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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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| 2. |
- Caplin, M. E., et al.
(författare)
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Pulmonary neuroendocrine (carcinoid) tumors : European Neuroendocrine Tumor Society expert consensus and recommendations for best practice for typical and atypical pulmonary carcinoids
- 2015
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 26:8, s. 1604-1620
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Tidskriftsartikel (refereegranskat)abstract
- Background: Pulmonary carcinoids (PCs) are rare tumors. As there is a paucity of randomized studies, this expert consensus document represents an initiative by the European Neuroendocrine Tumor Society to provide guidance on their management. Patients and methods: Bibliographical searches were carried out in PubMed for the terms 'pulmonary neuroendocrine tumors', 'bronchial neuroendocrine tumors', 'bronchial carcinoid tumors', 'pulmonary carcinoid', 'pulmonary typical/atypical carcinoid', and 'pulmonary carcinoid and diagnosis/treatment/epidemiology/prognosis'. A systematic review of the relevant literature was carried out, followed by expert review. Results: PCs are well-differentiated neuroendocrine tumors and include low-and intermediate-grade malignant tumors, i.e. typical (TC) and atypical carcinoid (AC), respectively. Contrast CT scan is the diagnostic gold standard for PCs, but pathology examination is mandatory for their correct classification. Somatostatin receptor imaging may visualize nearly 80% of the primary tumors and is most sensitive for metastatic disease. Plasma chromogranin A can be increased in PCs. Surgery is the treatment of choice for PCs with the aim of removing the tumor and preserving as much lung tissue as possible. Resection of metastases should be considered whenever possible with curative intent. Somatostatin analogs are the first-line treatment of carcinoid syndrome and may be considered as first-line systemic antiproliferative treatment in unresectable PCs, particularly of low-grade TC and AC. Locoregional or radiotargeted therapies should be considered for metastatic disease. Systemic chemotherapy is used for progressive PCs, although cytotoxic regimens have demonstrated limited effects with etoposide and platinum combination the most commonly used, however, temozolomide has shown most clinical benefit. Conclusions: PCs are complex tumors which require a multidisciplinary approach and long-term follow-up.
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| 4. |
- Caporale, N., et al.
(författare)
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From cohorts to molecules: Adverse impacts of endocrine disrupting mixtures
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375:6582
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Tidskriftsartikel (refereegranskat)abstract
- Convergent evidence associates exposure to endocrine disrupting chemicals (EDCs) with major human diseases, even at regulation-compliant concentrations. This might be because humans are exposed to EDC mixtures, whereas chemical regulation is based on a risk assessment of individual compounds. Here, we developed a mixture-centered risk assessment strategy that integrates epidemiological and experimental evidence. We identified that exposure to an EDC mixture in early pregnancy is associated with language delay in offspring. At human-relevant concentrations, this mixture disrupted hormone-regulated and disease-relevant regulatory networks in human brain organoids and in the model organisms Xenopus leavis and Danio rerio, as well as behavioral responses. Reinterrogating epidemiological data, we found that up to 54% of the children had prenatal exposures above experimentally derived levels of concern, reaching, for the upper decile compared with the lowest decile of exposure, a 3.3 times higher risk of language delay. © 2022 American Association for the Advancement of Science. All rights reserved.
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| 8. |
- Wymenga, A.N.M., et al.
(författare)
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Efficacy and Safety of Prolonged-Release Lanreotide in Patients with Gastrointestinal Neuroendocrine Tumors and Hormone-Related Symptoms
- 1999
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Ingår i: International Journal of Clinical Oncology. - 1341-9625 .- 1437-7772. ; 17:4, s. 1111-1117
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To evaluate the prolonged release (PR) of the long-acting somatostatin analog lanreotide in patients with gastrointestinal neuroendocrine tumors and its effect on hormone-related symptomatology, tumor markers, tumor size, tolerability, and quality of life (QOL). PATIENTS AND METHODS: Eligible patients had the following substantial daily symptoms: for patients with carcinoid tumors, three or more stools and/or 1.5 or more flushing episodes; for patients with gastrinoma, greater than 50% elevated basic acid output; and for patients with vasoactive intestinal peptide-secreting tumors (VIPomas), four or more stools and/or a stool volume of >/= 800 mL, a measurable tumor, and an elevated biochemical tumor marker (>/= two times the upper limit of the normal reference range). Lanreotide PR was administered intramuscularly every 14 days at 30 mg for 6 months. We measured efficacy by studying symptoms, tumor markers, tumor size, and QOL. Side effects were scored according to the National Cancer Institute's toxicity grading system and ultrasound examination of the gallbladder. RESULTS: Fifty-five patients were included in the study (48 patients with carcinoid tumors, six patients with gastrinoma, and one patient with VIPoma). Symptomatic improvement (> 50% reduction) occurred in 38% of the assessable patients with carcinoid tumors, in 67% of the gastrinoma patients, and in the VIPoma patient. Tumor markers normalized in two of 45 assessable patients, 19 patients exhibited a reduction (> 50%), 19 patients exhibited no change, and tumor markers rose by more than 50% in five patients. Tumor size was reduced in two of 31 assessable patients and remained stable in 25 patients; four patients experienced progression. QOL assessments after 1 month showed improvements in emotional and cognitive function, and diminished fatigue, sleeping disorders, and diarrhea. Eight of 30 assessable patients developed gallstones. CONCLUSION: Lanreotide PR is a well-tolerated somatostatin analog with significant clinical, biochemical, and antitumor effects that bring about a significant improvement in QOL for patients with neuroendocrine tumors.
