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Background To investigate the feasibility of cerebrospinal fluid (CSF) CYFRA 21-1 levels as a therapeutic monitoring biomarker in leptomeningeal carcinomatosis (LMC) patients undergoing ventriculo-lumbar perfusion (VLP) chemotherapy. Methods The levels of CYFRA 21-1 in 42 CSF samples from 15 LMC patients were analyzed using an electrochemiluminescence immunoassay. Samples were collected at individual time points during VLP chemotherapy. Therapeutic outcomes were measured as improvements in the Karnofsky Performance Status (KPS) score and decreasing intracranial pressure (ICP) as the main endpoint of VLP chemotherapy. Changes in CSF CYFRA 21-1 levels, protein levels, and cytology results were also investigated. We subsequently evaluated whether these changes were correlated with KPS score and ICP. Results The CSF CYFRA 21-1 levels at individual time points were associated with KPS score and ICP. The KPS scores (p= 0.007) and ICP (p= 0.018) of patients with high CSF CYFRA 21-1 levels were significantly different from those of patients with low CSF CYFRA 21-1 levels. By contrast, CSF protein levels and cytological responses were not significantly associated with KPS scores and ICP. Conclusions CSF CYFRA 21-1 may have utility as a therapeutic monitoring biomarker to design personalized therapeutic strategies in LMC patients undergoing VLP chemotherapy.

A 74-year-old woman presented with a month-long nausea and vomiting, then she could not take a meal. She had found an asymptomatic 4th ventricular mass 6 year ago as a preoperative work-up for ovarian cancer. And during the yearly follow-up, the mass had grown continuously over 6 years, and caused symptoms in the seventh year. MRI revealed a large ovoid extra-axial mass in the fourth ventricle compressing adjacent medulla and cerebellum. Surgery achieved near total resection since the tumor tightly adhered to the brain stem of 4th ventricle floor. The histological diagnosis was ependymoma (WHO grade II). She transferred rehabilitation facility for mild gait disturbance, hoarseness and swallowing difficulty. Fourth ventricle ependymoma in the elderly is extremely rare and the growth rate has not been reported. Here, we present a rare care of 4th ventricle ependymoma found asymptomatic at elderly but continuously grow to cause local pressure symptoms.

Magnetic resonance imagining (MRI) is helpful for diagnosis of leptomeningeal carcinomatosis (LMC) and localizing LMC symptoms. Goal of this study is how MRI findings of LMC are associated with clinical characteristics or prognosis in patients with non-small cell lung cancer (NSCLC). We retrospectively collected data on 283 patients with LMC from NSCLC, adenocarcinoma based on cerebrospinal fluid cytology. All patients had brain MRI with gadolinium enhancement at LMC diagnosis, and spinal MRI was performed at the physician’s discretion. We evaluated the prognostic factors for overall survival (OS) of all patients and subgroup of patients with central nervous system cause of death. Two-hundred sixteen patients (76%) had definite or suggestive LMC findings and 67 had negative findings on brain MRI. Of the 37 patients who presented with cauda equina syndrome, 35 (95%) exhibited typical spinal MRI findings. Median OS of all patients was 3.65 months (95% confidence interval, 3.06–4.18). There was no significant difference in median OS between MRI-negative and MRI-positive groups (4.31 vs. 3.48 months, p = 0.711), whereas negative MRI finding showed longer median OS significantly in a subgroup of 77 patients with a central nervous system cause of death (p = 0.035). Considering clinical characteristics, progressive systemic disease, and altered mentality were significant prognostic factors associated with poor OS, whereas presenting symptom of headache with nausea/vomiting, intra-CSF chemotherapy, WBRT after LMC diagnosis, and concurrent RTKi treatment were significant for favorable OS in multivariable analysis. Positive MRI findings suggests heavier disease burden than negative MRI findings in patients with LMC who died of a central nervous system cause. Spinal MRI findings in patients with LMC correlate with cauda equina symptoms.

We evaluated the potential serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) roles in diagnosing and monitoring brain metastases (BMs). We included 70 patients with newly diagnosed BMs, 71 age- and cancer type-matched patients without BMs, and 67 healthy controls (HCs). We compared sNfL and sGFAP levels among the groups using a single-molecule array immunoassay. We prospectively followed 26 patients with BMs every 2–3 months by measuring sNfL and sGFAP levels and performing magnetic resonance imaging (MRI) scans. The sNfL and the sGFAP levels were higher in patients with BMs (medians: sNfL, 63.7 µL, sGFAP, 819.5 pg/µL) than in those without BMs (sNfL, 13.3 µL, sGFAP, 154 pg/µL, p &lt, 0.001) and HCs (sNfL, 12.5 µL, sGFAP, 135 pg/µL, 0.001). The sNfL and the sGFAP cutoff levels had a sensitivity and a specificity of 91%. The sGFAP cutoff level had a sensitivity of 91% and a specificity of 97%. The sNfL and the sGFAP levels were related to the BM size but not to the primary cancer type. After BM treatment, sNfL and sGFAP levels decreased with reduced BM lesions on MRI, however, they increased when BMs progressed. sNfL and sGFAP are potential biomarkers for BM screening in cancer patients.

BACKGROUND To date, there has been no practical guidelines for the prescription of antiepileptic drugs (AEDs) in brain tumor patients in Korea. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, had begun preparing guidelines for AED usage in brain tumors since 2019. METHODS The Working Group was composed of 27 multidisciplinary medical experts in Korea. References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of the keywords. RESULTS The core contents are as follows. Prophylactic AED administration is not recommended in newly diagnosed brain tumor patients without previous seizure history. When AEDs are administered during peri/postoperative period, it may be tapered off according to the following recommendations. In seizure-naive patients with no postoperative seizure, it is recommended to stop or reduce AED 1 week after surgery. In seizure-naive patients with one early postoperative seizure (

