OMRT-15. Multidisciplinary management of non-small cell lung cancer patients with leptomeningeal metastasis in the TKI era

Abstract Background leptomeningeal metastasis (LM) is a devastating scenario in patients with non-small cell lung cancer (NSCLC), with an estimated median overall survival (OS) of 4–6 months from diagnosis. Several studies have clarified the prognosis of treatment modalities after LM. However, just a few studies have clarified the prognosis of LM patterns. We evaluate the prognosis based on various patterns of LM under multidisciplinary treatment (MDT). Method This retrospective study evaluated NSCLC patients treated at National Taiwan University Hospital between 2007–2019 with brain metastases (BM) and LM. LM was classified into LM only, LM concurrent with BM, and LM after BM. Treatments including systemic therapy, whole-brain radiotherapy (WBRT), stereotactic radiosurgery (SRS), and intrathecal chemotherapy with Methotrexate (IT MTX) were recorded. BM excision was done by a neurosurgeon using minimally invasive neurosurgery. The MDT was done according to patients’ clinical situations. Kaplan-Meier methodology was used to describe overall survival OS. Multivariate Cox regression model was used to access prognostic factors. Result One hunderd patients with NSCLC CNS metastasis was included in this study. Median OS in patients with single, oligo and multiple BM was 42.0 months (95% CI= 0.12–83.89), 58.1 months (95% CI= 13.00–103.26), and 21.3 months (95% CI= 16.93–25.73), respectively. The median OS of all LM patients was 9.8 months. The median OS of LM after BM, concurrent BMLM, and LM only was 8 months (95% CI= 2.58–13.56), 41.5 months (95% CI= 0.00–94.36), and 18.5 months (95% CI=3.68–33.32), respectively. Multivariate Cox regression analysis showed only IT MTX (p= 0.010, HR= 0.392, 95%CI= 0.19–0.80) was associated with survival. Conclusion MDT in the TKI era has led to a dramatic improvement of OS in patients with LM (4–6 months vs. 9.8 months). NSCLC patients with LM only and concurrent BM LM has a better prognosis and longer survival, and thus are worth receiving intensive MDT care.

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Correlation between anemia before treatment with survival in patients with advanced non-small cell lung cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.18211 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 18211-18211

Author(s):

S. R. Bella ◽

M. E. Richardet ◽

P. Gomez Storniolo ◽

P. Celiz ◽

A. Lingua ◽

...

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Regression Analysis ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Cox Regression ◽

Small Cell ◽

Hemoglobin Level ◽

Small Cell Lung ◽

Cox Regression Analysis

18211 Background: Prognostic factors identified in advanced non small cell lung cancer are: age, gender, PS, h. SWOG univariable analysis in patients with chemotheraphy; confirmed these factors and show a relationship between the hemoglobin level and the overall survival; in addition the metastasic site number and cisplatin- based chemotheraphy (7). To analyse and compare the hemoglobin level before cisplatin- based chemotheraphy with survival in patients with advanced non- small cell lung cancer. Methods: Retrospective study conducted at the IONC of the 179 clinical record were analized, over a 5 year period. The collected data were: age, gender, PS, histologic type, stage, chemotheraphy cycles number, smooke history, number and metastasic site. We analyzed median and overal survival using Kaplan Meier, and the anemia as a prognostic implication factor with univariable and multivariable Cox regression analysis. Istologic type and TNM (1–6). Results: The mean age was 59 (40–79); 146 (81.5%) male and 33 (18.5%) women; histological types found were squamous cell carcinomas in 66 (37%), and adenocarcinoma in 113 (63%); stage IIIB in 61 (34%) and IV in 118 (66%). 147 (82%) were smokers and 32 (18%) were never smokers. All the patients had PS 0–1. Median overall survival time was 11.53 months and 13.88 months in the haemoglobin level < or > 11 gr/ 100 ml, respectively. (p=0.3). In univariable Cox regression analysis, smoking rates and chemotheraphy cycles number were predictors of survival (p=0.05 y p=0.018, respectively). Hemoglobine (p=0.55). In multivariable Cox regression analysis, only the number of cycles was predictor of survival (p=0.026). Hemoglobine (p=0.34). Conclusions: In our experience, a greater survival tendency was observed in patients with advanced non- small cell lung cancer who presented levels of Hemoglobine greater than 11 gr/dl, previous to cisplatin- based chemotherapy without statistical significance. [Table: see text]

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Molecular identification of an immunity- and Ferroptosis-related gene signature in non-small cell lung Cancer

BMC Cancer ◽

10.1186/s12885-021-08541-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Taisheng Liu ◽

