Different spatial distributions of brain metastases from lung cancer by histological subtype and mutation status of epidermal growth factor receptor

Takano, Koji; Kinoshita, Manabu; Takagaki, Masatoshi; Sakai, Mio; Tateishi, Souichirou; Achiha, Takamune; Hirayama, Renzo; Nishino, Kazumi; Uchida, Junji; Kumagai, Toru; Okami, Jiro; Kawaguchi, Atsushı; Hashimoto, Naoya; Nakanishi, Katsuyuki; Imamura, Fumio; Higashiyama, Masahiko; Yoshimine, Toshiki

doi:10.1093/neuonc/nov266

Cited by 66 publications

(84 citation statements)

References 34 publications

(31 reference statements)

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“…In the case of lung cancers, brain lesions are typically multiple and disseminated, although interestingly, they do tend to localize in different regions of the brain than other cancer types- a fact that can have diagnostic significance. Specifically, lung cancer metastases to the brain tend to develop focal lesions in “watershed” regions of the brain- these are the regions where the vasculature is finest and most narrow (Takano et al, 2016). This suggests a potential role for hematogenous spread of lung tumor cells to the brain and their subsequent entrapment in fine vessels and extravasation into the tissue.…”

Section: Current Clinical Management Of Lung Tumor Brain Metastasismentioning

confidence: 99%

“…Indeed, treatment with these drugs, especially in patients with primary lung disease that demonstrates EGFR mutation shows superior efficacy versus traditional chemotherapies in shrinking brain metastases, with 60–80% response rates (reviewed in (Dempke et al, 2015)). Interestingly, patients with EGFR mutant disease treated with EGFR inhibitors show somewhat different patterns of brain metastasis, including metastases that are less deeply seeded within the brain (Takano et al, 2016). …”

Section: Current Clinical Management Of Lung Tumor Brain Metastasismentioning

confidence: 99%

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Brain metastasis in lung cancer: Building a molecular and systems-level understanding to improve outcomes

Ebben

You

2016

The International Journal of Biochemistry & Cell Biology

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Lung cancer is a clinically difficult disease with rising disease burden around the world. Unfortunately, most lung cancers present at a clinically advanced stage. Of these cancers, many also present with brain metastasis which complicates the clinical picture. This review summarizes current knowledge on the molecular basis of lung cancer brain metastases. We start from the clinical perspective, aiming to provide a clinical context for a significant problem that requires much deeper scientific investigation. We review new research governing the metastatic process, including tumor cell signaling, establishment of a receptive tumor niches in the brain and evaluate potential new therapeutic options that take advantage of these new scientific advances. Lung cancer remains the largest single cause of cancer mortality in the United States (Siegel et al., 2015). This continues to be the clinical picture despite significant advances in therapy, including the advent of targeted molecular therapies and newly adopted immunotherapies for certain subtypes of lung cancer. In the vast majority of cases, lung cancer presents as advanced disease; in many instances, this advanced disease state is intimately associated with micro and macrometastatic disease (Goldberg et al., 2015). For both non-small cell lung cancer and small cell lung cancer patients, the predominant metastatic site is the brain, with up to 68% of patients with mediastinal lymph node metastasis eventually demonstrating brain metastasis (Wang et al., 2009). The frequency (incidence) of brain metastasis is highest in lung cancers, relative to other common epithelial malignancies (Schouten et al., 2002). Other studies have attempted to predict the risk of brain metastasis in the setting of previously non-metastatic disease. One of the largest studies to do this, analyzing historical data from 1973 to 2011 using the SEER database revealed a 9% risk of patients with previously non-metastatic NSCLC developing brain metastasis over the course of their disease, while 18% of small cell lung cancer patients without previous metastasis went on to develop brain metastasis as their disease progressed (Goncalves et al., 2016). The reasons underlying this predilection for the central nervous system, as well as the recent increase in the frequency of brain metastasis identified in patients remain important questions for both clinicians and basic scientists. More than ever, the question of how brain metastasis develop and how they can be treated and managed requires the involvement of interdisciplinary teams—and more importantly—scientists who are capable of thinking like clinicians and clinicians who are capable of thinking like scientists. This review aims to present a translational perspective on brain metastasis. We will investigate the scope of the problem of brain metastasis and the current management of the metastatic disease process in lung cancer. From this clinical starting point, we will investigate the literature surrounding the molecular underpinnings of lung tumor ...

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Section: Current Clinical Management Of Lung Tumor Brain Metastasismentioning

confidence: 99%

Section: Current Clinical Management Of Lung Tumor Brain Metastasismentioning

confidence: 99%

Brain metastasis in lung cancer: Building a molecular and systems-level understanding to improve outcomes

Ebben

You

2016

The International Journal of Biochemistry & Cell Biology

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“…In addition, the median size of the tumors in patients with exon 19 deletion was smaller compared with wild‐type cancers, as was the associated peri‐tumoral edema. Radiographic analysis of 200 patients with brain metastases treated in Japan demonstrated that EGFR L858R was associated with more superficial lesions, preferentially located in the caudate, cerebellum, and temporal lobes compared with exon 19 patients. These data, while still preliminary, suggest that different EGFR mutations may result in somewhat different patterns of CNS metastasis.…”

Section: Resultsmentioning

confidence: 99%

Role of Epidermal Growth Factor Receptor (EGFR) Inhibitors and Radiation in the Management of Brain Metastases from EGFR Mutant Lung Cancers

et al. 2018

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Management of brain metastases in epidermal growth factor receptor (EGFR) mutant lung cancer is a common clinical problem. The question of whether to start initial therapy with an EGFR inhibitor or radiotherapy (either whole-brain radiotherapy or stereotactic radiosurgery) is controversial. The development of novel EGFR inhibitors with enhanced central nervous system (CNS) penetration is an important advance in the treatment of CNS disease. Multidisciplinary evaluation and evaluation of extracranial disease status are critical to choosing the best treatment option for each patient.

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“…29 Another study showed that brain metastases with exon 21 mutations were more common in the caudate, cerebellum, and temporal lobe compared with those with exon 19 deletions. 30 Other characteristic molecular changes of non-small-cell lung cancer are a Kras mutation and Alk rearrangement. 31,32 Patients who were Alk-positive and treated with the Alk TKI crizotinib in the second-line setting experienced improved progression-free survival compared with standard chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Diffusion-Weighted Imaging of Brain Metastasis from Lung Cancer: Correlation of MRI Parameters with the Histologic Type and Gene Mutation Status

Jung

Park²,

Hong

et al. 2018

AJNR Am J Neuroradiol

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Different spatial distributions of brain metastases from lung cancer by histological subtype and mutation status of epidermal growth factor receptor

Abstract: Background. The purpose of this study was to test the hypothesis that the genetic backgrounds of lung cancers could affect the spatial distribution of brain metastases.

Cited by 66 publications

References 34 publications

Brain metastasis in lung cancer: Building a molecular and systems-level understanding to improve outcomes

Brain metastasis in lung cancer: Building a molecular and systems-level understanding to improve outcomes

Role of Epidermal Growth Factor Receptor (EGFR) Inhibitors and Radiation in the Management of Brain Metastases from EGFR Mutant Lung Cancers

Diffusion-Weighted Imaging of Brain Metastasis from Lung Cancer: Correlation of MRI Parameters with the Histologic Type and Gene Mutation Status

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