BACKGROUND To evaluate the impact of adjuvant postoperative radiotherapy (PORT) in adult WHO grade II–III intracranial ependymoma (IEPN). METHODS A total of 172 pathologically confirmed adult grade II–III IEPN patients from 12 institutions were eligible. Of them, 106 (61.6%) and 66 (38.4%) patients were grade II and III, respectively. For grade II and III IEPNs, 51 (48.1%) and 59 (89.4%) patients received PORT, respectively. The median dose to the primary tumor bed was 54.0 Gy and 59.4 Gy for grade II and III patients, respectively. The prognostic impact of sex, age, performance, WHO grade, location, size, surgical extent, and PORT on local control (LC), progression-free survival (PFS), and overall survival (OS) were evaluated by univariate and multivariate analysis. RESULTS The median follow-up period for survivors was 88.1 months. The 5-/10-year LC, PFS, and OS rates were 64.8%/54.0%, 56.4%/44.8%, and 76.6%/71.0%, respectively. On multivariate analysis, adjuvant PORT significantly improved LC (P=0.002), PFS (P=0.002), and OS (P=0.043). Older age (P< 0.001), WHO grade III (P< 0.001), larger tumor size (P=0.004), and lesser surgical extent (P< 0.001) were also negative factors for OS. Adjuvant PORT also improved LC (P=0.010), PFS (P=0.007), and OS (P=0.069) on multivariate analysis for grade II IEPNs. CONCLUSION This multicenter retrospective study supports the role of adjuvant PORT in terms of disease control and survival in adult grade II–III IEPNs. Prospective randomized trials focused on individualized treatment based on molecular subtypes is warranted.

Leptomeningeal metastasis (LM) has a poor prognosis and is difficult to diagnose and predict the response of treatment. In this study, we suggested that the monitoring of changes in the concentration of extracellular vesicles in cerebrospinal fluid could help diagnose or predict outcomes for LM. We measured nanoparticles in 472 human cerebrospinal fluid (CSF) from patients including LM with both Dynamic Light Scattering (DLS) and Nanoparticle Tracking Analysis (NTA) after two-step centrifugations. NTA revealed that the concentration of CSF nanoparticles was significantly increased in LM compared to other groups (2.80 &times, 108 /mL vs. 1.49 &times, 108 /mL, p &lt, 0.01). Changes in NTA-measured nanoparticles concentration after intra-CSF chemotherapy were further examined in 33 non-small cell lung cancer patients with LM. Overall survival was longer for patients with increased EV than the others (442 vs. 165 days, p &lt, 0.001). Markers of extracellular vesicles (CD9/CD63/CD81) significantly decreased in the EV-decreased group. MicroRNA-21 expression decreased in this favorable prognostic group, whereas it increased in the EV-decreased group. In conclusion, the elevated concentration of extracellular vesicles in cerebrospinal fluid in patients with LM may be a predictive marker for survival duration. Moreover, EV changes combined with microRNA-21 might be a biomarker for monitoring the efficacy of intracranial chemotherapy of LM in non-small cell lung cancer patients.

To evaluate the impact of adjuvant postoperative radiotherapy (PORT) in adult WHO grade II-III intracranial ependymoma (IEPN).A total of 172 pathologically confirmed adult grade II-III IEPN patients from 12 institutions were eligible. Of them, 106 (61.6%) and 66 (38.4%) patients were grade II and III, respectively. For grade II and III IEPNs, 51 (48.1%) and 59 (89.4%) patients received PORT, respectively. The median dose to the primary tumor bed was 54.0 Gy and 59.4 Gy for grade II and III patients, respectively. The prognostic impact of sex, age, performance, WHO grade, location, size, surgical extent, and PORT on local control (LC), progression-free survival (PFS), and overall survival (OS) were evaluated by univariate and multivariate analysis.The median follow-up period for survivors was 88.1 months. The 5-/10-year LC, PFS, and OS rates were 64.8%/54.0%, 56.4%/44.8%, and 76.6%/71.0%, respectively. On multivariate analysis, adjuvant PORT significantly improved LC (P = 0.002), PFS (P = 0.002), and OS (P = 0.043). Older age (P 0.001), WHO grade III (P 0.001), larger tumor size (P = 0.004), and lesser surgical extent (P 0.001) were also negative factors for OS. Adjuvant PORT also improved LC (P = 0.010), PFS (P = 0.007), and OS (P = 0.069) on multivariate analysis for grade II IEPNs.This multicenter retrospective study supports the role of adjuvant PORT in terms of disease control and survival in adult grade II-III IEPNs. Prospective randomized trials focused on individualized treatment based on molecular subtypes is warranted.

Brain metastasis is a common complication in cancer patients. Local recurrence after total resection of metastatic brain tumor has been frequently reported. In this study, we developed a new hyperthermia device and applied it to metastatic brain tumor patients intra-operatively to study if hyperthermia treatment could reduce local tumor recurrence.A total of 63 metastatic brain patients were enrolled in the study with an informed consent obtained from every patient. After total resection of the tumor, the hyperthermia device was applied intra-operatively to the resection cavity. The surrounding brain tissue at 5 mm in depth from the tumor resection margin was raised to 42.5 °C for a total of 60 minutes (Clinical Research Information Service Registration Number: KCT0001308).A total of 10 local recurrences were observed in 63 patients who received hyperthermia treatment showing a local recurrence rate of 15.8%. It was significantly lower than the local recurrence rate of those who received conventional treatment (34%) when analyzed with one tailed z-test (p value: .001). Kaplan-Meier analysis also showed a significantly lower recurrence rate in the hyperthermia treatment group (p value: .0003). Complications included two cases of seizures and two cases of wound infection.Results of this study suggest that intra-operative hyperthermia treatment after total resection of metastatic brain tumor could reduce local recurrence of tumor. We believe that intra-operative hyperthermia treatment could be used as an adjuvant therapy to surgery and post-operative radiotherapy, or as a salvage treatment in patients who cannot receive further radiotherapy.

Objective The purpose of this pilot study was to examine the safety and function of the newly developed cerebrospinal fluid (CSF) reservoir called the V-Port. Methods The newly developed V-Port consists of a non-collapsible reservoir outlined with a titanium cage and a connector for the ventricular catheter to be assembled. It is designed to be better palpated and more durable to multiple punctures than the Ommaya reservoir. A total of nine patients diagnosed with leptomeningeal carcinomatosis were selected for V-Port insertion. Each patient was followed up for evaluation for a month after the operation. Results The average operation time for V-Port insertion was 42 minutes and the average incision size was 6.6 cm. The surgical technique of V-Port insertion was found to be intuitive by all neurosurgeons who participated in the pilot study. There was no obstruction or leakage of the V-Port during intrathecal chemotherapy or CSF drainage. Also, there were no complications including post-operative intracerebral hemorrhage, infection and skin problems related to the V-Port. Conclusion V-Port is a safe and an easy to use implantable CSF reservoir that addresses problems of other implantable CSF reservoirs. Further multicenter clinical trial is needed to prove the safety and the function of the V-Port.

