EGFR mutated non-small cell lung cancer patients: More prone to development of bone and brain metastases?

Hendriks, Lizza; Smit, Egbert F.; Vosse, Bettine A. H.; Mellema, Wouter W.; Heideman, Daniëlle A.M.; Bootsma, Gerben; Westenend, Marcel; Pitz, Cordula; Vries, Geeuwke J. de; Houben, Ruud; Grünberg, Katrien; Béndek, Mátyás; Speel, E-J. M.; Dingemans, A-M.C.

doi:10.1016/j.lungcan.2014.01.006

Cited by 104 publications

(91 citation statements)

References 30 publications

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“…The prevalence of EGFR mutation in Caucasians is less than 15% according to one report [27], which is much lower than that in the Asian population. The low prevalence of EGFR mutations in the Caucasian population may be the reason that some studies in nonAsian regions were unable to identify any difference in BM risk in patients with or without EGFR mutations [21,22]. Abbreviations: BM= brain metastases; CI= confidence interval; ECMO= extracranial metastases only; EGFR= epidermal growth factor receptor; N= node; T= tumor; OR= odd ratio.…”

Section: Discussionmentioning

confidence: 99%

A Retrospective Analysis in Patients With EGFR-Mutant Lung Adenocarcinoma: Is EGFR Mutation Associated With Higher Incidence of Brain Metastasis?

Hân

Tan

et al. 2015

International Journal of Radiation Oncology*Biology*Physics

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Lung adenocarcinomas are more commonly associated with brain metastases (BM). Epidermal growth factor receptor (EGFR) mutations have been demonstratedto be both predictive and prognostic for patients with lung adenocarcinoma. We aimed to explore the potential association between EGFR mutation and the risk of BM in pulmonary adenocarcinoma patients. Data of 234 patients from 2007 to 2014 were retrospectively reviewed. A total of 108 patients had EGFR mutations in the entire cohort. Among them, 76 patients developed BM during their disease course. The incidence of BM was statistically higher in patients with EGFR mutations both at initial diagnosis (P=0.014) and at last follow-up (P<0.001). Multivariate logistic regression analysis revealed that EGFR mutation significantly increased the risk of BM at initial diagnosis (OR=2.515, P=0.022). In patients without BM at initial diagnosis, the accumulative rate of subsequent BM was significantly higher with EGFR mutations (P=0.001). Multivariate Cox regression analysis identified EGFR mutation as the only independent risk factor for subsequent BM (HR=3.036, P=0.001). Patients with EGFR mutations demonstrated longer overall survival (OS) after BM diagnosis than patients with wild-type EGFR (P=0.028). Our data suggest that EGFR mutation is an independent predictive and prognostic risk factor for BM and a positive predictive factor for OS in patients with BM.

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Section: Discussionmentioning

confidence: 99%

A Retrospective Analysis in Patients With EGFR-Mutant Lung Adenocarcinoma: Is EGFR Mutation Associated With Higher Incidence of Brain Metastasis?

Hân

Tan

et al. 2015

International Journal of Radiation Oncology*Biology*Physics

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“…Patients with EGFR mutation-positive NSCLC appear to be particularly prone to the development of brain metastases [63]. Thus, efficacy and safety of EGFR TKIs in patients with EGFR mutation-positive NSCLC and brain metastases is of high importance.…”

Section: Factors Influencing First-line Treatment Choice: Brain Metasmentioning

confidence: 99%

Optimizing outcomes in EGFR Mutation-Positive Nsclc: Which Tyrosine Kinase Inhibitor and When?

Girard

2018

Future Oncol.

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Despite the efficacy of standard-of-care EGFR tyrosine kinase inhibitors (TKIs), erlotinib, gefitinib and afatinib, in EGFR mutation-positive non-small-cell lung cancer, resistance develops, most commonly due to the T790M mutation. Osimertinib showed clinical activity in the treatment of T790M-positive disease following progression on a first-line TKI, and is approved in this setting. Recently, osimertinib improved efficacy versus first-generation TKIs (erlotinib and gefitinib) in the first-line setting. Multiple factors can influence first-line treatment decisions, including subsequent therapy options, presence of brain metastases and tolerability, all of which should be considered in the long-term treatment plan. Further research into treatment sequencing is also needed, to optimize outcomes in EGFR mutation-positive non-small-cell lung cancer.

