Dabrafenib and Trametinib Therapy for Advanced Anaplastic Thyroid Cancer - Real-World Outcomes From UK Centres.

AIMS: Anaplastic thyroid cancer (ATC) is a rare but aggressive form of thyroid cancer with a median survival of 4 months. Recent advances in molecular profiling have shown that up to half of ATCs harbour the BRAF-V600E mutation. The aim of this study was to provide real-world data and experience on the use of combination therapy dabrafenib and trametinib in patients with BRAF-V600E-mutated advanced ATC. MATERIALS AND METHODS: We retrospectively evaluated patients with confirmed BRAF-V600E-mutated ATC, defined as patients with locally advanced or metastatic ATC with no locoregional, radical treatment options. Outcomes measured were overall survival, progression-free survival, response rate, discontinuation rate, dose reduction rate and toxicity data. RESULTS: Seventeen patients were evaluated and the mean age was 68 years. Ten patients died by the time of censoring. The median duration of follow-up was 12 months (3-43 months). The estimated median overall survival was 6.9 months (95% confidence interval 2.46 months - upper confidence interval not reached) and the median progression-free survival was 4.7 months (95% confidence interval 1.4-7.8 months). Dose interruptions and/or reductions were common, but none of the patients had to permanently discontinue treatment because of toxicities. Severe toxicities (grades 3 and 4) were uncommon. CONCLUSIONS: This study supports the indication of dabrafenib and trametinib in BRAF-V600E-mutated ATC as an effective and well-tolerated treatment in an historically difficult to treat cancer.

Nymph and Adult Biology of Euschistus cornutus Dallas: a Potential Soybean Pest in the Neotropics.

Laboratory studies with Euschistus cornutus Dallas indicated that nymphs complete development when feeding on green bean, Phaseolus vulgaris L. pod, on soybean, Glycine max (L.) Merrill pod, and on raw shelled peanut, Arachis hypogaea L., but not on fruit (berry) of privet, Ligustrum lucidum Ait. Total mortality was lower on green bean pod (45%), and higher on soybean pod and peanut raw (75 and 80%, respectively). Nymph developmental time was significantly longer for females feeding on green bean pod (37.4 days) than on soybean pod (27 days); a single data was observed on peanut raw (32 days). Males showed no significant differences in total nymph developmental time among foods (31.3 to 33.0 days). At adult emergency, fresh body weight of females (52.2 to 68.5 mg) and males (61.9 to 71.3 mg) did not show statistical differences among foods tested nor between genders. Survivorship of E. cornutus adult after 50 days was greater on peanut raw than on green bean or soybean pod; on privet berry, the majority of males and females (>80%) were dead after 20 days. The reproductive performance data was, in general, greater on peanut raw than on green bean or soybean pod; on privet fruit, no female laid eggs. Fresh body weight gain occurred on all foods, except on privet berry, on which adults lost weight over time. Records of specimens from insect collections in Brazil indicated that E. cornutus occurs in the Southeast and South regions (19° to 31° S latitude). The most common host plant is soybean, suggesting a potential pest status of this stink bug on this crop in the future.

Functional properties of lymphocytes in idiopathic thrombocytopenic purpura.

Idiopathic or immune thrombocytopenic purpura (ITP) is characterized by antibody-mediated destruction of platelets. The etiology is unknown. We postulated that increased autoantibody production in ITP might be attributable to either increased or prolonged expression of CD40 ligand (CD40L, CD154) in T or B lymphocytes, as has been previously observed in systemic lupus erythematosus (SLE). In addition, we hypothesized that ITP is characterized by increased levels of interleukin 4 (IL-4), a prototypic Th2 cytokine which, along with CD40 ligation, is required for B cell differentiation and production of several IgG subclasses. Cell surface CD154 expression was measured in freshly-isolated and in vitro-activated peripheral blood lymphocytes of sixteen ITP patients and eight healthy volunteers. Plasma levels of IL-4 and the prototypic Th1 cytokine interferon-gamma (IFNgamma) were determined. We observed that CD154 expression in unstimulated and in vitro-activated lymphocytes did not differ between ITP patients and healthy controls. Plasma levels of the Th2 cytokine IL-4 were significantly higher in the ITP patients. These studies indicate that overexpression of CD154 in lymphocytes is unlikely to be a primary pathophysiological defect in most patients with ITP. The data support that in addition to cell membrane antigens such as CD154, soluble cytokines such as IL-4 should be considered as potential targets for therapy in this disease.