Honglian Luo ◽

Jinye Zhang ◽

Xiaoshan Hu ◽

Jian Zhang

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Cox Regression ◽

Small Cell ◽

Low Risk ◽

Related Gene ◽

Small Cell Lung ◽

Cox Regression Analysis

Abstract Background Lung cancer is one of the dominant causes of cancer-related deaths worldwide. Ferroptosis, an iron-dependent form of programmed cell death, plays a key role in cancer immunotherapy. However, the role of immunity- and ferroptosis-related gene signatures in non-small cell lung cancer (NSCLC) remain unclear. Methods RNA-seq data and clinical information pertaining to NSCLC were collected from The Cancer Genome Atlas dataset. Univariate and multivariate Cox regression analyses were performed to identify ferroptosis-related genes. A receiver operating characteristic (ROC) model was established for sensitivity and specificity evaluation. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to explore the function roles of differentially expressed genes. Results A signature composed of five ferroptosis-related genes was established to stratify patients into high- and low-risk subgroups. In comparison with patients in the low-risk group, those in the high-risk one showed significantly poor overall survival in the training and validation cohorts (P < 0.05). Multivariate Cox regression analysis indicated risk score to be an independent predictor of overall survival (P < 0.01). Further, the 1-, 2-, and 3-year ROCs were 0.623 vs. 0.792 vs. 0.635, 0.644 vs. 0.792 vs. 0.634, and 0.631 vs. 0.641 vs. 0.666 in one training and two validation cohorts, respectively. Functional analysis revealed that immune-related pathways were enriched and associated with abnormal activation of immune cells. Conclusions We identified five immunity- and ferroptosis-related genes that may be involved in NSCLC progression and prognosis. Targeting ferroptosis-related genes seems to be an alternative to clinical therapy for NSCLC.

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Clinical Significance of Serum-Derived Exosomal LINC00917 in Patients With Non-Small Cell Lung Cancer

Frontiers in Genetics ◽

10.3389/fgene.2021.728763 ◽

2021 ◽

Vol 12 ◽

Author(s):

Dani Xiong ◽

Chuanlin Wang ◽

Zhaohui Yang ◽

Fusen Han ◽

Huaibing Zhan

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cancer Patients ◽

Cell Lung Cancer ◽

Cox Regression ◽

Small Cell ◽

Small Cell Lung ◽

Cox Regression Analysis ◽

Diagnostic Potential ◽

Nsclc Patients

Background: In this study, we aimed to explore the diagnostic potential of serum-based exosomal long intergenic noncoding RNA 917 (LINC00917) in non-small cell lung cancer (NSCLC).Methods: Exosomes were extracted from NSCLC patients’ serum samples. Exosomal LINC00917 expression levels were compared, by qRT-PCR, between cancer patients and healthy controls, as well as sub-populations of cancer patients. The association between exosomal LINC00917 expression and NSCLC patients’ clinicopathologic factors were investigated, and receiver operating characteristic (ROC) curves were drawn. In addition, NSCLC patients’ overall survivals (OSs) was examined based on exosomal LINC00917 expression and further evaluated by the cox regression analysis.Results: Serum-derived exosomal LINC00917 was highly expressed in NSCLC patients, and further upregulated in stage III/IV cancer patients. Exosomal LINC00917 yielded modestly good under the curve (AUC) values. Upregulated exosomal LINC00917 expression was closely associated with cancer patients’ advanced stages and shorter OSs.Conclusion: Serum-derived exosomal LINC00917 may hold diagnostic potential for patients with non-small cell lung cancer.

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A fourteen-lncRNA risk score system for prognostic prediction of patients with non-small cell lung cancer

Cancer Biomarkers ◽

10.3233/cbm-190505 ◽

2020 ◽

Vol 29 (4) ◽

pp. 493-508

Author(s):

Jia-Yi Song ◽

Xiao-Ping Li ◽

Xiu-Jiao Qin ◽

Jing-Dong Zhang ◽

Jian-Yu Zhao ◽

...

