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Prognosis of EGFR-mutant advanced lung adenocarcinoma patients with different intrathoracic metastatic patterns.

ABSTRACT: Introduction: Lung cancer diagnosed solely with the presence of intrathoracic metastases is classified as M1a. However, intrathoracic metastases can be further divided into different patterns. The objective of our study was to analyze the differences in survival between the different metastatic patterns of intrathoracic metastases in lung adenocarcinoma patients who have epidermal growth factor receptor (EGFR) mutations. Materials and Methods: Patients who were diagnosed only with intrathoracic metastasis between March 2011 and October 2016 and had EGFR-mutations were selected for this study. Prognosis was determined based on metastatic patterns by univariate and multivariate analysis. Results: A total of 137 patients (60 patients who only had pleural metastasis [Group A], 44 patients who only had contralateral lung metastasis [Group B] and 33 patients who had both pleural and contralateral lung metastasis with or without pericardial effusion [Group C]) were selected for this in the study. The median OS (overall survival) time was 38.1 (95%confidence interval [CI]: 27.8-48.4), 35.7(95%CI: 23.4-48.0), and 29.7(95%CI: 22.8-36.6) months for Group A, Group B, and Group C, respectively (p=0.037). Multivariate analysis demonstrated that Group A and Group B had higher OS compared to Group C (hazard ratio [HR]=0.524, 95%CI: 0.307-0.894, p=0.018; HR=0.473, 95%CI: 0.241-0.931, p=0.030, respectively) among lung adenocarcinoma patients with EGFR mutations. With regard to patients with pleural or contralateral metastasis only, OS benefit (p=0.579) was not significant between the two groups. Subgroup analysis demonstrated that OS benefit in Group A was significant in patients with N0-1 disease and 21L858R mutations but not in EGFR exon 19 deletions, N2-3 stage or T3-4 stage patients. Conclusion: The prognosis of EGFR-mutant lung adenocarcinoma patients diagnosed only with intrathoracic metastasis was different, indicating that M1a staging should be refined.

SUBMITTER: Hu F

PROVIDER: S-EPMC6400688 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Prognosis of EGFR-mutant advanced lung adenocarcinoma patients with different intrathoracic metastatic patterns.

Hu Fang F Zhang Bo B Li Changhui C Xu Jianlin J Wang Huimin H Gu Ping P Zheng Xiaoxuan X Nie Wei W Shen Yinchen Y Zhang Hai H Hu Ping P Zhang Xueyan X

Journal of Cancer 20190129 5

<b>Introduction</b>: Lung cancer diagnosed solely with the presence of intrathoracic metastases is classified as M1a. However, intrathoracic metastases can be further divided into different patterns. The objective of our study was to analyze the differences in survival between the different metastatic patterns of intrathoracic metastases in lung adenocarcinoma patients who have epidermal growth factor receptor (EGFR) mutations. <b>Materials and Methods</b>: Patients who were diagnosed only with ...[more]

PMID: 30854135

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Project description:BACKGROUND:Epidermal growth factor receptor (EGFR) gene mutation is closely related to the EGFR-TKI target treatment and prognosis of lung adenocarcinoma patients. The mutation status of EGFR is limited by tissue detection. The purpose of this study was to investigate the difference of EGFR mutants in plasmacirculating cell-free DNA (cfDNA) obtained from patients with non-small cell lung cancer (NSCLC) in three groups: pre-therapy, after traditional chemotherapy and targeted therapy. The aim of this study was to analyze whether the plasma cfDNA could effectively determine the EGFR mutations and monitor the drug resistant gene T790M, as well as its prognostic prediction value in patients with targeted therapy. METHODS:ARMS (amplification refractory mutation system)-PCR was used to detect EGFR mutations in 107 (50 of pre-therapy, 29 after traditional chemotherapy and 28 after targeted therapy) cases of paired plasma and tumor tissue specimens, followed by comparing their concordance. The sensitivity, specificity and the prognostic value of plasma cfDNA detection were also observed. RESULTS:The total rate of EGFR mutation was 56% (60/107) in all plasma samples and 77.6% (83/107) in corresponding tumor tissues. Completely the same mutants and wild-type EGFR were found in 68.2% cases of paired specimens. The sensitivity of plasma cfDNA detection was 72.3% and the specificity was up to 100%. Patients were sub-categorized according to therapy. The results showed that the highest consistent rate of cfDNA and tumor tissues was found in the group of pre-therapy (74%, 37/50). Whereas, the lowest consistent rate was observed in the targeted therapy group (57.1%, 16/28). It indicated that the targeted treatment could change the EGFR status in plasma cfDNA. Further analyses on inconsistent cases in this group revealed that 50% of them were compound EGFR mutations with T790M. Thereby, it suggested that targeted therapy might induce the emergence of drug resistance gene T790M. This speculation was confirmed by survival analyses. Based on plasma cfDNA results, patients with T790M mutant had significantly worse progression-free survival (PFS) and overall survival (OS). CONCLUSIONS:For EGFR testing, ARMS-PCR on plasma cfDNA is a promising methodology with the highest specificity and effective sensitivity. It is useful for EGFR testing in patients before treatment, especially the late-stage patients. Simultaneously, plasma cfDNA could be used to monitor the drug resistant mutation, T790M status and predict prognosis after targeted therapy.

Dataset Information

Prognosis of EGFR-mutant advanced lung adenocarcinoma patients with different intrathoracic metastatic patterns.

Publications

Prognosis of EGFR-mutant advanced lung adenocarcinoma patients with different intrathoracic metastatic patterns.

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