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“…The NOS was used to perform quality assessment on all 22 studies and 14 (17,18,(25)(26)(27)(28)30,(32)(33)(34)(35)(36)38,42) high-quality and 8 (16,19,29,31,37,(39)(40)(41) as low-quality.…”

Section: Study Description and Quality Assessmentmentioning

confidence: 99%

“…Considering the high heterogeneity, analyses stratified by study design ( Figure 2D) suggested that association was significant between EGFR mutations and the incidence of BMs in cohort (16)(17)(18)(19)(25)(26)(27)(28)(29)(30)(31)(36)(37)(38)(39)(40)(41)(42) (P=0.381, I 2 =6.1%) ( Figure 3A). Patients with EGFR mutations were more susceptible to BMs than wild type cases either in adenocarcinoma patients (OR =1.93; 95% CI, 1.59-2.35; P=0.000) or in advanced (stage IV) NSCLC patients (OR =1.83; 95% CI, 1.43-2.36; P=0.000).…”

Section: Incidence Of Bmsmentioning

confidence: 99%

Correlation between EGFR mutation status and the incidence of brain metastases in patients with non-small cell lung cancer

Luo

Lin

et al. 2017

J. Thorac. Dis.

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Background: Lung cancer is the leading cause of cancer-related death worldwide. Numerous studies have been performed to investigate the correlation between epidermal growth factor receptor (EGFR) mutation status and the incidence of brain metastases (BMs) in patients with non-small cell lung cancer (NSCLC), however, the outcomes were inconsistent. Thus, we performed this study to establish the role of EGFR mutation status in BMs. Methods: Electronic databases PubMed, Embase, Cochrane Library, CBM, WanFang, CNKI were searched to identify relevant trials. The primary endpoint was the incidence of BMs in EGFR mutations or wild type NSCLC and the secondary endpoint was overall survival calculated from the BMs emerging (BMOS). Results: Twenty-two studies incorporating 8,152 participants were eligible. EGFR mutations group possessed a significantly higher risk of BMs (OR =1.99; 95% CI, 1.59-2.48; P=0.000) than EGFR wild type group. In the stratified analysis, compared with EGFR wild type group, EGFR mutations group had a significant higher incidence (OR =2.01; 95% CI, 1.56-2.59; P=0.000) of subsequent BMs while only a trend of increasing the incidence of initial BMs (OR =1.38; 95% CI, 0.98-1.94; P=0.066). Moreover, exon 19 deletion had a trend of increasing the incidence of BMs than exon 21 mutation (OR =1.44; 95% CI, 0.77-2.68; P=0.252). Compared with EGFR wild type group, EGFR mutations group possessed a prolonged overall BMOS (HR =0.68; 95% CI, P=0.038) and a longer BMOS in initial BMs (HR =0.50; 95% CI, 0.31-0.80; P=0.004) but no significant difference in NSCLC with subsequent BMs (HR =0.95; 95% CI, 0.42-2.15; P=0.901). Conclusions: Patients with EGFR mutations were more susceptible to develop into BMs than those with EGFR wild type, especially during the course of disease.

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EGFR mutated non-small cell lung cancer patients: More prone to development of bone and brain metastases?

Cited by 104 publications

References 30 publications

A Retrospective Analysis in Patients With EGFR-Mutant Lung Adenocarcinoma: Is EGFR Mutation Associated With Higher Incidence of Brain Metastasis?

A Retrospective Analysis in Patients With EGFR-Mutant Lung Adenocarcinoma: Is EGFR Mutation Associated With Higher Incidence of Brain Metastasis?

Optimizing outcomes in EGFR Mutation-Positive Nsclc: Which Tyrosine Kinase Inhibitor and When?

Correlation between EGFR mutation status and the incidence of brain metastases in patients with non-small cell lung cancer

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