anxiety/blood
• Anxiety/epidemiology
• Anxiety/psychology
• Biomarkers/blood
• Chromogranin A/blood
• Depression/blood
• Depression/epidemiology
• Depression/psychology
• Female
• Humans
• Hydroxyindoleacetic Acid/blood
• Hydroxyindoleacetic Acid/metabolism
• Impulsive Behavior
• Intestinal Neoplasms/blood
• Intestinal Neoplasms/pathology
• Intestinal Neoplasms/psychology
• Male
• Malignant Carcinoid Syndrome/blood
• Malignant Carcinoid Syndrome/pathology
• Malignant Carcinoid Syndrome/psychology
• Middle Aged
• Neuroendocrine Tumors/blood
• Neuroendocrine Tumors/pathology
• Neuroendocrine Tumors/psychology
• Pancreatic Neoplasms/blood
• Pancreatic Neoplasms/pathology
• Pancreatic Neoplasms/psychology
• Patient Health Questionnaire
• Prevalence
• Quality of Life
• Serotonin/metabolism
• Stomach Neoplasms/blood
• Stomach Neoplasms/pathology
• Stomach Neoplasms/psychology

• Average Sales Price
• CLARINET
• GI-NETs
• PROMID
• Wholesale Acquisition Cost
• adverse events
• lanreotide
• octreotide LAR
• sensitivity analyses
• treatment cost

• MEN1 gene
• clinical management
• international MEN1 guidelines
• multiple endocrine neoplasia type 1 (MEN1)

• Humans
• Multiple Endocrine Neoplasia Type 1/pathology
• Multiple Endocrine Neoplasia Type 1/psychology
• Mutation
• Neuroendocrine Tumors/pathology
• Neuroendocrine Tumors/psychology
• Prognosis

• burden of illness
• neuroendocrine tumors
• patient-centered care
• quality of life
• surveys
• rare diseases

• Small cell carcinoma
• gastric
• poorly differentiated neuroendocrine carcinoma
• stomach

• Healthcare costs
• Healthcare resource utilization
• Neuroendocrine tumor
• Treatment patterns

• Adolescent
• Adult
• Antineoplastic Combined Chemotherapy Protocols/economics
• Combined Modality Therapy/economics
• Comorbidity
• Female
• Health Expenditures/statistics & numerical data
• Health Services/economics
• Health Services/statistics & numerical data
• Humans
• Insurance Claim Review/statistics & numerical data
• Male
• Middle Aged
• Neuroendocrine Tumors/complications
• Neuroendocrine Tumors/drug therapy
• Neuroendocrine Tumors/economics
• Neuroendocrine Tumors/surgery
• Retrospective Studies
• Young Adult