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- Strosberg, J., et al.
(författare)
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Phase 3 Trial of Lu-177-Dotatate for Midgut Neuroendocrine Tumors
- 2017
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 376:2, s. 125-135
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 (Lu-177)-Dotatate in patients with advanced, progressive, somatostatin-receptor-positive midgut neuroendocrine tumors. METHODS We randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either Lu-177-Dotatate (116 patients) at a dose of 7.4 GBq every 8 weeks (four intravenous infusions, plus best supportive care including octreotide long-acting repeatable [LAR] administered intramuscularly at a dose of 30 mg) (Lu-177-Dotatate group) or octreotide LAR alone (113 patients) administered intramuscularly at a dose of 60 mg every 4 weeks (control group). The primary end point was progression-free survival. Secondary end points included the objective response rate, overall survival, safety, and the side-effect profile. The final analysis of overall survival will be conducted in the future as specified in the protocol; a prespecified interim analysis of overall survival was conducted and is reported here. RESULTS At the data-cutoff date for the primary analysis, the estimated rate of progression-free survival at month 20 was 65.2% (95% confidence interval [CI], 50.0 to 76.8) in the Lu-177-Dotatate group and 10.8% (95% CI, 3.5 to 23.0) in the control group. The response rate was 18% in the Lu-177-Dotatate group versus 3% in the control group (P<0.001). In the planned interim analysis of overall survival, 14 deaths occurred in the Lu-177-Dotatate group and 26 in the control group (P = 0.004). Grade 3 or 4 neutropenia, thrombocytopenia, and lymphopenia occurred in 1%, 2%, and 9%, respectively, of patients in the Lu-177-Dotatate group as compared with no patients in the control group, with no evidence of renal toxic effects during the observed time frame. CONCLUSIONS Treatment with Lu-177-Dotatate resulted in markedly longer progression-free survival and a significantly higher response rate than high-dose octreotide LAR among patients with advanced midgut neuroendocrine tumors. Preliminary evidence of an overall survival benefit was seen in an interim analysis; confirmation will be required in the planned final analysis. Clinically significant myelosuppression occurred in less than 10% of patients in the Lu-177-Dotatate group. (Funded by Advanced Accelerator Applications; NETTER-1 ClinicalTrials. gov number, NCT01578239; EudraCT number 2011-005049-11.)
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- Rindi, G., et al.
(författare)
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TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system.
- 2006
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Ingår i: Virchows Archiv : an international journal of pathology. - : Springer Science and Business Media LLC. - 0945-6317 .- 1432-2307. ; 449:4, s. 395-401
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Forskningsöversikt (refereegranskat)abstract
- The need for standards in the management of patients with endocrine tumors of the digestive system prompted the European Neuroendocrine Tumor Society (ENETS) to organize a first Consensus Conference, which was held in Frascati (Rome) and was based on the recently published ENETS guidelines on the diagnosis and treatment of digestive neuroendocrine tumors (NET). Here, we report the tumor-node-metastasis proposal for foregut NETs of the stomach, duodenum, and pancreas that was designed, discussed, and consensually approved at this conference. In addition, we report the proposal for a working formulation for the grading of digestive NETs based on mitotic count and Ki-67 index. This proposal, which needs to be validated, is meant to help clinicians in the stratification, treatment, and follow-up of patients.
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- Strosberg, Jonathan R., et al.
(författare)
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NETTER-1 phase III : Progression-free survival, radiographic response, and preliminary overall survival results in patients with midgut neuroendocrine tumors treated with 177-Lu-Dotatate
- 2016
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Ingår i: Journal of Clinical Oncology. - Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Univ Kentucky, Lexington, KY USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Vet Adm Med Ctr, Iowa City, IA USA. Royal Free Hosp, Pond St, London NW3 2QG, England. Zent Klin Bad Berka, Bad Berka, Germany. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Mayo Clin, Coll Med, Dept Oncol, Rochester, MN USA. Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Los Angeles, CA 90048 USA. Univ Uppsala Hosp, Uppsala, Sweden. Adv Accelerator Applicat, New York, NY USA. Erasmus Univ, Med Ctr, Rotterdam, Netherlands. Beaujon Hosp, Clichy, France. Erasmus MC, Rotterdam, Netherlands.. - 0732-183X .- 1527-7755. ; 34:4
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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- Ambrosini, Valentina, et al.
(författare)
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Use and perceived utility of [18 F]FDG PET/CT in neuroendocrine neoplasms : A consensus report from the European Neuroendocrine Tumor Society (ENETS) Advisory Board Meeting 2022.
