Comparison of Adjuvant Therapies Using Quality-Of-Life Considerations

The benefit for patients with operable breast cancer treated with adjuvant systemic therapy is small, if reduction of early mortality within the context of randomized control trials is used for treatment comparison. One might consider that the 75%-85% of patients who die despite treatment are overtreated, as are patients who remain alive even without therapy within a given time frame. Larger treatment benefits in terms of avoided or delayed breast cancer relapse have been demonstrated even at early phases of follow-up in the vast majority of adjuvant trials. Exposure of all patients to adjuvant therapy at a time at which no symptoms of disease are present is detrimental in terms of quality of life. Based on our assumption that the quality of life of the patient is typically altered both by subjective toxic effects of adjuvant treatment and by the appearance of relapse, we developed a method of comparing treatment effects in terms of time without symptoms of disease and toxicity of treatment (TWiST). Because the impact of treatment on relapse rates appears earlier than survival effects in all adjuvant therapy trials, and because the value of time without relapse in terms of the quality of life of the patients is as yet poorly defined, we have generalized our method of comparing treatment attitudes to include individual qualitative judgment values. The experience gained from integrating quality-of-life issues into clinical trials for breast cancer might also be applied to other diseases characterized by a chronic course, toxic treatments, and gains in periods of relative or absolute freedom from toxic effects and progressive diseas

Water in the Lithospheric Mantle Beneath a Phanerozoic Continental Belt: FTIR Analyses of Alligator Lake Xenoliths (Yukon, Canada)

Water in the mantle influences melting, metasomatism, viscosity and electrical conductivity. The Alligator Lake mantle xenolith suite is one of three bimodal peridotite suites from the northern Canadian Cordillera brought to the surface by alkali basalts, i.e., it consists of chemically distinct lherzolites and harzburgites. The lherzolites have equilibration temperatures about 50 C lower than the harzburgites and are thought to represent the fertile upper mantle of the region. The harzburgites might have come from slightly deeper in the mantle and/or be the result of a melting event above an asthenospheric upwelling detected as a seismic anomaly at 400-500 km depth. Major and trace element data are best interpreted as the lherzolite mantle having simultaneously experienced 20-25% partial melting and a metasomatic event to create the harzburgites. Well-characterized xenoliths are being analyzed for water by FTIR. Harzburgites contain 29-52 ppm H2O in orthopyroxene (opx) and (is) approximately140 ppm H2O in clinopyroxene (cpx). The lherzolites have H2O contents of 27-150 ppm in opx and 46-361 ppm in cpx. Despite correlating with enrichments in LREE, the water contents of the harzburgite pyroxenes are low relative to those of typical peridotite xenoliths, suggesting that the metasomatic agents were water-poor, contrarily to what has been suggested before. The water content of cpx is about double that of opx indicating equilibrium. Olivine water contents are low ((is) less than 5 ppm H2O) and out of equilibrium with those of opx and cpx, which may be due to H loss during xenolith ascent. This is consistent with olivines containing more water in their cores than their rims. Olivines exclusively exhibit water bands in the 3400-3000 cm-1 range, which may be indicative of a reduced environment

Systemic treatments for women with breast cancer: outcome with relation to screening for the disease

Early detection and proper care of breast cancer are currently the best available approaches to the treatment of patients with the disease. In countries with a breast cancer screening programme, there has been a demonstrated reduction in breast cancer-related mortality. Such reduction has also been observed in Switzerland, a country in which no national programme of screening is available. Although there is no doubt that early diagnosis might have had a major role in reducing breast cancer mortality the magnitude of this effect is unknown. Research with tailored approaches on alternative imaging for early detection of breast cancer in high-risk women and on treatments offered according to proper criteria of responsiveness to therapies is warrante

Temperature And Lifetime Measurements In The SSX Wind Tunnel

We describe ion and electron temperature measurements in the Swarthmore Spheromak Experiment (SSX) MHD wind tunnel with the goal of understanding limitations on the lifetime of our Taylor-state plasma. A simple model based on the equilibrium eigenvalue and Spitzer resistivity predicted the lifetime satisfactorily during the first phase of the plasma evolution. We measured an average Tₑ along a chord by taking the ratio of the CIII97.7 nm to CIV155 nm line intensities using a vacuum ultraviolet (VUV) monochromator. We also recorded local measurements of Tₑ and nₑ using a double Langmuir probe in order to inform our interpretation of the VUV data. Our results indicated that the plasma decayed inductively during a large part of the evolution. Ion Doppler spectroscopy measurements suggested that ions cooled more slowly than would be expected from thermal equilibration with the electrons, which maintained a constant temperature throughout the lifetime of the plasma

New treatments for breast cancer: Breakthroughs for patient care or just steps in the right direction?

