Melanoma trials that defined surgical management.

Treatment of regional lymph nodes in melanoma has been controversial for more than a century. A series of clinical trials evaluating elective lymph node dissection and then sentinel lymph node biopsy have helped define the current standard of care. These trials resulted in increasingly selective application of surgical intervention for regional lymph nodes in melanoma. First by focusing on optimal candidates for elective lymph node dissection and then by identifying patients through sentinel lymph node biopsy. The current standard of sentinel lymph node biopsy for appropriately selected patients and nodal observation for many patients, even with involved sentinel nodes is both more accurate in staging and much less morbid than what came before.

Evolution of eligibility criteria for diffuse large B-cell lymphoma randomised controlled trials over 30 years.

Eligibility criteria for randomised control trials (RCT) in diffuse large B-cell lymphoma (DLBCL) may be becoming increasingly strict. In this analysis, 42 first-line phase III RCTs enrolling DLBCL patients since 1990 were identified from PubMed and clinicaltrials.gov. Changes in 31 individual eligibility criteria were assessed using three pre-defined eras [(1) 1993-2005; (2) 2006-2013; and (3) 2014-2020]. The presence of 15/31 criteria increased significantly over time, and the total number of criteria per study also increased over time [median Era 1: 14·5, interquartile range (IQR) 12·6-16·4; Era 2: 21, 18·8-23·3; Era 3: 23, 21-25; P < 0·001]. When each trial's eligibility criteria were applied to 215 consecutive patients from an institutional database treated between 2010 and 2020, a median of 57% (IQR 47-70) of patients were hypothetically eligible for trial enrolment. The median percentage of patients eligible was 68% (56-91), 54% (37-81) and 47% (38-82) for Era 1, 2 and 3 respectively (P = 0·004). Phase III front-line DLBCL trial criteria have become increasingly restrictive over the last three decades, resulting in a diminishing proportion of trial-eligible patients, with less than 50% of our patients eligible for modern-era studies. This potentially impacts generalisability of recent trial results and will likely limit recruitment to ongoing studies.

Anagrelide: what was new in 2004 and 2005?

Anagrelide is an established platelet-reducing drug. Although there are gaps in the understanding of its mechanism of action, two randomized comparisons with other drugs used for therapy of patients with essential thrombocythemia (ET) have been performed. Recent progress has been made in this field with the development of better determination techniques, with the characterization of metabolites, and with studies of their mechanism of action on megakaryocytes and platelets. More data are now available from various noncomparative clinical trials on its clinical efficacy and safety. Only few investigations are available that document its long-term effects. Although the drug should not be used during pregnancy, there are a few studies that report that pregnant women have taken this drug without harm to the newborn. Studies have also investigated the effects of anagrelide on platelets, indicating that platelet function is as important as platelet counts in ET. Preliminary analyses of the mechanism of action of anagrelide have revealed that the drug interferes with the signal transduction of the thrombopoietin receptor. Results of the first phase III trial (PT1) that compared anagrelide/aspirin with hydroxyurea/aspirin have sparked an intense discussion, given that the combination of anagrelide and aspirin causes more bleeding complications in the gastrointestinal tract. It has been speculated that the higher number of transient ischemic attacks in this study arm is not caused by thrombotic events but by small bleedings that would be responsible for transient hemorrhagic attacks. More insights are expected from the recently completed ANAHYDRET trial that compared monotherapy with hydroxyurea and anagrelide.