Modernizing family health history: achievable strategies to reduce implementation gaps

Family health history (FHH) is a valuable yet underused healthcare tool for assessing health risks for both prevalent disorders like diabetes, cancer, and cardiovascular diseases, and for rare, monogenic disorders. Full implementation of FHH collection and analysis in healthcare could improve both primary and secondary disease prevention for individuals and, through cascade testing, make at risk family members eligible for pre-symptomatic testing and preventative interventions. In addition to risk assessment in the clinic, FHH is increasingly important for interpreting clinical genetic testing results and for research connecting health risks to genomic variation. Despite this value, diverse implementation gaps in clinical settings undermine its potential clinical value and limit the quality of connected health and genomic data. The NHGRI Family Health History Group, an open-membership, US-based group with international members, believes that integrating FHH in healthcare and research is more important than ever, and that achievable implementation advances, including education, are urgently needed to boost the pace of translational utility in genomic medicine. An inventory of implementation gaps and proposed achievable strategies to address them, representing a consensus developed in meetings from 2019-2020, is presented here. The proposed measures are diverse, interdisciplinary, and are guided by experience and ongoing implementation and research efforts.Prevention, Population and Disease management (PrePoD)Public Health and primary car

A phase II/III randomized study to compare the efficacy and safety of rigosertib plus gemcitabine versus gemcitabine alone in patients with previously untreated metastatic pancreatic cancer

BACKGROUND: Rigosertib (ON 01910.Na), a first-in-class Ras mimetic and small-molecule inhibitor of multiple signaling pathways including polo-like kinase 1 (PLK1) and phosphoinositide 3-kinase (PI3K), has shown efficacy in preclinical pancreatic cancer models. In this study, rigosertib was assessed in combination with gemcitabine in patients with treatment-naïve metastatic pancreatic adenocarcinoma. MATERIALS AND METHODS: Patients with metastatic pancreatic adenocarcinoma were randomized in a 2:1 fashion to gemcitabine 1000 mg/m(2) weekly for 3 weeks of a 4-week cycle plus rigosertib 1800 mg/m(2) via 2-h continuous IV infusions given twice weekly for 3 weeks of a 4-week cycle (RIG + GEM) versus gemcitabine 1000 mg/m(2) weekly for 3 weeks in a 4-week cycle (GEM). RESULTS: A total of 160 patients were enrolled globally and randomly assigned to RIG + GEM (106 patients) or GEM (54). The most common grade 3 or higher adverse events were neutropenia (8% in the RIG + GEM group versus 6% in the GEM group), hyponatremia (17% versus 4%), and anemia (8% versus 4%). The median overall survival was 6.1 months for RIG + GEM versus 6.4 months for GEM [hazard ratio (HR), 1.24; 95% confidence interval (CI) 0.85-1.81]. The median progression-free survival was 3.4 months for both groups (HR = 0.96; 95% CI 0.68-1.36). The partial response rate was 19% versus 13% for RIG + GEM versus GEM, respectively. Of 64 tumor samples sent for molecular analysis, 47 were adequate for multiplex genetic testing and 41 were positive for mutations. The majority of cases had KRAS gene mutations (40 cases). Other mutations detected included TP53 (13 cases) and PIK3CA (1 case). No correlation between mutational status and efficacy was detected. CONCLUSIONS: The combination of RIG + GEM failed to demonstrate an improvement in survival or response compared with GEM in patients with metastatic pancreatic adenocarcinoma. Rigosertib showed a similar safety profile to that seen in previous trials using the IV formulation