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BackgroundResistance to immune checkpoint inhibitors (ICIs) has been linked to local immunosuppression independent of major ICI targets (e.g., PD-1). Clinical experience with response prediction based on PD-L1 expression suggests that other factors influence sensitivity to ICIs in non-small cell lung cancer (NSCLC) patients.MethodsTumor specimens from 120 NSCLC patients from 10 institutions were evaluated for PD-L1 expression by immunohistochemistry, and global proliferative profile by targeted RNA-seq.ResultsCell proliferation, derived from the mean expression of 10 proliferation-associated genes (namely BUB1, CCNB2, CDK1, CDKN3, FOXM1, KIAA0101, MAD2L1, MELK, MKI67, and TOP2A), was identified as a marker of response to ICIs in NSCLC. Poorly, moderately, and highly proliferative tumors were somewhat equally represented in NSCLC, with tumors with the highest PD-L1 expression being more frequently moderately proliferative as compared to lesser levels of PD-L1 expression. Proliferation status had an impact on survival in patients with both PD-L1 positive and negative tumors. There was a significant survival advantage for moderately proliferative tumors compared to their combined highly/poorly counterparts (p = 0.021). Moderately proliferative PD-L1 positive tumors had a median survival of 14.6 months that was almost twice that of PD-L1 negative highly/poorly proliferative at 7.6 months (p = 0.028). Median survival in moderately proliferative PD-L1 negative tumors at 12.6 months was comparable to that of highly/poorly proliferative PD-L1 positive tumors at 11.5 months, but in both instances less than that of moderately proliferative PD-L1 positive tumors. Similar to survival, proliferation status has impact on disease control (DC) in patients with both PD-L1 positive and negative tumors. Patients with moderately versus those with poorly or highly proliferative tumors have a superior DC rate when combined with any classification schema used to score PD-L1 as a positive result (i.e., TPS ≥ 50% or ≥ 1%), and best displayed by a DC rate for moderately proliferative tumors of no less than 40% for any classification of PD-L1 as a negative result. While there is an over representation of moderately proliferative tumors as PD-L1 expression increases this does not account for the improved survival or higher disease control rates seen in PD-L1 negative tumors.ConclusionsCell proliferation is potentially a new biomarker of response to ICIs in NSCLC and is applicable to PD-L1 negative tumors.

Walking is correlated with both improved physical and emotional health. However, walking behavior is often heavily influenced by environmental conditions. The goal of this study was to examine actual and perceived walkability safety and the relationship between perceived walkability safety and self-rated levels of walkability participation, defined as the number of places one walks within the community on a regular basis. Researchers used a mixed-methods approach, combining direct observations of traffic safety and in-person surveys within a specific Chicago neighborhood from 2015 to 2016 and from 2016 to 2017, respectively. We conducted behavioral assessments on 25 intersections and 48 sidewalks and surveyed 96 pedestrians on perceived walkability safety and walkability participation. Findings showed 68% and 81% of vehicles in 2015 and 2016, respectively did not obey street signs, placing pedestrians at significant risk. Pedestrians expressed concerns about the safety of walking in their neighborhood yet walked to a median of eight places weekly. The results indicated a marginally significant positive relationship between self-reported community participation and walking habits, as well as relationships between various factors of perceived walkability and age, gender, or language of survey completion. It is clear from the results of this study that walkability in this community is not a safe activity. However, walking habits may also be influenced by community satisfaction and SES factors. Communities need to engage in safe driving campaigns and educate walkers on how to protect themselves from distracted drivers. Local governments should implement policy initiatives such as police enforcement and drivers' education campaigns.

Asset mapping is a participatory methodology that engages community members in identifying services and settings that promote health and well‐being. This study aimed to identify community assets from the perspective of Latinx immigrant families with youth with disabilities. Latinx immigrant families (n = 21) participated in the mapping, followed by a reflection session and an open forum (n = 30). The findings revealed that families identified faith‐based organizations and social service agencies as some of the main assets in their communities, while they identified mental health services as the most needed. The results also showed that participants preferred to utilize services and resources that are within walking distance of their homes, provide safe spaces, treat them well, offer bilingual services, do not require documentation, and are affordable. This study has important implications for community scholars and practitioners interested in implementing asset‐based methodologies that focus on participants as experts of their own realities and agents of change and that promote advocacy and empowerment actions. Highlights: Churches provide Latinx families with formal and informal services.Latinx immigrant families identifed the need for mental health services.Latinx families identifed services provided in Spanish as assets.Some community settings like local parks received mixed reviews from immigrant families. [ABSTRACT FROM AUTHOR]

Background: Despite the approval of mTOR inhibitor everolimus and CDK4/6 inhibitors in the management of hormone-receptor-positive HER2 non-amplified metastatic breast cancer (HR+ HER2-MBC), the optimal sequence of therapy is unclear. There are no clinical data on efficacy of everolimus in HR+ HER2-MBC after cancer progresses on CDK4/6 inhibitors., Objective: The objective of this study is to find the efficacy of everolimus in HR+ HER2-MBC after they progress on a CDK4/6 inhibitor palbociclib., Methods: This is a retrospective, 2-institute review of HR+ HER2-MBC from Jan 2015 to March 2018 treated with everolimus after progression on palbociclib. Primary end point was median progression-free survival (PFS), secondary end points objective response rate (ORR), clinical benefit ratio (CBR), and overall survival (OS)., Results: Out of 41 women with median age 61 years (33, 87) enrolled, 66% had received adjuvant systemic therapy, 61% had visceral disease, and 95% had prior nonsteroidal aromatase inhibitors. About 83% women had 3 or more chemotherapy or hormonal therapies prior to everolimus. Kaplan-Meier estimates showed a median PFS of 4.2 months (95% confidence interval [CI]: 3.2-6.2). The median OS was 18.7 months (95% CI 9.5 to not reached). Objective response rate and CBR were both 17.1%., Conclusion: Everolimus was associated with modest PFS and ORR in HR+ HER2-MBCs postprogression on palbociclib., Competing Interests: Declaration of conflicting interests:The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: E.G.L. has received royalty from UpToDate. A.B. has/had consulting or advisory role for Agendia, Bayer, bioTheranostics, Celgene, Genentech/Roche, Genomic Health, Lilly, NanoString Technologies, Novartis, Pfizer, and Puma Biotechnology. A.P.E. has received honorarium from Pfizer. M.O. has received research fund from Pfizer/NCCN and has/had consulting or advisory role for Novartis and AstraZeneca. A.D. has received honorarium from Daiichi Sankyo. All other authors declare that they have no conflict of interest., (© The Author(s) 2020.)