• Radiation Oncology Journal
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• v.33 no.3
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• pp.207-216
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• 2015

Purpose: Stereotactic radiosurgery (SRS) has been introduced for small-sized single and oligo-metastases in the brain. The aim of this study is to assess treatment outcome, efficacy, and prognostic variables associated with survival and intracranial recurrence. Materials and Methods: This study retrospectively reviewed 123 targets in 64 patients with non-small cell lung cancer (NSCLC) treated with SRS between January 2006 and December 2012. Treatment responses were evaluated using magnetic resonance imaging. Overall survival (OS) and intracranial progression-free survival (IPFS) were determined. Results: The median follow-up was 13.9 months. The median OS and IPFS were 14.1 and 8.9 months, respectively. Fifty-seven patients died during the follow-up period. The 5-year local control rate was achieved in 85% of 108 evaluated targets. The 1- and 2-year OS rates were 55% and 28%, respectively. On univariate analysis, primary disease control (p < 0.001), the Eastern Cooperative Oncology Group (ECOG) performance status (0-1 vs. 2; p = 0.002), recursive partitioning analysis class (1 vs. 2; p = 0.001), and age (<65 vs. ${\geq}65$ years; p = 0.036) were significant predictive factors for OS. Primary disease control (p = 0.041) and ECOG status (p = 0.017) were the significant prognostic factors for IPFS. Four patients experienced radiation necrosis. Conclusion: SRS is a safe and effective local treatment for brain metastases in patients with NSCLC. Uncontrolled primary lung disease and ECOG status were significant predictors of OS and intracranial failure. SRS might be a tailored treatment option along with careful follow-up of the intracranial and primary lung disease status.

• Journal of Korean Neurosurgical Society
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• v.51 no.3
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• pp.141-143
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• 2012

The authors describe a case of choriocarcinoma that metastasized to the cerebral cortex, vertebral body, and intramedullary spinal cord. A 21-year-old woman presented with sudden headache, vomiting and a visual field defect. Brain computed tomography and magnetic resonance examinations revealed an intracranial hemorrhage in the left temporo-parietal lobe and two enhancing nodules in the left temporal and right frontal lobe. After several days, the size of the hemorrhage increased, and a new hemorrhage was identified in the right frontal lobe. The hematoma and enhancing mass in the left temporo-parietal lobe were surgically removed. Choriocarcinoma was diagnosed after histological examination. At 6 days after the operation, her consciousness had worsened and she was in a state of stupor. The size of the hematoma in the right frontal lobe was enlarged. We performed an emergency operation to remove the hematoma and enhancing mass. Her mental status recovered slowly. Two months thereafter, she complained of paraplegia with sensory loss below the nipples. Whole spine magnetic resonance imaging revealed a well-enhancing mass in the thoracic intramedullary spinal cord and L2 vertebral body. Despite chemotherapy and radiotherapy, the patient died 13 months after the diagnosis.

• Journal of the Korean Society of Radiology
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• v.85 no.4
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• pp.785-788
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• 2024

This study describes a unique case of single mucin-rich brain metastasis in a patient with breast cancer, mimicking the T2-fluid attenuation inversion recovery (FLAIR) mismatch sign and masquerading as an isocitrate dehydrogenase-mutant astrocytoma. This case highlights the importance of considering mucin-rich lesions in the differential diagnosis of intracranial tumors exhibiting T2-FLAIR mismatch. Clinicians must recognize the potential convergence in imaging characteristics between these metastases and gliomas to guarantee prompt and accurate patient care.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5699-5703
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• 2013

