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Taek-Kyun Nam, Jung-Il Lee, Young-Jo Jung, Yong-Seok Im, Hee-Ye An, Do-Hyun Nam, Kwan Park and Jong-Hyun Kim

Object. This study was performed to evaluate the role of gamma knife surgery (GKS) in patients with a large number (four or more) of metastatic brain lesions.

Methods. The authors retrospectively reviewed the outcome in 130 patients who underwent GKS for metastatic lesions. Eighty-four patients presented with one to three lesions (Group A) and 46 presented with four or more lesions (Group B). The overall median survival time after GKS was 35 weeks. The median survival time in Group A (48 weeks) was significantly longer (p = 0.005) than the survival time in Group B (26 weeks). The recursive partitioning analysis (RPA) class was the only significant prognostic factor identified in multivariate analysis. The median survival for patients in RPA Classes I, II, and III was 72, 48, and 19 weeks, respectively, in Group A and 36 and 13 weeks for Classes II and III in Group B. The number of lesions, tumor volume, whole brain radiotherapy, primary tumor site, age, and sex did not affect survival significantly.

Conclusions. It is suggested that GKS provides an increase in survival time even in patients with a large number (four or more) of metastatic lesions. Concerning the selection of patients for GKS, RPA class should be considered as the most important factor and multiplicity of the lesions alone should not be a reason for withholding GKS.

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Jong-Hyuk Park, Yong-Sook Park, Jong-Sik Suk, Seung-Won Park, Sung-Nam Hwang, Taek-Kyun Nam, Young-Baeg Kim and Won-Bok Lee

Object

Cerebrospinal fluid typically enters the subarachnoid space from the ventricles via the fourth ventricular foramina. However, there is clinical evidence that CSF also flows in the opposite direction. Ventricular reflux of CSF from a cistern is a well-known phenomenon in radioisotope studies in patients with normal-pressure hydrocephalus. Additionally, the presence of ventricular blood in acute subarachnoid hemorrhage is frequently observed. The goal of this investigation was to examine the potential CSF pathways from cisterns to ventricles. The authors examined pathways in rat models in which they occluded the fourth ventricular outlets and injected a tracer into the subarachnoid space.

Methods

The model for acute obstructive hydrocephalus was induced using N-butyl cyanoacrylate (NBCA) in 10 Sprague-Dawley rats. After 3 days, cationized ferritin was infused into the lumbar subarachnoid space to highlight retrograde CSF flow pathways. The animals were sacrificed at 48 hours, and the brains were prepared. The CSF flow pathway was traced by staining the ferritin with ferrocyanide.

Results

Ferritin was observed in the third ventricle in 7 of 8 rats with hydrocephalus and in the temporal horn of the lateral ventricles in 4 of 8 rats with hydrocephalus. There was no definite staining in the aqueduct, which suggests that the ventricular reflux originated from routes other than through the fourth ventricular outlets.

Conclusions

The interfaces between the quadrigeminal cistern and third ventricle and those between the ambient cistern and lateral ventricle appear to be potential sites of CSF reflux from cisterns to ventricles in obstructive hydrocephalus.

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Byung Sup Kim, Yuil Kim, Doo-Sik Kong, Do-Hyun Nam, Jung-Il Lee, Yeon-Lim Suh and Ho Jun Seol

OBJECTIVE

The authors conducted this retrospective study to investigate the clinical outcomes of intracranial solitary fibrous tumor (SFT) and hemangiopericytoma (HPC), defined according to the 2016 WHO classification of central nervous system (CNS) tumors.

METHODS

Histopathologically proven intracranial SFT and HPC cases treated in the period from June 1996 to September 2014 were retrospectively reviewed and analyzed. Two neuropathologists reviewed pathological slides and regraded the specimens according to the 2016 WHO classification. Factors associated with progression-free survival (PFS) and overall survival (OS) were statistically evaluated with uni- and multivariate analyses.