We performed this study to identify the treatment patterns of patients with low-grade gliomas (LGG) in Korea. A total of 555 patients diagnosed as WHO grade II gliomas between 2000 and 2010 at 14 Korean institutions were included. The patients were divided into four adjuvant treatment groups: adjuvant fractionated radiotherapy (RT, N = 204), adjuvant chemotherapy (N = 20), adjuvant fractionated RT and chemotherapy (N = 65), and non-adjuvant treatment (N = 266) groups. We examined differences among the groups and validated patient/tumor characteristics associated with the adjuvant treatments. Astrocytoma was diagnosed in 210 patients (38%), oligoastrocytoma in 85 patients (15%), and oligodendroglioma in 260 patients (47%). Gross total resection was performed in 200 patients (36%), subtotal resection in 153 (28%), partial resection in 71 patients (13%), and biopsy in 131 patients (24%). RT was most commonly applied as an adjuvant treatment. The use of chemotherapy with or without RT decreased after 2008 (from 38 to 4%). The major chemotherapeutic regimen was procarbazine, lomustine, and vincristine (PCV); however, the proportion of temozolomide increased since 2005 (up to 69%). Patient/tumor characteristics related with RT were male gender, non-seizure, multiple lobes involvement, and non-gross total resection. Chemotherapy was associated with non-gross total resection and non-astrocytoma. A preference for RT and increased use of temozolomide was evident in the treatment pattern of LGG. The extent of resection was associated with a decision to perform RT and chemotherapy. To establish a robust guideline for LGG, further studies including molecular information are needed.

When distant metastases are discovered, it is important to determine receptor profiles of these lesions through histologic examination. However, brain metastasis sites are difficult to reach to be routinely biopsied. The purpose of this study was to determine expression profiles of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) in breast cancer brain metastasis (BCBM) and the existence of discordance between primary breast cancer and brain metastasis. A total of 37 patients who underwent craniotomies for metastatic brain tumors arising from breast cancer at National Cancer Center (NCC) of Korea between 2002 and 2014 were retrospectively reviewed. Clinicopathologic data were collected from electronic medical records. Receptor profiles of primary breast cancer and brain metastasis in each patient were identified. Data of ER, PR, and HER2 expression in brain metastasis were available in electronic medical records for 21 (56.8%) of 37 cases. Results of ER, PR, and HER2 expression were positive in 47.6, 42.9, and 38.1% of patients with brain metastasis, respectively. Receptor conversion occurred in 11 (52.4%) of 21 patients (for ER, 9.5%; for PR, 38.1%; for HER2, 23.8%). Overall survival was longer in patients with concordant receptor expression patterns between primary breast cancer and brain lesion compared to that in patients with discordant patterns. However, such difference was not statistically significant (discordant vs. concordant median survival: 19.2 versus 31.1 months, p = 0.181). Receptor conversion in BCBMs was observed in over 50% of Korean patients used in this study. HER2 conversion was observed in 23.8% of patients in this study. Therefore, if resistance to anti-HER2 treatment is suspected in patients with BCBM, biopsy is needed to determine receptor profiles of brain lesion.

The incidence of leptomeningeal dissemination (LMD) of anaplastic glioma has been increasing. LMD can be observed at the time of initial presentation or the time of recurrence. As a result of both rarity and unusual presentation, a standard therapy has not yet been suggested. In contrast to leptomeningeal carcinomatosis for systemic solid cancers, a relatively prolonged survival is observed in some patients with LMD of anaplastic gliomas. Treatment modalities include whole craniospinal irradiation, intra-cerebrospinal fluid (CSF) chemotherapy, and systemic chemotherapy. In some cases, response to temozolomide (TMZ), with or without combined radiation has been reported. Here, we report two cases of LMD of an anaplastic glioma. In one case LMD presented at the time of diagnosis, and in the other at the time of recurrence after radiation. CSF cytology was positive in both cases, and persisted in spite of intrathecal methotrexate chemotherapy. Later, TMZ was prescribed for progressing brain parenchymal lesions, and both radiological and cytological responses were obtained after oral TMZ treatment.

// Byong Chul Yoo 1 , Jun Hwa Lee 1 , Kyung-Hee Kim 1 , Weiwei Lin 2 , Jong Heon Kim 2 , Jong Bae Park 2 , Hyun Jin Park 3 , Sang Hoon Shin 4 , Heon Yoo 4 , Ji Woong Kwon 4 and Ho-Shin Gwak 2, 4 1 Biomarker Branch, Research Institute, National Cancer Center, Goyang, Republic of Korea 2 Department of Cancer Biomedical Science, National Cancer Center, Graduate School of Cancer Science and Policy, Goyang, Republic of Korea 3 Center for Pediatric Cancer, National Cancer Center, Goyang, Republic of Korea 4 Neuro-oncology Clinic, National Cancer Center, Goyang, Republic of Korea Correspondence to: Ho-Shin Gwak, email: nsghs@ncc.re.kr Keywords: cerebrospinal fluid, metabolome, leptomeningeal carcinomatosis, profile, diagnosis Received: July 28, 2017 Accepted: August 28, 2017 Published: September 18, 2017 ABSTRACT Purpose: Early diagnosis of leptomeningeal carcinomatosis (LMC) is necessary to improve outcomes of this formidable disease. However, cerebrospinal fluid (CSF) cytology is frequently false negative. We examined whether CSF metabolome profiles can be used to differentiate patients with LMC from patients having a risk for development of LMC. Results: A total of 10,905 LMIs were evaluated using PCA-DA. The LMIs defined Group 2 with a sensitivity of 85% and a specificity of 91%. After selecting 33 LMIs, including diacetylspermine and fibrinogen fragments, the CSF metabolomics profile had a sensitivity of 100% and a specificity of 93% for discriminating Group 1b from the other groups. After selecting 21 LMIs, including phosphatidylcholine, the CSF metabolomics profile differentiated LMC (Group 2) patients from the high-risk groups of Group 3 and Group 4 with 100% sensitivity and 100% specificity. Materials and Methods: We prospectively collected CSF from five groups of patients: Group 1a, systemic cancer; Group 1b, no tumor; Group 2, LMC; Group 3, brain metastasis; Group 4, brain tumor other than brain metastasis. All metabolites in the CSF samples were detected as low-mass ions (LMIs) using mass spectrometry. Principal component analysis-based discriminant analysis (PCA-DA) and two search algorithms were used to select the LMIs that differentiated the patient groups of interest from controls. Conclusions: Analysis of CSF metabolite profiles could be used to diagnose LMC and exclude patients at high-risk of LMC with a 100% accuracy. We expect a future validation trial to evaluate CSF metabolic profiles supporting CSF cytology.

