Baseline mutational profiles of patients with carcinoma of unknown primary origin enrolled in the CUPISCO study.

BACKGROUND: Patients with unfavorable carcinoma of unknown primary origin (CUP) have an extremely poor prognosis of ∼1 year or less, stressing the need for more tailored treatments, which are currently being tested in clinical trials. CUPISCO (NCT03498521) was a phase II randomized study of targeted therapy/cancer immunotherapy versus platinum-based chemotherapy in patients with previously untreated, unfavorable CUP, defined as per the European Society for Medical Oncology guidelines. We present a preliminary, descriptive molecular analysis of 464 patients with stringently diagnosed, unfavorable CUP enrolled in the CUPISCO study. MATERIALS AND METHODS: Genomic profiling was carried out on formalin-fixed, paraffin-embedded tissue to detect genomic alterations and assess tumor mutational burden and microsatellite instability. RESULTS: Overall, ∼32% of patients carried a potentially targetable genomic alteration, including PIK3CA, FGFR2, ERBB2, BRAFV600E, EGFR, MET, NTRK1, ROS1, and ALK. Using hierarchical clustering of co-mutational profiles, 10 clusters were identified with specific genomic alteration co-occurrences, with some mirroring defined tumor entities. CONCLUSIONS: Results reveal the molecular heterogeneity of patients with unfavorable CUP and suggest that genomic profiling may be used as part of informed decision-making to identify the potential primary tumor and targeted treatment options. Whether stringently diagnosed patients with unfavorable CUP benefit from targeted therapies in a similar manner to those with matched known primaries will be a key learning from CUPISCO.

[ASSOCIATION OF AGE OBESITY AND METABOLIC SYNDROME IN MEN].

The study included 253 men aged 22 to 74 years. Was shown that at the end of the first period of middle age the accumulation of adipose tissue was enhanced that was associated with the change of dominance from the gynoid to the android type of obesity. The most pronounced increase in the frequency of occurrence of individual components and the overall metabolic syndrome was diagnosed in men in the second period of middle age with a following decrease in the frequency such components as hypertriglyceridemia, low HDL cholesterol and hyperglycemia in elderly age. In the all three age groups the value of the index of visceral obesity was significantly higher in men with android type of obesity compared with gynoid. Thus, the men with gynoid compared with android type of obesity have a lower risk of development metabolic syndrome in all age groups.

[Adipokines and a risk for metabolic disturbances in different types of female obesity]. / Adipokiny i risk razvitiya metabolicheskikh narushenii pri raznykh tipakh ozhireniya u zhenshchin.

AIM: To investigate the effects of adiponectin and leptin on the development of metabolic disturbances in women with android and gynoid fat distribution. MATERIAL AND METHODS: A total of 101 women aged 40 to 65 years were examined. Anthropometric measurements were made; overweight and obese women with a waist/hip (W/H) ratio of less than 0.83 were referred to as a gynoid fat distribution (GFD) group; and those with a W/H ratio of 0.83 or more were to an android fat distribution (AFD) group. The serum concentrations of triglycerides, high-density lipoprotein cholesterol, and glucose were measured; the levels of insulin, leptin, and adiponectin were determined by enzyme immunoassay. Insulin resistance (IR), HOMA IR, and visceral obesity index (VOI) were calculated. RESULTS: With the same excess adipose tissue accumulation, the women with GFD had a less magnitude of hormonal and metabolic disturbances than those with AFD, whose HOMA-IR also pointed to the presence of IR. VOI was insignificantly higher in the women with GFD and 2.4-fold greater than that in normal weight (NW) women. In the women with GFD and AFD, the concentration of leptin was higher than that in the NW women, which was characteristic of obesity, but the concentration of adiponectin proved to be significantly lower in the patients with AFD and to be unchanged in those with GFD as compared with that in the NW women. CONCLUSION: The women with AFD are typified by a high VOI, hypoadiponectinemia, IR, and metabolic disturbances, which determine a high risk for cardiovascular events and type 2 diabetes mellitus. In the women with GFD, obesity is associated with normal adiponectinemia and a low VOI and, in terms of hormonal and metabolic characteristics, may be characterized as metabolically healthy obesity.