Lung Cancer in Non-smokers in Czech Republic: Data from LUCAS Lung Cancer Clinical Registry.

BACKGROUND/AIM: LUCAS is a clinical lung cancer registry (ClinicalTrials.gov identifier is NCT04228237), prospectively collecting data from newly diagnosed lung cancer patients in seven pneumooncology centers in the Czech Republic, since June 1, 2018. The aim of the study was to assess the stage of the disease at the time of diagnosis, percentage of morphological types, survival, percentage of driving mutations, eligibility for radical surgery, and percentage of patients who undergo radical surgery, in the non-smoking population in comparison with smokers and former smokers. PATIENTS AND METHODS: The total number of patients in the registry at the time of the analysis was 2,743. Only 2,439 patients with complete records (smoking status, stage, and type of tumor) were included in this study. RESULTS: The analysis indicated that non-smokers are diagnosed at a later stage of the disease but they have a better survival rate than smokers. Fewer smokers with stage III disease who are eligible for radical surgery will undergo surgery compared to non-smokers with the same clinical stage. Driving mutations are more common in non-smokers, even after adjustment for the more frequent occurrence of adenocarcinoma in the group of non-smokers. CONCLUSION: The data from LUCAS registry are consistent with already known facts, suggesting that the LUCAS registry is a useful clinical tool.

Prognostic value of tumor-infiltrating lymphocytes (TILs) and their association with PD-L1 expression and DNA repair protein RAD51 in patients with resected non-small cell lung carcinoma.

OBJECTIVES: DNA repair proteins have emerged as potential predictors for immunotherapy response alongside PD-L1 expression, tumor-infiltrating lymphocytes (TILs) and tumor mutational burden. We analyzed expression of PD-L1, TILs count and expression of the homologous recombination (HR) protein RAD51, as potential prognostic factors in patients with resected non-small-cell lung carcinoma (NSCLC). MATERIALS AND METHODS: Discovery set included 96 NSCLC patients from the University Hospital Olomouc (Czech Republic) and a replication set included 1109 NSCLC patients from University Hospital Zurich (Switzerland). Tissue microarrays (TMAs) were stained using the automated staining platform Ventana Benchmark Ultra with antibodies against RAD51,CD3, CD8, CD68 and PD-L1. RESULTS: Loss of nuclear RAD51 protein was associated with high TILs (r=-0.25, p = 0.01) and PD-L1 status (10.6 vs. 2.4 %, p = 0.012) in patients receiving neoadjuvant chemo-/radiotherapy (CT/RT). In silico analysis from the TCGA data set showed a negative relationship between RAD51 mRNA expression and CD45 (r = ‒0.422, p < 0.0001), CD68 (r = ‒0.326, p < 0.001), CD3 (r = ‒0.266, p < 0.001) and CD8 (r = ‒0.102, p < 0.001). RAD51 low/PD-L1 high patients were clustered as separate entity in the replication set and in TCGA dataset. High TILs status was significantly associated with improved OS in the replication set (unadjusted HR = 0.57, 95 % CI 0.42-0.76, p < 0.001). Similar results have been seen for CD3, CD8 and CD68. CONCLUSIONS: In conclusion, RAD51 nuclear loss is weakly associated with increased TILs and high PD-L1 at the time of surgery in curatively resected NSCLC and after prior exposure to neoadjuvant chemo- or radiotherapy. Both high TILs and RAD51 nuclear loss were confirmed as independent prognostic factors in curatively resected NSCLC.

Sphingosine kinase-1 predicts overall survival outcomes in non-small cell lung cancer patients treated with carboplatin and navelbine.

Sphingosine 1-phosphate (S1P) is a bioactive lipid metabolite associated with cancer cell proliferation, survival, migration and regulation of tumor angiogenesis in various cellular and animal models. Sphingosine kinase-1 (SphK1) and S1P lyase are the main enzymes that respectively control the synthesis and degradation of S1P. The present study analyzed the prognostic and predictive value of SphK1 and S1P lyase expression in patients with non-small cell lung cancer (NSCLC), treated with either surgery alone or in combination with adjuvant carboplatin and navelbine. Formalin-fixed, paraffin-embedded tissue samples from 176 patients with NSCLC were stained immunohistochemically using antibodies against SphK1 and S1P lyase, and their expression was correlated with all available clinicopathological factors. Increased expression of SphK1 was significantly associated with shorter overall and disease free survival in patients treated with adjuvant platinum-based chemotherapy. No prognostic relevance for S1P lyase expression was observed. Collectively, the results suggest that the immunohistochemical detection of SphK1 may be a promising predictive marker in NSCLC patients treated with adjuvant platinum-based chemotherapy.

Tumor autophagy is associated with survival outcomes in patients with resected non-small cell lung cancer.

OBJECTIVES: LC3A protein is associated with autophagosomes, and LC3A immunohistochemistry (IHC) is used for the detection of autophagy activity. The aim of this study was to assess the prognostic value of LC3A expression in patients with resected non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: We used tissue microarrays (TMAs) constructed from 116 resected stage IB-III NSCLC patients. Standard immunohistochemistry was performed on formalin-fixed paraffin-embedded tissue sections using antibody against LC3A autophagic potein. Stained slides were scanned by Olympus dotSlide Digital Virtual Microscopy System (Japan) and the LC3A staining was evaluated digitally. Groups were compared using the Mann Whitney U test, and correlations were assessed using Spearman's rank test. Survival was calculated using Kaplan-Meier analysis. Primary study endpoint was overall survival (OS), secondardy study endpoint disease-free survival (DFS). Cut-off optimization for LC3A prognostic value was performed using the "cut-off finder' 'software (Charite, Berlin, Germany). In addition, the Kaplan Meier plotter (KmPlot) was used to assess the relationship between LC3A mRNA expression and clinical outcome (OS and DFS) in patients with NSCLC. RESULTS: From 116 patients, 88 tissue samples were available for final examination. No significant association was found between LC3A staining and other clinicopathological variables, including tumor grade, stage and histological subtype. A higher number of LC3A stone-like structures (SLSs) (>20), was significanly associated with poor OS (HR = 2.27, p = 0.011) and DFS (HR = 2.27, p = 0.003). A significant association between high LC3A mRNA and both a worse OS and worse DFS was found by KMPlot analysis in patients with stage I-III NSCLC. CONSLUSION: This retrospective study suggests that SLSs as assessed by LC3A IHC as well as LC3A mRNA expression has a clinically relevant negative prognostic value in patients with resected NSCLC, and should be further investigated.