Journal of clinical oncology : official journal of the American Society of Clinical Oncology
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The somatic genomic alterations in pediatric cancers to some extent overlap with those seen in adult cancers, but the exact distribution throughout the genome and the types and frequency of alterations differ. The ultimate goal of genomic research in children, as with adults, is translation to the clinic to achieve more accurate diagnosis, more precise risk stratification, and more effective, less toxic therapy. The genomic features of pediatric malignancies and pediatric-specific issues in clinical investigation may make translating genomic discoveries to the clinic more difficult. However, through large-scale molecular profiling of pediatric tumors, continued coordinated efforts to evaluate novel therapies in the pediatric population, thoughtful phase II and III trial design, and continued drug development, genomically based therapies will become more common in the pediatric oncology clinic in the future.
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Randomized Controlled Trial
AVEREL: a randomized phase III Trial evaluating bevacizumab in combination with docetaxel and trastuzumab as first-line therapy for HER2-positive locally recurrent/metastatic breast cancer.
PURPOSE The AVEREL trial [A Study of Avastin (Bevacizumab) in Combination With Herceptin (Trastuzumab)/Docetaxel in Patients With HER2-Positive Metastatic Breast Cancer] evaluated first-line bevacizumab-containing therapy for human epidermal growth factor receptor 2 (HER2) -positive locally recurrent/metastatic breast cancer (LR/MBC). PATIENTS AND METHODS Patients with measurable/evaluable HER2-positive LR/MBC who had not received trastuzumab or chemotherapy for LR/MBC were stratified by prior adjuvant trastuzumab, prior (neo)adjuvant taxane, hormone receptor status, and measurable disease and were randomly assigned to receive docetaxel 100 mg/m(2) plus trastuzumab 8 mg/kg loading dose followed by 6 mg/kg either with bevacizumab 15 mg/kg or without bevacizumab, all administered every 3 weeks. The primary end point was progression-free survival (PFS). ⋯ High baseline plasma vascular endothelial growth factor A (VEGF-A) concentrations were associated with greater bevacizumab benefit (not statistically significant). CONCLUSION Combining bevacizumab with docetaxel and trastuzumab did not significantly improve investigator-assessed PFS. The potential predictive value of plasma VEGF-A is consistent with findings in HER2-negative LR/MBC, warranting prospective evaluation.
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Multicenter Study
Three-gene immunohistochemical panel adds to clinical staging algorithms to predict prognosis for patients with esophageal adenocarcinoma.
Esophageal adenocarcinoma (EAC) is a highly aggressive disease with poor long-term survival. Despite growing knowledge of its biology, no molecular biomarkers are currently used in routine clinical practice to determine prognosis or aid clinical decision making. Hence, this study set out to identify and validate a small, clinically applicable immunohistochemistry (IHC) panel for prognostication in patients with EAC. ⋯ We identified and validated a clinically applicable IHC biomarker panel, consisting of EGFR, TRIM44, and SIRT2, that is independently associated with OS and provides additional prognostic information to current survival predictors such as stage.
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Emerging evidence suggests muscle depletion predicts survival of patients with cancer. ⋯ CT images reveal otherwise occult muscle depletion. Patients with cancer who are cachexic by the conventional criterion (involuntary weight loss) and by two additional criteria (muscle depletion and low muscle attenuation) share a poor prognosis, regardless of overall body weight.