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Small Cell Lung Cancer ◽

Risk Score ◽

Cell Lung Cancer ◽

Small Cell ◽

Small Cell Lung ◽

Cox Regression Analysis ◽

Score Model ◽

Nsclc Patients

Growing evidence has underscored long non-coding RNAs (lncRNAs) serving as potential biomarkers for cancer prognosis. However, systematic tracking of a lncRNA signature for prognosis prediction in non-small cell lung cancer (NSCLC) has not been accomplished yet. Here, comprehensive analysis with differential gene expression analysis, univariate and multivariate Cox regression analysis based on The Cancer Genome Atlas (TCGA) database was performed to identify the lncRNA signature for prediction of the overall survival of NSCLC patients. A risk-score model based on a 14-lncRNA signature was identified, which could classify patients into high-risk and low-risk groups and show poor and improved outcomes, respectively. The receiver operating characteristic (ROC) curve revealed that the risk-score model has good performance with high AUC value. Multivariate Cox’s regression model and stratified analysis indicated that the risk-score was independent of other clinicopathological prognostic factors. Furthermore, the risk-score model was competent for the prediction of metastasis-free survival in NSCLC patients. Moreover, the risk-score model was applicable for prediction of the overall survival in the other 30 caner types of TCGA. Our study highlighted the significant implications of lncRNAs as prognostic predictors in NSCLC. We hope the lncRNA signature could contribute to personalized therapy decisions in the future.

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MicroRNA-1298 is downregulated in non-small cell lung cancer and suppresses tumor progression in tumor cells

Diagnostic Pathology ◽

10.1186/s13000-019-0911-4 ◽

2019 ◽

Vol 14 (1) ◽

Cited By ~ 4

Author(s):

Zhonghai Du ◽

Jun Wu ◽

Juan Wang ◽

Yan Liang ◽

Sensen Zhang ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Cox Regression ◽

Small Cell ◽

Migration And Invasion ◽

Small Cell Lung ◽

Poor Overall Survival ◽

Cox Regression Analysis ◽

Nsclc Patients

Abstract Background MicroRNAs (miRNAs) have been reported to serve pivotal roles in tumorigenesis. This study sough to assess the expression and clinical significance of microRNA-1298 (miR-1298) in patients with non-small cell lung cancer (NSCLC), and explore the functional role of miR-1298 in tumorigenesis. Methods One hundred and twenty-one NSCLC patients were recruited in this study. The expression of miR-1298 was estimated using quantitative real-time PCR. Kaplan-Meier survival curves and Cox regression analysis were used to evaluate the prognostic value of miR-1298. Gain- and loss-of-function experiments were preformed to explore the biological function of miR-1298 in NSCLC cells. Results Expression levels of miR-1298 were downregulated in NSCLC tissues and cells compared with the corresponding normal controls. The decreased expression of miR-1298 was associated with patients’ lymph node metastasis and TNM stage. The low expression of miR-1298 predicted poor overall survival and served as an independent prognostic indicator in NSCLC patients. According to the cell experiments, NSCLC cell proliferation, migration and invasion were inhibited by the overexpression of miR-1298. Conclusion All the data indicated that the downregulation of miR-1298 predicts poor prognosis of NSCLC, and the overexpression of miR-1298 in NSCLC cells leads to inhibited tumorigenesis. The aberrant miR-1298 may serve as a novel biomarker and therapeutic target in NSCLC.

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Prognostic factors of oligometastatic non-small-cell lung cancer following radical therapy: a multicentre analysis

European Journal of Cardio-Thoracic Surgery ◽

10.1093/ejcts/ezz384 ◽

2020 ◽

Vol 57 (6) ◽

pp. 1166-1172 ◽

Cited By ~ 2

Author(s):

Isabelle Opitz ◽

Miriam Patella ◽

Loic Payrard ◽

Jean Yannis Perentes ◽

Rolf Inderbitzi ◽

...

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Prognostic Factors ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Cox Regression ◽

Small Cell ◽

Small Cell Lung ◽

Curative Intent ◽

Cox Regression Analysis

Abstract OBJECTIVES Patients with oligometastatic non-small-cell lung cancer (NSCLC) may benefit from therapy with curative intent. Our goal was to identify prognostic factors related to better prognosis in a multicentre analysis of patients who underwent surgery of primary tumours in combination with radical treatment of all metastatic sites. METHODS We retrospectively reviewed the records of oligometastatic patients who underwent resection of primary tumours at 4 centres (August 2001–February 2018). Oligometastasis was defined as ≤5 synchronous metastases in ≤2 organs. Radical metastatic treatment was surgery, radiotherapy or a combination. The Cox proportional hazards model was used for identification of prognostic factors on overall survival. RESULTS We treated 124 patients; 72 (58%) were men, mean age 60 ± 9.8 years, with 87 (70%) adenocarcinoma. Sixty-seven (54%) patients had positive pathologic-N stage (pN). Brain metastases were most common (n = 76; 61%) followed by adrenal (n = 13; 10%) and bone (n = 12; 10%). Systemic therapy was administered in 101 (82%) patients. Median follow-up was 60 months [95% confidence interval (CI) 41–86]. Thirty- and 90-day mortality rates were 0 and 2.4%, respectively. One-, 2-, and 5-year overall survival were 80%, 58% and 36%, respectively. Cox regression analysis showed that patients ≤60 years [hazard ratio (HR) 0.41, 95% CI 0.24, 0.69; P = 0.001] and patients with pN0 (HR 0.38, 95% CI 0.21–0.69; P = 0.002) had a significant survival benefit. The presence of bone metastases negatively affected survival (HR 2.53, 95% CI 1.05–6.09; P = 0.04). CONCLUSIONS Treatment with curative intent of selected oligometastatic NSCLC, including resection of the primary tumour, can be performed safely and with excellent 5-year survival rates, especially in younger patients with pN0 disease.

