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- Abe, O, et al.
(författare)
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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Ingår i: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Tidskriftsartikel (refereegranskat)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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- Christlieb, N., et al.
(författare)
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The Hamburg/ESO R-process Enhanced Star survey (HERES). I. Project description, and discovery of two stars with strong enhancements of neutron-capture elements
- 2004
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Ingår i: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 428:3, s. 1027-1037
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Tidskriftsartikel (refereegranskat)abstract
- We report on a dedicated effort to identify and study metal-poor stars strongly enhanced in r-process elements ([r/Fe]>1 dex; hereafter r-IIstars), the Hamburg/ESO R-process Enhanced Star survey (HERES).Moderate-resolution (∼2 Å) follow-up spectroscopy has been obtained for metal-poor giant candidates selected from the Hamburg/ESO objective-prism survey (HES) as well as the HK survey to identify sharp-lined stars with [Fe/H]<-2.5 dex. For several hundred confirmed metal-poor giants brighter than B∼ 16.5 mag (most of them from theHES), ``snapshot'' spectra (R∼ 20 000; S/N ∼ 30 per pixel) are being obtained with VLT/UVES, with the main aim of finding the 2-3% r-II stars expected to be among them. These are studied in detail by means of higher resolution and higher S/N spectra. In this paper we describe a pilot study based on a set of 35 stars, including 23 from the HK survey,eight from the HES, and four comparison stars. We discovered two new r-II stars, CS 29497-004 ([Eu/Fe]=1.64± 0.22) and CS 29491-069([Eu/Fe]=1.08± 0.23). A first abundance analysis of CS 29497-004 yields that its abundances of Ba to Dy are on average enhanced by 1.5 dex with respect to iron and the Sun and match a scaled solar r-process pattern well, while Th is underabundant relative to that pattern by 0.3dex, which we attribute to radioactive decay. That is, CS 29497-004 seems not to belong to the class of r-process enhanced stars displaying an ``actinide boost'', like CS 31082-001 (Hill et al. 2002), or CS30306-132 (Honda et al. 2004b). The abundance pattern agrees well with predictions of the phenomenological model of Qian & Wasserburg.Based in large part on observations collected at the European Southern Observatory, Paranal, Chile (proposal number 68.B-0320).}
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- Coombes, R C, et al.
(författare)
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Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial.
- 2007
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Ingår i: Lancet. - 1474-547X. ; 369:9561, s. 559-70
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Early improvements in disease-free survival have been noted when an aromatase inhibitor is given either instead of or sequentially after tamoxifen in postmenopausal women with oestrogen-receptor-positive early breast cancer. However, little information exists on the long-term effects of aromatase inhibitors after treatment, and whether these early improvements lead to real gains in survival. METHODS: 4724 postmenopausal patients with unilateral invasive, oestrogen-receptor-positive or oestrogen-receptor-unknown breast cancer who were disease-free on 2-3 years of tamoxifen, were randomly assigned to switch to exemestane (n=2352) or to continue tamoxifen (n=2372) for the remainder of a 5-year endocrine treatment period. The primary endpoint was disease-free survival; overall survival was a secondary endpoint. Efficacy analyses were intention-to-treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN11883920. RESULTS: After a median follow-up of 55.7 months (range 0-89.7), 809 events contributing to the analysis of disease-free survival had been reported (354 exemestane, 455 tamoxifen); unadjusted hazard ratio 0.76 (95% CI 0.66-0.88, p=0.0001) in favour of exemestane, absolute benefit 3.3% (95% CI 1.6-4.9) by end of treatment (ie, 2.5 years after randomisation). 222 deaths occurred in the exemestane group compared with 261 deaths in the tamoxifen group; unadjusted hazard ratio 0.85 (95% CI 0.71-1.02, p=0.08), 0.83 (0.69-1.00, p=0.05) when 122 patients with oestrogen-receptor-negative disease were excluded. CONCLUSIONS: Our results suggest that early improvements in disease-free survival noted in patients who switch to exemestane after 2-3 years on tamoxifen persist after treatment, and translate into a modest improvement in overall survival.
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- Grant, S. C., et al.
(författare)
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Alginate assessment by NMR microscopy
- 2005
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Ingår i: Journal of materials science. Materials in medicine. - : Springer Science and Business Media LLC. - 0957-4530 .- 1573-4838. ; 16:6, s. 511-514
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Tidskriftsartikel (refereegranskat)abstract
- Alginate hydrogels have long been used to encapsulate cells for the purpose of cell transplantation. However, they also have been criticized because they fail to consistently maintain their integrity for extended periods of time. Two issues of critical importance that have yet to be thoroughly addressed concerning the long-term integrity of alginate/poly-L-lysine/alginate microcapsules are: (i) are there temporal changes in the alginate/poly-L-lysine interaction and (ii) are there temporal changes in the alginate gel structure. NMR microscopy is a non-invasive analytical technique that can address these issues. in this report, we present data to demonstrate the utility of H-1 NMR microscopy to (i) visualize the poly-L-lysine layer in an effort to address the first question, and (ii) to observe temporal changes in the alginate matrix that may represent changes in the gel structure.
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- Herlitz, Johan, et al.
(författare)
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A comparison between patients suffering in-hospital and out-of-hospital cardiac arrest in terms of treatment and outcome
- 2000
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Ingår i: Journal of Internal Medicine. - : Wiley-Blackwell Publishing Ltd.. - 0954-6820 .- 1365-2796. ; 248:1, s. 53-60
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To compare treatment and outcome amongst patients suffering in-hospital and out-of-hospital cardiac arrest in the same community. PATIENTS: All patients suffering in-hospital cardiac arrest in Sahlgrenska University Hospital covering half the catchment area of the community of Göteborg (500 000 inhabitants) and all patients suffering out-of-hospital cardiac arrest in the community of Göteborg. Criteria for inclusion were that resuscitation efforts should have been attempted. TIME OF SURVEY: From 1 November 1994 to 1 November 1997. METHODS: Data were recorded both prospectively and retrospectively. RESULTS: In total, 422 patients suffered in-hospital cardiac arrest and 778 patients suffered out-of-hospital cardiac arrest. Patients with in-hospital cardiac arrest included more women and were more frequently found in ventricular fibrillation. The median interval between collapse and defibrillation was 2 min in in-hospital cardiac arrest compared with 7 min in out-of-hospital cardiac arrest (< 0.001). The proportion of patients being discharged from hospital was 37.5% after in-hospital cardiac arrest, compared with 8.7% after out-of-hospital cardiac arrest (P < 0.001). Corresponding figures for patients found in ventricular fibrillation were 56.9 vs. 19.7% (P < 0.001) and for patients found in asystole 25.2 vs. 1.8% (P < 0.001). CONCLUSION: In a survey evaluating patients with in-hospital and out-of-hospital cardiac arrest in whom resuscitation efforts were attempted, we found that the former group had a survival rate more than four times higher than the latter. Possible strong contributing factors to this observation are: (i) shorter time interval to start of treatment, and (ii) a prepared selection for resuscitation efforts.
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