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Accurate and reproducible staging is crucial for management of malignant lymphomas. Disease stage influences treatment decisions more significantly than any other clinical information in most lymphoma subtypes, and contributes with important prognostic information on its own or as part of clinical prognostic scores. Information derived from medical imaging is the single most important determinant of disease stage, and the introduction PET/CT for lymphoma has led to substantial changes in the concept as well as practice of lymphoma staging. Over time, the most important change in lymphoma staging has been the abandonment of extensive pathologic staging intended in the original Ann Arbor classification. The 2014 Lugano Classification represents the most recent expert recommendation for staging of lymphoma. This revision recognizes the improved diagnostic accuracy of PET/CT over stand-alone CT and recommended PET/CT for routine staging of all FDG-avid lymphomas. Routine bone marrow biopsies are also discouraged in Hodgkin lymphoma as well as in selected cases of diffuse large B-cell lymphoma. The scope of this review is to give the reader insight into the history of staging, the purpose of lymphoma staging in the context of contemporary treatment strategies, and the advantages of PET/CT staging over conventional staging. We also discuss the controversies of PET/CT replacing conventional bone marrow biopsies in different lymphoma subtypes and summarize recommendations by the recent Lugano classification. [ABSTRACT FROM AUTHOR]

Positron emission tomography (PET) is a molecular functional imaging technique that provides qualitative and quantitative information about the localization and activity of pathophysiological processes. The most commonly used tracer for oncological purposes is 2-[18F]fluoro-2-deoxy-d-glucose (FDG). FDG-PET has within recent years become the most important nuclear medicine imaging modality in the management of lymphoma. This review summarizes the data published so far concerning the value of FDG-PET in staging, treatment monitoring, therapy planning, and follow-up of Hodgkin lymphoma (HL). FDG-PET detects more disease sites and involved organs than conventional staging procedures including computerized tomography (CT) and has a large influence on staging. FDG-PET during and after therapy appears to provide considerable prognostic information. However, the impact on patient outcome is not clear since no controlled trials are conducted and follow-up periods are generally short. The value of dual-modality PET/CT and its potential role in the radiotherapy planning is discussed. [Copyright &y& Elsevier]

Purpose Development of secondary central nervous system involvement (SCNS) in patients with diffuse large B-cell lymphoma is associated with poor outcomes. The CNS International Prognostic Index (CNS-IPI) has been proposed for identifying patients at greatest risk, but the optimal model is unknown. Methods We retrospectively analysed patients with diffuse large B-cell lymphoma diagnosed between 2001 and 2013, staged with PET/CT and treated with R-CHOP(-like) regimens. Baseline clinicopathologic characteristics, treatments, and outcome data were collected from clinical databases and medical files. We evaluated the association between candidate prognostic factors and modelled different risk models for predicting SCNS. Results Of 1532 patients, 62 (4%) subsequently developed SCNS. By multivariate analysis, disease stage III/IV, elevated serum LDH, kidney/adrenal and uterine/testicular involvement were independently associated with SCNS. There was a strong correlation between absolute number of extranodal sites and risk of SCNS; the 144 patients (9%) with >2 extranodal sites had a 3-year cumulative incidence of SCNS of 15.2% (95% confidence interval [CI] 9.2–21.2%) compared with 2.6% (95% CI 1.7–3.5) among those with ≤2 sites ( P < 0.001). The 3-year cumulative risks of SCNS for CNS-IPI defined risk groups were 11.2%, 3.1% and 0.4% for high-, intermediate- and low-risk patients, respectively. All risk models analysed had high negative predictive values, but only modest positive predictive values. Conclusions Patients with >2 extranodal sites or high-risk disease according to the CNS-IPI should be considered for baseline CNS staging. Clinical risk prediction models suffer from limited positive predictive ability, highlighting the need for more sensitive biomarkers to identify patients at highest risk of this devastating complication. [ABSTRACT FROM AUTHOR]

Abstract: A number of novel fused thiophene derivatives have been prepared and identified as potent inhibitors of MEK. The SAR data of selected examples and the in vivo profiling of compound 13h demonstrates the functional activity of this class of compounds in HT-29 PK/PD models. [Copyright &y& Elsevier]

The jatrophane class of natural products exhibit a wide range of biological activities with certain members of this family of complex sesquiterpenes being P-glycoprotein inhibitors. Considerable attention has been paid to the synthesis of biologically active jatrophanes although very few have succumbed to total synthesis. Herein we report a synthesis of the cyclopentane core of pepluanin A, a potent P-glycoprotein inhibitor, that features an iodocarbocyclization and an invertive acetal formation as key steps. Image 1 • Synthesis of the core of the P-glycoprotein inhibitor pepluanin A reported. • Key methods involve selective iodocyclization and invertive acetal formation. • Exploration of cylization - lactonization reported. [ABSTRACT FROM AUTHOR]