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| 9. |
- Coutens, A., et al.
(författare)
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The ALMA-PILS survey: First detections of deuterated formamide and deuterated isocyanic acid in the interstellar medium
- 2016
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 590
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Tidskriftsartikel (refereegranskat)abstract
- Formamide (NH2CHO) has previously been detected in several star-forming regions and is thought to be a precursor for different prebiotic molecules. Its formation mechanism is still debated, however. Observations of formamide, related species, and their isopotologues may provide useful clues to the chemical pathways leading to their formation. The Protostellar Interferometric Line Survey (PILS) represents an unbiased, high angular resolution and sensitivity spectral survey of the low-mass protostellar binary IRAS 16293-2422 with the Atacama Large Millimeter/submillimeter Array (ALMA). For the first time, we detect the three singly deuterated forms of NH2CHO (NH2CDO, cis-and trans-NHDCHO), as well as DNCO towards the component B of this binary source. The images reveal that the different isotopologues are all present in the same region. Based on observations of the 13C isotopologues of formamide and a standard 12C/13C ratio, the deuterium fractionation is found to be similar for the three different forms with a value of about 2%. The DNCO/HNCO ratio is also comparable to the D/H ratio of formamide (~1%). These results are in agreement with the hypothesis that NH2CHO and HNCO are chemically related through grain-surface formation.
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| 10. |
- Diarbakerli, E., et al.
(författare)
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Learning from the past to plan for the future: A scoping review of musculoskeletal clinical research in Sweden 2010-2020
- 2022
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 127:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aims of this study are to 1) determine the scope of musculoskeletal (MSK)-related clinical research in Sweden; 2) collate the amount of first-tier funding received; 3) discuss strategies and infrastructure supporting future MSK clinical trials in Sweden. Methods: A systematic scoping review protocol was applied in PubMed, Scopus, and SweCRIS databases. The articles were examined, and data were extracted in multiple stages by three blinded authors. Results: The search strategy resulted in 3,025 publications from 479 Swedish-affiliated authors. Primary health care was the basis for 14% of the publications, 84% from secondary health care, and 2% from occupational health care with a similar proportional distribution of first-tier research grant financing. Approximately one in six publications were randomized controlled trials (RCTs), while the majority were of observational cohort design. The majority of publications in primary and occupational health care were related to pain disorders (51 and 67%, respectively), especially diagnosis, prognosis, and healthcare organizational-related interventions (34%) and rehabilitation (15%) with similar proportional distribution of first-tier research grant financing. In secondary health care, rheumatic inflammatory disorder-related publications were most prevalent (30%), most frequently concerning diagnosis, prognosis, and healthcare organizational-related interventions (20%), attracting approximately half of all first-tier funding. Publications related to degenerative joint disorders (25%), fractures (16%), and joint, tendon, and muscle injuries (13%) frequently concerned surgical and other orthopedic-related interventions (16, 6, and 8%, respectively). Pain disorder-related publications (10%) as well as bone health and osteoporosis-related publications (4%) most frequently concerned diagnosis, prognosis, and healthcare organizational-related interventions (5 and 3%, respectively). Conclusions: Swedish-affiliated MSK disorder research 2010-2020 was predominantly observational cohort rather than RCT based. There was skewed first-tier funding allocation considering prevalence/incidence and burden of disease. Use of infrastructure supporting register-based RCTs, placebo-controlled RCTs, and hybrid effectiveness-implementation studies on prevention and clinical intervention is important strategies for the future in all healthcare sectors.
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