Purpose In this retrospective study, we compared the incidence of leptomeningeal carcinomatosis or dural metastasis (LMCDM) in patients who received whole brain radiotherapy (WBRT), partial radiotherapy (PRT), or no radiotherapy (RT) following resection of brain metastases from breast cancer. Materials and Methods Fifty-one patients with breast cancer underwent surgical resection for newly diagnosed brain metastases in two institutions between March 2001 and March 2015. Among these, 34 received postoperative WBRT (n=24) or PRT (n=10) and 17 did not. Results With a median follow-up of 12.4 months (range, 2.3 to 83.6 months), 22/51 patients developed LMCDM at a median of 8.6 months (range, 4.8 to 51.2 months) after surgery. The 18-months LMCDM-free survival (LMCDM-FS) rates were 77.5%, 30.0%, and 13.6%, in the WBRT, PRT, and no RT groups, respectively (p=0.013). The presence of a tumor adjacent to cerebrospinal fluid flow and no systemic treatment after treatment for brain metastases were also associated with poor LMCDM-FS rate. Multivariate analysis showed that WBRT compared to PRT (p=0.009) and systemic treatment (p < 0.001) were independently associated with reduced incidence of LMCDM. Conclusion WBRT improved LMCDM-FS rate after resection of brain metastases compared to PRT in breast cancer patients.

// Jae-Won Hyun 1, 6 , Ji Hyun Park 2 , Boo Gil Kang 3 , Eun Young Park 4 , Boram Park 4 , Jungnam Joo 4 , Jong Kuk Kim 5 , Su-Hyun Kim 1 , Jee Hyang Jeong 6 , Hyang Woon Lee 6 , Kee Duk Park 6 , Kyung Gyu Choi 6 , Sang-Hyun Hwang 3, 7 , Ho-Shin Gwak 7 and Ho Jin Kim 1, 7 1 Department of Neurology, National Cancer Center, Goyang, Korea 2 Department of Oncology, Konkuk University of Medical College, Seoul, Korea 3 Department of Laboratory Medicine, National Cancer Center, Goyang, Korea 4 Biometric Research Branch, National Cancer Center, Goyang, Korea 5 Department of Neurology, Dong-A University College of Medicine, Busan, Korea 6 Department of Neurology, Ewha Womans University School of Medicine and Ewha Medical Research Institute, Seoul, Korea 7 Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea Correspondence to: Ho Jin Kim, email: hojinkim@ncc.re.kr Keywords: leptomeningeal carcinomatosis, diagnosis, prognosis, CSF, CYFRA 21-1 Received: November 30, 2016 Accepted: May 18, 2017 Published: June 08, 2017 ABSTRACT Objectives: To investigate the diagnostic and prognostic values of cerebrospinal fluid (CSF) CYFRA 21-1 in patients with leptomeningeal carcinomatosis (LMC). Methods: Concentration of CSF CYFRA 21-1 was detected using electro-chemiluminescent immunoassay. The difference in level of CYFRA 21-1 between 61 patients with LMC and 200 patients with other neurological disease was evaluated, and diagnostic performance of CSF CYFRA 21-1 was investigated. In LMC patients treated with ventriculo-lumbar perfusion (VLP) chemotherapy, prognostic performance of CSF CYFRA 21-1 was evaluated. Results: The CSF CYFRA 21-1 was significantly higher in LMC patients than that in patients with other neurological diseases (p

Background There have been no guidelines for the management of adult patients with diffuse midline glioma (DMG), H3K27M-mutant in Korea since the 2016 revised WHO classification newly defined this disease entity. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, had begun preparing guidelines for DMG since 2019. Methods The Working Group was composed of 27 multidisciplinary medical experts in Korea. References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of keywords. As 'diffuse midline glioma' was recently defined, and there was no international guideline, trials and guidelines of 'diffuse intrinsic pontine glioma' or 'brain stem glioma' were thoroughly reviewed first. Results The core contents are as follows. The DMG can be diagnosed when all of the following three criteria are satisfied: the presence of the H3K27M mutation, midline location, and infiltrating feature. Without identification of H3K27M mutation by diagnostic biopsy, DMG cannot be diagnosed. For the primary treatment, maximal safe resection should be considered for tumors when feasible. Radiotherapy is the primary option for tumors in case the total resection is not possible. A total dose of 54 Gy to 60 Gy with conventional fractionation prescribed at 1-2 cm plus gross tumor volume is recommended. Although no chemotherapy has proven to be effective in DMG, concurrent chemoradiotherapy (± maintenance chemotherapy) with temozolomide following WHO grade IV glioblastoma's protocol is recommended. Conclusion The detection of H3K27M mutation is the most important diagnostic criteria for DMG. Combination of surgery (if amenable to surgery), radiotherapy, and chemotherapy based on comprehensive multidisciplinary discussion can be considered as the treatment options for DMG.