RESULTS

The records of 47 patients—10 with SFT, 33 with HPC, and 4 with anaplastic HPC—were reviewed. A malignant transition from conventional SFT to WHO grade III SFT/HPC was observed in 2 cases, and 13 HPC cases were assigned grade III SFT/HPC. Mean and median follow-ups were 114.6 and 94.7 months, respectively (range 7.1–366.7 months). Gross-total resection (GTR) was significantly associated with longer PFS and OS (p = 0.012 for both), and adjuvant radiation therapy versus no such therapy led to significantly longer PFS (p = 0.018). Extracranial metastases to the liver, bone, lung, spine, and kidney occurred in 10 patients (21.3%). Grade III SFT/HPC was strongly correlated with the development of extracranial metastases (p = 0.031).

CONCLUSIONS

The 2016 WHO classification of CNS tumors reflected the different types of pathological malignant progression and clinical outcomes better than prior classifications. Gross-total resection should be the primary treatment goal in patients with SFT/HPC, regardless of the pathological grade, and radiation can be administered as adjuvant therapy for patients with SFT/HPC that shows an aggressive phenotype or that is not treated with GTR.

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Sang Kun LEE, Kwang-ki Kim, Hyunwoo Nam, Jong Bai Oh, Chang Ho Yun and Chun-Kee Chung

Object. The aim of this study was to investigate changes in electroencephalography (EEG) patterns obtained from added or repositioned electrodes after those initially implanted had failed to indicate the true local ictal onset zone. The authors focused on the following matters: rationale for adding or repositioning electrodes, topographic and frequency characteristics of ictal onset before and after adding or repositioning electrodes, the effect of the procedures, and the relationship between changes in intracranial EEG onset patterns and surgical outcomes.

Methods. Of 183 patients with intracranial recordings, 18 experienced repositioning of existing or implanting of additional electrodes 7 or 10 days later. All patients underwent resection and were followed up for more than 1 year. In particular, the relationship between surgical outcome and distribution/frequency of intracranial seizure onset was analyzed. Results of noninvasive presurgical evaluations in patients who had undergone single and double invasive studies were also evaluated.

By adding or repositioning electrodes, a new ictal onset zone was revealed in 13 patients. In another four, the second evaluation led to a change in defining the resection margin. Ictal onset in the partially sampled area, simultaneous or independent onset in two separate areas, and onset in the distal end of the electrode strip or grid were common reasons for failing to localize the ictal onset zone during the initial evaluation. Seven of 11 patients who were ultimately found to have a focal ictal onset zone on the second evaluation became seizure free after the operation. Only one of six patients with a regional ictal onset zone identified on the second evaluation became seizure free. There was no relationship between the frequency of the ictal rhythm and surgical outcome. Note, however, that surgical outcome was more favorable in patients who had undergone a single invasive study than in those who had undergone double invasive studies. The patients who needed a second evaluation had less localizing information and less concordant results on presurgical evaluations. When comparing nonlesional cases, surgical outcomes were not significantly different among patients with a single invasive study and those with double invasive studies. No additional morbidity or death occurred during the second study.

Conclusions. The addition or reposition of intracranial electrodes with a short-term interval should be considered in selected patients. Spatial restriction of the ictal onset rhythm identified on repeated evaluation is the most important predictor of a good surgical outcome.

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Kyung Hwan Kim, So Jeong Kang, Jung-Won Choi, Doo-Sik Kong, Ho Jun Seol, Do-Hyun Nam and Jung-Il Lee

OBJECTIVE

This study aimed to verify the effect of proactive Gamma Knife surgery (GKS) in the treatment of asymptomatic meningioma compared with the natural course without any therapeutic intervention.

METHODS

From January 2006 to May 2017, 354 patients newly diagnosed with asymptomatic meningioma were reviewed and categorized into GKS (n = 153) and observation (n = 201) groups. Clinical and radiological progression rates were examined, and changes in volume were analyzed.

