Background: First-line treatment for patients with non-small cell lung cancer (NSCLC) with a sensitizing epidermal growth factor receptor (EGFR) mutation is a tyrosine kinase inhibitor (TKI). Despite higher response rates and prolonged progression free survival (PFS) compared with platinum doublet chemotherapy, a subset of these patients do not receive prolonged benefit from these agents. We investigate if the neutrophil-to-lymphocyte ratio (NLR) and other markers of cachexia and chronic inflammation correlate with worse outcomes in these patients. Methods: This study is a retrospective review of 137 patients with advanced EGFR-mutated NSCLC treated with TKIs at Rush University Medical Center and University of Chicago Medicine from August 2011 to July 2019, with outcomes followed through July 2020. The predictive value of NLR and body mass index (BMI) was assessed at the start of therapy, and after 6 and 12 weeks of treatment by univariable and multivariable analyses. Results: On univariable analysis, NLR ≥ 5 or higher NLR on a continuous scale were both associated with significantly worse PFS and overall survival (OS) at treatment initiation, and after 6 or 12 weeks of treatment. On multivariable analysis, NLR ≥ 5 was associated with increased risk of death at 12 weeks of therapy (HR 3.002, 95% CI 1.282–7.029, p = 0.011), as was higher NLR on a continuous scale (HR 1.231, 95% CI 1.063–1.425, p = 0.0054). There was no difference in PFS and OS and amongst BMI categories though number of disease sites and Eastern Cooperative Oncology Group (ECOG) performance status was associated with worse PFS and OS. Conclusions: Patients with NLR ≥ 5 have a worse median PFS and median OS than patients with NLR < 5. NLR may have value as a predictive biomarker and may be useful for selecting patients for therapy intensification in the front-line setting either at diagnosis or after 12 weeks on therapy. NLR needs to be validated prospectively.

Neuroblastoma is a common childhood cancer with poor prognosis when at its advanced stage. Checkpoint molecule inhibition is successful in treating multiple advanced adult cancers. We investigated PD-L1 and other checkpoint molecule expression to determine their roles in drug resistance and usefulness as targets for drug therapy. We developed three doxorubicin-resistant (DoxR) cell lines from parental cell lines. Matrigel in vitro invasion assays were used to compare invasiveness. Western blot assays were used to compare PD-L1 expression. Immuno-oncology checkpoint protein panels were used to compare concentrations of 17 checkpoint molecules both cellular and soluble. PD-L1 and 12 other checkpoint molecules were present in all cell lysates of each cell line without significantly different levels. Three were solubilized in the media of each cell line. PD-L1 is expressed in all DoxR and parental neuroblastoma cells and may be a potential target for drug therapy although its role in drug resistance remains unclear. Benchmarking checkpoint molecules provides the basis for future studies identifying targets for directed therapy and biomarkers for cancer detection or prognosis.

Due to poor compliance and uptake of LDCT screening among high-risk populations, lung cancer is often diagnosed in advanced stages where treatment is rarely curative. Based upon the American College of Radiology’s Lung Imaging and Reporting Data System (Lung-RADS) 80–90% of patients screened will have clinically “non-actionable” nodules (Lung-RADS 1 or 2), and those harboring larger, clinically “actionable” nodules (Lung-RADS 3 or 4) have a significantly greater risk of lung cancer. The development of a companion diagnostic method capable of identifying patients likely to have a clinically actionable nodule identified during LDCT is anticipated to improve accessibility and uptake of the paradigm and improve early detection rates. Using protein microarrays, we identified 501 circulating targets with differential immunoreactivities against cohorts characterized as possessing either actionable (n = 42) or non-actionable (n = 20) solid pulmonary nodules, per Lung-RADS guidelines. Quantitative assays were assembled on the Luminex platform for the 26 most promising targets. These assays were used to measure serum autoantibody levels in 841 patients, consisting of benign (BN; n = 101), early-stage non-small cell lung cancer (NSCLC; n = 245), other early-stage malignancies within the lung (n = 29), and individuals meeting United States Preventative Screening Task Force (USPSTF) screening inclusion criteria with both actionable (n = 87) and non-actionable radiologic findings (n = 379). These 841 patients were randomly split into three cohorts: Training, Validation 1, and Validation 2. Of the 26 candidate biomarkers tested, 17 differentiated patients with actionable nodules from those with non-actionable nodules. A random forest model consisting of six autoantibody (Annexin 2, DCD, MID1IP1, PNMA1, TAF10, ZNF696) biomarkers was developed to optimize our classification performance; it possessed a positive predictive value (PPV) of 61.4%/61.0% and negative predictive value (NPV) of 95.7%/83.9% against Validation cohorts 1 and 2, respectively. This panel may improve patient selection methods for lung cancer screening, serving to greatly reduce the futile screening rate while also improving accessibility to the paradigm for underserved populations.