| 11. |
- Falkmer, Ursula G., et al.
(författare)
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Malignant presacral ghrelinoma with long-standing hyperghrelinaemia
- 2015
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Ingår i: Uppsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 120:4, s. 299-304
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Tidskriftsartikel (refereegranskat)abstract
- Background. A 57-year old man with low-back pain was found to have a 3 x 3 x 3 cm presacral neuroendocrine tumour (NET) with widespread metastases, mainly to the skeleton. His neoplastic disease responded well to peptide receptor radionuclide therapy (PRRT) with the radiotagged somatostatin agonist Lu-177-DOTATATE. During almost 10 years he was fit for a normal life. He succumbed to an intraspinal dissemination. Procedures. A resection of the rectum, with a non-radical excision of the adjacent NET, was made. In addition to computerized tomography (CT), receptor positron emission tomography (PET) with Ga-68-labelled somatostatin analogues was used. Observations. The NET showed the growth pattern and immunoprofile of a G2 carcinoid. A majority cell population displayed immunoreactivity to ghrelin, exceptionally with co-immunoreactivity to motilin. Somatostatin receptor scintigraphy and Ga-68-DOTATATE PET-CT demonstrated uptake in the metastatic lesions. High serum concentrations of total (desacyl-)ghrelin were found with fluctuations reflecting the severity of the symptoms. In contrast, the concentrations of active (acyl-)ghrelin were consistently low, as were those of chromogranin A (CgA).Conclusions. Neoplastically transformed ghrelin cells can release large amounts of desacyl-ghrelin, evoking an array of non-specific clinical symptoms. Despite an early dissemination to the skeleton, a ghrelinoma can be compatible with longevity after adequate radiotherapy.
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| 13. |
- Strosberg, Jonathan, et al.
(författare)
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Health-Related Quality of Life in Patients With Progressive Midgut Neuroendocrine Tumors Treated With Lu-177-Dotatate in the Phase III NETTER-1 Trial
- 2018
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Ingår i: Journal of Clinical Oncology. - : AMER SOC CLINICAL ONCOLOGY. - 0732-183X .- 1527-7755. ; 36:25, s. 2578-2584
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Tidskriftsartikel (refereegranskat)abstract
- PurposeNeuroendocrine tumor (NET) progression is associated with deterioration in quality of life (QoL). We assessed the impact of Lu-177-Dotatate treatment on time to deterioration in health-related QoL.MethodsThe NETTER-1 trial is an international phase III study in patients with midgut NETs. Patients were randomly assigned to treatment with Lu-177-Dotatate versus high-dose octreotide. European Organisation for Research and Treatment of Cancer quality-of-life questionnaires QLQ C-30 and G.I.NET-21 were assessed during the trial to determine the impact of treatment on health-related QoL. Patients completed the questionnaires at baseline and every 12 weeks until tumor progression. QoL scores were converted to a 100-point scale according to European Organisation for Research and Treatment of Cancer instructions, and individual changes from baseline scores were assessed. Time to QoL deterioration (TTD) was defined as the time from random assignment to the first QoL deterioration 10 points for each patient in the corresponding domain scale. All analyses were conducted on the intention-to-treat population. Patients with no deterioration were censored at the last QoL assessment date.ResultsTTD was significantly longer in the Lu-177-Dotatate arm (n = 117) versus the control arm (n = 114) for the following domains: global health status (hazard ratio [HR], 0.406), physical functioning (HR, 0.518), role functioning (HR, 0.580), fatigue (HR, 0.621), pain (HR, 0.566), diarrhea (HR, 0.473), disease-related worries (HR, 0.572), and body image (HR, 0.425). Differences in median TTD were clinically significant in several domains: 28.8 months versus 6.1 months for global health status, and 25.2 months versus 11.5 months for physical functioning.ConclusionThis analysis from the NETTER-1 phase III study demonstrates that, in addition to improving progression-free survival, Lu-177-Dotatate provides a significant QoL benefit for patients with progressive midgut NETs compared with high-dose octreotide.
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| 14. |
- Strosberg, Jonathan, et al.
