Development and validation of a nomogram for the prediction of brain metastases in small cell lung cancer.

INTRODUCTION: The aim was to develop and validate a nomogram for the prediction of brain metastases (BM) in small cell lung cancer (SCLC), to explore the risk factors and assist clinical decision-making. METHODS: We reviewed the clinical data of SCLC patients between 2015 and 2021. Patients between 2015 and 2019 were included to develop, whereas patients between 2020 and 2021 were used for external validation. Clinical indices were analysed by using the least absolute shrinkage and selection operator (LASSO) logistic regression analyses. The final nomogram was constructed and validated by bootstrap resampling. RESULTS: A total of 631 SCLC patients between 2015 and 2019 were included to construct model. Gender, T stage, N stage, Eastern Cooperative Oncology Group (ECOG), haemoglobin (HGB), the absolute value of lymphocyte (LYMPH #), platelet (PLT), retinol-binding protein (RBP), carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) were identified as risk factors and included into the model. The C-indices were 0.830 and 0.788 in the internal validation by 1000 bootstrap resamples. The calibration plot revealed excellent agreement between the predicted and the actual probability. Decision curve analysis (DCA) showed better net benefits with a wider range of threshold probability (net clinical benefit was 1%-58%). The model was further externally validated in patients between 2020 and 2021 with a C-index of 0.818. CONCLUSIONS: We developed and validated a nomogram to predict the risk of BM in SCLC patients, which could help clinicians to rationally schedule follow-ups and promptly implement interventions.

Identifying optimal first-line immune checkpoint inhibitors based regiments for advanced non-small cell lung cancer without oncogenic driver mutations: A systematic review and network meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have changed the treatment pattern of advanced and metastatic NSCLC. A series of ICI based therapies have emerged in the first-line treatment field, but the comparative efficacy was unclear. METHOD: We searched multiple databases and abstracts of major conference proceedings up to Apri1, 2022 for phase III randomised trials of advanced driver-gene wild type NSCLC patients receiving first-line therapy. Outcomes analyzed included progression free survival (PFS), overall survival (OS), and et al. RESULTS: Thirty-two double-blind RCTs were included, involving 18,656 patients assigned to 22 ICI-based first-line regimens. A series of ICI regiments (including ICI plus chemotherapy), ICI monotherapy, doublet ICIs, doublet ICIs plus chemotherapy) emerged, and showed significant PFS and OS benefit than chemotherapy and chemotherapy + bevacizumab (BEV) for advanced wild-type NSCLC. In comprehensive terms of PFS, chemoimmunotherapy (CIT) were significantly more effective than ICI monotherapy and doublet ICIs. In terms of OS for patients with non-squamous NSCLC, pembrolizumab containing CIT was associated with a median rank of the best regimens, and followed by Atezolizumab+BEV based CIT; while for OS in patients with squamous NSCLC, Cemiplimab and sintilimab based CIT were the most effective regimens. For more than 2 years follow-up, the atezolizumab, pembrolizumab, nivolumab and durvalumab containing ICI therapy all provide a durable long-term OS benefit over chemotherapy and BEV + chemotherapy. CONCLUSIONS: The findings of the present NMA represent the most comprehensive evidence, which might suggest or provide basis for first-line ICI therapy decision for advanced NSCLC patients without oncogenic driver mutations.

Higher blood cotinine level is associated with worse cognitive functioning in non-smoking older adults.

Introduction: Secondhand smoke (SHS) is common in older adults; however, its cognitive effect is unclear. We aimed to examine the association between serum cotinine level and cognitive functioning among non-smoking older adults. Materials and methods: A total of 2,703 older adults aged 60 and above from the National Health and Nutrition Examination (NHANES) Survey 2011-2014 were included. Serum cotinine level was analyzed in the laboratory. A level ≤10 ng/ml and a response of "no" to the question "Do you currently smoke?" were used to select non-smokers. Cognitive functioning was measured using the Consortium to Establish a Registry for Alzheimer's disease Word Learning subtest (CERAD-WL) immediate and delayed recall tests, the Animal Fluency test (AFT), and the Digit Symbol Substitution test (DSST). Multivariable linear regression models were constructed to examine the association between serum cotinine level quartile and test-specific and global cognition z scores adjusting for age, race/ethnicity, education, depressive symptoms, body mass index, alcohol use, smoking history, prevalent coronary heart disease (CHD), stroke, and systolic blood pressure. Results: About half of the participants (mean age 70.5 years) were female (53.6%), non-Hispanic White (48.3%), and completed some college and above (50.2%). Multivariate linear regressions with a reference group being those in the 1st quantile (lowest) showed that participants in the 4th quartile (highest) of serum cotinine level had lower immediate recall [ß = -0.16, 95% confidence interval (CI) = -0.29, -0.03], AFT (ß = -0.19, 95% CI = -0.33, -0.05), DSST (ß = -0.27, 95% CI = -0.39, -0.15), and global cognition (ß = -0.26, 95% CI = -0.39, -0.14) z scores. Participants in the 3rd quartile had lower immediate recall (ß = -0.16, 95% CI = -0.30, -0.02) and global cognition (ß = -0.16, 95% CI = -0.29, -0.02) z scores. Participants in the 2nd quartile had lower delayed recall z scores (ß = -0.16, 95% CI = -0.29, -0.02). Conclusion: Higher serum cotinine level was associated with worse cognitive functioning in non-smoking older adults. Prevention and reduction of SHS in older adults may help protect their cognitive functioning.