Proteogenomic analysis of lung adenocarcinoma reveals tumor heterogeneity, survival determinants, and therapeutically relevant pathways.

We present a deep proteogenomic profiling study of 87 lung adenocarcinoma (LUAD) tumors from the United States, integrating whole-genome sequencing, transcriptome sequencing, proteomics and phosphoproteomics by mass spectrometry, and reverse-phase protein arrays. We identify three subtypes from somatic genome signature analysis, including a transition-high subtype enriched with never smokers, a transversion-high subtype enriched with current smokers, and a structurally altered subtype enriched with former smokers, TP53 alterations, and genome-wide structural alterations. We show that within-tumor correlations of RNA and protein expression associate with tumor purity and immune cell profiles. We detect and independently validate expression signatures of RNA and protein that predict patient survival. Additionally, among co-measured genes, we found that protein expression is more often associated with patient survival than RNA. Finally, integrative analysis characterizes three expression subtypes with divergent mutations, proteomic regulatory networks, and therapeutic vulnerabilities. This proteogenomic characterization provides a foundation for molecularly informed medicine in LUAD.

Practice patterns for peer review in radiation oncology.

PURPOSE: Physician peer review seeks to improve the quality of care through the evaluation of physician performance, specifically medical decision making and technical expertise. To establish current peer review practice patterns, evaluate interest in recommendations for peer review, and establish a framework for future recommendations, the American Society for Radiation Oncology (ASTRO) surveyed its physician members. METHODS AND MATERIALS: A radiation oncology-specific peer review survey instrument was developed, formally tested, and found to meet established levels of reliability and validity. The final instrument was delivered using a web-based survey platform including reminders. All ASTRO physician-members and members-in-training worldwide were invited by email to participate. RESULTS: A total of 5674 physicians were contacted starting in January 2013. A total of 572 physicians participated (10%) yielding a ±4% margin of error. Those responding were split evenly between academic providers and private practice and others. The median time since training=16 years, median number of new patients per year=215, and median practice size=6 physicians; 83% of respondents were involved in peer review and 75% were comfortable with their program. Of those involved, 65% report doing some review before radiation begins. Of patients treated by these physicians, 56% are reviewed before treatment. Peer review elements reviewed include overall treatment strategy (86%), dose and fractionation (89%), contouring (59%), and isodose or dose-volume histogram (75%). Ninety percent of physicians have changed radiation plans because of peer review. These providers make changes in 7%-10% of cases. Seventy-four percent of physicians agree that ASTRO should make formal peer review recommendations, with 7% in opposition. CONCLUSIONS: This survey suggests that peer review in radiation oncology is common and leads to changes in management in a meaningful fraction of cases. There is much variation in the manner of conducting, and reported utility of, peer review. The majority of ASTRO physician members support formal recommendations and guidance on peer review.