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Wing C. Chan and James O. Armitage

The application of gene expression profiling to the study of lymphomas will significantly influence the way these tumors are diagnosed and treated. Diffuse large B-cell lymphoma is now known to consist of several different genetic entities with different clinical presentations and therapeutic outcomes. In both follicular and diffuse large B-cell lymphoma, these studies have shown that host–tumor interactions have a major impact on the clinical course. Findings of gene expression profiling in diffuse large B-cell lymphoma has indicated the frequent up-regulation of the nuclear factor-κB and B-cell receptor signaling pathways in the activated B-cell type. Drugs targeting these pathways may be effective in the treatment of these cases and clinical trials have been initiated based on these findings. Gene expression profiling may assist in the selection of treatments based on specific metabolic pathways shown to be active in a particular lymphoma. These techniques offer the promise of truly personalized medicine for patients with lymphoma.

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Jerald P. Radich, Andrew D. Zelenetz, Wing C. Chan, Carlo M. Croce, Myron S. Czuczman, Harry P. Erba, Sandra J. Horning, Jane Houldsworth, B. Douglas Smith, David S. Snyder, Hema M. Sundar, Meir Wetzler, and Jane N. Winter

The introduction of targeted therapies has revolutionized treatment and improved outcomes in patients with leukemias and lymphomas. However, many patients experience relapse caused by the persistence of residual malignant cells. Cytogenetic and molecular techniques are increasingly being used to assess and quantify minimal residual disease (MRD). The emergence of advanced technologies has led to the discovery of multiple novel molecular markers that can be used to detect MRD and predict outcome in patients with leukemias and lymphomas. Gene expression signatures that predict clinical outcomes in patients with non-Hodgkin's lymphoma have been identified. In chronic myelogenous leukemia, molecular monitoring has become more important in assessing response and detecting resistance to therapy. In acute leukemias, several new markers have shown potential in prognostication and monitoring treatment. In leukemias and lymphomas, microRNAs have been identified that may be useful in diagnostics and prognostication. To address these issues, the National Comprehensive Cancer Network (NCCN) organized a task force consisting of a panel of experts in leukemia and lymphoma to discuss recent advances in the field of molecular markers and monitoring MRD.

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Julie Hallet, Bourke Tillman, Jesse Zuckerman, Matthew P. Guttman, Tyler Chesney, Alyson L. Mahar, Wing C. Chan, Natalie Coburn, Barbara Haas, and members of the Recovery after Surgical Therapy for Older adults Research–Cancer (RESTORE-Cancer) Group

Background: Although frailty is known to impact short-term postoperative outcomes, its long-term impact is unknown. This study examined the association between frailty and remaining alive and at home after cancer surgery among older adults. Methods: Adults aged ≥70 years undergoing cancer resection were included in this population-based retrospective cohort study using linked administrative datasets in Ontario, Canada. The probability of remaining alive and at home in the 5 years after cancer resection was evaluated using Kaplan-Meier methods. Extended Cox regression with time-varying effects examined the association between frailty and remaining alive and at home. Results: Of 82,037 patients, 6,443 (7.9%) had preoperative frailty. With median follow-up of 47 months (interquartile range, 23–81 months), patients with frailty had a significantly lower probability of remaining alive and at home 5 years after cancer surgery compared with those without frailty (39.1% [95% CI, 37.8%–40.4%] vs 62.5% [95% CI, 62.1%–63.9%]). After adjusting for age, sex, rural living, material deprivation, immigration status, cancer type, surgical procedure intensity, year of surgery, and receipt of perioperative therapy, frailty remained associated with increased hazards of not remaining alive and at home. This increase was highest 31 to 90 days after surgery (hazard ratio [HR], 2.00 [95% CI, 1.78–2.24]) and remained significantly elevated beyond 1 year after surgery (HR, 1.56 [95% CI, 1.48–1.64]). This pattern was observed across cancer sites, including those requiring low-intensity surgery (breast and melanoma). Conclusions: Preoperative frailty was independently associated with a decreased probability of remaining alive and at home after cancer surgery among older adults. This relationship persisted over time for all cancer types beyond short-term mortality and the initial postoperative period. Frailty assessment may be useful for all candidates for cancer surgery, and these data can be used when counseling, selecting, and preparing patients for surgery.