| 1. |
- Ambrosini, Valentina, et al.
(författare)
-
Consensus on molecular imaging and theranostics in neuroendocrine neoplasms
- 2021
-
Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 146, s. 56-73
-
Forskningsöversikt (refereegranskat)abstract
- 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.
|
|
| 2. |
- Capdevila, Jaume, et al.
(författare)
-
Streptozotocin, 1982-2022 : Forty Years from the FDA's Approval to Treat Pancreatic Neuroendocrine Tumors
- 2022
-
Ingår i: Neuroendocrinology. - : S. Karger. - 0028-3835 .- 1423-0194. ; 112:12, s. 1155-1167
-
Forskningsöversikt (refereegranskat)abstract
- In May 1982, the US Food and Drug Administration (FDA) approved the use of streptozotocin to treat pancreatic neuroendocrine tumors (panNETs). Thus, this year marks 40 years since that landmark date. This review of streptozotocin to treat panNETs is intended to commemorate this anniversary. A historical perspective of the chemical structure, pharmacokinetics, and mechanism of action of streptozotocin is followed by data from prospective and retrospective clinical studies. The last section of the review addresses the latest aspects and takes note of the prospects that lie ahead on the future horizon of the use of streptozotocin to treat panNETs, including ongoing clinical trials.
|
|
| 3. |
- Chazot, Nicolas, et al.
(författare)
-
Conserved ancestral tropical niche but different continental histories explain the latitudinal diversity gradient in brush-footed butterflies
- 2021
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- The global increase in species richness toward the tropics across continents and taxonomic groups, referred to as the latitudinal diversity gradient, stimulated the formulation of many hypotheses to explain the underlying mechanisms of this pattern. We evaluate several of these hypotheses to explain spatial diversity patterns in a butterfly family, the Nymphalidae, by assessing the contributions of speciation, extinction, and dispersal, and also the extent to which these processes differ among regions at the same latitude. We generate a time-calibrated phylogeny containing 2,866 nymphalid species (~45% of extant diversity). Neither speciation nor extinction rate variations consistently explain the latitudinal diversity gradient among regions because temporal diversification dynamics differ greatly across longitude. The Neotropical diversity results from low extinction rates, not high speciation rates, and biotic interchanges with other regions are rare. Southeast Asia is also characterized by a low speciation rate but, unlike the Neotropics, is the main source of dispersal events through time. Our results suggest that global climate change throughout the Cenozoic, combined with tropical niche conservatism, played a major role in generating the modern latitudinal diversity gradient of nymphalid butterflies.
|
|
| 4. |
- Dawod, Mohammed, et al.
(författare)
-
Antiproliferative Systemic Therapies for Metastatic Small Bowel Neuroendocrine Tumours
- 2021
-
Ingår i: Current Treatment Options in Oncology. - : Springer Nature. - 1527-2729 .- 1534-6277. ; 22:8
-
Forskningsöversikt (refereegranskat)abstract
- Neuroendocrine neoplasms (NENs) are a heterogeneous group of malignancies with rising incidence and prevalence. Outcome and therapy of small bowel neuroendocrine tumours (SBNETs) is variable, depending on the grade, differentiation, tumour burden, as well as the site of the tumour origin. Because of this, multidisciplinary approach is essential. Large randomized clinical trials, with somatostatin analogues (PROMID, CLARINET) or with peptide receptor radionuclide therapy (PRRT) with 177-lutetium (NETTER-1 trial) as well as the mammalian target of rapamycin inhibitor (mTOR) everolimus (RADIANT trials), represent milestones for the medical management of unresectable grade 1 and 2 SBNETS over the last decade. Novel therapies, such as tyrosine kinase inhibitors (TKI), are on the cutting edge. However, multiple unsolved questions remain. This review provides a comprehensive review of the main systemic therapeutic options for advanced SBNETs and discusses the latest guideline recommendations for palliative treatment.
|
|
| 5. |
- Dehasque, Marianne, et al.
(författare)
-
Combining Bayesian age models and genetics to investigate population dynamics and extinction of the last mammoths in northern Siberia
- 2021
-
Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 259
-
Tidskriftsartikel (refereegranskat)abstract
- To understand the causes and implications of an extinction event, detailed information is necessary. However, this can be challenging when working with poorly resolved paleontological data sets. One approach to increase the data resolution is by combining different methods. In this study, we used both radiocarbon and genetic data to reconstruct the population history and extinction dynamics of the woolly mammoth in northern Siberia. We generated 88 new radiocarbon dates and combined these with previously published dates from 626 specimens to construct Bayesian age models. These models show that mammoths disappeared on the eastern Siberian mainland before the onset of the Younger Dryas (12.9–11.7 ky cal BP). Mammoths did however persist in the northernmost parts of central and western Siberia until the early Holocene. Further genetic results of 131 high quality mitogenomes, including 22 new mitogenomes generated in this study, support the hypothesis that mammoths from, or closely related to, a central and/or west- Siberian population recolonized Wrangel Island over the now submerged northern Siberian plains. As mammoths became trapped on the island due to rising sea levels, they lived another ca. 6000 years on Wrangel Island before eventually going extinct ca. 4000 years ago.
|
|
| 6. |
- Dillon, Joseph S., et al.
