• Journal of Korean Neurosurgical Society
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• v.64 no.6
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• pp.983-994
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• 2021

Objective : The effectiveness of gamma knife radiosurgery (GKR) in the treatment of brain metastases is well established. The aim of this study was to evaluate the efficacy and safety of maximizing the radiation dose in GKR and the factors influencing tumor control in cases of small and medium-sized brain metastases from non-small cell lung cancer (NSCLC). Methods : We analyzed 230 metastatic brain tumors less than 5 mL in volume in 146 patients with NSCLC who underwent GKR. The patients had no previous radiation therapy for brain metastases. The pathologies of the tumors were adenocarcinoma (n=207), squamous cell carcinoma (n=18), and others (n=5). The radiation doses were classified as 18, 20, 22, and 24 Gy, and based on the tumor volume, the tumors were categorized as follows : small-sized (less than 1 mL) and medium-sized (1-3 and 3-5 mL). The progression-free survival (PFS) of the individual 230 tumors and 146 brain metastases was evaluated after GKR depending on the pathology, Eastern Cooperative Oncology Group (ECOG) performance score (PS), tumor volume, radiation dose, and anti-cancer regimens. The radiotoxicity after GKR was also evaluated. Results : After GKR, the restricted mean PFS of individual 230 tumors at 24 months was 15.6 months (14.0-17.1). In small-sized tumors, as the dose of radiation increased, the tumor control rates tended to increase (p=0.072). In medium-sized tumors, there was no statistically difference in PFS with an increase of radiation dose (p=0.783). On univariate analyses, a statistically significant increase in PFS was associated with adenocarcinomas (p=0.001), tumors with ECOG PS 0 (p=0.005), small-sized tumors (p=0.003), radiation dose of 24 Gy (p=0.014), synchronous lesions (p=0.002), and targeted therapy (p=0.004). On multivariate analyses, an improved PFS was seen with targeted therapy (hazard ratio, 0.356; 95% confidence interval, 0.150-0.842; p=0.019). After GKR, the restricted mean PFS of brain at 24 months was 9.8 months (8.5-11.1) in 146 patients, and the pattern of recurrence was mostly distant within the brain (66.4%). The small and medium-sized tumors treated with GKR showed radiotoxicitiy in five out of 230 tumors (2.2%), which were controlled with medical treatment. Conclusion : The small-sized tumors were effectively controlled without symptomatic radiation necrosis as the radiation dose was increased up to 24 Gy. The medium-sized tumors showed potential for symptomatic radiation necrosis without signifcant tumor control rate, when greater than 18 Gy. GKR combined targeted therapy improved the tumor control of GKR-treated tumors.

• Journal of Korean Neurosurgical Society
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• v.45 no.5
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• pp.275-283
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• 2009

Objective : We retrospectively analyzed survival, local control rate, and incidence of radiation toxicities after radiosurgery for recurrent metastatic brain lesions whose initial metastases were treated with whole-brain radiotherapy. Various radiotherapeutical indices were examined to suggest predictors of radiation-related neurological dysfunction. Methods : In 46 patients, total 100 of recurrent metastases (mean 2.2, ranged 1-10) were treated by CyberKnife radiosurgery at average dose of 23.1 Gy in 1 to 3 fractions. The median prior radiation dose was 32.7 Gy, the median time since radiation was 5.0 months, and the mean tumor volume was $12.4cm^3$. Side effects were expressed in terms of radiation therapy oncology group (RTOG) neurotoxicity criteria. Results : Mass reduction was observed in 30 patients (65%) on MRI. After the salvage treatment, one-year progression-free survival rate was 57% and median survival was 10 months. Age(<60 years) and tumor volume affected survival rate(p=0.03, each). Acute (${\leq}$1 month) toxicity was observed in 22% of patients, subacute and chronic (>6 months) toxicity occurred in 21 %, respectively. Less acute toxicity was observed with small tumors (<$10cm^3$. p=0.03), and less chronic toxicity occurred at lower cumulative doses (<100 Gy, p=0.004). "Radiation toxicity factor" (cumulative dose times tumor volume of <1,000 Gy${\times}cm^3$) was a significant predictor of both acute and chronic CNS toxicities. Conclusion: Salvage CyberKnife radiosurgery is effective for recurrent brain metastases in previously irradiated patients, but careful evaluation is advised in patients with large tumors and high cumulative radiation doses to avoid toxicity.

• Journal of Korean Neurosurgical Society
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• v.46 no.3
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• pp.245-251
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• 2009

Objective : The authors analyzed the effectiveness and therapeutic response of Novalis shaped beam radiosurgery for metastatic brain tumors, and the prognostic factors which influenced the outcome. Methods : We performed a retrospective analysis of 106 patients who underwent 159 treatments for 640 metastatic brain lesions between January 2000 and April 2008. The pathologies of the primary tumor were mainly lung (45.3%), breast (18.2%) and GI tract (13.2%). We classified the patients using Radiation Therapy Oncology Group Recursive Partitioning Analysis (RPA) and then analyzed the survival and prognostic factors according to the Kaplan Meier method and univariate analysis. Results : The overall median actuarial survival rate was 7.3 months from the time of first radiosurgery treatment while 1 and 2 year actuarial survival estimates were 31% and 14.4%, respectively. Median actuarial survival rates for RPA classes I, II, and III were 31.3 months, 7.5 months and 1.7 months, respectively. Patients' life spans, higher Karnofsky performance scores and age correlated closely with RPA classes. However, sex and the number of lesions were not found to be significantly associated with length of survival. Conclusion : This result suggests that Novalis radiosurgery can be a good treatment option for treatment of the patients with brain metastases.

