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In patients with lung cancer (LC), understanding factors that impact the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-spike antibody (SAb) titers over time is critical, but challenging, due to evolving treatments, infections, vaccinations, and health status. The objective was to develop a time-dependent regression model elucidating individual contributions of factors influencing SAb levels in LC patients using a prospective, longitudinal, multi-institutional cohort study initiated in January 2021. The study evaluated 296 LC patients—median age 69; 55% female; 50% stage IV. Blood samples were collected every three months to measure SAb levels using FDA-approved ELISA. Asymptomatic and unreported infections were documented through measurement of anti-nucleocapsid Ab levels (Meso Scale Discovery). Associations between clinical characteristics and titers were evaluated using a time-dependent linear regression model with a generalized estimating equation (GEE), considering time-independent variables (age, sex, ethnicity, smoking history, histology, and stage) and time-dependent variables (booster vaccinations, SARS-CoV-2 infections, cancer treatment, steroid use, and influenza vaccination). Significant time-dependent effects increasing titer levels were observed for prior SARS-CoV-2 infection (p < 0.001) and vaccination/boosters (p < 0.001). Steroid use (p = 0.043) and chemotherapy (p = 0.033) reduced titer levels. Influenza vaccination was associated with increased SAb levels (p < 0.001), independent of SARS-CoV-2 vaccine boosters. Prior smoking significantly decreased titers in females (p = 0.001). Age showed no association with titers. This GEE-based linear regression model unveiled the nuanced impact of multiple variables on patient anti-spike Ab levels over time. After controlling for the major influences of vaccine and SARS-CoV-2 infections, chemotherapy and steroid use were found to have negatively affected titers. Smoking in females significantly decreased titers. Surprisingly, influenza vaccinations were also significantly associated, likely indirectly, with improved SARS-CoV-2 titers. [ABSTRACT FROM AUTHOR]

Although aberrant EGFR signaling is widespread in cancer, EGFR inhibition is effective only in a subset of non-small cell lung cancer (NSCLC) with EGFR activating mutations. A majority of NSCLCs express EGFR wild type (EGFRwt) and do not respond to EGFR inhibition. TNF is a major mediator of inflammation-induced cancer. We find that a rapid increase in TNF level is a universal adaptive response to EGFR inhibition in NSCLC, regardless of EGFR status. EGFR signaling actively suppresses TNF mRNA levels by inducing expression of miR-21, resulting in decreased TNF mRNA stability. Conversely, EGFR inhibition results in loss of miR-21 and increased TNF mRNA stability. In addition, TNF-induced NF-κB activation leads to increased TNF transcription in a feed-forward loop. Inhibition of TNF signaling renders EGFRwt-expressing NSCLC cell lines and an EGFRwt patient-derived xenograft (PDX) model highly sensitive to EGFR inhibition. In EGFR-mutant oncogene-addicted cells, blocking TNF enhances the effectiveness of EGFR inhibition. EGFR plus TNF inhibition is also effective in NSCLC with acquired resistance to EGFR inhibition. We suggest concomitant EGFR and TNF inhibition as a potentially new treatment approach that could be beneficial for a majority of lung cancer patients.

Radiation Therapy Oncology Group (RTOG) 3505 is a randomized phase 3 study of concurrent chemoradiation followed by immune checkpoint inhibitor therapy or placebo in patients with locally advanced non-small-cell lung cancer (NSCLC). Patients with surgically unresectable stage 3 NSCLC will receive thoracic radiotherapy to 60 Gy with concurrent cisplatin 50 mg/m2 intravenously (I.V.) on days 1, 8, 29, and 36, and etoposide 50 mg/m2 I.V. on days 1 to 5 and days 29 to 33. Between 4 and 12 weeks after completion of concurrent chemoradiation, eligible patients will be randomized to the anti-programmed death 1 (PD-1) monoclonal antibody nivolumab 240 mg I.V. or placebo every 2 weeks for up to 1 year. The primary end points are overall survival (OS) and progression-free survival (PFS), as determined by central independent radiology review. Secondary objectives include toxicity assessment, patient-reported outcomes and quality of life, and OS and PFS in programmed death ligand 1 (PD-L1) expressors (≥ 1%) and PD-L1 nonexpressors (< 1%). Assuming a rate of 16.7% due to ineligibility and dropout before randomization, a total of 660 patients will be enrolled to ensure 550 patients will be randomized after completion of chemoradiation. This sample size will provide ≥ 90% power to detect a hazard ratio of 0.7 for OS with 2-sided type I error of 0.04, and to detect a hazard ratio of 0.667 for PFS 2-sided type I error of 0.01. (NCT02768558).