RESULTS

Clinical progression (i.e., clinician-judged progression), combining symptomatic progression (n = 43) and clinician-judged increase in size using images routinely acquired (n = 34), occurred in 4 patients (2.6%) and 73 patients (36.3%) in the GKS and observation groups, respectively (p < 0.001). The clinical progression-free survival (PFS) rates in the GKS and observation groups were 98.7% and 64.6%, respectively, at 5 years (p < 0.001), and 92.9% and 42.7%, respectively, at 10 years (p < 0.001). The radiological tumor control rate was 94.1% in the GKS group, and radiological progression was noted in 141 patients (70.1%) in the observation group. The radiological PFS rates in the GKS and observation groups were 94.4% and 38.5%, respectively, at 5 years (p < 0.001), and 88.5% and 7.9%, respectively, at 10 years (p < 0.001). Young age, absence of calcification, peritumoral edema, and high T2 signal intensity were correlated with clinical progression in the observation group. Volumetric analysis showed that untreated tumors gradually increased in size. However, GKS-treated tumors shrank gradually, although transient volume expansion was observed in the first 6 months. Adverse events developed in 26 of the 195 GKS-treated patients (13.3%), including 1 (0.5%) major event requiring microsurgery due to severe edema after GKS. Peritumoral edema was related to the development of adverse events (p = 0.004).

CONCLUSIONS

Asymptomatic meningioma is a benign disease; however, nearly two-thirds of patients experience tumor growth and one-third of untreated patients eventually require neurosurgical interventions during watchful waiting. GKS can control tumors clinically and radiologically with high probability. Although the risk of transient adverse events exists, proactive GKS may be a reasonable treatment option when there are no comorbidities limiting life expectancy.

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Doo-Sik Kong, Do-Hyun Nam, Jung-Il Lee, Kwan Park and Jong Hyun Kim

Object

The authors conducted a retrospective study to evaluate the efficacy of Gamma Knife surgery (GKS) followed by radiotherapy for the treatment of unresectable glioblastomas multiforme (GBMs) on patient survival and quality of life.

Methods

A total of 19 patients with unresectable GBMs located in eloquent areas of the brain were eligible for this study. Beginning in January 2002, 10 patients underwent GKS followed by fractionated radiotherapy. Nine patients who had undergone radiotherapy alone after biopsy-proven diagnosis served as the control group. The mean patient ages were 53 years and 56 years, respectively. Preoperative Karnofsky Performance Scale (KPS) scores were 80 (range 60–100) and 90 (range 50–100), respectively. The median margin dose for GKS was 12 Gy (9–16 Gy), and the total dose for radiotherapy was 60 Gy in 30 fractions. The mean follow-up duration was 7.2 months, the median patient survival time was 52 weeks (95% confidence interval [CI] 22–110.6 weeks) in the GKS group, and the median overall survival time was 28 weeks (95% CI 22.5–33.5 weeks) in the control group. The difference was not statistically significant (p = 0.0758). The estimated progression-free survival rate at 3 months was 75% in the GKS group and 45% in the control group (p = 0.082). The posttreatment KPS scores were either unchanged or improved in the GKS group, whereas it deteriorated by 20 or more points in six of nine patients of the control group (p = 0.004).

Conclusions

Gamma Knife surgery prior to radiotherapy may be helpful in preserving patients' daily activities in the adjuvant management of unresectable GBM.

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Nam Ik Cho, Chang Ju Hwang, Ho Yeon Kim, Jong-Min Baik, Youn Suk Joo, Choon Sung Lee, Mi Young Lee, So Jeong Yoon and Dong-Ho Lee

OBJECTIVE

The need for scoliosis screening remains controversial. Nationwide school screening for scoliosis has not been performed in South Korea, and there are few studies on the referral patterns of patients suspected of having scoliosis. This study aimed to examine the referral patterns to the largest scoliosis center in South Korea in the absence of a school screening program and to analyze the factors that influence the appropriateness of referral.