OBJECTIVE Elevated cell counts and protein levels in cerebrospinal fluid (CSF) result from disease activity in patients with leptomeningeal carcinomatosis (LMC). Previous studies evaluated the use of CSF profiles to monitor a treatment response or predict prognosis. CSF profiles vary, however, according to the sampling site and the patient's systemic condition. We compared lumbar and ventricular CSF profiles collected before intraventricular chemotherapy for LMC and evaluated the association of these profiles with patients' systemic factors and LMC disease activity. METHODS CSF profiles were retrospectively collected from 228 patients who underwent Ommaya reservoir insertion for intraventricular chemotherapy after a diagnosis of LMC. Lumbar samples taken via lumbar puncture were used for the diagnosis, and ventricular samples were obtained later at the time of Ommaya reservoir insertion. LMC disease activity was defined as the presence of LMC-related symptoms such as increased intracranial pressure, hydrocephalus, cranial neuropathy, and cauda equina syndrome. RESULTS Cell counts (median : 8 vs. 1 cells/mL) and protein levels (median : 68 vs. 17 mg/dL) significantly higher in lumbar CSF than in ventricular CSF (p

PURPOSE The purpose of this study was to investigate the feasibility and survival benefits of combined treatment with radiotherapy and adjuvant temozolomide (TMZ) in a Korean sample. MATERIALS AND METHODS A total of 750 Korean patients with histologically confirmed glioblastoma multiforme, who received concurrent chemoradiotherapy with TMZ (CCRT) and adjuvant TMZ from January 2006 until June 2011, were analyzed retrospectively. RESULTS After the first operation, a gross total resection (GTR), subtotal resection (STR), partial resection (PR), biopsy alone were achieved in 388 (51.7%), 159 (21.2%), 96 (12.8%), and 107 (14.3%) patients, respectively. The methylation status of O6-methylguanine-DNA methyltransferase (MGMT) was reviewed retrospectively in 217 patients. The median follow-up period was 16.3 months and the median overall survival (OS) was 17.5 months. The actuarial survival rates at the 1-, 3-, and 5-year OS were 72.1%, 21.0%, and 9.0%, respectively. The median progression-free survival (PFS) was 10.1 months, and the actuarial PFS at 1-, 3-, and 5-year PFS were 42.2%, 13.0%, and 7.8%, respectively. The patients who received GTR showed a significantly longer OS and PFS than those who received STR, PR, or biopsy alone, regardless of the methylation status of the MGMT promoter. Patients with a methylated MGMT promoter also showed a significantly longer OS and PFS than those with an unmethylated MGMT promoter. Patients who received more than six cycles of adjuvant TMZ had a longer OS and PFS than those who received six or fewer cycles. Hematologic toxicity of grade 3 or 4 was observed in 8.4% of patients during the CCRT period and in 10.2% during the adjuvant TMZ period. CONCLUSION Patients treated with CCRT followed by adjuvant TMZ had more favorable survival rates and tolerable toxicity than those who did not undergo this treatment.

BACKGROUND Diagnosis of leptomeningeal metastasis (LM) in medulloblastoma is made by positive findings in either MRI or CSF cytology. We studied if CSF metabolomics profile can differentiate the discordant results between MRI and CSF cytology and reflect the sampling time related to treatment. MATERIALS AND METHODS We prospectively collected 83 CSF samples from 45 medulloblastoma patients. A total of 6,527 low-mass ions (LMIs) were detected using liquid chromatography tandem mass spectrometry (LC-MS/MS). Discriminative low-mass ions (LMIs) between four different MRI and cytology results groups were evaluated and representative LMIs were identified. RESULTS CSF cytology and MRI finding were both positive for LM in 8 samples and both negative for 47 samples. Tests were cytology (-) and MRI (+) in 20 samples, whereas cytology (+) and MRI (-) status were in the remaining 8 samples. The diagnostic accuracy by area under the curve (AUC) was 0.722 for cytology and 0.888 for MRI each. Based on the exclusiveness of LMI between groups, we verified 27 discriminative LMIs in MRI (+)/ cytology (+), 9 LMIs in MRI (+)/ cytology (-), and 12 LMIs in MRI (-) and cytology (+) group, separately. Metabolic pathways involved in MRI (+)/ cytology (+) group were linoleic acid, phenylalanine, TCA cycle, retinol, arginine-ornithine, nicotinate-nicotinamide, etc. Low-mass-ion discriminant equation (LOME), which could differentiate both different MRI and cytology results and the sampling time or presence of LM-related symptoms was found. CONCLUSION Non-targeted MSanalysis CSF metabolite in medulloblastomas revealed significantly different profiles, and these results suggest LMI profiles might have a higher sensitivity for LM diagnosis than either MRI or cytology.

Background The Guideline Working Group of the Korean Society for Neuro-Oncology (KSNO) conducted a nationwide questionnaire survey for diverse queries faced in the treatment of brain tumors. As part I of the survey, the aim of this study is to evaluate national patterns of clinical practice about antiepileptic drug (AED) and steroid usage for management of brain tumors. Methods A web-based survey was sent to all members of the KSNO by email. The survey included 9 questions of AED usage and 5 questions of steroid usage for brain tumor patients. All questions were developed by consensus of the Guideline Working Group. Results The overall response rate was 12.8% (54/423). Regarding AED usage, the majority of respondents (95.2%) routinely prescribed prophylactic AEDs for patients with seizure at the peri/postoperative period. However, as many as 72.8% of respondents prescribed AED routinely for seizure-naïve patients, and others prescribed AED as the case may be. The duration of AED prophylaxis showed wide variance according to the epilepsy status and the location of tumor. Levetiracetam (82.9%) was the most preferred AED for epilepsy prophylaxis. Regarding steroid usage, 90.5% of respondents use steroids in perioperative period, including 34.2% of them as a routine manner. Presence of peritumoral edema (90.9%) was considered as the most important factor determining steroid usage followed by degree of clinical symptoms (60.6%). More than half of respondents (51.2%) replied to discontinue the steroids within a week after surgery if there are no specific medical conditions, while 7.3% preferred slow tapering up to a month after surgery. Conclusion The survey demonstrated the prevailing practice patterns on AED and steroid usage in neuro-oncologic field among members of the KSNO. This information provides a point of reference for establishing a practical guideline in the management of brain tumor patients.

