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Background: Treatment of non-small lung cancer (NSCLC) has evolved in recent years, benefiting from advances in immunotherapy and targeted therapy. However, limited biomarkers exist to assist clinicians and patients in selecting the most effective, personalized treatment strategies. Targeted next-generation sequencing–based genomic profiling has become routine in cancer treatment and generated crucial clinicogenomic data over the last decade. This has made the development of mutational biomarkers for drug response possible. Methods: To investigate the association between a patient's responses to a specific somatic mutation treatment, we analyzed the NSCLC GENIE BPC cohort, which includes 2,004 tumor samples from 1,846 patients. Results: We identified somatic mutation signatures associated with response to immunotherapy and chemotherapy, including carboplatin-, cisplatin-, pemetrexed- or docetaxel-based chemotherapy. The prediction power of the chemotherapy-associated signature was significantly affected by epidermal growth factor receptor (EGFR) mutation status. Therefore, we developed an EGFR wild-type–specific mutation signature for chemotherapy selection. Conclusion: Our treatment-specific gene signatures will assist clinicians and patients in selecting from multiple treatment options. [ABSTRACT FROM AUTHOR]

Background: Diet quality in older people with chronic obstructive pulmonary disease (COPD) is associated with better health and lung function. Social factors, such as social support, social networks and participation in activities, have been linked with diet quality in older age. A social network tool—GENIE (Generating Engagement in Network Involvement)—was implemented in a COPD community care context. The study aimed to assess the feasibility of the GENIE intervention to promote diet quality and other health behaviours in COPD. Methods: Twenty-two community-dwelling older adults with COPD were recruited from a local COPD service. Participants were offered usual care or the GENIE intervention. Process evaluation methods were used to assess intervention implementation, context and mechanisms of impact; these included observations of patient interactions with the intervention, documented in observational field notes and in films of a patient group discussion. Diet quality was assessed by food frequency questionnaire; 'prudent' diet scores were used to describe diet quality at baseline and at 3-month follow-up. Change in diet quality was expressed per month, from baseline to follow-up. Results: Feasibility data showed that the GENIE intervention could be implemented in this sample of community-living older people. The intervention was acceptable to clinicians and older people with COPD, especially for those with less severe disease, when facilitated appropriately and considering the levels of literacy of participants. There was no significant change in diet quality in the intervention group over the follow-up period (median change in prudent diet score per month (interquartile range (IQR), 0.03 (− 0.24–0.07)), whereas an overall fall in diet quality was observed in the control group (− 0.15 (− 0.24–0.03)). Conclusion: The process evaluation findings suggest that this intervention is feasible and acceptable to both patients and clinicians. Although the sample size achieved in this study was small, findings suggest that the intervention may have a protective effect against declines in diet quality, and other health behaviours, in an older COPD population. Findings from this feasibility study indicate that further evaluation of the GENIE intervention is warranted in a larger study, with a longer follow-up. Trial registration: ClinicalTrials.gov, NCT02935452. NIH U.S. National Library of Medicine. Registered 17 October 2016. [ABSTRACT FROM AUTHOR]

Background: Significant numbers of variants detected in cancer patients are often left labeled only as variants of unknown significance (VUS). In order to expand precision medicine to a wider population, we need to extend our knowledge of pathogenicity and drug response in the context of VUS's.Methods: In this study, we analyzed variants from AACR Project GENIE Consortium APG (Cancer Discov 7:818-831, 2017) and compared them to the COSMIC database Forbes et al. (Nucleic Acids Res 43:D805-811, 2015) to identify recurrent variants that would merit further study. We filtered out known hotspot variants, inactivating variants in tumor suppressors, and likely benign variants by comparing with COSMIC and ExAC Lee et al. (Science 337:967-971, 2012).Results: We have identified 45,933 novel variants with unknown significance unique to GENIE. In our analysis, we found on average six variants per patient where two could be considered as pathogenic or likely pathogenic and the majority are VUS's. More importantly, we have discovered 730 recurrent variants that appear more than 3 times in GENIE but less than 3 in COSMIC. If we combine the recurrences of GENIE and COSMIC for all variants, 2586 are newly identified as occurring more than 3 times than when using COSMIC alone.Conclusions: Although it would be inappropriate to blindly accept these recurrent variants as pathogenic, they may warrant higher priority than other observed VUS's. These newly identified recurrent variants might affect the molecular profiles of approximately 1 in 6 patients. Further analysis and characterization of these variants in both research and clinical contexts will improve patient treatments and the development of new therapeutics. [ABSTRACT FROM AUTHOR]