EGFR Mutation and Brain Metastasis in Pulmonary Adenocarcinomas

Shin, Dong Yeop; Na, Im Il; Kim, Cheol Hyeon; Park, Sunhoo; Baek, HeeJong; Yang, Sung Hyun

doi:10.1097/jto.0000000000000069

Cited by 266 publications

(207 citation statements)

References 30 publications

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“…As known, EGFR mutations, being deemed to be a biological marker of NSCLC in recent decades, account for 10%‐25% of NSCLC 53. As a result of its constitutive activation of EGFR signaling and oncogenic transformation, EGFR was confirmed to be an independent risk factor and served as a crucial role 54. So, it is meaningful to evaluate metastatic characteristics in patients with EGFR mutation during clinical screening and treatment 55…”

Section: The Mechanism Of Brain Metastasismentioning

confidence: 99%

Emerging findings into molecular mechanism of brain metastasis

Chen

2018

Cancer Medicine

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Brain metastasis is an important cause of morbidity and mortality in cancer patients. Hence, the need to develop improved therapies to prevent and treat metastasis to the brain is becoming urgent. Recent studies in this area are bringing about some advanced progress on brain metastasis. It was concluded that the occurrence and poor prognosis of brain metastasis have been mostly attributed to the exclusion of anticancer drugs from the brain by the blood‐brain barrier. And several highly potent new generation targeted drugs with enhanced CNS distribution have been developed constantly. However, the noted “seed and soil” hypothesis also suggests that the outcome of metastasis depends on the relationship between unique tumor cells and the specific organ microenvironment. Moreover, increasing studies in multiple tumor types demonstrated that brain metastasis has great molecular differences between primary tumors and extracranial metastasis to a large extent. Here, the authors summarized the most common malignancies that could lead to brain metastasis—lung cancer, breast cancer and melanoma and their related mutated factors. Only by comprehending a deeper understanding of the molecular mechanisms, more effective brain‐specific therapies will be developed for brain metastasis.

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Section: The Mechanism Of Brain Metastasismentioning

confidence: 99%

Emerging findings into molecular mechanism of brain metastasis

Chen

2018

Cancer Medicine

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“…Dong-Yeop Shin et al previously reported that the frequency of EGFR mutation was statistically higher for patients with brain metastases than those without brain metastases, and a strong association between EGFR mutation status and brain metastasis was observed (adjusted odds ratio = 3.83, p = 0.001) 22) . A unique intracranial metastasis system might be suggested in EGFR-mutated NSCLC patients.…”

Section: Discussionmentioning

confidence: 99%

Carcinomatous meningitis and <i>EGFR</i> mutation

Ishikawa

Yamazaki

Mio

et al. 2015

Ann. Cancer Res. Therap.

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Background: Carcinomatous meningitis (CM) in non-small cell lung cancer (NSCLC) has no standard treatment and poor prognosis, with a median survival of 4-9 weeks. Recently, NSCLC subgroups with driver mutations were identified, with mutation of epidermal growth factor receptor gene (EGFR) being the most frequent. This retrospective study investigated the frequency and characteristics of CM in EGFR-mutated patients. Methods: From April 2007 to June 2013, consecutive NSCLC patients were screened for EGFR mutations using the PNA-LNA PCR Clamp in one institution. Diagnosis of CM was based on the presence of malignant cells in cerebrospinal fluid and/or MRI detection of leptomeningeal enhancement. Incidence and clinical features of CM patients were investigated from medical records. Results: Of 1343 NSCLC patients, 387 (28.8%) harboring EGFR mutations. Thirty-five patients (2.6%) developed CM; the rate of CM in EGFR-mutated patients (25/387, 6.46%) was significantly higher than in patients lacking the mutations (10/956, 1.04%; p < 0.01). Multiplex logistic analysis indicated strong associations between CM and EGFR mutation (p < 0.0001), brain metastasis (p < 0.0001) and non-squamous cell carcinoma histology (p = 0.026). Conclusions: NSCLC patients with EGFR mutations are more likely to develop CM than those with wild EGFR.

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“…RTOG 0933 was a single-arm phase II study of radiotherapy for brain metastasis, and the results from this study showed that hippocampal-avoidance WBRT was associated with preservation of memory and QOL as compared with historical series (46). Notable, patient with EGFR mutation has the relatively high risk of developing brain metastases, and the reported intracranial progression during the course of TKI therapy is approximately 30% (39). Therefore, it is interesting to explore the role of PCI in the patients treated with TKIs, provided that preservation of memory and QOL can be ensured with modern radiotherapy techniques.…”

Section: Prophylactic Cranial Irradiation (Pci)mentioning

confidence: 99%

“…Of note, the risk of brain metastases is relatively high in patients with EGFR mutation at the time of diagnosis, as well as during the course of follow up in those who administrated with surgery. Shin et al reported a dramatic correlation of EGFR mutation status and brain metastasis (adjusted odds ratio =3.83, P=0.001) in 314 patients with testing of EGFR mutation and brain magnetic resonance imaging at diagnosis (39). In this study, they also found that, in a subgroup analysis of 133 patients treated with surgical resection, EGFR mutation status was a poor prognostic factor for the risk of brain metastasis [hazard ratio (HR) =4.49, P=0.026] after adjustment for pathologic N stage.…”

Section: Brain Metastasis and Egfr Mutationmentioning

confidence: 99%

Management of non-small cell lung cancer with EGFR mutation: the role of radiotherapy in the era of tyrosine kinase inhibitor therapy—opportunities and challenges

Xia

Zhang

2017

J. Thorac. Dis.

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In recent years, the treatment of advanced non-small cell lung cancer (NSCLC) was greatly promoted by the discovery of oncogenic drivers and the development of targeted therapies specific for these drivers. Somatic mutations in epidermal growth factor receptor (EGFR) are the most common type in patients with NSCLC. Small-molecule tyrosine kinase inhibitor (TKI) targeting EGFR produced relatively high response rate and long duration with acceptable toxicity profile. Also, the life expectancy in patients with active EGFR mutation has been significantly prolonged than the past. Additionally, evolution of advanced imaging and radiation techniques has expanded the indications for radiotherapy in complex clinical situation. All of those factors contributed to the widely use of radiotherapy for advanced NSCLC treated with TKI therapy. In this review, we will discuss how to integrate radiotherapy into the comprehensive treatment of patients with TKI therapy in order to maximize the therapeutics effect.

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EGFR Mutation and Brain Metastasis in Pulmonary Adenocarcinomas

Abstract: We found a significant association between EGFR mutation and risk of brain metastases at the time of diagnosis and follow-up after curative resection for pulmonary adenocarcinoma. This result indicates the distinct clinical features of EGFR-mutated tumors in terms of brain metastases.

Cited by 266 publications

References 30 publications

Emerging findings into molecular mechanism of brain metastasis

Emerging findings into molecular mechanism of brain metastasis

Carcinomatous meningitis and <i>EGFR</i> mutation

Management of non-small cell lung cancer with EGFR mutation: the role of radiotherapy in the era of tyrosine kinase inhibitor therapy—opportunities and challenges

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