(författare)
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Impact of liver tumour burden, alkaline phosphatase elevation, and target lesion size on treatment outcomes with Lu-177-Dotatate : an analysis of the NETTER-1 study
- 2020
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : SPRINGER. - 1619-7070 .- 1619-7089. ; 47:10, s. 2372-2382
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To assess the impact of baseline liver tumour burden, alkaline phosphatase (ALP) elevation, and target lesion size on treatment outcomes with Lu-177-Dotatate. Methods In the phase 3 NETTER-1 trial, patients with advanced, progressive midgut neuroendocrine tumours (NET) were randomised to 177Lu-Dotatate (every 8 weeks, four cycles) plus octreotide long-acting release (LAR) or to octreotide LAR 60 mg. Primary endpoint was progression-free survival (PFS). Analyses of PFS by baseline factors, including liver tumour burden, ALP elevation, and target lesion size, were performed using Kaplan-Meier estimates; hazard ratios (HRs) with corresponding 95% CIs were estimated using Cox regression. Results Significantly prolonged median PFS occurred with Lu-177-Dotatate versus octreotide LAR 60 mg in patients with low (< 25%), moderate (25-50%), and high (> 50%) liver tumour burden (HR 0.187, 0.216, 0.145), and normal or elevated ALP (HR 0.153, 0.177), and in the presence or absence of a large target lesion (diameter > 30 mm; HR, 0.213, 0.063). Within the Lu-177-Dotatate arm, no significant difference in PFS was observed amongst patients with low/moderate/high liver tumour burden (P = 0.7225) or with normal/elevated baseline ALP (P = 0.3532), but absence of a large target lesion was associated with improved PFS (P = 0.0222). Grade 3 and 4 liver function abnormalities were rare and did not appear to be associated with high baseline liver tumour burden. Conclusions Lu-177-Dotatate demonstrated significant prolongation in PFS versus high-dose octreotide LAR in patients with advanced, progressive midgut NET, regardless of baseline liver tumour burden, elevated ALP, or the presence of a large target lesion. : NCT01578239, EudraCT: 2011-005049-11
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| 15. |
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| 16. |
- 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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| 17. |
- Öberg, Kjell, et al.
(författare)
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A Delphic consensus assessment : imaging and biomarkers in gastroenteropancreatic neuroendocrine tumor disease management
- 2016
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Ingår i: Endocrine Connections. - 2049-3614. ; 5:5, s. 174-187
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Tidskriftsartikel (refereegranskat)abstract
- The complexity of the clinical management of neuroendocrine neoplasia (NEN) is exacerbated by limitations in imaging modalities and a paucity of clinically useful biomarkers. Limitations in currently available imaging modalities reflect difficulties in measuring an intrinsically indolent disease, resolution inadequacies and inter-/intra-facility device variability and that RECIST (Response Evaluation Criteria in Solid Tumors) criteria are not optimal for NEN. Limitations of currently used biomarkers are that they are secretory biomarkers (chromogranin A, serotonin, neuron-specific enolase and pancreastatin); monoanalyte measurements; and lack sensitivity, specificity and predictive capacity. None of them meet the NIH metrics for clinical usage. A multinational, multidisciplinary Delphi consensus meeting of NEN experts (n = 33) assessed current imaging strategies and biomarkers in NEN management. Consensus (>75%) was achieved for 78% of the 142 questions. The panel concluded that morphological imaging has a diagnostic value. However, both imaging and current single-analyte biomarkers exhibit substantial limitations in measuring the disease status and predicting the therapeutic efficacy. RECIST remains suboptimal as a metric. A critical unmet need is the development of a clinico-biological tool to provide enhanced information regarding precise disease status and treatment response. The group considered that circulating RNA was better than current general NEN biomarkers and preliminary clinical data were considered promising. It was resolved that circulating multianalyte mRNA (NETest) had clinical utility in both diagnosis and monitoring disease status and therapeutic efficacy. Overall, it was concluded that a combination of tumor spatial and functional imaging with circulating transcripts (mRNA) would represent the future strategy for real-time monitoring of disease progress and therapeutic efficacy.
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