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Prognostic characterization of immune molecular subtypes in non-small cell lung cancer to immunotherapy

BMC Pulmonary Medicine ◽

10.1186/s12890-021-01765-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Chenlu Li ◽

Jingjing Pan ◽

Jing Luo ◽

Xupeng Chen

Keyword(s):

Lung Cancer ◽

Regression Analysis ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Cox Regression ◽

Small Cell ◽

Risk Scores ◽

Small Cell Lung ◽

Cox Regression Analysis ◽

Nsclc Patients

Abstract Background Non-small cell lung cancer (NSCLC) was usually associated with poor prognosis and invalid therapeutical response to immunotherapy due to biological heterogeneity. It is urgent to screen reliable biomarkers, especially immunotherapy-associated biomarkers, that can predict outcomes of these patients. Methods Gene expression profiles of 1026 NSCLC patients were collected from The Cancer Genome Atlas (TCGA) datasets with their corresponding clinical and somatic mutation data. Based on immune infiltration scores, molecular clustering classification was performed to identify immune subtypes in NSCLC. After the functional enrichment analysis of subtypes, hub genes were further screened using univariate Cox, Lasso, and multivariate Cox regression analysis, and the risk score was defined to construct the prognostic model. Other microarray data and corresponding clinical information of 603 NSCLC patients from the GEO datasets were applied to conduct random forest models for the prognosis of NSCLC with 100 runs of cross-validation. Finally, external datasets with immunotherapy and chemotherapy were further applied to explore the significance of risk-scores in clinical immunotherapy response for NSCLC patients. Results Compared with Subtype-B, the Subtype-A, associated with better outcomes, was characterized by significantly higher stromal and immune scores, T lymphocytes infiltration scores and up-regulation of immunotherapy markers. In addition, we found and validated an eleven -gene signatures for better application of distinguishing high- and low-risk NSCLC patients and predict patients’ prognosis and therapeutical response to immunotherapy. Furthermore, combined with other clinical characteristics based on multivariate Cox regression analysis, we successfully constructed and validated a nomogram to effectively predict the survival rate of NSCLC patients. External immunotherapy and chemotherapy cohorts validated the patients with higher risk-scores exhibited significant therapeutic response and clinical benefits. Conclusion These results demonstrated the immunological and prognostic heterogeneity within NSCLC and provided a new clinical application in predicting the prognosis and benefits of immunotherapy for the disease.

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Comprehensive Analysis of Acetylation-Related lncRNAs and Identified AC099850.3 as Prognostic Biomarker in Non-Small Cell Lung Cancer

Journal of Oncology ◽

10.1155/2021/4405697 ◽

2021 ◽

Vol 2021 ◽

pp. 1-19

Author(s):

Junliang Zhou ◽

Mingyan Zhang ◽

Huanhuan Dong ◽

Meiqi Wang ◽

Yue Cheng ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Cox Regression ◽

Small Cell ◽

Small Cell Lung ◽

Clinical Prognosis ◽

Cox Regression Analysis ◽

Potential Biomarker ◽

Nsclc Patients

The present study aimed to analyze the effects of acetylation-related lncRNAs in non-small-cell lung cancer (NSCLC). A total of 399 differentially expressed lncRNAs (DElncRNAs) have been identified between 497 NSCLC tissues and 54 normal tissues in the TCGA database, and 105 of which were correlated with acetylation regulators. By using univariate cox regression analysis and combining it with clinical prognosis information, 12 prognostic-related lncRNAs were selected for the subsequent analysis. The NSCLC patients were divided into two subgroups (cluster 1 and cluster 2) by clustering software, and immunocyte infiltration analysis, microenvironmental analysis, and clinical relevance analysis were performed between the two subgroups. A risk model was also built to further assess the prognosis value of prognostic-related lncRNAs in NSCLC patients. We found that AC099850.3 was significantly higher in both cluster 1 and high-risk subgroups, which may serve as a potential biomarker for the prognosis of NSCLC patients. Then, based on ceRNA competition mechanisms, the pathway enrichment of 105 acetylation-related lncRNAs was conducted by GO and KEGG analyses. We found the acetylation-related lncRNAs were primarily enriched in MAPK and EGFR signaling pathways, which were closely associated with NSCLC development. Finally, we validated the expression levels of AC099850.3 in NSCLC tissues and adjacent non-cancerous tissues and confirmed that AC099850.3 was significantly highly expressed in NSCLC tissues and cells. These results may provide clues for our understanding of the role of acetylation-related lncRNAs and valuable information for future clinical diagnosis and prognosis in NSCLC patients.