METHODS

The medical records of patients who visited a single scoliosis center for a spinal deformity evaluation were reviewed. Among 1895 new patients who visited this scoliosis center between April 2014 and March 2016, 1211 with presumed adolescent idiopathic scoliosis were included in the study. Patients were classified into 4 groups according to the referral method: non–health care provider, primary physician, hospital specialist, or school screening program. The appropriateness of referral was labeled as inappropriate, late, or appropriate. In total, 213 of 1211 patients were excluded because they had received treatment at another medical facility; 998 patients were evaluated to determine the appropriateness of referral.

RESULTS

Of the 998 referrals of new patients with presumed adolescent idiopathic scoliosis, 162 (16.2%) were classified as an inappropriate referral, 272 (27.3%) were classified as a late referral, and 564 (56.5%) were classified as an appropriate referral. Age, sex, Cobb angle of the major curve, and skeletal maturity were identified as statistically significant factors that correlated with the appropriateness of referral. The referral method did not correlate with the appropriateness of referral.

CONCLUSIONS

Under the current health care system in South Korea, a substantial number of patients with presumed adolescent idiopathic scoliosis are referred either late or inappropriately to a tertiary medical center. Although patients referred by school screening programs had a significantly lower late referral rate and higher appropriate referral rate than the other 3 groups, the referral method was not a significant factor in terms of the appropriateness of referral.

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Heon Yoo, Young Zoon Kim, Byung Ho Nam, Sang Hoon Shin, Hee Seok Yang, Jin Soo Lee, Jae Il Zo and Seung Hoon Lee

Object

The goal of this study was to evaluate the therapeutic impact of the resection of metastatic brain tumor cells infiltrating adjacent brain parenchyma.

Methods

Between July 2001 and February 2007, 94 patients (67 males and 27 females, with a mean age of 55.0 ±12.0 years) underwent resection of a single brain metastasis, followed by systemic chemotherapy with or without radiotherapy. In 43 patients with tumors located in noneloquent areas, the authors performed microscopic total resections (MTRs) that included tumor cells infiltrating adjacent brain parenchyma, and they pathologically confirmed during surgery that the resection margins were free of tumor cells (MTR group). In 51 patients with lesions in eloquent locations, gross-total resections (GTRs) were performed without the removal of neighboring brain parenchyma (GTR group). The 2 groups were then compared for local recurrence and survival.

Results

The MTR group had better local control of the tumor than did the GTR group; 10 (23.3%) of 43 patients in the MTR group and 22 (43.1%) of 51 patients in the GTR group had a local recurrence (p = 0.04). The median time to tumor progression in the MTR group could not be calculated using the Kaplan-Meier method, whereas it was 11.4 months in the GTR group. The 1- and 2-year respective local recurrence rates were 29.1 and 29.1% in the MTR group and 58.6 and 63.2% in the GTR group (p = 0.01). Multivariate analysis showed that the MTR procedure was associated with a decreased risk of local recurrence (p = 0.003). A Cox regression analysis revealed that the hazard ratio for a local recurrence in the MTR group versus the GTR group was 3.14 (95% CI 1.47–6.72, p = 0.003). There was no significant difference in the local recurrence rate between the MTR group without radiotherapy (10 [30.3%] of 33) and the GTR group with postoperative radiotherapy (5 [26.3%] of 19).

Conclusions

The results in this study suggest that MTRs including tumor cells infiltrating adjacent brain parenchyma for a single brain metastasis provide better local tumor control.

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Min Ho Lee, Kyung Hwan Kim, Kyung Rae Cho, Jung Won Choi, Doo-Sik Kong, Ho Jun Seol, Do-Hyun Nam and Jung-Il Lee

OBJECTIVE

Fractionated Gamma Knife surgery (FGKS) has recently been used to treat large brain metastases. However, little is known about specific volume changes of lesions during the course of treatment. The authors investigated short-term volume changes of metastatic lesions during FGKS.

