Lung squamous cell carcinomas (LSCC) pathogenesis remains incompletely understood and biomarkers predicting treatment response remain lacking. Here we describe novel murine LSCC models driven by loss of Trp53 and Keap1, both of which are frequently mutated in human LSCCs. Homozygous inactivation of Keap1 or Trp53 promoted airway basal stem cell (ABSC) self-renewal, suggesting that mutations in these genes lead to expansion of mutant stem cell clones. Deletion of Trp53 and Keap1 in ABSCs, but not more differentiated tracheal cells, produced tumors recapitulating histological and molecular features of human LSCCs, indicating that they represent the likely cell of origin in this model. Deletion of Keap1 promoted tumor aggressiveness, metastasis, and resistance to oxidative stress and radiotherapy (RT). KEAP1/NRF2 mutation status predicted risk of local recurrence after RT in non-small lung cancer (NSCLC) patients and could be non-invasively identified in circulating tumor DNA. Thus, KEAP1/NRF2 mutations could serve as predictive biomarkers for personalization of therapeutic strategies for NSCLCs.

Background As a high patient-throughput clinic, the Royal Children's Hospital's multidisciplinary burns clinic's efficiency of clinic workflow and streamlined patient assessment is crucial. The clinic has been using a customized “burns assessment tool” (BAT) as part of its integrated electronic health record (EHR) since 2016. Objectives The aim was to assess the usage patterns of the BAT at baseline, followed by re-evaluation following interventions to improve efficiency and utilization of the BAT. Methods This study was a prospective observational time–motion quality improvement study. Observations of 19 clinicians in the pediatric burns clinic by five trained observers using a validated time–motion capture tool (TimeCaT 3.9) to map clinician workflow, with specific reference to time spent on a list of predetermined tasks, were conducted. Baseline data were collected for 7 weeks followed by three cycles of interventions and observations over 5 months. Results At baseline, the median time for a patient visit was 24.56 minutes (range: 2.78–73.72 minutes, interquartile range: 14.17–27 minutes), with most of the time spent on documentation (34.6%) and patient contact tasks (26.0%). In each of the study cycles, the median time spent on documentation within the EHR was significantly reduced compared with baseline (cycle 1 29.8%, p = 0.08; cycle 2 20.4%, p ≤ 0.01; cycle 3 27.32%, p = 0.04). The time spent on patient contact increased when comparing baseline to data of cycles 1, 2, and 3 (25.96 vs. 33.27% of visit, p = 0.04). There was no significant change in absolute time spent on the BAT during the study. Conclusion The study findings of clear, significant, and sustained improvement in documentation efficiency and the corresponding increase in patient contact time after interventions were introduced reinforce the importance of integration of an EHR with clinical workflow.

<p>Supplementary Table S2. Genotyping results for NSCLC patients treated with radiotherapy.</p>