Citations

PURPOSE Intrahepatic cholangiocarcinoma (IHCCA), a global health problem, is increasing in incidence and has differing etiologies worldwide. Next-generation sequencing (NGS) is rapidly being incorporated into the clinical management of biliary cancers. IHCCA is enriched with actionable mutations, and there are several promising targeted therapies under development. NGS data from Asia, where IHCCA is most prevalent, are limited. METHODS Comprehensive genomic profiling of formalin-fixed paraffin-embedded tumor tissue from 164 Asian and 283 Western patients with IHCCA was performed using NGS. We measured the distribution of DNA repair genetic aberrations (GAs) in IHCCA, along with actionable mutations. Also, we evaluated the association between DNA repair GAs and tumor mutation burden (TMB). Based on the TMB status, patients were distinguished into 3 levels: low (< 6 mut/Mb), intermediate (6-10 mut/Mb), and high (TMB-H; ≥ 10 mut/Mb). RESULTS Seventy-two percent of Asian patients had ≥ 1 actionable GA, with a significantly higher frequency in KMT2C , BRCA1/2, and DDR2 compared with Western patients ( P = .02, .003, and .003, respectively); 60.9% of Western patients had ≥ 1 actionable GA and higher frequency of CDKN2A/B and IDH1/2 GAs ( P = .0004 and < .001, respectively). GAs in nuclear factor kappa B pathway regulators and DNA repair genes occurred more frequently in Asian patients ( P = .006 and .001, respectively). There was a higher frequency of TMB-H in Asian compared with the Western cohort (12.2% v 5.9%; P = .07). CONCLUSION A higher burden of DNA repair mutations and frequency of patients with TMB-H in the Asian IHCCA cohort compared with the Western patients suggests a potential role for DNA repair and immune checkpoint inhibitors in the Asian population. Future clinical trials should account for this genetic heterogeneity.

Background. Shared decision making (SDM) is recommended prior to initiation of statin therapy for primary prevention but is underutilized. We designed an informatics decision-support tool to facilitate use of the Mayo Clinic Statin Choice decision aid at the point-of-care and evaluated its impact. Methods. Using an iterative approach, we designed and implemented a single-click decision-support tool embedded within the electronic health records (EHRs) to automate the calculation of 10-year atherosclerotic cardiovascular disease (ASCVD) risk and populate the Statin Choice decision aid. We surveyed primary care providers at two clinics regarding their attitudes about SDM before and after deployment of intervention, as well as their usage of and perceived competence regarding SDM for primary prevention statin therapy. Three-month web traffic to the Statin Choice website was calculated before and after deployment of the intervention. Results. Pre–post surveys were completed by 60 primary care providers (24 [40%] attending physicians and 36 [60%] housestaff physicians). After deployment of the EHR tool, respondents were more aware of the Statin Choice decision aid ( P < 0.001), reported being more competent regarding SDM ( P = 0.047), and reported using decision aids more often when considering statin initiation ( P = 0.043). There was no significant change in attitudes about SDM as measured through the Patient Provider Orientation Scale (pre 4.23 ± 0.40 v. post 4.16 ± 0.38, P = 0.11) and the SDM belief scale (pre 21.4 ± 2.1 v. post 21.1 ± 2.0, P = 0.35). Web-based usage rates for the Statin Choice decision aid increased from 3.4 to 5.2 per 1,000 outpatient clinic visits ( P = 0.002). Conclusions. Implementation of a point-of-care decision-support tool increased the usage of decision aids for primary prevention statin therapy. This effect does not appear to be mediated by any concomitant changes in physician attitude toward SDM.