Nature Clinical Practice. Oncology最新文献

A variety of epigenetic changes contribute to transcriptional dysregulation in myelodysplastic syndromes (MDSs) and acute myeloid leukemia (AML). DNA methyltransferase (DNMT) inhibitors--azacitidine and decitabine--have significant activity in the treatment of MDS. Despite marked activity in myeloid malignancy, monotherapy with DNMT inhibitors is limited by low complete and partial response rates (7-20%) and median response durations of 15 months. As with classical cytotoxic therapy, the targeting of biologic pathways and mechanisms may best be accomplished using a combination of agents offering complementary mechanisms and synergistic pharmacodynamic interactions. The goal of this approach is to improve response rates, quality, and duration, and to minimize adverse events. There are a number of new therapies under development for the management of MDS and AML. This review article touches on some of the more promising combination regimens in various phases of investigation. The treatment of MDS and AML is undergoing rapid evolution. Cytogenetic complete remission and prolonged survival represent important goals. Incremental improvements in disease state and quality-of-life issues are also important for patients. Given the overall failure of cytotoxic chemotherapy in the achievement of cures in MDS and MDS-related AML, the application of less toxic, biologically directed agents may represent a more promising approach to treatment. Combination therapies with DNMT inhibitors using optimal dosing regimens to focus on methylation reversal with lower doses over longer periods of time, rather than direct cytotoxic effects, are beginning to suggest promising results in MDS and AML.

New mucosal ablative techniques that can be used in the esophagus have emerged over the past two decades. These techniques have been develop primarily to treat the precursors of esophageal adenocarcinoma: dyspla, in Barrett's esophagus and early esophageal cancer. Although high-grade dysplasia and early stage cancer can be treated with esophagectomy, the inherent morbidity and mortality of esophageal adenocarcinoma and the morbidities, difficulties, costs and limitations of the current technology mean that there has been a significant increase in interest and research regarding alternative treatments such as ablative techniques. At this stage it is not clear which of the numerous endoscopic ablative techniques available---photodynamic therapy, laser therapy, multipolar electrocoagulation, argon plasma coagulation, endoscopic mucosal resection, radiofrequency ablation or cryotherapy--will emerge as superior. In addition, it has yet to be determined whether the risks associated with ablation therapy are less than the risk of Barrett's esophagus progressing to cancer. Whether ablation therapy eliminates o significantly reduces the risk of cancer, eliminates the need for surveillance endoscopy, or is cost-effective, also remains to be seen. Comparative triads that are now underway should help to answer these questions.

Despite years of research and hundreds of reports on tumor markers in oncology, the number of markers that have emerged as clinically useful is pitifully small. Often initially reported studies of a marker show great promise, but subsequent studies on the same or related markers yield inconsistent conclusions or stand in direct contradiction to the promising results. It is imperative that we attempt to understand the reasons why multiple studies of the same marker lead to differing conclusions. A variety of methodological problems have been cited to explain these discrepancies. Unfortunately, many tumor marker studies have not been reported in a rigorous fashion, and published articles often lack sufficient information to allow adequate assessment of the quality of the study or the generalizability of study results. The development of guidelines for the reporting of tumor marker studies was a major recommendation of the National Cancer Institute-European Organisation for Research and Treatment of Cancer (NCI-EORTC) First International Meeting on Cancer Diagnostics in 2000. As for the successful CONSORT initiative for randomized trials and for the STARD statement for diagnostic studies, we suggest guidelines to provide relevant information about the study design, preplanned hypotheses, patient and specimen characteristics, assay methods, and statistical analysis methods. In addition, the guidelines provide helpful suggestions on how to present data and important elements to include in discussions. The goal of these guidelines is to encourage transparent and complete reporting so that the relevant information will be available to others to help them to judge the usefulness of the data and understand the context in which the conclusions apply.