Objective: To investigate the clinical effects of whole brain radiotherapy concomitant with targeted therapy for brain metastasis in non-small cell lung cancer (NSCLC) patients with chemotherapy failure. Materials and Methods: Of the 157 NSCLC patients with chemotherapy failure followed by brain metastasis admitted in our hospital from January 2009 to August 2012, the combination group (65 cases) were treated with EGFR-TKI combined with whole brain radiotherapy while the radiotherapy group (92 cases) were given whole brain radiotherapy only. Short-term effects were evaluated based on the increased MRI in brain 1 month after whole brain radiotherapy. Intracranial hypertension responses, hematological toxicity reactions and clinical effects of both groups were observed. Results: There were more adverse reactions in the combination group than in radiotherapy group, but no significant differences were observed between the two groups in response rate (RR) and disease control rate (DCR) (P>0.05). Medium progression free survival (PFS), medium overall survival (OS) and 1-year survival rate in combination group were 6.0 months, 10.6 months and 42.3%, while in the radiotherapy group they were 3.4 months, 7.7 months and 28.0%, respectively, which indicated that there were significant differences in PFS and OS between the two groups (P<0.05). Additionally, RPA grading of each factor in the combination group was a risk factor closely related with survival, with medium PFS in EGFR and KRAS mutation patients being 8.2 months and 11.2 months, and OS being 3.6 months and 6.3 months, respectively. Conclusions: Whole brain radiotherapy concomitant with target therapy is favorable for adverse reaction tolerance and clinical effects, being superior in treating brain metastasis in NSCLC patients with chemotherapy failure and thus deserves to be widely applied in the clinic.

• Brain Tumor Research and Treatment
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• v.6 no.2
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• pp.73-77
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• 2018

Germinoma is the most common type of intracranial germ cell tumors (GCTs). Pineal gland and suprasellar region are the most frequent sites of central nervous system (CNS) involvement. Intracranial masses caused by Langerhans cell histiocytosis (LCH) mimics features of CNS GCTs. LCH frequently involve spine and is the most common cause of vertebra plana in children. A 15-year-old boy presented with progressing symptoms of polydipsia, polyuria, general headache, nausea and severe back pain. Brain MRI showed brain tumor with simultaneous involvement of suprasellar region and pineal gland. An excisional biopsy of suprasellar mass was done. The pathologic assessment confirmed the diagnosis of germinoma. Patient's treatment continued accordingly. A spine MRI, done due to persistent backache, showed a vertebra plana. We reevaluated the primary diagnosis suspecting LCH. Germinoma of CNS was confirmed and a biopsy of vertebral lesion resulted in hemangioma. Thus we report a case of CNS germinoma with co-occurrence of vertebra plana. We emphasized the importance of histopathologic diagnosis of pineal/suprasellar masses and primary investigation of other CNS regions including spine for possible metastasis or comorbidities.

• Molecules and Cells
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• v.42 no.4
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• pp.321-332
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• 2019

The brain is the most common metastatic site of lung adenocarcinoma; however, the mechanism of this selective metastasis remains unclear. We aimed to verify the hypothesis that exposure of tumor cells to the brain microenvironment leads to changes in their gene expression, which promotes their oriented transfer to the brain. A549 and H1299 lung adenocarcinoma cells were exposed to human astrocyte-conditioned medium to simulate the brain microenvironment. Microarray analysis was used to identify differentially expressed genes, which were confirmed by quantitative real-time PCR and western blotting. Knockdown experiments using microRNAs and the overexpression of genes by cell transfection were performed in addition to migration and invasion assays. In vitro findings were confirmed in clinical specimens using immunohistochemistry. We found and confirmed a significant increase in insulin-like growth factor binding protein-3 (IGFBP3) levels. Our results also showed that the up-regulation of IGFBP3 promoted A549 cell epithelial-mesenchymal transition, migration, and invasion, while the knockdown of IGFBP3 resulted in decreased cell motility. We also found that Transforming growth factor-${\beta}$ (TGF-${\beta}$)/Mothers against decapentaplegic homolog 4 (Smad4)-induced epithelial-mesenchymal transition was likely IGFBP3-dependent in A549 cells. Finally, expression of IGFBP3 was significantly elevated in pulmonary cancer tissues and intracranial metastatic tissues. Our data indicate that up-regulation of IGFBP3 might mediate brain metastasis in lung adenocarcinoma, which makes it a potential therapeutic target.