• Journal of Korean Neurosurgical Society
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• v.61 no.5
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• pp.592-599
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• 2018

Objective : Metastatic brain tumors (MBTs) often present with intracerebral hemorrhage. Although Gamma Knife surgery (GKS) is a valid treatment option for hemorrhagic MBTs, its efficacy is unclear. To achieve oncologic control and reduce radiation toxicity, we used a radiosurgical targeting technique that confines the tumor core within the hematoma when performing GKS in patients with such tumors. We reviewed our experience in this endeavor, focusing on local tumor control and treatment-associated morbidities. Methods : From 2007 to 2014, 13 patients with hemorrhagic MBTs were treated via GKS using our targeting technique. The median marginal dose prescribed was 23 Gy (range, 20-25). GKS was performed approximately 2 weeks after tumor bleeding to allow the patient's condition to stabilize. Results : The primary sites of the MBTs included the liver (n=7), lung (n=2), kidney (n=1), and stomach (n=1); in two cases, the primary tumor was a melanoma. The mean tumor volume was $4.00cm^3$ (range, 0.74-11.0). The mean overall survival duration after GKS was 12.5 months (range, 3-29), and three patients are still alive at the time of the review. The local tumor control rate was 92% (tumor disappearance 23%, tumor regression 46%, and stable disease 23%). There was one (8%) instance of local recurrence, which occurred 11 months after GKS in the solid portion of the tumor. No GKS-related complications were observed. Conclusion : Our experience shows that GKS performed in conjunction with our targeting technique safely and effectively treats hemorrhagic MBTs. The success of this technique may reflect the presence of scattered metastatic tumor cells in the hematoma that do not proliferate owing to the inadequate microenvironment of the hematoma. We suggest that GKS can be a useful treatment option for patients with hemorrhagic MBTs that are not amenable to surgery.

• Progress in Medical Physics
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• v.35 no.1
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• pp.1-9
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• 2024

Margin inclusion or exclusion remains the most critical and controversial aspect of stereotactic radiosurgery (SRS) for metastatic brain tumors. This review aimed to examine the available literature on the impact of margins in SRS of brain metastasis and to assess the response of some medical physicists on the use of these margins. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses method was used to review articles published in PubMed, Embase, and Science Direct databases from January 2012 to December 2022 using the following keywords: planning target volume, brain metastasis, margin, and stereotactic radiosurgery. A simple survey consisting of five questions was completed by ten medical physicists with experience in SRS treatment planning. The results were analyzed using IBM SPSS Statistics version 26.0. Of the 1,445 articles identified, only 38 articles were chosen. Of these, eight papers were deemed relevant to the focus of this review. These papers showed an increase in the risk of radionecrosis, whereas differences in local control were variable as the margin increased. In the survey, the response rate to whether or not to use margins in SRS, a critical question, was 50%. Margin addition increases the risk of radio necrosis. The local control rate varies among treatment modalities and cannot be generalized. From the survey, no consensus was reached regarding the use of these margins. This calls for further deliberations among professionals directly involved in SRS.

• Journal of Korean Neurosurgical Society
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• v.54 no.6
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• pp.453-460
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• 2013

Objective : There is a rich literature confirming the default mode network found compatible with task-induced deactivation regions in normal subjects, but few investigations of alterations of the motor deactivation in patients with intracranial lesions. Therefore, we hypothesized that an intracranial lesion results in abnormal changes in a task-induced deactivation region compared with default mode network, and these changes are associated with specific attributes of allocated regions. Methods : Blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) during a motor task were obtained from 27 intracranial lesion patients (mean age, 57.3 years; range 15-78 years) who had various kinds of brain tumors. The BOLD fMRI data for each patient were evaluated to obtain activation or deactivation regions. The distinctive deactivation regions from intracranial lesion patients were evaluated by comparing to the literature reports. Results : There were additive deactivated regions according to intracranial lesions : fusiform gyrus in cavernous hemangioma; lateral occipital gyrus in meningioma; crus cerebri in hemangiopericytoma; globus pallidus, lateral occipital gyrus, caudate nucleus, fusiform gyrus, lingual gyrus, claustrum, substantia nigra, subthalamic nucleus in GBM; fusiform gyrus in metastatic brain tumors. Conclusion : There is increasing interest in human brain function using fMRI. The authors report the brain function migrations and changes that occur in patients with intracranial lesions.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3571-3574
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• 2014