Three areas of clinical research in breast cancer treatment led to news breaking presentations at the American Society of Clinical Oncology (ASCO) meeting, 1998, in Los Angeles. All three subjects represent important advances in cancer medicine. Prevention: Two related drugs, tamoxifen and raloxifene, were found in placebo controlled trials to significantly reduce the incidence of breast cancer for women at increased risk of developing the disease. Patterns of relapse showed that the reduced rate of breast cancer was exclusively observed for tumors expressing estrogen receptors, while the rate of tumors classified as estrogen-receptor negative was similar for the treatment and the control groups. This may indicate that the observed reduction in breast cancer incidence is due to a treatment effect on occult disease rather than its prevention. We certainly have no adequate information on mortality prevention. Adjuvant therapies: Taxol given every three weeks for four courses following an adjuvant treatment with four courses of doxorubicin and cyclophosphamide (AC) combination was found to be superior to not adding treatment after the four courses of AC in a trial involving 3170 patients. At 22 months of median follow-up, the quoted P-values were P = 0.0077 for disease-free survival and P = 0.039 for overall survival, but these did not cross the prospectively defined interim analysis boundaries for statistical significance at the 0.05 level. The difference was observed early during follow-up, and was exclusively seen in the 40% of patients who had ER-negative primaries and, therefore, did not receive tamoxifen following chemotherapy. One may thus argue that the early difference observed was primarily due to differences in the duration of the treatment regimens in the two groups and the early entry into the trial of patients with particularly aggressive neoplasia (e.g., ER-negative primaries) who would have benefited from a longer duration treatment. Treatment of advanced disease: The use of monoclonal antibodies to c-erb-B2 was found to induce responses in metastatic breast cancer. Patients with tumors expressing c-erb-B2 responded to weekly infusions of this biological agent. It was particularly impressive that the response rate for patients receiving infusion of the monoclonal antibodies together with the cytotoxics was superior to that with chemotherapy alone in a randomized trial. It is important to note that only patients with tumors overexpressing c-erbB-2 (the overall incidence is about 20%) were tested. It must still be demonstrated that the effect of these monoclonal antibodies is indeed confined to cells overexpressing c-erbB-2. Treatment related cardiac tox-icity remains a problem, and the effects of treatment in various subsets of patients need to be defined before starting investigations in the adjuvant setting, which is a clear further objective of this specific research. The significant findings from clinical research opened several new questions, which must be answered before allowing them to be employed in routine patient car

A mineral systems approach to the development of structural targeting criteria for orogenic gold deposits in the Asankrangwa gold belt of the Kumasi Basin, South-west Ghana

The Kumasi Basin in South-west Ghana lies at the centre of the best-endowed Paleoproterozoic gold province in the world. The Kumasi Basin and margins of the adjacent volcanic belts are host to six world class gold camps: (1) 62 Moz Obuasi camp, (2) 22 Moz Prestea-Bogoso camp, (3) 11 Moz Asanko Gold Mine camp, (4) 9 Moz Edikan camp, (5) 7 Moz Bibiani camp, (6) 5 Moz Chirano camp, as well as several additional minor gold camps and many more prospects. Cumulatively these camps account for>116 Moz of endowment and contribute to making south-west Ghana the greatest Paleoproterozoic gold province in the world. Gold deposits in the Kumasi Basin are shear zone hosted and mineralisation ranges from disseminated to massive sulphide refractory deposits, to free milling quartz vein style deposits. Structural relationships and age dating indicate that most deposits are genetically related and were formed during a single episode of gold mineralisation during the D4 NNW-SSE crustal shortening deformation event of the Eburnean Orogeny (2125 – 1980 Ma). The understanding of structural controls on mineralisation is critical for exploration success as it allows exploration to focus on areas where these structural controls exist. This study uses a mineral systems approach to understand the relationship between the geodynamic history and structural controls on gold mineralisation in the Kumasi Basin at various scales, and define targeting criteria which can be applied for the purpose of developing predictive exploration models for making new discoveries in the Asanko Gold Mine camp located in the Asankrangwa Belt. The study used a quantitative analysis to establish residual endowment potential in the Asankrangwa Belt, providing the basis for a business model and resulting exploration strategy. Once established, a Fry autocorrelation analysis was applied to identify trends in deposit and camp spatial distribution to which critical geological processes were ascribed. Observed trends were mapped from multi-scale geophysical data sets and through interpretation of existing geophysical structure models, and structural criteria for targeting orogenic gold deposits at the regional and camp scales were developed. Results show that different structural controls on mineralisation act at the regional and camp scale. At the regional scale the distribution of gold camps was found to be controlled by fundamental N-S and NW-SE basement structures with gold camps forming where they intersect NE-SW first and second order structural corridors. At the Asanko Gold Mine camp scale, deposit distribution was found to be related to the intersection between major second order D3 NE-SW shear zones, minor third order D4 NNE-SSW brittle faults, and cryptic NW-SE upward propagating basement structures. In addition to these structural criteria, deposits in the Asanko Gold Mine camp were found to be aligned along a NNE-SSW lineament caused by the interaction between the N-S basement structure and the NE-SW trending Asankrangwa Belt shear corridor

Q-TWiST analysis of lapatinib combined with capecitabine for the treatment of metastatic breast cancer

The addition of lapatinib (Tykerb/Tyverb) to capecitabine (Xeloda) delays disease progression more effectively than capecitabine monotherapy in women with previously treated HER2+ metastatic breast cancer (MBC). The quality-adjusted time without symptoms of disease or toxicity of treatment (Q-TWiST) method was used to compare treatments. The area under survival curves was partitioned into health states: toxicity (TOX), time without symptoms of disease progression or toxicity (TWiST), and relapse period until death or end of follow-up (REL). Average times spent in each state, weighted by utility, were derived and comparisons of Q-TWiST between groups performed with varying combinations of the utility weights. Utility weights of 0.5 for both TOX and REL, that is, counting 2 days of TOX or REL as 1 day of TWiST, resulted in a 7-week difference in quality-adjusted survival favouring combination therapy (P=0.0013). The Q-TWiST difference is clinically meaningful and was statistically significant across an entire matrix of possible utility weights. Results were robust in sensitivity analyses. An analysis with utilities based on EQ-5D scores was consistent with the above findings. Combination therapy of lapatinib with capecitabine resulted in greater quality-adjusted survival than capecitabine monotherapy in trastuzumab-refractory MBC patients