Global challenges in access to diagnostics and treatment for neuroendocrine tumor (NET) patients.

SCAN, an online survey, measured access to diagnosis, treatments and monitoring of neuroendocrine tumor (NET) patients globally. Between September and November 2019, NET patients and healthcare professionals (HCPs) completed an online, semi-standardized survey with 54 patient questions and 33 HCP questions. A total of 2359 patients with NETs and 436 HCPs responded. Misdiagnosis was common (44% [1043/2359]). Mean time to diagnosis was 4.8 years (standard deviation [SD], 6.2). Compared with global figures (60% [1407/2359]), the availability of 68 Ga-DOTA positron emission tomography (PET)/computed tomography (CT) was significantly lower in Asia (45% [126/280]) and higher in Oceania (86% [171/200]). HCPs reported that 68 Ga-DOTA PET/CT was free/affordable to fewer patients in Emerging and Developing Economies (EDE) than Advanced Economies (AE; 17% [26/150] and 59% [84/142], respectively). Compared with global data (52% [1234/2359]), patient-reported availability of peptide receptor radionuclide therapy (PRRT) was significantly lower in Asia (31% [88/280]) and higher in Oceania (61% [122/200]). Significant differences were observed in average annual NET specialist costs between AE and EDE ($1081 and $2915, respectively). Compared with AE, patients in EDE traveled further for NET specialists (1032 [SD, 1578] and 181 [SD, 496] km, respectively). Patients and HCPs both recommended referral to HCPs that were more knowledgeable in the field of NETs and had better access to NET experts/specialist centers. National care pathways, enhancing HCP NET knowledge and ensuring effective diagnostics and access to appropriate treatments are crucial to improving patient survival and NET care worldwide.

The impact of COVID-19 on the management of neuroendocrine tumors (NETS): An international NET CONNECT survey of NET patients and healthcare professionals treating net patients.

The COVID-19 outbreak has added complexity in the management of patients with neuroendocrine tumors (NETs). Little information is currently available regarding the real impact of the pandemic in current practice. The present study aimed to capture patients' and healthcare professionals' experiences on how the NET management has changed during the pandemic and how it should be modified in a foreseeable post-pandemic environment. Physicians and nurses working in ENETS Centers of Excellence or other hospitals with high volume of NET patients (n = 48), as well as NET patients residing worldwide (n = 353), were asked to respond to two online anonymous surveys addressing different aspects of NET care. Deferred diagnoses, delayed surveillance procedures and postponed elective surgeries were among the main negative consequences of the COVID-19 outbreak according to 40%, 54% and 46% of healthcare professionals (HPs) respectively. Somatostatin analogs were increasingly used as bridging strategy for delaying surgery based on the views of 31% of HPs and were self-injected or delivered by home care services more frequently than before the initiation of the pandemic (53% of patients during the pandemic vs. 44% before the pandemic). Multidisciplinary tumor boards kept their usual schedule according to 58% of HPs, but were held virtually in the 77% of cases. The contact with healthcare professionals was maintained by remote methods more often than in the past (69% of patients), but only 34% of patients (59% among subjects < 41 years) would prefer telemedicine to face-to-face consultations in the future. New health policy measures should guarantee the highest standard of treatment to NET patients, regardless of the trajectory followed by the COVID-19 pandemic in the next months. Pros and cons of telemedicine should be carefully weighted before systematic implementation.

Incidence and survival of neuroendocrine neoplasia in England 1995-2018: A retrospective, population-based study.

Background: Neuroendocrine neoplasia (NEN) incidence is rising internationally. We aimed to evaluate the epidemiology of NEN in England and examine changes in survival over time. Methods: A retrospective, population-based study using nationally representative data between 1995 and 2018 from the National Cancer Registry and Analysis Service (NCRAS) in England was conducted on 63,949 tumours. Age-standardized incidence was calculated using Office for National Statistics (ONS) data. Overall survival (OS) was calculated using the Kaplan-Meier estimator. Multivariable analysis was performed using an accelerated failure time model. Findings: Of 63,949 cases, 50.5% (32,309) were female. Age-adjusted incidence increased 3.7-fold between 1995 and 2018 from 2.35 to 8.61 per 100,000. In 2018, highest incidence occurred in lung (1.47 per 100,000), small intestine (1.46 per 100,000), pancreas (1.00 per 100,000) and appendix (0.95 per 100,000). In multivariable analysis, age, sex, morphology, stage, site and deprivation were independent predictors of survival (p < 0.001). Survival of the entire cohort, and by primary site, is improving over time. Interpretation: NEN incidence continues to rise in England with survival improving over time. Relatively high survival compared to other cancers is an issue for long-term outcomes and funding of care. Funding: Data were extracted and transferred using a grant from Neuroendocrine cancer UK.

The Role of Patient Support Groups in Neuroendocrine Neoplasms.

