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- Strosberg, J., et al.
(author)
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Phase 3 Trial of Lu-177-Dotatate for Midgut Neuroendocrine Tumors
- 2017
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In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 376:2, s. 125-135
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Journal article (peer-reviewed)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. |
- Bonebrake, Timothy C., et al.
(author)
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Managing consequences of climate-driven species redistribution requires integration of ecology, conservation and social science
- 2018
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In: Biological Reviews. - : Wiley-Blackwell Publishing Inc.. - 1464-7931 .- 1469-185X. ; 93:1, s. 284-305
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Research review (peer-reviewed)abstract
- Climate change is driving a pervasive global redistribution of the planet's species. Species redistribution poses new questions for the study of ecosystems, conservation science and human societies that require a coordinated and integrated approach. Here we review recent progress, key gaps and strategic directions in this nascent research area, emphasising emerging themes in species redistribution biology, the importance of understanding underlying drivers and the need to anticipate novel outcomes of changes in species ranges. We highlight that species redistribution has manifest implications across multiple temporal and spatial scales and from genes to ecosystems. Understanding range shifts from ecological, physiological, genetic and biogeographical perspectives is essential for informing changing paradigms in conservation science and for designing conservation strategies that incorporate changing population connectivity and advance adaptation to climate change. Species redistributions present challenges for human well-being, environmental management and sustainable development. By synthesising recent approaches, theories and tools, our review establishes an interdisciplinary foundation for the development of future research on species redistribution. Specifically, we demonstrate how ecological, conservation and social research on species redistribution can best be achieved by working across disciplinary boundaries to develop and implement solutions to climate change challenges. Future studies should therefore integrate existing and complementary scientific frameworks while incorporating social science and human-centred approaches. Finally, we emphasise that the best science will not be useful unless more scientists engage with managers, policy makers and the public to develop responsible and socially acceptable options for the global challenges arising from species redistributions.
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| 3. |
- Laubenstein, Taryn, et al.
(author)
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Threats to Australia's oceans and coasts : A systematic review
- 2023
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In: Ocean and Coastal Management. - : Elsevier. - 0964-5691 .- 1873-524X. ; 231
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Research review (peer-reviewed)abstract
- Oceans and coasts provide important ecosystem, livelihood, and cultural values to humans and the planet but face current and future compounding threats from anthropogenic activities associated with expanding pop-ulations and their use of and reliance on these environments. To respond to and mitigate these threats, there is a need to first systematically understand and categorise them. This paper reviewed 226 articles from the period 2010-2020 on threats to Australia's oceans and coasts, resulting in the identification of a total of 307 threats. Threats were grouped into three broad categories - threats from use and extraction; environmental and human -induced threats; and policy and socio-political threats -then ranked by frequency. The most common 'threats from use and extraction' were recreational activities, non-point source pollution, and urban development; the most common 'environmental and human-induced threat' was increased temperatures; and the most common 'policy and socio-political threat' was policy gaps and failures (e.g., a lack of coastal climate adaptation policies). The identification of threats across all three categories increased over time; however, the identification of 'threats from use and extraction' increased most rapidly over the last four years (2017-2020). Threats were most often described for their impacts on environmental values (68%), followed by economic (14%), socio-cultural (12%), and Indigenous (6%) values. Only 45 of the 226 papers (20%) discussed multiple threats. The threats facing Australia's oceans and coasts are rising, cumulative, and multi-faceted, and the inherent tensions between varied uses, along with intensification of uses that derive short-term anthropogenic benefit, will continue to degrade the ecological sustainability of ocean and coastal systems if actions are not taken.
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| 4. |
- Pecl, Gretta T., et al.
(author)
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Biodiversity redistribution under climate change : Impacts on ecosystems and human well-being
- 2017
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 355:6332
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Research review (peer-reviewed)abstract
- Distributions of Earth's species are changing at accelerating rates, increasingly driven by human-mediated climate change. Such changes are already altering the composition of ecological communities, but beyond conservation of natural systems, how and why does this matter? We review evidence that climate-driven species redistribution at regional to global scales affects ecosystem functioning, human well-being, and the dynamics of climate change itself. Production of natural resources required for food security, patterns of disease transmission, and processes of carbon sequestration are all altered by changes in species distribution. Consideration of these effects of biodiversity redistribution is critical yet lacking in most mitigation and adaptation strategies, including the United Nation's Sustainable Development Goals.
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