Dataset Information

Driver genes as predictive indicators of brain metastasis in patients with advanced NSCLC: EGFR, ALK, and RET gene mutations.

ABSTRACT:

Background

A retrospective analysis verified the role of gene mutations in brain metastasis in patients with non-small cell lung cancer (NSCLC).

Methods

Data from 552 patients with advanced NSCLC treated from January 2015 to June 2017 in the Affiliated Cancer Hospital of Zhengzhou University were retrospectively analyzed. Next-generation sequencing was used to detect mutations in eight reported driver genes and various risk factors were evaluated.

Results

Of the 552 patients with advanced NSCLC, 153 (27.7%) had brain metastases. The univariate analysis showed that age (P = .008), gender (P = .016), smoking history (P = .010), lymph node metastasis (P = .003), and three driver genes, positive epidermal growth factor receptor (EGFR) mutation (P = .001), positive anaplastic lymphoma kinase (ALK) gene fusion (P = .021), and positive rearranged during transfection (RET) gene fusion (P = .003), were the factors influencing the incidence of brain metastasis. Logistic multivariate regression analysis revealed that positive EGFR mutation (P = .012), positive ALK gene fusion (P = .015), positive RET gene fusion (P = .003), pathological type (P = .009), lymph node N2-3 metastasis (P < .001), and a younger age (P < .001) were independent risk factors for brain metastasis. In addition, a receiver operating characteristic (ROC) curve was plotted with the above factors with an area under the curve = 0.705 (P < .001).

Conclusions

An EGFR mutation, ALK gene fusion, and RET gene fusion in advanced NSCLC patients play roles in brain metastasis as positive driver genes.

Impact

An EGFR mutation, and ALK and RET gene fusions are risk factors for brain metastasis in advanced NSCLC patients.

SUBMITTER: Wang H

PROVIDER: S-EPMC6970058 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Publications

Driver genes as predictive indicators of brain metastasis in patients with advanced NSCLC: EGFR, ALK, and RET gene mutations.

Wang Huijuan H Wang Ziqi Z Zhang Guowei G Zhang Mina M Zhang Xiaojuan X Li Haixia H Zheng Xuanxuan X Ma Zhiyong Z

Cancer medicine 20191125 2

<h4>Background</h4>A retrospective analysis verified the role of gene mutations in brain metastasis in patients with non-small cell lung cancer (NSCLC).<h4>Methods</h4>Data from 552 patients with advanced NSCLC treated from January 2015 to June 2017 in the Affiliated Cancer Hospital of Zhengzhou University were retrospectively analyzed. Next-generation sequencing was used to detect mutations in eight reported driver genes and various risk factors were evaluated.<h4>Results</h4>Of the 552 patient ...[more]

PMID: 31769228

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Project description:IntroductionTargeted somatic genomic analysis (EGFR, anaplastic lymphoma receptor tyrosine kinase gene [ALK], and ROS1) and programmed death ligand 1 (PD-L1) tumor proportion score (TPS) determined by immunohistochemistry (IHC) are used for selection of first-line therapies in advanced lung cancer; however, the frequency of overlap of these biomarkers in routine clinical practice is poorly reported.MethodsWe retrospectively probed the first 71 pairs of patients with lung adenocarcinoma from our institution. They were analyzed for PD-L1 by IHC using the clone 22C3 pharmDx kit (Agilent Technologies, Santa Clara, CA) and evaluated for co-occurrence of genomic aberrations and clinicopathologic characteristics.ResultsSurgical resection specimens, small biopsy (transbronchial or core needle) samples, and cytologic cell blocks (needle aspirates or pleural fluid) were tested. A PD-L1 TPS of at least ≥50% was seen in 29.6% of tumors. Of 19 tumors with EGFR mutations, ALK fluorescence in situ hybridization positivity, or ROS1 fluorescence in situ hybridization positivity, 18 had a PD-L1 TPS less than 50% versus only one tumor with a PD-L1 TPS of at least 50% (p = 0.0073). Tumors with a PD-L1 TPS of at least 50% were significantly associated with smoking status compared with tumors with a PD-L1 TPS less than 50% but were not associated with patient sex, ethnicity, tumor stage, biopsy site, or biopsy type/preparation.ConclusionsPD-L1 IHC can be performed on routine clinical lung cancer specimens. A TPS of at least 50% seldom overlaps with presence of driver oncogenes with approved targeted therapies. Three biomarker-specified groups of advanced lung adenocarcinomas can now be defined, each paired with a specific palliative first-line systemic therapy of proven clinical benefit: (1) EGFR/ALK/ROS1-affected adenocarcinoma paired with a matched tyrosine kinase inhibitor (∼20% of cases), (2) PD-L1-enriched adenocarcinoma (TPS ≥50%) paired with anti-PD-1 pembrolizumab (∼30% of cases), and (3) biomarker-negative (i.e., EGFR/ALK/ROS1/PD-L1-negative) adenocarcinoma paired with platinum doublet chemotherapy with or without bevacizumab (∼50% of cases).

Dataset Information

Driver genes as predictive indicators of brain metastasis in patients with advanced NSCLC: EGFR, ALK, and RET gene mutations.

Background

Methods

Results

Conclusions

Impact

Publications

Driver genes as predictive indicators of brain metastasis in patients with advanced NSCLC: EGFR, ALK, and RET gene mutations.

Similar Datasets

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