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.
Wing C. Chan and James O. Armitage
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.
Julie Hallet, Calvin Law, Simron Singh, Alyson Mahar, Sten Myrehaug, Victoria Zuk, Haoyu Zhao, Wing Chan, Angela Assal, and Natalie Coburn
Background: Although patients with neuroendocrine tumors (NETs) are known to have prolonged overall survival, the contribution of cancer-specific and noncancer deaths is undefined. This study examined cancer-specific and noncancer death after NET diagnosis. Methods: We conducted a population-based retrospective cohort study of adult patients with NETs from 2001 through 2015. Using competing risks methods, we estimated the cumulative incidence of cancer-specific and noncancer death and stratified by primary NET site and metastatic status. Subdistribution hazard models examined prognostic factors. Results: Among 8,607 included patients, median follow-up was 42 months (interquartile range, 17–82). Risk of cancer-specific death was higher than that of noncancer death, at 27.3% (95% CI, 26.3%–28.4%) and 5.6% (95% CI, 5.1%–6.1%), respectively, at 5 years. Cancer-specific deaths largely exceeded noncancer deaths in synchronous and metachronous metastatic NETs. Patterns varied by primary tumor site, with highest risks of cancer-specific death in bronchopulmonary and pancreatic NETs. For nonmetastatic gastric, small intestine, colonic, and rectal NETs, the risk of noncancer death exceeded that of cancer-specific deaths. Advancing age, higher material deprivation, and metastases were independently associated with higher hazards, and female sex and high comorbidity burden with lower hazards of cancer-specific death. Conclusions: Among all NETs, the risk of dying of cancer was higher than that of dying of other causes. Heterogeneity exists by primary NET site. Some patients with nonmetastatic NETs are more likely to die of noncancer causes than of cancer causes. This information is important for counseling, decision-making, and design of future trials. Cancer-specific mortality should be included in outcomes when assessing treatment strategies.