Univariate analysis on OS and PFS.

<p>Univariate analysis on OS and PFS.</p

Correlation of COP-LMR with the clinicopathological and laboratory parameters of NSCLC patients.

<p>Correlation of COP-LMR with the clinicopathological and laboratory parameters of NSCLC patients.</p

Progression free survival of the stage IV NSCLC patients.

<p>PFS between the different COP LMR groups (P<0.001). <i>COP-LMR</i>: <i>combination of platelet and lymphocyte to monocyte ratio; PFS</i>: <i>progression free survival</i>.</p

Multivariate analysis on OS and PFS.

<p>Multivariate analysis on OS and PFS.</p

Prognostic value of platelet count and lymphocyte to monocyte ratio combination in stage IV non-small cell lung cancer with malignant pleural effusion

<div><p>Introduction</p><p>A combination of platelet and lymphocyte to monocyte ratio (LMR) (abbreviated as COP-LMR) has been recently evaluated as systemic inflammatory marker for prognostication in lung cancer. While previous study on COP-LMR has evaluated its prognostic value in NSCLC patients who underwent curative resections, the combination of these two markers has not been evaluated in advanced NSCLC yet.</p><p>Objectives</p><p>In this study, we evaluated the prognostic value of COP-LMR in stage IV NSCLC with malignant pleural effusion under active anticancer treatment.</p><p>Methods</p><p>Between January 2012 and July 2016, 217 patients with stage IV NSCLC and MPE undergoing active anticancer treatment were selected for evaluation. If patients had both low LMR (< 2.47) and increased platelet (> 30.0 ×10⁴ mm-3), they were assigned to COP-LMR group 2. Patients with one parameter were assigned to COP-LMR group 1. If none, patients were assigned to COP-LMR group 0.</p><p>Results</p><p>Median overall survival (OS) (P < 0.001), progression free survival (PFS) (P < 0.001) and histological feature (P = 0.003) showed significant differences among COP-LMR groups. For COP-LMR groups 0, 1 and 2, median survival times were 35.9, 14.7 and 7.4 months, respectively, while median progression free times were 19.2, 13.3 and 7.4 months, respectively. Older age, male, low albumin, high CRP and high COP-LMR (0 vs 1, P = 0.021, hazard ratio (HR): 1.822, 95% confidence interval (CI): 1.096–3.027 and 0 vs 2, P = 0.003, HR: 2.464, 95% CI: 1.373–4.421) were independent predictive factors for shorter OS. Age, sex, histology, albumin, or CRP had no significant influence on PFS. High COP-LMR was the significant factor in predicting shorter PFS (0 vs 1, P = 0.116 and 0 vs 2, P = 0.007, HR: 1.902, 95% CI: 1.194–3.028).</p><p>Conclusions</p><p>A combination of pretreatment LMR and platelet levels can be used to predict short survival in stage IV NSCLC patients who underwent active anticancer treatment.</p></div

Overall survival and progression free survival of the stage IV NSCLC patients without positive driver mutations between the different COP LMR groups.

<p><b>A:</b> OS showed significant difference (P = 0.001) between COP-LMR groups 1 and 2. OS showed no significant difference between COP-LMR groups 0 and 1 (P = 0.071); <b>B:</b> PFS showed decreasing tendency as the COP-LMR score is higher, however with no statistical significance (P = 0.056). <i>COP LMR</i>: <i>combination of platelet and lymphocyte to monocyte ratio; NSCLC</i>: <i>non-small cell lung cancer; OS</i>: <i>overall survival; PFS</i>: <i>progression free survival</i>.</p

Chronic Obstructive Pulmonary Disease-Related Non-Small-Cell Lung Cancer Exhibits a Low Prevalence of EGFR and ALK Driver Mutations

<div><p>Lung cancer and chronic obstructive pulmonary disease (COPD) are two major lung diseases. Epidermal growth factor receptor (EGFR) mutations, v‐Ki‐ras2 Kirsten rat sarcoma (KRAS) mutations and anaplastic lymphoma kinase (ALK) gene rearrangements represent driver mutations that are frequently assessed on initial evaluation of non-small-cell lung cancer (NSCLC). The present study focused on the expression of driver mutations in NSCLC patients presenting with COPD and further evaluated the association between NSCLC and COPD. Data from 501 consecutive patients with histologically proven recurrent or metastatic NSCLC were analyzed retrospectively. The patients underwent spirometry and genotyping of EGFR, ALK, and KRAS in tissue samples. Patient characteristics and expression of driver mutations were compared between the COPD and non-COPD groups.</p><p>Among 350 patients with spirometric results, 106 (30.3%) were diagnosed with COPD, 108 (30.9%) had EGFR mutations, 31 (8.9%) had KRAS mutations, and 34 (9.7%) showed ALK rearrangements. COPD was independently associated with lower prevalences of EGFR mutations (95% confidence interval [CI], 0.254–0.931, <i>p</i> = 0.029) and ALK rearrangements (95% CI, 0.065–0.600, <i>p</i> = 0.004). The proportions of EGFR mutations and ALK rearrangements decreased as the severity of airflow obstruction increased (<i>p</i> = 0.001). In never smokers, the prevalence of EGFR mutations was significantly lower in the COPD group than in the non-COPD group (12.7% vs. 49.0%, <i>p</i> = 0.002). COPD-related NSCLC patients exhibited low prevalences of EGFR mutations and ALK rearrangements compared with the non-COPD group. Further studies are required regarding the molecular mechanisms underlying lung cancer associated with COPD.</p></div

Comparison of prevalence of major driver mutations between COPD and non-COPD groups.

<p>(A) EGFR mutations (B) KRAS mutations and (C) ALK rearrangements.</p

Representative photographs of a patient with ALK rearranged adenocarcinoma in pleural fluid cell blocks.

<p>(A) Tumor with H&E stain. (B) Tumor with positive TTF-1 stain. (C) FISH analysis interpreted as positive; 15 ALK rearranged cells in 57 tumor cells (ALK FISH split >15%). <i>Abbreviations</i> H&E: hematoxylin and eosin; TTF-1; thyroid transcription factor 1.</p

Association between EGFR mutations and the presence of COPD in non-smokers (n = 199).

<p>Association between EGFR mutations and the presence of COPD in non-smokers (n = 199).</p