Background Mixed response (MR), a scenario featuring discordant tumor changes, has been reported primarily with targeted therapies or immunotherapy. We determined the incidence and prognostic significance of MR in advanced non–small cell lung cancer (NSCLC) treated with cytotoxic chemotherapy. Patients and Methods We analyzed patient-level data from ECOG-ACRIN E5508 (carboplatin-paclitaxel + bevacizumab induction followed by randomization to maintenance therapy regimens). For patients with at least 2 target lesions and available measurements after cycle 2, we characterized response as homogeneous response (HR, similar behavior of all lesions), MR (similar behavior but >30% difference in magnitude of best and least responding lesions), or true mixed response (TMR, best and least responding lesions showing different behavior: ≥10% growth versus ≥10% shrinkage). We compared category characteristics using Mann-Whitney U and Chi-square tests, and overall survival (OS) using log-rank test and Cox models. Results Among 965 evaluable patients, HR occurred in 609 patients (63%), MR in 208 (22%), and TMR in 148 (15%). Median OS was 13.6 months for HR, 12.0 months for MR, and 7.6 months for TMR (P  < .001). Compared to HR, TMR had inferior OS among stable disease cases (HR 1.62; 95% CI, 1.23-2.12; P  < .001) and a trend toward inferior OS among progressive disease cases (HR 1.39; 95% CI, 0.83-2.33; P  = .2). In multivariate analysis, TMR was associated with worse OS (HR 1.48; 95% CI, 1.22-1.79; P  < .001). Conclusion True mixed response occurs in a substantial minority of lung cancer cases treated with chemotherapy and independently confers poor prognosis. [ABSTRACT FROM AUTHOR]

Introduction The use of molecular biomarkers to guide lung cancer management has led to increasing frequency and amounts of tissue required for repeat lung biopsies. While patient safety and reporting of adverse events has been increasingly emphasized in recent decades, the safety of lung biopsies in patients with lung cancer has only been studied in small cohorts. We therefore analyzed adverse events in patients with lung cancer undergoing lung biopsies in the National Hospital Discharge Survey (NHDS) database. Methods Data were abstracted using ICD-9 lung cancer diagnosis (162.X) and lung biopsy procedure codes (33.20, 33.24, 33.25, 33.26, 33.27, 33.28) from 2001 to 2010. Agency for Healthcare Research and Quality (AHRQ) Patient-Safety Indicators (PSI) were used to identify hospital-acquired adverse events. Weighted analyses were performed using SAS version 9.4. Results A total of 540,747 patients were included for analysis. The number of biopsies increased over time, from 51,221 in 2001, to 63,239 in 2010 (P < 0.001). Overall, 159,683 (30%) patients suffered [greater than or equal to] 1-PSI event during their hospitalization. Incidence of PSI varied by biopsy type: bronchoscopic (26%), percutaneous (34%), surgical (39%). The proportion of patients with [greater than or equal to] 1 PSI event increased from 24% in 2001 to 38% in 2010 (P < 0.001). Patients with [greater than or equal to] 1 PSI had longer length of stay (mean, 11.6 vs 8.1 days; P < 0.001) and higher in-hospital mortality (adjusted odds ratio, 5.9, 95% CI 3.9-8.9; P < 0.001). Conclusions The frequency of lung biopsies performed and rate of documented adverse events in hospitalized lung cancer patients have increased. These findings have policy, funding, research, and practice implications., Author(s): Mitchell S. von Itzstein [sup.1] , Arjun Gupta [sup.1] [sup.6] , Kristin C. Mara [sup.2] , Sahil Khanna [sup.3] , David E. Gerber [sup.1] [sup.4] [sup.5] [sup.7] Author Affiliations: [...]