(författare)
-
Time to Sustained Improvement in Bowel Movement Frequency with Telotristat Ethyl : Analyses of Phase III Studies in Carcinoid Syndrome
- 2021
-
Ingår i: Journal of Gastrointestinal Cancer. - : Springer Science and Business Media LLC. - 1941-6628 .- 1941-6636. ; 52:1, s. 212-221
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundTelotristat ethyl is approved to treat carcinoid syndrome diarrhea in combination with somatostatin analogs. In TELESTAR and TELECAST phase III studies, patients with carcinoid syndrome received telotristat ethyl 250 or 500 mg 3 times per day (tid) or placebo tid in addition to somatostatin analogs. The aim of this prespecified analysis was to examine the time to reductions in bowel movements (BMs) in the TELESTAR and TELECAST studies using survival analysis methods.MethodsFirst occurrence of sustained response was defined as the time to the first day of 2 consecutive weeks with a mean BM frequency improvement of ≥ 30% from baseline during the 12-week double-blind treatment periods. Time to first ≥ 30% worsening in BM frequency was also measured. Treatments were compared with the log-rank test; Cox regression models provided point and confidence interval estimates of the hazard ratios for each trial.ResultsIn TELESTAR and TELECAST, majority of patients (69%) on telotristat ethyl experienced a sustained ≥ 30% improvement in BM frequency. The median time to sustained reduction of at least 30% in BM frequency was significantly faster (fewer days to onset) for telotristat ethyl compared with placebo in both TELESTAR (250 mg, HR = 2.3 [95% CI, 1.3–4.1, P = 0.004]; 500 mg, HR = 2.2 [95% CI, 1.2–3.9, P = 0.009]) and TELECAST (250 mg, HR = 3.9 [95% CI, 1.6–11.1, P = 0.003]; 500 mg, HR = 4.2 [95% CI, 1.7–11.7, P = 0.002]). In TELECAST, 42% of patients on placebo experienced sustained worsening in BM frequency compared with 20% on telotristat ethyl; no significant difference was observed in TELESTAR.ConclusionThe time of onset of sustained BM frequency improvement mean and range are important when considering use of telotristat ethyl in patients with carcinoid syndrome diarrhea. Telotristat ethyl may also reduce sustained worsening in BM frequency.
|
|
| 7. |
- Dromain, Clarisse, et al.
(författare)
-
ENETS standardized (synoptic) reporting for radiological imaging in neuroendocrine tumours
- 2022
-
Ingår i: Journal of neuroendocrinology. - : John Wiley & Sons. - 0953-8194 .- 1365-2826. ; 34:3 SI
-
Tidskriftsartikel (refereegranskat)abstract
- This expert consensus document represents an initiative by the European Neuroendocrine Tumor Society (ENETS) to provide guidance for synoptic reporting of radiological examinations critical to the diagnosis, grading, staging and treatment of neuroendocrine neoplasms (NENs). Template drafts for initial tumor staging and follow-up by computed tomography (CT) and magnetic resonance imaging (MRI) were established, based on existing institutional and organisational reporting templates relevant for NEN imaging, and applying the RadLex lexicon of radiological information (Radiological Society of North America), for consistency regarding the radiological terms. During the ENETS Scientific Advisory Board meeting 2018, the template drafts were subject to iterative interdisciplinary discussions among experts in imaging, surgery, gastroenterology, oncology and pathology. Members of the imaging group stated a strong preference for a combination of limited and standardised options by way of drop-down menus. Separate templates were produced for the initial work-up and for follow-up, respectively. To provide a detailed description of the radiological findings of the primary tumor and its local extension and spread, different templates were developed for bronchial, pancreatic and gastrointestinal NENs for CT and MRI, respectively. Each template was structured in 10 sections: clinical details, comparative imaging modality, acquisition technique, primary tumor findings, regional lymph node metastases, distant metastases, TNM classification, reference lesions according to RECIST 1.1, additional findings and conclusion. Two templates were developed for follow-up, for CT and MRI, respectively, and were specifically focused on assessment of therapy response. These included a qualitative response assessment, such as decrease of vascularisation and presence of necrosis, and a quantitative assessment according to RECIST 1.1 and the modified RECIST (mRECIST) for assessing tumor response following transarterial chemoembolisation.
|
|
| 8. |
- Dromain, Clarisse, et al.
