PURPOSE In a single-institution phase II study, we evaluated the safety of a 5-day dose-equivalent neoadjuvant radiotherapy (RT) regimen for high-risk primary soft tissue sarcoma. PATIENTS AND METHODS Patients received neoadjuvant RT alone (30 Gy in five fractions) to the primary tumor with standard margins. The primary endpoint was grade ≥2 late-radiation toxicity. Major wound complications, local recurrences, and distant metastases were also examined. In exploratory analysis, we evaluated germline biomarkers for wound toxicity and the effects of the study on treatment utilization. RESULTS Over 2 years, 52 patients were enrolled with median follow-up of 29 months. Seven of 44 evaluable patients (16%) developed grade ≥2 late toxicity. Major wound complications occurred in 16 of 50 patients (32%); a signature defined by 19 germline SNPs in miRNA-binding sites of immune and DNA damage response genes, in addition to lower extremity tumor location, demonstrated strong predictive performance for major wound complications. Compared with the preceding 2-year period, the number of patients treated with neoadjuvant RT alone at our institution increased 3-fold, with a concomitant increase in the catchment area. CONCLUSIONS A shorter 5-day neoadjuvant RT regimen results in favorable rates of wound complications and grade ≥2 toxicity after 2-year follow-up. Five-day RT significantly increased utilization of neoadjuvant RT at our high-volume sarcoma center. With further validation, a putative germline biomarker for wound complications may guide safer RT utilization. ©2020 American Association for Cancer Research.PURPOSE Acute myeloid leukemia (AML) patients frequently do not respond to conventional therapies. Leukemic cell survival and treatment resistance has been attributed to the overexpression of B-cell lymphoma 2 (BCL-2) and aberrant DNA hypermethylation. In a Phase-Ib study in elderly AML patients, combining the BCL-2 selective inhibitor venetoclax with hypomethylating agents (HMAs) azacitidine (5-Aza) or decitabine resulted in 67% overall response rate; however, the underlying mechanism for this activity is unknown. EXPERIMENTAL DESIGN We studied the consequences of combining two therapeutic agents venetoclax and 5-Aza, in AML preclinical models and primary patient samples. We measured expression changes in the integrated stress response (ISR) and the BCL-2 family by western blot and qPCR. Subsequently we engineered PMAIP1 (NOXA)- and BBC3 (PUMA)-deficient AML cell lines using CRISPR-Cas9 methods to understand their respective role in driving the venetoclax/5-Aza combinatorial activity. RESULTS In this study, we demonstrate that venetoclax and 5-Aza act synergistically to kill AML cells in vitro and display combinatorial anti-tumor activity in vivo. We uncover a novel non-epigenetic mechanism for 5-Aza-induced apoptosis in AML cells through transcriptional induction of the pro-apoptotic BH3-only protein NOXA. This induction occurred within hours of treatment and was mediated by the ISR pathway. NOXA was detected in complex with anti-apoptotic proteins, suggesting that 5-Aza may be "priming" the AML cells for venetoclax-induced apoptosis. PMAIP1 knockout confirmed its major role in driving venetoclax and 5-Aza synergy. CONCLUSIONS These data provide a novel non-epigenetic mechanism of action for 5-Aza and its combinatorial activity with venetoclax through the ISR-mediated induction of PMAIP1. Copyright ©2020, American Association for Cancer Research.INTRODUCTION Despite American Indian/Alaska Native (AI/AN) people having the highest prevalence of cigarette smoking nationwide, few studies have evaluated e-cigarette use among AI/AN adults who smoke. The primary objective of this observational pilot cohort study was to determine if e-cigarette use is associated with cigarette smoking cessation or reduction among adult AI individuals who smoke. METHODS In 2016, we collected baseline survey and biomarker data among AI adults who smoke. The survey included questions about cigarette consumption and use of e-cigarettes and biomarkers, such as salivary cotinine markers and exhaled carbon monoxide. After 18 months, we repeated data collection, and asked about changes in cigarette smoking status and cigarettes per day (CPD). Comparisons between groups were performed using the χ2 test, Fisher's exact test or Wilcoxon rank-sum test. RESULTS Of 375 baseline participants, 214 (57.07%) returned for follow-up and were included in analyses. Of these, 20 (9.3%) reported having stopped cigarette smoking and had biochemical verification of cigarette smoking abstinence. Among those who quit smoking, 15% were baseline e-cigarette users; while among those who continued to smoke at follow-up, about 11% were baseline e-cigarette users. This difference was not statistically significant (p=0.48). Among all those who continued to smoke at follow-up, there was no overall decrease in CPD, nor a significant difference in change in CPD between baseline e-cigarette users and non-users (p=0.98). CONCLUSIONS E-cigarette use at baseline was not associated with smoking cessation or a change in CPD in this cohort of AI adults who smoke after an 18-month follow-up period. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVE Cutaneous adverse events (CAE) from FreeStyle Libre include allergic contact dermatitis (ACD) caused by the allergen isobornyl acrylate (IBOA). We aim to report CAE from this glucose sensor, ACD to IBOA in particular, and the outcome of using barrier films as a prevention. https://www.selleckchem.com/products/ml385.html RESEARCH DESIGN AND METHODS A monocentric, retrospective review of medical files from adult and pediatric patients with diabetes using Freestyle Libre, in the period between December 2016 and April 2019, was performed with a focus on CAE. RESULTS Fifty-seven of 1,036 patients with diabetes (5.5%) were referred to our Dermatology department because of CAE from FreeStyle Libre. Thirty-nine of 1,036 (3.8%) had ACD due to IBOA. Only two patients, of whom one sensitized to IBOA, had a benefit from using barrier films. CONCLUSIONS CAE occurred in 5.5% of FreeStyle Libre users, and 3.8% suffered from ACD due to IBOA. Barrier films had a limited value in the prevention. © 2020 by the American Diabetes Association.