The Association between Polluted Neighborhoods and TP53-Mutated Non-Small Cell Lung Cancer.

BACKGROUND: Poor patients often reside in neighborhoods of lower socioeconomic status (SES) with high levels of airborne pollutants. They also have higher mortality from non-small cell lung cancer (NSCLC) than those living in wealthier communities. We investigated whether living in polluted neighborhoods is associated with somatic mutations linked with lower survival rates, i.e., TP53 mutations. METHODS: In a retrospective cohort of 478 patients with NSCLC treated at a comprehensive cancer center between 2015 and 2018, we used logistic regression to assess associations between individual demographic and clinical characteristics, including somatic TP53 mutation status and environmental risk factors of annual average particulate matter (PM2.5) levels, and neighborhood SES. RESULTS: 277 patients (58%) had somatic TP53 mutations. Of those, 45% lived in neighborhoods with "moderate" Environmental Protection Agency-defined PM2.5 exposure, compared with 39% of patients without TP53 mutations. We found significant associations between living in neighborhoods with "moderate" versus "good" PM2.5 concentrations and minority population percentage [OR, 1.06; 95% confidence interval (CI), 1.04-1.08]. There was a significant association between presence of TP53 mutations and PM2.5 exposure (moderate versus good: OR, 1.66; 95% CI, 1.02-2.72) after adjusting for patient characteristics, other environmental factors, and neighborhood-level SES. CONCLUSIONS: When controlling for individual- and neighborhood-level confounders, we find that the odds of having a TP53-mutated NSCLC are increased in areas with higher PM2.5 exposure. IMPACT: The link between pollution and aggressive biology may contribute to the increased burden of adverse NSCLC outcomes in individuals living in lower SES neighborhoods.

Urine test for EGFR analysis in patients with non-small cell lung cancer.

Precision medicine approaches in oncology are reliant on the accurate genomic characterization of tumors. While tissue remains the mainstay specimen for molecular testing, tumor biopsies are riddled with challenges and limitations due to their invasive and site-specific nature. Tumor inaccessibility and intratumoral heterogeneity, in particular, represent significant obstacles to the identification of actionable genetic alterations and hence effective mono- and combination therapy strategies. Proof-of-concept studies indicate that circulating tumor DNA (ctDNA) released from multiple tumor regions and anatomical locations is more reflective of intra- and intertumoral heterogeneity. Non-invasive liquid biopsy approaches that allow for the analysis of ctDNA are thus being increasingly implemented in routine patient care for the detection and monitoring of cancer-associated mutations. Indeed, the use of plasma testing to screen for epidermal growth factor receptor (EGFR) T790M mutant positive non-small cell lung cancer (NSCLC) patients eligible for treatment with third-generation EGFR inhibitors was recently approved by the U.S. Food and Drug Administration and is incorporated into the most recent version of the National Comprehensive Cancer Center guidelines as an alternative to tissue biopsy. Urine represents another liquid biopsy specimen that is distinguished by its ease of collection, option for home collection, and lack of temporal and volumetric collection restrictions. Importantly, there is an accumulating body of evidence supporting the clinical validity of urinary EGFR mutant testing for the identification and stratification of patients likely to benefit from EGFR-directed therapies and as a means to assess patient response, the presence of residual disease, and emergence of resistant tumor cell populations.

Therapeutic monoclonal antibodies for respiratory diseases: Current challenges and perspectives, March 31 - April 1, 2016, Tours, France.

Monoclonal antibody (mAb) therapeutics have tremendous potential to benefit patients with lung diseases, for which there remains substantial unmet medical need. To capture the current state of mAb research and development in the area of respiratory diseases, the Research Center of Respiratory Diseases (CEPR-INSERM U1100), the Laboratory of Excellence "MAbImprove," the GDR 3260 "Antibodies and therapeutic targeting," and the Grant Research program ARD2020 "Biotherapeutics" invited speakers from industry, academic and government organizations to present their recent research results at the Therapeutic Monoclonal Antibodies for Respiratory Diseases: Current challenges and perspectives congress held March 31 - April 1, 2016 in Tours, France.