(författare)
-
Tumour Growth Rate to predict the outcome of patients with Neuroendocrine Tumours : Performance and sources of variability
- 2021
-
Ingår i: Neuroendocrinology. - : S. Karger. - 0028-3835 .- 1423-0194. ; 111:9, s. 831-839
-
Tidskriftsartikel (refereegranskat)abstract
- 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 (DISCUSSION/CONCLUSION: TGR3m is a robust and early radiological biomarker able to predict PFS. It may be used to identify patients with advanced NETs who require closer radiological follow-up.
|
|
| 9. |
- Hörsch, Dieter, et al.
(författare)
-
Long-Term Treatment with Telotristat Ethyl in Patients with Carcinoid Syndrome Symptoms : Results from the TELEPATH Study
- 2022
-
Ingår i: Neuroendocrinology. - : S. Karger. - 0028-3835 .- 1423-0194. ; 112:3, s. 298-309
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Telotristat ethyl is indicated for use in combination with somatostatin analogs (SSAs) to treat carcinoid syndrome (CS) diarrhea uncontrolled by SSAs alone in adults, but long-term safety and efficacy data beyond 48 weeks are needed.Objectives: The aims of the study were to evaluate the long-term safety and tolerability of telotristat ethyl and its effect on quality of life (QOL) in patients with CS.Methods: In this phase 3, nonrandomized, multicenter, open-label, long-term extension study (TELEPATH), patients who participated in phase 2 or 3 trials of telotristat ethyl continued treatment at their present dose level (250 or 500 mg thrice daily) for 84 weeks. Safety and tolerability, the primary endpoint, were assessed by monitoring adverse events (AEs), serious AEs, AEs of special interest (AESIs; including liver-related AEs, depression, and gastrointestinal AEs), and deaths. The secondary objective was to evaluate changes in patients’ QOL using validated cancer questionnaires and a subjective global assessment of CS symptoms.Results: In 124 patients exposed to telotristat ethyl for a mean of 102.6 ± 53.2 weeks, the type and frequency of AEs were consistent with those reported in previous trials. The occurrence of AESIs was not related to dosage or duration of therapy. Most AEs were mild to moderate in severity, and no deaths were related to telotristat ethyl. QOL scores remained stable, and the majority of patients reported adequate symptom relief throughout the study.Conclusions: Safety results of TELEPATH support the long-term use of telotristat ethyl in patients with CS diarrhea. Telotristat ethyl was well-tolerated and associated with sustained improvement in QOL scores (NCT02026063).
|
|
| 10. |
- Koumarianou, Anna, et al.
(författare)
-
Efficacy, safety and unmet needs of evolving medical treatments for carcinoid syndrome.
- 2022
-
Ingår i: Journal of neuroendocrinology. - : Wiley-Blackwell Publishing Inc.. - 0953-8194 .- 1365-2826. ; 34:7
-
Forskningsöversikt (refereegranskat)abstract
- This review reports on the currently available medical treatment options for the control of symptoms due to carcinoid syndrome in patients with neuroendocrine tumors. The efficacy and adverse events (AEs) of approved drugs such as somatostatin analogues (SSA), telotristat ethyl (TE) and interferon-alpha, are reviewed. Somatostatin analogues remain the standard treatment of carcinoid syndrome based on the high expression of somatostatin receptors and the resulting inhibition of secretion of bioactive compounds; their use is associated with relatively mild AEs, involving mainly the gastrointestinal system, and being usually transient. Although dose escalation of SSA remains an unapproved option, it is clinically implemented to alleviate symptoms in refractory carcinoid syndrome and supported by the most recent guidelines. The side effects associated with the increased dose are in general mild and consistent with standard dose of SSA. Telotristat ethyl, an oral inhibitor of tryptophan hydroxylase, the rate-limiting enzyme in serotonin biosynthesis, represents a rather novel innovative treatment option in patients with carcinoid syndrome suffering from diarrhea and complements the standard therapy of SSA. Given the low toxicity profile, TE may be considered an early add-on treatment to SSA in patients with uncontrolled carcinoid syndrome. However, further prolonged follow-up of patients treated with TE may be needed to exclude potential AEs, such as liver toxicity or depressed mood, in patients with long-term treatment. Interferon alpha is a cytokine with direct inhibitory effect on hormone secretion and tumor cell proliferation and an approved therapy in carcinoid syndrome but is associated with significant AEs in the majority of the patients requiring frequently dose reduction. The finding of a more favorable tolerability of pegylated interferon needs to be confirmed in a prospective study.
|
|