Background: Brain metastasis occurs when cancerous cells come from a known (or sometimes an unknown) primary tumor to the brain and implant and grow there. This event is potentially lethal and causes neurologic symptoms and signs. These patients are treated in order to decrease their neurologic problems, increase quality of life and overall survival. Materials and Methods: In this study we evaluated clinical characteristics of 206 patients with brain metastases referred to our center from 2004 to 2011. Results: The mean age was 53.6 years. The primary tumors were breast cancer (32%), lung cancer (24.8%), lymphoma (4.4%), sarcoma (3.9%), melanoma (2.9%), colorectal cancer (2.4%) and renal cell carcinoma (1.5%). In 16.5% of the patients, brain metastasis was the first presenting symptom and the primary site was unknown. Forty two (20.4%) patients had a single brain metastasis, 18 patients (8.7%) had two or three lesions, 87 (42.2%) patients had more than three lesions. Leptomeningeal involvement was seen in 49 (23.8%) patients. Thirty five (17%) had undergone surgical resection. Whole brain radiation therapy was performed for all of the patients. Overall survival was 10.1 months (95%CI; 8.65-11.63). One and two year survival was 27% and 12% respectively. Conclusions: Overall survival of patients who were treated by combination of surgery and whole brain radiation therapy was significantly better than those who were treated with whole brain radiation therapy only [13.8 vs 9.3 months (p=0.03)]. Age, sex, primary site and the number of brain lesions did not show significant relationships with overall survival.

• 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.30 no.2
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• pp.53-61
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• 2012

Purpose: To determine feasibility of RapidArc in sequential or simultaneous integrated tumor boost in whole brain radiation therapy (WBRT) for poor prognostic patients with four or more brain metastases. Materials and Methods: Nine patients with multiple (${\geq}4$) brain metastases were analyzed. Three patients were classified as class II in recursive partitioning analysis and 6 were class III. The class III patients presented with hemiparesis, cognitive deficit, or apraxia. The ratio of tumor to whole brain volume was 0.8-7.9%. Six patients received 2-dimensional bilateral WBRT, (30 Gy/10-12 fractions), followed by sequential RapidArc tumor boost (15-30 Gy/4-10 fractions). Three patients received RapidArc WBRT with simultaneous integrated boost to tumors (48-50 Gy) in 10-20 fractions. Results: The median biologically effective dose to metastatic tumors was 68.1 $Gy_{10}$ and 67.2 $Gy_{10}$ and the median brain volume irradiated more than 100 $Gy_3$ were 1.9% (24 $cm^3$) and 0.8% (13 $cm^3$) for each group. With less than 3 minutes of treatment time, RapidArc was easily applied to the patients with poor performance status. The follow-up period was 0.3-16.5 months. Tumor responses among the 6 patients who underwent follow-up magnetic resonance imaging were partial and stable in 3 and 3, respectively. Overall survival at 6 and 12 months were 66.7% and 41.7%, respectively. The local progression-free survival at 6 and 12 months were 100% and 62.5%, respectively. Conclusion: RapidArc as a component in whole brain radiation therapy for poor prognostic, multiple brain metastases is an effective and safe modality with easy application.

• Radiation Oncology Journal
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• v.11 no.2
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• pp.241-247
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• 1993

Between July 1988 and December 1992, we treated 45 patients who had deep seated inoperable or residual and/or recurrent intracranial tumors using LINAC based stereotactic radiosurgery at the Department of Therapeutic Radiology, Kangnam St. Mary's Hospital, Catholic University Medical College. Treated intracranial tumors included pituitary tumors (n=15), acoustic neurinomas (n=8), meningiomas (n=7), gliomas (n=6), craniopharyngiomas (n=4), pinealomas (n=3), hemangioblastomas (n=2), and solitary metastatic tumor from lung cancer (n=1). The dimension of treatment field varied from 0.23 to 42.88 $cm^3\;(mean;\;7.26\;cm^3)$. The maximum tumor doses ranging from 5 to 35.5 Gy (mean; 29.9 Gy) were given, and depended on patients' age, target volume, location of lesion and previous history of irradiation. There were 22 male and 23 female patients. The age was varied from 5 to 74 years of age (a median age; 43 years). The mean duration of follow-up was 35 months (2~55 months). To date, 18 $(39.1\%)$ of 46 intracranial tumors treated with SRS showed absent or decrease of the tumor by serial follow-up CT and/or MRI and 16 $(34.8\%)$ were stationary, e.g. growth arrest. From the view point of the clinical aspects, 34 $(73.9\%)$ of 46 tumors were considered improved status, that is, alive with no evidence of active tumor and 8 $(17.4\%)$ of them were stable, alive with disease but no deterioration as compared with before SRS. Although there showed slight increase of the tumor in size according to follow-up imagings of 4 cases (pituitary tumor 1, acoustic neurinomas 2, pinealoma 1), they still represented clinically stable status. Clinically, two $(4.4\%)$ Patients who were anaplastic astrocytoma (n=1) and metastatic brain tumor (n=1) were worsened following SRS treatment. So far, no serious complications were found after treatment. The minor degree headache which could be relieved by steroid or analgesics and transient focal hair loss were observed in a few cases. There should be meticulous long term follow-up inall cases.