- 2024
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Ingår i: Journal of neuroendocrinology. - 0953-8194 .- 1365-2826. ; 36:1, s. e13359-
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Tidskriftsartikel (refereegranskat)abstract
- 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 addressed by further research.
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- Caplin, B., et al.
(författare)
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International Collaboration for the Epidemiology of eGFR in Low and Middle Income Populations - Rationale and core protocol for the Disadvantaged Populations eGFR Epidemiology Study (DEGREE)
- 2017
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Ingår i: Bmc Nephrology. - : Springer Science and Business Media LLC. - 1471-2369. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is an increasing recognition of epidemics of primarily tubular-interstitial chronic kidney disease (CKD) clustering in agricultural communities in low-and middle-income countries (LMICs). Although it is currently unclear whether there is a unified underlying aetiology, these conditions have been collectively termed CKD of undetermined cause (CKDu). CKDu is estimated to have led to the premature deaths of tens to hundreds of thousands of young men and women over the last 2 decades. Thus, there is an urgent need to understand the aetiology and pathophysiology of these condition (s). International comparisons have provided the first steps in understanding many chronic diseases, but such comparisons rely on the availability of standardised tools to estimate disease prevalence. This is a particular problem with CKD, since the disease is asymptomatic until the late stages, and the biases inherent in the methods used to estimate the glomerular filtration rate (GFR) in population studies are highly variable across populations. Method: We therefore propose a simple standardised protocol to estimate the distribution of GFR in LMIC populations - The Disadvantaged Populations eGFR Epidemiology (DEGREE) Study. This involves the quantification of renal function in a representative adult population-based sample and a requirement for standardisation of serum creatinine measurements, along with storage of samples for future measurements of cystatin C and ascertainment of estimates of body composition, in order to obtain valid comparisons of estimated GFR (eGFR) within and between populations. Discussion: The methodology we present is potentially applicable anywhere, but our particular focus is on disadvantaged populations in LMICs, since these appear to be most susceptible to CKDu. Although the protocol could also be used in specific groups (e.g. occupational groups, thought to be at excess risk of CKDu) the primary aim of the DEGREE project is characterise the population distribution of eGFR in multiple regions so that international comparisons can be performed. It is only with a standardised approach that it will be possible to estimate the scale of, and variation in, impaired kidney function between affected areas. These data should then provide insights into important social, demographic and environmental risk factors for this increasingly recognised disease.
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- Gonzalez-Quiroz, M., et al.
(författare)
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Rationale and population-based prospective cohort protocol for the disadvantaged populations at risk of decline in EGFR (CO-DEGREE)
- 2019
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Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 9:9
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Tidskriftsartikel (refereegranskat)abstract
- Introduction A recently recognised form of chronic kidney disease (CKD) of unknown origin (CKDu) is afflicting communities, mostly in rural areas in several regions of the world. Prevalence studies are being conducted in a number of countries, using a standardised protocol, to estimate the distribution of estimated glomerular filtration rate (eGFR), and thus identify communities with a high prevalence of reduced glomerular filtration rate (GFR). In this paper, we propose a standardised minimum protocol for cohort studies in high-risk communities aimed at investigating the incidence of, and risk factors for, early kidney dysfunction. Methods and analysis This generic cohort protocol provides the information to establish a prospective population-based cohort study in low-income settings with a high prevalence of CKDu. This involves a baseline survey that included key elements from the DEGREE survey (eg, using the previously published DEGREE methodology) of a population-representative sample, and subsequent follow-up visits in young adults (without a pre-existing diagnosis of CKD (eGFR<60 mL/min/1.73m 2), proteinuria or risk factors for CKD at baseline) over several years. Each visit involves a core questionnaire, and collection and storage of biological samples. Local capacity to measure serum creatinine will be required so that immediate feedback on kidney function can be provided to participants. After completion of follow-up, repeat measures of creatinine should be conducted in a central laboratory, using reference standards traceable to isotope dilution mass spectrometry (IDMS) quality control material to quantify the main outcome of eGFR decline over time, alongside a description of the early evolution of disease and risk factors for eGFR decline. Ethics and dissemination Ethical approval will be obtained by local researchers, and participants will provide informed consent before the study commences. Participants will typically receive feedback and advice on their laboratory results, and referral to a local health system where appropriate. © © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.
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- Hörsch, Dieter, et al.
(författare)
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Long-Term Treatment with Telotristat Ethyl in Patients with Carcinoid Syndrome Symptoms : Results from the TELEPATH Study
- 2022
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Ingår i: Neuroendocrinology. - : S. Karger. - 0028-3835 .- 1423-0194. ; 112:3, s. 298-309
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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).
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