A randomized, non-comparative phase 2 study of neoadjuvant immune-checkpoint blockade in retroperitoneal dedifferentiated liposarcoma and extremity/truncal undifferentiated pleomorphic sarcoma.

Based on the demonstrated clinical activity of immune-checkpoint blockade (ICB) in advanced dedifferentiated liposarcoma (DDLPS) and undifferentiated pleomorphic sarcoma (UPS), we conducted a randomized, non-comparative phase 2 trial ( NCT03307616 ) of neoadjuvant nivolumab or nivolumab/ipilimumab in patients with resectable retroperitoneal DDLPS (n = 17) and extremity/truncal UPS (+ concurrent nivolumab/radiation therapy; n = 10). The primary end point of pathologic response (percent hyalinization) was a median of 8.8% in DDLPS and 89% in UPS. Secondary end points were the changes in immune infiltrate, radiographic response, 12- and 24-month relapse-free survival and overall survival. Lower densities of regulatory T cells before treatment were associated with a major pathologic response (hyalinization > 30%). Tumor infiltration by B cells was increased following neoadjuvant treatment and was associated with overall survival in DDLPS. B cell infiltration was associated with higher densities of regulatory T cells before treatment, which was lost upon ICB treatment. Our data demonstrate that neoadjuvant ICB is associated with complex immune changes within the tumor microenvironment in DDLPS and UPS and that neoadjuvant ICB with concurrent radiotherapy has significant efficacy in UPS.

South Carolina 20 Years of Diabetes--A Public Health Concern.

OBJECTIVE: To assess and enumerate the trends in diabetes prevalence, morbidity and mortality rates in South Carolina (SC) within the past 2 decades. MATERIALS AND METHODS: We analyzed state-level data from vital records, Behavioral Risk Factor Surveillance System, Children's Health Assessment Survey and Administrative Claim Files. RESULTS: Over the past 20 years, there has been an average 2.5% annual increase in diabetes prevalence among adults in SC (P < 0.01). Although a typical reduction in mortality rate of 2.2% has been observed during the same period, the increased number of people living with diabetes (from 5.0% in 1995 to 12.0% in 2014) has brought more need for diabetes care, particularly for severe in-hospital cases and cases with crisis at the emergency department, totaling $404 million in annual costs. CONCLUSIONS: SC has experienced an epidemic of diabetes. Coupled with declining trends in mortality and increased hospitalization and emergency department visits, the state is experiencing historical morbidity and complications due to diabetes. The shift in complexity of the disease onset and management has resulted in more individuals living with cardiovascular disease and other comorbidities. The cost of care for all South Carolinians with diabetes is estimated to exceed 2.8 billion dollars in 2014 and projected to be more than 4 billion dollars by 2020. If the diabetes prevalence trend of increasing rates continues over the next 20 years, the number of individuals living with diabetes and its complications would rise to 1.3 million in SC.