• Investigative Magnetic Resonance Imaging
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• v.25 no.1
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• pp.23-34
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• 2021

Purpose: Differentiating between glioblastoma and solitary metastasis is very important for the planning of further workup and treatment. We assessed the ability of various morphological parameters using conventional MRI and diffusion-based techniques to distinguish between glioblastomas and solitary metastases in tumoral and peritumoral regions. Materials and Methods: We included 38 patients with solitary brain tumors (21 glioblastomas, 17 solitary metastases). To find out if there were differences in the morphologic parameters of enhancing tumors, we analyzed their shape, margins, and enhancement patterns on postcontrast T1-weighted images. During analyses of peritumoral regions, we assessed the extent of peritumoral non-enhancing lesion on T2- and postcontrast T1-weighted images. We also aimed to detect peritumoral neoplastic cell infiltration by visual assessment of T2-weighted and diffusion-based images, including DWI, ADC maps, and exponential DWI, and evaluated which sequence depicted peritumoral neoplastic cell infiltration most clearly. Results: The shapes, margins, and enhancement patterns of tumors all significantly differentiated glioblastomas from metastases. Glioblastomas had an irregular shape, ill-defined margins, and a heterogeneous enhancement pattern; on the other hand, metastases had an ovoid or round shape, well-defined margins, and homogeneous enhancement. Metastases had significantly more extensive peritumoral T2 high signal intensity than glioblastomas had. In visual assessment of peritumoral neoplastic cell infiltration using T2-weighted and diffusion-based images, all sequences differed significantly between the two groups. Exponential DWI had the highest sensitivity for the diagnosis of both glioblastoma (100%) and metastasis (70.6%). A combination of exponential DWI and ADC maps was optimal for the depiction of peritumoral neoplastic cell infiltration in glioblastoma. Conclusion: In the differentiation of glioblastoma from solitary metastatic lesions, visual morphologic assessment of tumoral and peritumoral regions using conventional MRI and diffusion-based techniques can also offer diagnostic information.

• Radiation Oncology Journal
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• v.35 no.2
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• pp.153-162
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• 2017

Purpose: To evaluate intracranial control after surgical resection according to the adjuvant treatment received in order to assess the optimal radiotherapy (RT) dose and volume. Materials and Methods: Between 2003 and 2015, a total of 53 patients with brain oligometastases from non-small cell lung cancer (NSCLC) underwent metastasectomy. The patients were divided into three groups according to the adjuvant treatment received: whole brain radiotherapy (WBRT) ${\pm}$ boost (WBRT ${\pm}$ boost group, n = 26), local RT/Gamma Knife surgery (local RT group, n = 14), and the observation group (n = 13). The most commonly used dose schedule was WBRT (25 Gy in 10 fractions, equivalent dose in 2 Gy fractions [EQD2] 26.04 Gy) with tumor bed boost (15 Gy in 5 fractions, EQD2 16.25 Gy). Results: The WBRT ${\pm}$ boost group showed the lowest 1-year intracranial recurrence rate of 30.4%, followed by the local RT and observation groups, at 66.7%, and 76.9%, respectively (p = 0.006). In the WBRT ${\pm}$ boost group, there was no significant increase in the 1-year new site recurrence rate of patients receiving a lower dose of WBRT (EQD2) <27 Gy compared to that in patients receiving a higher WBRT dose (p = 0.553). The 1-year initial tumor site recurrence rate was lower in patients receiving tumor bed dose (EQD2) of ${\geq}42.3Gy$ compared to those receiving <42.3 Gy, although the difference was not significant (p = 0.347). Conclusions: Adding WBRT after resection of brain oligometastases from NSCLC seems to enhance intracranial control. Furthermore, combining lower-dose WBRT with a tumor bed boost may be an attractive option.

