Marc Buyse

..Contemporary biomarker-based clinical trials in oncology are used as examples...

..We investigated whether progression-free survival (PFS) could be considered a valid surrogate for OS in advanced colorectal cancer...

..Data from several meta-analyses suggest that progression-free survival is an acceptable surrogate in advanced colorectal and ovarian cancer, but not in breast and prostate cancer...

..No consensus yet exists on processes or standards for pragmatic evaluation and adoption of biomarkers and surrogate end points in the absence of robust statistical validation...

..We also show that they lead to a general measure of the difference between the groups called the 'proportion in favor of treatment', denoted Δ, which is related to traditional measures of treatment effect for a single variable...

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..We conclude that IL-2 alone is not an effective remission maintenance therapy for AML patients in CR1...

..98). In this article, we show how these discrepant results can be reconciled through the estimation of expected survival curves...

..We aimed to assess whether leukemia-free survival is an acceptable statistical surrogate for overall survival when applied to remission maintenance therapy for acute myeloid leukemia...

..86. One trial with a large treatment effect on PFS and OS had a strong influence on the results in advanced disease. DFS (and PFS in advanced disease) are acceptable surrogates for OS in colorectal cancer...

..All of these potential contributions are illustrated with examples in early and advanced colorectal cancer...

..However, signatures were never compared on an independent population of untreated breast cancer patients, where risk assessment was computed using the original algorithms and microarray platforms...

..88 and 0.89, respectively. CONCLUSIONS: The 70-gene signature adds independent prognostic information to clinicopathologic risk assessment for patients with early breast cancer...

..The aims of this study conducted by TRANSBIG were to independently validate these results and to compare the outcome with clinical risk assessment...

..We apply the previous methodology using data from two clinical studies in psychiatry and ophthalmology...

..We briefly present a hierarchical framework that incorporates ideas from Prentice's work and is uniformly applicable to different types of surrogate and true clinical outcomes...

..However, although the basal and the ErbB2 subtypes are repeatedly recognized, identification of estrogen receptor (ER) -positive subtypes has been inconsistent. Therefore, refinement of their molecular definition is needed...

..Implications for design and for predicting the effect of treatment in a new trial, based on the surrogate, are discussed. A case study in schizophrenia is analysed...

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..Clearly statistical evidence should only be seen as a component in a decision making process that also involves a number of clinical and biological considerations...

..One of its interesting features, apart from providing information relevant to the practical use of a surrogate endpoint, is its natural interpretation from a clinical point of view...

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..J Clin Oncol 22:484-492, 2004). Our analysis supports the conclusion of Sargent et al. and shows that using DFS at 2 or 3 years would be the best option for the prediction of OS at 5 years...

..To summarize the additional uncertainty from using a predicted instead of true result for the estimated treatment effect, we compute its multiplier of standard error. Software is available for download...

..In this paper, we argue that such a multiunit approach should be adopted because it overcomes difficulties that necessarily surround validation efforts based on a single trial. These difficulties are highlighted...

..We examined whether histologic grade was associated with gene expression profiles of breast cancers and whether such profiles could be used to improve histologic grading...

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..The Breast International Group 02-98 randomized trial tested the effect of incorporating docetaxel into anthracycline-based adjuvant chemotherapy and compared sequential vs concurrent administration of doxorubicin and docetaxel...

..4% of these patients. CONCLUSION: Oxaliplatin can be safely stopped after six cycles in a FOLFOX regimen. Further study is needed to fully evaluate oxaliplatin reintroduction...

..The purpose of this meta-analysis is to assess the survival and disease-free survival benefits of treating patients after surgical resection of a primary colorectal tumor with oral fluoropyrimidines for 1 year...

..This phase III study investigated two sequences: folinic acid, FU, and irinotecan (FOLFIRI) followed by folinic acid, FU, and oxaliplatin (FOLFOX6; arm A), and FOLFOX6 followed by FOLFIRI (arm B)...

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..The interested reader can refer to the statistical appendix for details on the methodology used for all meta-analyses...

..This review describes the research carried out in this field through randomized trials and meta-analyses aimed at optimizing the efficacy of front-line chemotherapy...

..Therefore, recommending general population screening with biennial FOBT is still an open question...

..A shorter-term end point providing convincing evidence to allow treatment comparisons could significantly speed the translation of advances into practice...

..We previously validated disease-free survival (DFS) after 3-year follow-up as an excellent predictor of 5-year OS results. Here we explore shorter term DFS and OS end points, as well as stage dependency...

..We hope that this article will trigger further discussion about the difficulties of setting up and analyzing trials aimed at establishing the worth of new methods for better selection of patients for cancer treatment...

..The proposed guidelines may add to the quality and cross-comparability of future studies of adjuvant treatments for cancer...

..This meta-analysis uses data from all relevant trials to detect any advantages of taxanes in terms of tumor response, progression-free survival (PFS), and survival...

..Abdominal obesity is associated with metabolic abnormalities and increased risk of atherosclerotic cardiovascular disease. However, no obesity management strategy has demonstrated the ability to slow progression of coronary disease...

..The purpose of this review is to discuss recently published work on endpoints for early and advanced colorectal cancer, as well as the statistical approaches used to validate surrogate endpoints...