METHODS

The authors analyzed 33 patients with 40 lesions who underwent FGKS for intracranial metastases of non–small-cell lung cancer (NSCLC; 25 patients with 32 lesions) and breast cancer (8 patients with 8 lesions). FGKS was performed in 3–5 fractions. Baseline MRI was performed before the first fraction. MRI was repeated after 1 or 2 fractions. Adaptive planning was executed based on new images. The median prescription dose was 8 Gy (range 6–10 Gy) with a 50% isodose line.

RESULTS

On follow-up MRI, 18 of 40 lesions (45.0%) showed decreased tumor volumes (TVs). A significant difference was observed between baseline (median 15.8 cm3) and follow-up (median 14.2 cm3) volumes (p < 0.001). A conformity index was significantly decreased when it was assumed that adaptive planning was not implemented, from baseline (mean 0.96) to follow-up (mean 0.90, p < 0.001). The average reduction rate was 1.5% per day. The median follow-up duration was 29.5 weeks (range 9–94 weeks). During the follow-up period, local recurrence occurred in 5 lesions.

CONCLUSIONS

The TV showed changes with a high dose of radiation during the course of FGKS. Volumetric change caused a significant difference in the clinical parameters. It is expected that adaptive planning would be helpful in the case of radiosensitive tumors such as NSCLCs or breast cancer to ensure an adequate dose to the target area and reduce unnecessary exposure of normal tissue to radiation.

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Kyung Hwan Kim, Doo-Sik Kong, Kyung Rae Cho, Min Ho Lee, Jung-Won Choi, Ho Jun Seol, Sung Tae Kim, Do-Hyun Nam and Jung-Il Lee

OBJECTIVE

Fractionated Gamma Knife radiosurgery (GKS) represents a feasible option for patients with large brain metastases (BM). However, the dose-fractionation scheme balanced between local control and radiation-induced toxicity remains unclear. Therefore, the authors conducted a dose-escalation study using fractionated GKS as the primary treatment for large (> 3 cm) BM.

METHODS

The exclusion criteria were more than 3 lesions, evidence of leptomeningeal disease, metastatic melanoma, poor general condition, and previously treated lesions. Patients were randomized to receive 24, 27, or 30 Gy in 3 fractions (8, 9, or 10 Gy per fraction, respectively). The primary endpoint was the development of radiation necrosis assessed by a neuroradiologist blinded to the study. The secondary endpoints included the local progression-free survival (PFS) rate, change in tumor volume, development of distant intracranial progression, and overall survival.

RESULTS

Between September 2016 and April 2018, 60 patients were eligible for the study, with 46 patients (15, 17, and 14 patients in the 8-, 9-, and 10-Gy groups, respectively) available for analysis. The median follow-up duration was 9.6 months (range 2.5–25.1 months). The 6-month estimated cumulative incidence of radiation necrosis was 0% in the 8-Gy group, 13% (95% confidence interval [CI] 0%–29%) in the 9-Gy group, and 37% (95% CI 1%–58%) in the 10-Gy group. Being in the 10-Gy group was a significant risk factor for the development of radiation necrosis (p = 0.047; hazard ratio [HR] 7.2, 95% CI 1.1–51.4). The 12-month local PFS rates were 65%, 80%, and 75% in the 8-, 9-, and 10-Gy groups, respectively. Being in the 8-Gy group was a risk factor for local treatment failure (p = 0.037; HR 2.5, 95% CI 1.1–29.6). The mean volume change from baseline was a 47.5% decrease in this cohort. Distant intracranial progression and overall survival did not differ among the 3 groups.

CONCLUSIONS

In this dose-escalation study, 27 Gy in 3 fractions appeared to be a relevant regimen of fractionated GKS for large BM because 30 Gy in 3 fractions resulted in unacceptable toxicities and 24 Gy in 3 fractions was associated with local treatment failure.