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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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- Chijimatsu, M., et al.
(författare)
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Numerical study of the THM effects on the near-field safety of a hypothetical nuclear waste repository - BMT1 of the DECOVALEX III project. Part 1 : Conceptualization and characterization of the problems and summary of results
- 2005
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Ingår i: International Journal of Rock Mechanics And Mining Sciences. - : Elsevier BV. - 1365-1609 .- 1873-4545. ; 42:5-6, s. 720-730
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Tidskriftsartikel (refereegranskat)abstract
- Geological disposal of the spent nuclear fuel often uses the concept of multiple barrier systems. In order to predict the performance of these barriers, mathematical models have been developed, verified and validated against analytical solutions, laboratory tests and field experiments within the international DECOVALEX III project. These models in general consider the full coupling of thermal (T), hydraulic (H) and mechanical (M) processes that would prevail in the geological media around the repository. For Bench Mark Test no. 1 (BMTI) of the DECOVALEX III project, seven multinational research teams studied the implications of coupled THM processes on the safety of a hypothetical nuclear waste repository at the near-field and are presented in three accompanying papers in this issue. This paper is the first of the three companion papers, which provides the conceptualization and characterization of the BMT1 as well as some general conclusions based on the findings of the numerical studies. It also shows the process of building confidence in the mathematical models by calibration with a reference T-H-M experiment with realistic rock mass conditions and bentonite properties and measured outputs of thermal, hydraulic and mechanical variables.
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- Millard, A., et al.
(författare)
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Numerical study of the THM effects on the near-field safety of a hypothetical nuclear waste repository - BMT1 of the DECOVALEX III project. Part 2 : Effects of THM coupling in continuous and homogeneous rocks
- 2005
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Ingår i: International Journal of Rock Mechanics And Mining Sciences. - : Elsevier BV. - 1365-1609 .- 1873-4545. ; 42:5-6, s. 731-744
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Tidskriftsartikel (refereegranskat)abstract
- An evaluation of the importance of the thermo-hydro-mechanical couplings (THM) on the performance assessment of a deep underground radioactive waste repository has been made as a part of the international DECOVALEX III project. It is a numerical study that simulates a generic repository configuration in the near field in a continuous and homogeneous hard rock. A periodic repository configuration comprises a single vertical borehole, containing a canister surrounded by an over-pack and a bentonite layer, and the backfilled upper portion of the gallery. The thermo-hydro-mechanical evolution of the whole configuration is simulated over a period of 100 years. The importance of the rock mass's intrinsic permeability has been investigated through scoping calculations with three values: 10(-17), 10(-18) and 10(-19) m(2). Comparison of the results predicted by fully coupled THM analysis as well as partially coupled TH, TM and HM analyses, in terms of several predefined indicators of importance for performance assessment, enables us to identify the effects of the different combinations of couplings, which play a crucial role with respect to safety issues. The results demonstrate that temperature is hardly affected by the couplings. In contrast, the influence of the couplings on the mechanical stresses is considerable.
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- Fransson, Åsa, 1971, et al.
(författare)
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A new parameter to assess hydromechanical effects in single-hole hydraulic testing and grouting
- 2007
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Ingår i: International Journal of Rock Mechanics and Minings Sciences. - : Elsevier BV. - 1365-1609. ; 44:7, s. 1011-1021
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Tidskriftsartikel (refereegranskat)abstract
- Grouting or filling of the open voids in fractured rock is done by introducing a fluid (grout) through boreholes under pressure. The grout may be either a Newtonian fluid or a Bingham fluid. The penetration of the grout and the resulting pressure profile may give rise to hydromechanical effects, which depend on factors such as the fracture aperture, the pressure at the borehole, and the rheological properties of the grout. In this paper, we postulate that a new parameter, Å, which is the areal integral of the fluid pressure change over the fracture plane, is an appropriate measure to describe the change in fracture aperture volume due to a change in effective stress. In many cases, analytic expressions are available to calculate pressure profiles and the Å parameter. The approach is verified using a fully coupled hydromechanical simulator for the case of a Newtonian fluid. Results of the verification exercise show that the new approach is reasonable and that the Å parameter is a good measure for the fracture volume change: i.e., the larger the Å parameter, the larger the fracture volume change, in an almost linear fashion. To demonstrate the application of the approach, short duration hydraulic tests and constant pressure grouting are studied. It is concluded that using analytic expressions for penetration lengths and pressure profiles to calculate the Å parameter provides a possibility to describe a complex situation and compare, discuss and weigh the impact of hydromechanical couplings for different alternative grouting strategies. Further, the analyses identify an effect of high-pressure grouting, that of uncontrolled grouting of larger fractures and insufficient (or less-than-expected) sealing of finer fractures under certain grouting conditions. © 2007 Elsevier Ltd. All rights reserved.
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- Hudson, John A., et al.
(författare)
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Characterising and modelling the excavation damaged zone in crystalline rock in the context of radioactive waste disposal
- 2009
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Ingår i: Environmental Geology. - : Springer Science and Business Media LLC. - 0943-0105 .- 1432-0495. ; 57:6, s. 1275-1297
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Tidskriftsartikel (refereegranskat)abstract
- This paper describes current knowledge about the nature of and potential for thermo-hydro-mechanical-chemical modelling of the excavation damaged zone (EDZ) around the excavations for an underground radioactive waste repository. In the first part of the paper, the disturbances associated with excavation are explained, together with reviews of Workshops that have been held on the subject. In the second part of the paper, the results of a DECOVALEX [DEmonstration of COupled models and their VALidation against EXperiment: research funded by an international consortium of radioactive waste regulators and implementers (http://www.decovalex.com)] research programme on modelling the EDZ are presented. Four research teams used four different models to simulate the complete stress-strain curve for Avro granite from the Swedish A"spo Hard Rock Laboratory. Subsequent research extended the work to computer simulation of the evolution of the repository using a 'wall-block model' and a 'near-field model'. This included assessing the evolution of stress, failure and permeability and time-dependent effects during repository evolution. As discussed, all the computer models are well suited to sensitivity studies for evaluating the influence of their respective supporting parameters on the complete stress-strain curve for rock and for modelling the EDZ.
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