Dataset Information

Prognostic value analysis of mutational and clinicopathological factors in non-small cell lung cancer.

ABSTRACT:

Introduction

Targeting activating oncogenic driver mutations in lung adenocarcinoma has led to prolonged survival in patients harboring these specific genetic alterations. The prognostic value of these mutations has not yet been elucidated. The prevalence of recently uncovered non-coding somatic mutation in promoter region of TERT gene is also to be validated in lung cancer. The purpose of this study is to show the prevalence, association with clinicalpathological features and prognostic value of these factors.

Methods

In a cohort of patients with non-small cell lung cancer (NSCLC) (n = 174, including 107 lung adenocarcinoma and 67 lung squamous cell carcinoma), EGFR, KRAS, HER2 and BRAF were directly sequenced in lung adeoncarcinoma, ALK fusions were screened using FISH (Fluorescence in situ Hybridization).TERT promoter region was sequenced in all of the 174 NSCLC samples. Associations of these somatic mutations and clinicopathological features, as well as prognostic factors were evaluated.

Results

EGFR, KRAS, HER2, BRAF mutation and ALK fusion were mutated in 25.2%, 6.5%, 1.9%, 0.9% and 3.7% of lung adenocarcinomas. No TERT promoter mutation was validated by reverse-sided sequencing. Lung adenocarcinoma with EGFR and KRAS mutations showed no significant difference in Disease-free Survival (DFS) and Overall Survival (OS). Cox Multi-variate analysis revealed that only N stage and HER2 mutation were independent predictors of worse overall survival (HR = 1.653, 95% CI 1.219-2.241, P = 0.001; HR = 12.344, 95% CI 2.615-58.275, P = 0.002).

Conclusions

We have further confirmed that TERT promoter mutation may only exist in a very small fraction of NSCLCs. These results indicate that dividing lung adenocarcinoma into molecular subtypes according to oncogenic driver mutations doesn't predict survival difference of the disease.

SUBMITTER: Li C

PROVIDER: S-EPMC4157862 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Prognostic value analysis of mutational and clinicopathological factors in non-small cell lung cancer.

Li Chenguang C Hao Ligang L Li Yue Y Wang Shengguang S Chen Hui H Zhang Lianmin L Ke Bin B Yin Yuesong Y Suo Haijin H Sun Bingsheng B Zhang Bin B Wang Changli C

PloS one 20140908 9

<h4>Introduction</h4>Targeting activating oncogenic driver mutations in lung adenocarcinoma has led to prolonged survival in patients harboring these specific genetic alterations. The prognostic value of these mutations has not yet been elucidated. The prevalence of recently uncovered non-coding somatic mutation in promoter region of TERT gene is also to be validated in lung cancer. The purpose of this study is to show the prevalence, association with clinicalpathological features and prognostic ...[more]

PMID: 25198510

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Project description:ImportancePrevious studies have suggested the importance of the baseline derived neutrophil to lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH) level as prognostic markers. The lung immune prognostic index (LIPI) was shown to be associated with progression-free survival (PFS) and overall survival (OS) among patients with metastatic non-small cell lung cancer (mNSCLC) treated with immune checkpoint inhibitors (ICIs) but not cytotoxic chemotherapy (CCT).ObjectiveTo determine whether the LIPI is associated with long-term outcomes in pooled analyses of clinical studies of ICI and targeted therapy (TT) for patients with mNSCLC.Design, setting, and participantsAn exploratory pooled analysis was performed of the LIPI on data from 11 randomized clinical multinational trials evaluating ICIs and TT submitted to the US Food and Drug Administration between January 1, 2013, and December 31, 2017, for 4914 patients with mNSCLC. Lung immune prognostic index scores were calculated based on the dNLR and the LDH level per previous publications to generate good, intermediate, and poor composite scores. Multivariable Cox proportional PFS and OS hazard ratios were generated for the dNLR, the LDH level, age, smoking status, histologic characteristics, and Eastern Cooperative Oncology Group performance score.Main outcomes and measuresOverall survival and PFS and their association with good, intermediate, or poor prognostic LIPI scores.ResultsEleven mNSCLC randomized trials were analyzed, including 3987 patients with available data. In 5 ICI trials comprising 2440 patients, 1368 patients received ICIs and 1072 patients received CCT. In 6 TT trials comprising 1547 patients, 1110 patients received TT and 437 patients received CCT. A good LIPI score was associated with better OS among patients receiving ICIs (hazard ratio, 0.34; 95% CI, 0.28-0.42), TT (hazard ratio, 0.28; 95% CI, 0.21-0.37), and CCT (hazard ratio, 0.49; 95% CI, 0.40-0.60 in ICI trials; hazard ratio, 0.41; 95% CI, 0.27-0.61 in TT trials) than those with poor LIPI scores. Similar findings were observed in terms of PFS (ICIs: hazard ratio, 0.59; 95% CI, 0.48-0.72; TT: hazard ratio, 0.46; 95% CI, 0.37-0.57; and CCT: hazard ratio, 0.56; 95% CI, 0.45-0.68 in ICI trials; hazard ratio, 0.51; 95% CI, 0.38-0.69 in TT trials).Conclusions and relevanceThe baseline LDH level and dNLR are important prognostic biomarkers irrespective of treatment modality for patients with mNSCLC. As further prospective clinical trial information is collected, the role of the LIPI score can be better defined.

Dataset Information

Prognostic value analysis of mutational and clinicopathological factors in non-small cell lung cancer.

Introduction

Methods

Results

Conclusions

Publications

Prognostic value analysis of mutational and clinicopathological factors in non-small cell lung cancer.

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