• Journal of Korean Neurosurgical Society
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• v.64 no.2
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• pp.271-281
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• 2021

Objective : Immune checkpoint inhibitors (ICIs) are approved for treating non-small-cell lung cancer (NSCLC); however, the safety and efficacy of combined ICI and Gamma Knife radiosurgery (GKS) treatment remain undefined. In this study, we retrospectively analyzed patients treated with ICIs with or without GKS at our institute to manage patients with brain metastases from NSCLC. Methods : We retrospectively reviewed medical records of patients with brain metastases from NSCLC treated with ICIs between January 2015 and December 2017. Of 134 patients, 77 were assessable for brain responses and categorized into three groups as follows : group A, ICI alone (n=26); group B, ICI with concurrent GKS within 14 days (n=24); and group C, ICI with non-concurrent GKS (n=27). Results : The median follow-up duration after brain metastasis diagnosis was 19.1 months (range, 1-77). At the last follow-up, 53 patients (68.8%) died, 20 were alive, and four were lost to follow-up. The estimated median overall survival (OS) of all patients from the date of brain metastasis diagnosis was 20.0 months (95% confidence interval, 12.5-27.7) (10.0, 22.5, and 42.1 months in groups A, B, and C, respectively). The OS was shorter in group A than in group C (p=0.001). The intracranial disease progression-free survival (p=0.569), local progression-free survival (p=0.457), and complication rates did not significantly differ among the groups. Twelve patients showed leptomeningeal seeding (LMS) during follow-up. The 1-year LMS-free rate in treated with ICI alone group (69.1%) was significantly lower than that in treated with GKS before ICI treatment or within 14 days group (93.2%) (p=0.004). Conclusion : GKS with ICI showed no favorable OS outcome in treating brain metastasis from NSCLC. However, GKS with ICI did not increase the risk of complications. Furthermore, compared with ICI alone, GKS with ICI may be associated with a reduced incidence of LMS. Further understanding of the mechanism, which remains unknown, may help improve the quality of life of patients with brain metastasis.

• Investigative Magnetic Resonance Imaging
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• v.1 no.1
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• pp.86-93
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• 1997

Purpose: To assess the ability of in vivo H-1 MRS to determine the degree of malignancy and to characterize the histopathologic type of intracranial solid tumors. Materials and Methods: In vivo H-1 MR spectra of the pathologically-proven 81 intracranial soild tumors (low-grade glioma 17 cases, high-grade glioma 31 cases, lymphoma 9 cases, meningioma 8 cases, central neurocytoma 4 cases, medulloblastoma 3 cases, PNET 3 cases, metastasis 2 cases, others 4 cases) were analyzed. H-1 MR spectroscopy was performed on a 1.5T MR unit using PRESS sequence with a TR of 2000ms, a TE of 270 or 135ms and a voxel size of $2{\times}2{\times}2cm^3$ for all spectra. N-acetyl aspartate (NAA)/Creatine complex(Cr), Choline complex (Cho)/Cr, and lactate (Lac)/Cr ratios were measured on the peak heights of each resonance and compared among the different tumors. Results: All intracranial solid tumors demonstrated decreased NAA, elevated Cho and lactate, and variable Cr levels. All tumors showed increased Cho/Cr and Lac/Cr, whereas NAA/Cr level was decreased. Mean Cho/Cr and Lac/Cr ratios were significantly higher in high-grade gliomas than in low-grade gliomas. However, NAA/Cr ratio showed no significant difference between low-grade and high-grade gliomas. Very high Cho peaks were seen in lymphomas, meningiomas, medulloblastomas, and neurocytomas in addition to high-grade gliomas. Conclusion: H-1 MRS may be useful in differentiating between low-grade and high-grade gliomas, however cannot characterize the histologic types or subtypes of tumors.