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SFRP1 Decline in Non-Small Cell Lung Cancer (NSCLC) and its Importance in Prognoses

10.21203/rs.3.rs-55343/v1 ◽

2020 ◽

Author(s):

Yue Zhao ◽

Xiangjun Kong ◽

Hongbing Wang

Keyword(s):

Lung Cancer ◽

Overall Survival ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Protein Level ◽

Small Cell ◽

Migration And Invasion ◽

Small Cell Lung ◽

Cox Regression Analysis ◽

Nsclc Patients

Abstract Background: In the present study, we sought to detect the expression of secreted fizzled-related protein-1 (SFRP1) and investigate its role in the progression and prognosis of patients with non-small cell lung cancer (NSCLC). Methods: The expression of SFRP1 at both mRNA and protein level were examined by quantitative real-time polymerase chain reaction (qRT-PCR) and Immunohistochemistry analysis, respectively. The relationship between SFRP1 expression and clinical factors of patients with NSCLC was analyzed by chi-square test. Transwell assay was conducted to determine the influences of SFRP1 on migratory and invasive of NSCLC cells. Kaplan-Meier analysis was used to describe the overall survival of NSCLC patients. Cox regression analysis was conducted to estimate the prognostic value of SFRP1 in NSCLC.Results: The expression of SFRP1 was down-regulated in NSCLC tissues compared to that in adjacent normal controls both at mRNA and protein level (P<0.05). And the low SFRP1 expression was related to the distant metastasis, vascular invasion and TNM stage. The overexpression of SFRP1 in vitro significantly inhibited the migration and invasion of NSCLC cells. The overall survival of patients with high SFRP1 expression was was proved to be longer than those with low expression (log rank test, P<0.001). In addition, univariate and multivariate analyses suggested that SFRP1 was an independent prognostic molecule marker for NSCLC patients. Conclusion: Taken together, our findings indicated that the decreased of SFRP1 could influence the cell migration and invasion as well as be regarded as an independent prognostic marker in NSCLC.

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Efficacy and toxicity hypofractionated radiotherapy for centrally located non-small cell lung cancer

Journal of Radiotherapy in Practice ◽

10.1017/s1460396921000376 ◽

2021 ◽

pp. 1-4

Author(s):

Tanzeel Janjua ◽

Fei Sun ◽

Katy Clarke ◽

Pete Dickinson ◽

Kevin Franks ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Cox Regression ◽

Early Stage ◽

Performance Status ◽

Small Cell ◽

Small Cell Lung ◽

Early Stage Lung Cancer ◽

Cox Regression Analysis

Abstract Aim: Centrally located early-stage non-small cell lung cancer in patients who are unfit for surgery are treated with fractionated radiotherapy. We present the outcomes of a moderately hypofractionated accelerated dose regimen of 50 Gy in 15 fractions from a single centre in the UK. Materials and methods: Electronic case notes and radiotherapy records of lung cancer patients treated between January 2014 and December 2016 were retrospectively reviewed. Adult Comorbidity Evaluation-27 score was used to evaluate comorbidities. Mean lung doses and percentage of lung receiving more than 20 Gy were calculated for all patients. Survival outcomes were estimated using Kaplan–Meier curves. Results: Fifty-three patients were included in the study; the median follow-up was 20.2 months. 87% of patients had stage I disease. There was no 30-day post-treatment mortality. Ninety-day mortality rate after radiotherapy was 3.8%. Grade 2 pneumonitis was seen in five patients while no grade 3 or 4 pneumonitis was observed. The median progression-free survival (PFS) and overall survival (OS) were 18.5 months and 28.2 months, respectively. The estimated 1 and 2 years PFS were 62.3% and 41.3%, respectively, and OS were 77.4% and 56.6%, respectively. Worsening performance status was associated with worse survival on cox regression analysis. Disease relapsed in 36% of patients. 7.5% of patients with relapsed disease had infield recurrence. Findings: 50 Gy in 15 fractions radiotherapy for central early-stage lung cancer is a feasible choice that requires further randomised trials.

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