Background As the application of radiotherapy to brain metastasis (BM) increases, the incidence of radiation necrosis (RN) as a late toxicity of radiotherapy also increases. However, no specific treatment for RN is indicated except long-term steroids. Here, we summarize the clinical results of bevacizumab (BEV) for RN. Methods Ten patients with RN who were treated with BEV monotherapy (7 mg/kg) were retrospectively reviewed. RN diagnosis was made using MRI with or without perfusion MRI. Radiological response was based on Response Assessment in Neuro-Oncology criteria for BM. The initial response was observed after 2 cycles every 2 weeks, and maintenance observed after 3 cycles every 3-6 weeks of increasing length intervals. Results The initial response of gadolinium (Gd) enhancement diameter maintained stable disease (SD) in 9 patients, and 1 patient showed partial response (PR). The initial fluid-attenuated inversion recovery (FLAIR) response showed PR in 4 patients and SD in 6 patients. The best radiological response was observed in 9 patients. Gd enhancement response was 6 PR and 3 SD between 15-43 weeks. Reduction of FLAIR showed PR in 5 patients and SD in 4 patients. Clinical improvement was observed in all but 1 patient. Five patients were maintained on protocol with durable response up to 23 cycles. However, 2 patients stopped treatment due to primary cancer progression, 1 patient received surgical removal from tumor recurrence, and 1 patient changed to systemic chemotherapy for new BM. Grade 3 intractable hypertension occurred in 1 patient who had already received antihypertensive medication. Conclusion BEV treatment for RN from BM radiotherapy resulted in favorable radiological (60%) and clinical responses (90%). Side effects were expectable and controllable. We anticipate prospective clinical trials to verify the effect of BEV monotherapy for RN.

Background Leptomeningeal carcinomatosis (LMC) is frequently associated with hydrocephalus, which quickly devastates the performance of the patient. Cerebrospinal fluid (CSF) shunt is a widely accepted treatment of choice, but the clinical outcomes in patients with LMC are not well studied. This study aimed to examine the efficacy of a CSF shunt in patients with LMC. Methods Seventy patients with LMC confirmed by cytology or magnetic resonance imaging (MRI) underwent ventriculoperitoneal (VP) or lumboperitoneal (LP) shunt surgery. We retrospectively analyzed the clinical characteristics of patients, symptom improvement after the shunt, rate of complications associated with the surgery, and overall survival. Results Fifty-five patients had systemic cancer as a preceding disease, including lung cancer (45), breast cancer (6), and others (4). Primary brain tumors were mainly glioma (7) and medulloblastoma (5). Fifty-one patients had VP shunt, and 19 had LP shunt. After surgery, preoperative symptoms “improved” in 35 patients (50%) and were “normalized” in 24 of those patients (34%). Shunt malfunction occurred in eight patients, and infection occurred in eight patients. Seventeen patients underwent revision due to infection, shunt malfunction, or over-drainage. There were no complications associated with peritoneal seeding during a median follow-up of 3.3 months after surgery. The median overall survival was 8.7 months (95% confidence interval, 6.0–11.4) from LMC diagnosis and 4.1 months from shunt surgery. Conclusion VP or LP shunt is effective for patients with hydrocephalus from LMC in terms of symptom improvement and prolonging of overall survival with an acceptable rate of procedure-related complications. Trial registration This study was approved by the Institutional Review Board (IRB) of the National Cancer Center (retrospectively registered, NCC2018-0051).

ObjectivesThe most appropriate treatments for brain metastases from ovarian cancer have not been established mainly because of its rarity. The objective of this study was to describe clinical results of treatment and prognostic factors of patients with brain metastases from ovarian cancer treated at a single institution.Materials and MethodsWe retrieved information from the electronic medical records of 56 consecutive patients (2.8%) with brain metastases, from a total of 2008 patients with ovarian cancer. Endpoints were the pattern of treatment failure, progression-free survival, and overall survival (OS).ResultsRadiation was the most common initial treatment for brain metastases (59%), followed by surgery (23%). The median progression-free survival was 9.8 months. Radiological progression was confirmed in 20 patients: 7 had leptomeningeal carcinomatosis (37%), 8 had local recurrence, and 5 had distant recurrence. Median OS was 11.25 months, and the 1-year OS rate was 48.2%. Patients received surgery for single metastasis as initial treatment showed median OS of 24.1 months, which was significantly prolonged compared with the other patients (P = 0.0002). Of the 48 patients who died, 29 (60%) died of systemic disease and 7 (15%) died of central nervous system progression. Karnofsky Performance Status greater than or equal to 70, control of systemic cancer, serous histology, and surgery for brain metastases were associated with improved OS in multivariable analysis (P < 0.05).ConclusionsSurgical resection for single or symptomatic brain metastases from ovarian cancer prolonged OS significantly. Multimodality treatment, including control of systemic cancer, appeared to be an important factor in prolonging OS.

Purpose To investigate the clinical outcome of proton therapy (PT) in patients with chordoma. Materials and methods Fifty-eight patients with chordoma treated with PT between June 2007 and December 2015 at the National Cancer Center, Korea, were retrospectively analyzed. The median total dose was 69.6 cobalt gray equivalent (CGE; range, 64.8 to 79.2 CGE). Local progression-free survival (LPFS), distant metastasis-free survival (DMFS), overall survival (OS), and diseasespecific survival (DSS) rates were calculated by the Kaplan-Meier method. Results With the median follow-up of 42.8 months (range, 4 to 174 months), the 5-year LPFS, DMFS, OS, and DSS rates were 87.9%, 86.7%, 88.3%, and 92.9%, respectively. The tumor location was associated with the patterns of failure: the LPFS rates were lower for cervical tumors (57.1%) than for non-cervical tumors (93.1%) (p = 0.02), and the DMFS rates were lower for sacral tumors (53.5%) than for non-sacral tumors (100%) (p = 0.001). The total dose was associated with both the LPFS rate and DMFS rate. The initial tumor size was associated with the DMFS rate, but was not associated with the LPFS rate. Three patients had grade 3 late toxicity with none ≥grade 4. Conclusion PT is an effective and safe treatment in patients with chordomas. The tumor location was associated with the patterns of failure: local failure was common in cervical tumors, and distant failure was common in sacral tumors. Further refinement of PT, such as the utilization of intensity modulated PT for cervical tumors, is warranted to improve the outcome.