PURPOSE OF REVIEW: The purpose of this review is to establish the role patient support groups play in NENs. RECENT FINDINGS: Published data on the role and work done by these groups is extremely sparse, so the review references publications in the wider cancer advocacy context. For the purposes of the review, a survey was carried out among the members of a global umbrella organization to ascertain the level of activities undertaken in support of the NEN patient community. The concept of "support groups" has changed significantly, as these groups have evolved from patient peer-to-peer support provision to a strategic focus on improving awareness and education among all stakeholders, generating patient evidence to influence policies for access to optimal diagnostics, treatment, and care, and setting the research agenda. Today, NEN patient organizations have an instrumental role of catalysts of change across the healthcare spectrum-especially relevant in a setting of less common and not well-understood diseases, where clear pathways and guidelines are still a challenge.

Consensus on molecular imaging and theranostics in neuroendocrine neoplasms.

Nuclear medicine plays an increasingly important role in the management neuroendocrine neoplasms (NEN). Somatostatin analogue (SSA)-based positron emission tomography/computed tomography (PET/CT) and peptide receptor radionuclide therapy (PRRT) have been used in clinical trials and approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). European Association of Nuclear Medicine (EANM) Focus 3 performed a multidisciplinary Delphi process to deliver a balanced perspective on molecular imaging and radionuclide therapy in well-differentiated neuroendocrine tumours (NETs). NETs form in cells that interact with the nervous system or in glands that produce hormones. These cells, called neuroendocrine cells, can be found throughout the body, but NETs are most often found in the abdomen, especially in the gastrointestinal tract. These tumours may also be found in the lungs, pancreas and adrenal glands. In addition to being rare, NETs are also complex and may be difficult to diagnose. Most NETs are non-functioning; however, a minority present with symptoms related to hypersecretion of bioactive compounds. NETs often do not cause symptoms early in the disease process. When diagnosed, substantial number of patients are already found to have metastatic disease. Several societies' guidelines address Neuroendocrine neoplasms (NENs) management; however, many issues are still debated, due to both the difficulty in acquiring strong clinical evidence in a rare and heterogeneous disease and the different availability of diagnostic and therapeutic options across countries. EANM Focus 3 reached consensus on employing 68gallium-labelled somatostatin analogue ([68Ga]Ga-DOTA-SSA)-based PET/CT with diagnostic CT or magnetic resonance imaging (MRI) for unknown primary NET detection, metastatic NET, NET staging/restaging, suspected extra-adrenal pheochromocytoma/paraganglioma and suspected paraganglioma. Consensus was reached on employing 18fluorine-fluoro-2-deoxyglucose ([18F]FDG) PET/CT in neuroendocrine carcinoma, G3 NET and in G1-2 NET with mismatched lesions (CT-positive/[68Ga]Ga-DOTA-SSA-negative). Peptide receptor radionuclide therapy (PRRT) was recommended for second line treatment for gastrointestinal NET with [68Ga]Ga-DOTA-SSA uptake in all lesions, in G1/G2 NET at disease progression, and in a subset of G3 NET provided all lesions are positive at [18F]FDG and [68Ga]Ga-DOTA-SSA. PRRT rechallenge may be used for in patients with stable disease for at least 1 year after therapy completion. An international consensus is not only a prelude to a more standardised management across countries but also serves as a guide for the direction to follow when designing new research studies.

Practical recommendations for the management of patients with gastroenteropancreatic and thoracic (carcinoid) neuroendocrine neoplasms in the COVID-19 era.

Neuroendocrine neoplasms (NENs) are a heterogeneous family of uncommon tumours with challenging diagnosis, clinical management and unique needs that almost always requires a multidisciplinary approach. In the absence of guidance from the scientific literature, along with the rapidly changing data available on the effect of COVID-19, we report how 12 high-volume NEN centres of expertise in 10 countries at different stages of the evolving COVID-19 global pandemic along with members of international neuroendocrine cancer patient societies have suggested to preserve high standards of care for patients with NENs. We review the multidisciplinary management of neuroendocrine neoplasms during the COVID-19 pandemic, and we suggest potential strategies to reduce risk and aid multidisciplinary treatment decision-making. By sharing our joint experiences, we aim to generate recommendations for proceeding to other institutions facing the same challenges.

Unmet needs in the international neuroendocrine tumor (NET) community: Assessment of major gaps from the perspective of patients, patient advocates and NET health care professionals.

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.

Impact of neuroendocrine morphology on cancer outcomes and stage at diagnosis: a UK nationwide cohort study 2013-2015.

BACKGROUND: The diagnosis of neuroendocrine neoplasms (NENs) is often delayed. This first UK population-based epidemiological study of NENs compares outcomes with non-NENs to identify any inequalities. METHODS: Age-standardised incidence rate (ASR), 1-year overall survival, hazard ratios and standardised mortality rates (SMRs) were calculated for all malignant NENs diagnosed 2013-2015 from UK national Public Health records. Comparison with non-NENs assessed 1-year overall survival (1YS) and association between diagnosis at stage IV and morphology. RESULTS: A total of 15,222 NENs were identified, with an ASR (2013-2015 combined) of 8.6 per 100,000 (95% CI 8.5-8.7); 4.6 per 100 000 (95% CI, 4.5-4.7) for gastro-entero-pancreatic (GEP) NENs. The 1YS was 75% (95% CI, 73.9-75.4) varying significantly by sex. Site and morphology were prognostic. NENs (predominantly small cell carcinomas) in the oesophagus, bladder, prostate, and female reproductive organs had a poorer outcome and were three times more likely to be diagnosed at stage IV than non-NENs. CONCLUSION: Advanced stage at diagnosis with significantly poorer outcomes of some NENs compared with non-NENs at the same anatomical site, highlight the need for improved access to specialist services and targeted service improvement.

