Update on recommendations for assessing response from the Third International Workshop on Waldenstrom's Macroglobulinemia
ABSTRACT This report by an international consensus panel updates current recommendations for defining clinical response in Waldenstrom's macroglobulinemia (WM). The previously published response criteria incorporated parameters for monoclonal protein reduction and/or improvement of marrow and nodal involvement, and included definitions of complete and partial remissions. The criteria have been updated to include minor response and stable disease categories. In addition, the criteria now recognize that delayed responses after treatment with nucleoside analogues and biologic agents and the time point for assessing response in patients with WM should be considered so as to not miss or miscategorize a response. The new criteria should therefore help in better delineating responses to therapy in patients with WM, particularly with the wide use of nucleoside analogues and biologically based agents for this disease.
SourceAvailable from: Sergio Nery Simoes[Show abstract] [Hide abstract]
ABSTRACT: Various statistical and machine learning based algorithms have been proposed in literature for selecting an informative subset of genes from microarray data sets. The recent trend is to use functional knowledge to aid the gene selection process. In this paper we propose a clustering algorithm which generates multiple views (clusters) from the microarray expression profiles, each representing a particular facet of the data. Such multiple clusters are found to represent strongly connected regions of the known protein–protein interaction (PPI) networks, perhaps corresponding to those responsible for certain biological processes. Thus we integrate microarray data clustering with PPI knowledge to obtain enriched gene sets. Results on benchmark microarray data sets demonstrate the competitiveness of our method compared to gene selection techniques.IEEE International Conference on BioInformatics and BioEngineering, Boca Raton; 11/2014
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ABSTRACT: Informative censoring in a progression-free survival (PFS) analysis arises when patients are censored for initiation of an effective anticancer treatment before the protocol-defined progression, and these patients are at a different risk for treatment failure than those who continue on therapy. This may cause bias in the estimated PFS when using the Kaplan-Meier method for analysis. Although there are several articles that discuss this issue from a theoretical perspective or in randomized phase III studies, there are little data to demonstrate the magnitude of the bias on the estimated quantities from a phase II trial. This article describes the issues by using two oncology phase II trials as examples, evaluates the impact of the bias using simulations, and provides recommendations. The two trials were selected because they demonstrate two different reasons for censoring. Simulations show that the magnitude of the bias depends primarily on the proportion of patients who are informatively censored and secondarily on the hazard ratio between the group of patients who remain on study and the group of patients who are informatively censored. Recommendations include using an alternative end point, which includes inadequate response and initial signs of clinical progression as treatment failure, and a competing risk analysis for studies in which competing events preclude or modify the probability of observing the primary event of interest. If informative censoring cannot be avoided, then all patients should be observed until progression, and sensitivity analyses should be used as appropriate.Journal of Clinical Oncology 08/2014; 32(27). DOI:10.1200/JCO.2014.55.6340 · 17.88 Impact Factor
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ABSTRACT: The combination of bortezomib and rituximab was evaluated in patients with mantle cell lymphoma (MCL), follicular lymphoma (FL) and Waldenström macroglobulinaemia (WM), in a Phase I and later, a randomized Phase II study. In the randomized study, 42 patients with recurrent/refractory disease received either: bortezomib 1·3 mg/m(2) on days 1, 4, 8 and 11 of a 3-week cycle with rituximab 375 mg/m(2) on day 1 (21 patients) or: bortezomib 1·6 mg/m(2) and rituximab on days 1, 8, 15 and 22 of a 5-week cycle (with rituximab being given only in cycles 1 and 4).Twenty-eight patients were withdrawn (toxicity 16, progression 7, and 'patient choice' 5). The main toxicities were neurological, gastro-intestinal and haematological. The overall response rate was 28/42(67%) and by histology: MCL 11/19, FL 8/15, and WM 9/10. Ten of 28 responding patients remained progression-free at 1-3·5 years. Toxicity and efficacy were equivalent between the two groups. The combination has significant toxicity but is effective, particularly in patients with WM.British Journal of Haematology 11/2010; 151(4):346-53. DOI:10.1111/j.1365-2141.2010.08340.x · 4.96 Impact Factor