Intracranial metastasis from thyroid cancer is extremely rare. However, less is known about the risk factors for intracranial metastasis and its treatment from few retrospective studies. The aim of this study was to contribute to the understanding of this disease by analyzing patients with intracranial metastases from thyroid cancer. Between 2001 and 2014, the database of the National Cancer Center of Korea was searched for thyroid cancer patients. The clinical characteristics and site of distant metastasis according to the histological type were evaluated in the thyroid cancer cohort. Among the patients with intracranial metastases, the characteristics, histological type of primary cancer and metastatic brain tumor, additional synchronous or previous distant metastasis, treatment modalities, locations and characteristics on radiologic findings, time interval between the first diagnosis of the primary thyroid cancer and brain metastasis, thyroglobulin level at the first detection of intracranial metastasis and survival were reviewed. A total of 10 (0.032 %) out of 3,090 thyroid cancer patients in the National Cancer Center database were identified as having intracranial metastases. The histological types of the primary thyroid cancers were papillary for six patients, follicular for three, and poorly differentiated carcinoma for one. Six of these ten patients underwent surgical resection for intracranial lesions. Whole-brain radiotherapy or tyrosine kinase inhibitors were applied to the patients as postoperative adjuvant treatment, and stereotactic radiosurgery was considered for recurrent or surgically inoperable lesions. The overall median survival time was 33 months (range, 0.5-78 months) after diagnosis of intracranial metastasis. Surgical resection and adjuvant treatments in the contemporary era seem to result in improved survival after intracranial metastases compared with what has been reported in past studies. Considering the grave course of intracranial metastasis, the early detection and aggressive treatment of patients with a good performance status are crucial.

Radiation therapy has an important role in postoperative treatment of neoplasms originated from central nervous system, but may induce secondary malignancies like as sarcomas, gliomas, and meningiomas. The prognosis of radiation-induced osteosarcomas is known as poor, because they has aggressive nature invasive locally and intractable to multiple treatment strategies like as surgical resection, chemotherapy, and so on. We report a case of radiation-induced osteosarcoma developed from skull after 7 years of craniospinal radiotherapy for pineoblastoma.

Cystic brain metastases (CBM) have been recently reported in a minority of patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). All previously reported ALK-positive CBM developed during crizotinib treatment and were often asymptomatic and indolent, even without CNS-directed therapy. Thus, crizotinib was suggested as an etiologic agent for the development of CBM. Here, we report a case of de novo CBM in a patient with ALK-positive NSCLC prior to crizotinib treatment; the ALK-positive NSCLC had initially been misdiagnosed as neurocysticercosis because of the atypical radiological presentation of brain metastases.

Prognosis of diffuse intrinsic pontine glioma (DIPG) is poor, with a median survival of 10 months after radiation. At present, chemotherapy has failed to show benefits over radiation. Advances in biotechnology have enabled the use of autopsy specimens for genomic analyses and molecular profiling of DIPG, which are quite different from those of supratentorial high grade glioma. Recently, combined treatments of cytotoxic agents with target inhibitors, based on biopsied tissue, are being examined in on-going trials. Spontaneous DIPG mice models have been recently developed that is useful for preclinical studies. Finally, the convection-enhanced delivery could be used to infuse drugs directly into the brainstem parenchyma, to which conventional systemic administration fails to achieve effective concentration. The WHO glioma classification defines a diffuse midline glioma with a H3-K27M-mutation, and we expect increase of tissue confirmation of DIPG, which will give us the biological information helping the development of a targeted therapy.

Necrosis is a hallmark of glioblastoma (GBM) and is responsible for poor prognosis and resistance to conventional therapies. However, the molecular mechanisms underlying necrotic microenvironment-induced malignancy of GBM have not been elucidated. Here, we report that transglutaminase 2 (TGM2) is upregulated in the perinecrotic region of GBM and triggered mesenchymal (MES) transdifferentiation of glioma stem cells (GSC) by regulating master transcription factors (TF), such as C/EBPβ, TAZ, and STAT3. TGM2 expression was induced by macrophages/microglia-derived cytokines via NF-κB activation and further degraded DNA damage–inducible transcript 3 (GADD153) to induce C/EBPβ expression, resulting in expression of the MES transcriptome. Downregulation of TGM2 decreased sphere-forming ability, tumor size, and radioresistance and survival in a xenograft mouse model through a loss of the MES signature. A TGM2-specific inhibitor GK921 blocked MES transdifferentiation and showed significant therapeutic efficacy in mouse models of GSC. Moreover, TGM2 expression was significantly increased in recurrent MES patients and inversely correlated with patient prognosis. Collectively, our results indicate that TGM2 is a key molecular switch of necrosis-induced MES transdifferentiation and an important therapeutic target for MES GBM. Cancer Res; 77(18); 4973–84. ©2017 AACR.

Glioblastoma multiforme (GBM) is well known as the most common malignant primary brain tumor. It could easily spread into the adjacent or distant brain tissue by infiltration, direct extension and cerebro-spinal fluid dissemination. The extranueural metastatic spread of GBM is relatively rare but it could have more progressive disease course. We report a 39-year-old man who had multiple bone metastases and malignant pleural effusion of the GBM without primary site recurrence.

PURPOSE For comparing the distribution and concentrations of nano-sized micro-molecules in cerebrospinal fluid (CSF) according to different central nervous system (CNS) disease METHODS We have collected CSF of 447 patients from 6 different groups (systemic cancer, healthy control, leptomeningeal carcinomatosis (LMC), brain metastasis, other brain tumor, and other CNS disease). After cell down by centrifugation, proportion of nano-sized particle is measured by Nano-sizer and absolute number of extracellular vesicle (EV, 100–1,000 nm) is counted by Nano-sight. We verified exosomes in our CSF samples by exosome purification and Western blot. RESULTS In Nano-sizer, two peaks appeared at mean 10.5 nm and 174 nm. The small peak is presumed to be nucleic acid and protein as we could decrease or eliminate the peak by nucleic acid elimination kit or proteinase. The proportion of large peak, presumed to represent EVs, is significantly higher in LMC group than all other groups (mean 64% vs. 44%, p < 0.001). And also, the count of EV is significantly higher in patients with LMC (7.15 x 108 vs. 3.46 x 108, p < 0.001). Furthermore, we evaluated paired EV concentration of pre- and post-treatment of intra-CSF chemotherapy in non-small lung cancer patients with LMC (n=33). Overall survival of patients was significantly prolonged in patients with increased EV count compared to those of decreased or ‘no-change’ (< 20%) (442 vs. 165 days, p < 0.001). The expression level of onco-microRNA (miR-21) is decreased significantly after the treatment in this favorable prognostic group (p < 0.01). CONCLUSION We expect to obtain appropriate variables representing cancer cell activity in the CSF samples by observing this nano-sized molecule proportion and EV concentration with onco-miR expression. KEY WORDS: cerebrospinal fluid, exosome, extracellular vesicle, microRNA, leptomeningeal carcinomatosis