Delays and routes to diagnosis of neuroendocrine tumours.

BACKGROUND: Neuroendocrine tumours are uncommon tumours; there is often a long period between the onset of symptoms and diagnosis. This study aims to address the symptoms prior to diagnosis of people with known neuroendocrine tumours and also the involvement of healthcare providers prior to the diagnosis. METHODS: A web based survey was designed to cover two broad areas of patient symptoms and healthcare interactions prior to diagnosis. This was tested and adapted by patient and clinician input prior to distribution via Survey Monkey. RESULTS: The results demonstrated a median time from first symptom to diagnosis of 53.8 months. The most frequent initial symptoms were of pain, change in bowel habit and fatigue. 31% of respondents noted weight loss prior to diagnosis. 80% of respondents visited their GP regarding the symptoms a median of 11 times. 58% of respondents were referred to secondary care where they were seen a median 3 times. 30% presented acutely to A&E and this led to their diagnosis. CONCLUSION: In conclusion, there is a long time from onset of symptoms to diagnosis in all types of NETs. This is despite many respondents having alarm symptoms at diagnosis. Further education and awareness regarding malignancy may help with earlier diagnosis.

Prevalence of self-reported side effects in neuroendocrine tumour patients prescribed somatostatin analogues.

Somatostatin analogues (SSA) are a common treatment for some forms of neuroendocrine tumours (NETs). Patients report a variety of side effects after starting these drugs, so in most cases they require a lot of nutritional input. The authors used an online survey to invite responses from patients worldwide to determine the extent of reported side effects. Patients were asked which SSA they were taking and how they rated the severity of their side effects. They were provided with a list of 11 options to choose from, but not given any guidance or a definition of terms. The most commonly reported side effect was constipation (85%), with 8.6% of these respondents rating its severity as 10/10. The survey found that many self-reported side effects from the use of SSAs were experienced more frequently than previous clinical studies or the patient information leaflets reported. As this was an online survey, so the findings are limited in that first, this was a self-selected sample of patients and second, patients were able to respond more than once.

[Hemodialysis procedure in a patient treated with radioactive iodine]. / Procédure d'hémodialyse chez un patient traité par iode 131.

The treatment of a patient with 131I at activity over 740 mega Becquerel (MBq) must be performed in a nuclear medicine department. Isolation is stopped if the patient radiation level is less than 20 muSv/hour at one meter. As regards patients with chronic renal failure treated with hemodialysis (HD), the first HD session will eliminate the major part of the radioactivity. French regulations do not give definite recommendations for this session. However, it imposes to collect liquid and solid wastes contaminated by radioactivity. Thus, it seems necessary to collect dialysate and solid wastes and to stock them in a room dedicated to radiation decay. The risk for dialysis staff is to be contaminated by an accidental ingestion of a biologic fluid from the patient. The usual protection barriers used during the HD session are sufficient: mask, gloves, overgarments, cap. There is no risk linked to external exposure to radiations. The maximal theoretical dose received by the staff during the session is 65 muSv, while annual maximal dose for public exposed to radiations is 1000 muSv. Although the dosimetric follow-up of dialysis staff is not mandatory, the nuclear medicine department of Marseille University Hospital has decided to do it in an information perspective. The session is performed in the presence of a radiation safety technician who gives film badges and active dosimeters to the dialysis staff. He reports the dialysis staff to the nuclear safety agency (Autorité de sûreté nucléaire).

The TrkC receptor induces apoptosis when the dependence receptor notion meets the neurotrophin paradigm.

The TrkC/NT-3 receptor/ligand pair is believed to be part of the classic neurotrophic theory claiming that neuronal death occurs by default when neurotrophic factors become limited, through loss of survival signals. Here, we show that TrkC is a dependence receptor and, as such, induces caspase-dependent apoptotic death in the absence of NT-3 in immortalized cells, a proapoptotic activity inhibited by the presence of NT-3. This proapoptotic activity of TrkC relies on the caspase-mediated cleavage of the intracellular domain of TrkC, which permits the release of a proapoptotic fragment. This fragment induces apoptosis through a caspase-9-dependent mechanism. Finally, we show that the death of dorsal root ganglion (DRG) neurons provoked by NT-3 withdrawal is inhibited when TrkC-proapoptotic activity is antagonized. Thus, the death of neurons upon disappearance of NT-3 is not only due to a loss of survival signals but also to the active proapoptotic activity of the unbound TrkC dependence receptor.