We sought to identify risk factors associated with the time to febrile neutropenia in patients with intermediate-grade, non-Hodgkin's lymphoma (NHL) who were receiving treatment with CHOP chemotherapy. Data were collected from 12 community and academic oncology practices participating in the Oncology Practice Pattern Study between 1991 and 1999. We reviewed the medical records of 577 intermediate-grade NHL patients who received initial CHOP chemotherapy and evaluated risk factors associated with time to first febrile neutropenic event. A febrile neutropenic event was defined as a body temperature of > 100.6 degrees F and an ANC nadir < 1000/mm3. A total of 160 patients experienced 224 febrile neutropenic events. The risk of febrile neutropenia was significantly associated with age > or = 65 years (p = 0.001), cardiovascular disease (p = 0.020), renal disease (p = 0.006), baseline hemoglobin < 12 g/dl (p = 0.018), > 80% planned average relative dose intensity (ARDI; p = 0.018), and no prophylactic colony-stimulating factor (CSF) use (p = 0.046). First febrile neutropenic events occurred by day 14 of cycle 1 in one-half of patients experiencing febrile neutropenia. In multivariate analysis, the risk of febrile neutropenia remained significantly associated with age > or = 65 years (HR = 1.65, 95% CI: 1.18-2.32), renal disease (HR = 1.91. 95% CI: 1.10-3.30), cardiovascular disease (HR = 1.54, 95% CI: 1.02-2.33), baseline hemoglobin < 12 g/dl (HR = 1.44, 95% CI: 1.04-2.00), > 80% planned CHOP ARDI (HR = 2.41, 95% CI: 1.30-4.47), and no CSF prophylaxis (HR = 2.13, 95% CI: 1.20-3.76). Such a model may permit the identification of patients at greatest risk of febrile neutropenia and, therefore, candidates for the selective prophylactic use of the hematopoietic growth factors.

Trastuzumab has been shown to be an effective therapy for women with breast cancer that overexpresses the human epidermal growth factor receptor 2 (HER2) protein. In the pivotal metastatic breast cancer trials, cardiac dysfunction was observed in women treated with trastuzumab and chemotherapy. The incidence and severity of cardiac dysfunction was greatest among patients who received trastuzumab in combination with anthracycline-based therapy. Those findings influenced the design of subsequent trastuzumab trials to include prospective evaluations of cardiac effects and protocols for cardiac monitoring and management. The risk of cardiotoxicity has also driven efforts to develop non-anthracycline-based regimens for women with HER2-positive breast cancers.With the increasing use of trastuzumab, particularly in the curative adjuvant setting, the need for a rational approach to the treatment and cardiac management of the relevant patient population is clear. The mandate of the Canadian Trastuzumab Working Group was to formulate recommendations, based on available data, for the assessment and management of cardiac complications during adjuvant trastuzumab therapy. The panel formulated recommendations in four areas:• Risk factors for cardiotoxicity • Effects of various regimens • Monitoring • ManagementThe recommendations published here are expected to evolve as more data become available and experience with trastuzumab in the adjuvant setting grows.

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This is an up-to-date introduction to, and overview of, marginal likelihood computation for model selection and hypothesis testing. Computing normalizing constants of probability models (or ratio of constants) is a fundamental issue in many applications in statistics, applied mathematics, signal processing and machine learning. This article provides a comprehensive study of the state-of-the-art of the topic. We highlight limitations, benefits, connections and differences among the different techniques. Problems and possible solutions with the use of improper priors are also described. Some of the most relevant methodologies are compared through theoretical comparisons and numerical experiments.

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