Background To evaluate the efficacy of modified ventriculolumbar perfusion (VLP) chemotherapy with methotrexate on leptomeningeal carcinomatosis in terms of symptomatic response and side effects. Methods Previous infusion rate of 20 mL/h was reduced to 15 mL/h for the purpose of decreasing constitutional side effects of VLP such as nausea/vomiting, insomnia and confusion. The primary outcome was the response rate of increased intracranial pressure (ICP), and the secondary outcome was the occurrence of side effects compared to previous 20 mL/h trial. This interim analysis to validate the reduced infusion rate is not to affect the original effect of VLP chemotherapy. Results All forty-seven patients were enrolled including 22 patients with increased ICP. Thirteen patients out of these (59%) got normalized ICP after VLP chemotherapy. Moderate to severe (grade 2-3) confusion was observed in 3 patients (6%) and it was significantly reduced compared to those (23%) in the VLP 20 mL/h (p=0.017). Grade 2-3 nausea/vomiting was also reduced from 64% to 45% but failed to reach statistical significance (p=0.08). Median overall survival (OS) was 5.3 months (95% confidence interval, 3.55-7.05) and patients OS, who received maintenance VLP was significantly prolonged compared to patients who underwent induction VLP only (5.8 vs. 3.4 months, p=0.025). Conclusion VLP of reduced perfusion rate (15 mL/h) showed compatible control rate of increased ICP at this interim analysis. Decreased moderate to severe side effects and prolonged OS in patients received maintenance VLP encourage us to evaluate the effectiveness of this trial further.

Objective Patients with symptomatic brain metastases secondary to mass effect are often candidates for surgery. However, many of these surgical candidates are also found to have multiple asymptomatic tumors. This study aimed to determine the outcome of surgical resection of symptomatic brain metastases followed by chemotherapy or radiotherapy (RT) for the remnant asymptomatic lesions in non-small cell lung cancer (NSCLC) patients with multiple brain metastases. Methods We conducted a retrospective review of the medical records of 51 NSCLC patients with symptomatic multiple brain metastases who underwent surgical resection, of whom 38 had one or more unresected asymptomatic lesions subsequently treated with chemotherapy and/or RT. Thirteen patients underwent resection of all metastatic lesions. Results Median survival for overall patient population after surgical resection was 10.8 months. Median survival for patients with surgical resection of all brain metastases was not significantly different with patients who underwent surgical resection of only symptomatic lesions (6.5 months vs. 10.8 months; p=0.97). There was no statistically significant difference in survival according to the number of tumors (p=0.86, 0.16), or post-surgical treatment modalities (p=0.69). Conclusion The survival time of NSCLC patients with multiple brain metastases after surgery for only symptomatic brain metastases is similar to that of patients who underwent surgery for all brain metastases. The remaining asymptomatic lesions may be treated with chemotherapy or radiotherapy. The optimal treatment modality, however, needs to be defined in prospective trials with larger patient cohort.

OBJECTIVE Intracavitary injection of beta-emitting radiation source for control of cystic tumors has been tried with a benefit of localized internal radiation. The authors treated cystic brain tumor patients with Holmium-166-chitosan complex (Ho-166-chico), composed of a beta-emitting radionuclide Holmium-166 and biodegradable chit polymer, and evaluated the safety and effective measurement for response. METHODS Twenty-two patients with recurrent cystic brain tumor and/or located in a deep or eloquent area were enrolled in this pilot study. The cyst volume and wall thickness were determined on CT or MRI to assess radiological response. The activity of Ho-166-chico injected via Ommaya reservoir was prescribed to be 10-25 Gy to the cyst wall in a depth of 4 mm. RESULTS There was neither complications related to systemic absorption nor leakage of Ho-166-chico in all 22 patients. But, two cases of oculomotor paresis were observed in patients with recurrent craniopharyngioma. Radiological response was seen in 14 of 20 available follow-up images (70%). Seven patients of 'evident' radiological response experienced more than 25% decrease of both cyst volume and wall thickness. Another 7 patients with 'suggestive' response showed decrease of cyst volume without definitive change of the wall thickness or vice versa. All patients with benign tumors or low grade gliomas experienced symptomatic improvement. CONCLUSION Ho-166-chico intracavitary radiation therapy for cystic tumor is a safe method of palliation without serious complications. The determination of both minimal effective dosage and time interval of repeated injection through phase 1 trial could improve the results in the future.

Reports on the treatment result of leptomeningeal carcinomatosis (LMC) from a single primary cancer are rare and mixed treatment modalities make it even more difficult to interpret the results properly. Here, we report clinical outcomes of an intraventricular chemotherapy for LMC from non-small-cell lung cancer.Medical records of 105 patients were retrieved and retrospectively analyzed to find the prognostic factors of patients' survival and symptom responses, including intracranial pressure (ICP) control.There were 44 men and 61 women, with a median age of 56 years (range, 31-75 years). Patients received a median five rounds of intraventricular chemotherapy (range, 1-49 rounds). The most common presenting symptom was headache (77%) with nausea or vomiting, which showed the highest response rate of 42%. Altered mentality (36%), cranial neuropathy (15%), and cauda equina symptoms (12%) revealed 10% or less of symptom response. Only eight patients (7.6%) showed negative conversion of cerebrospinal fluid cytology. Median overall survival was 3.0 months (range, 0.5-21.5 months). Age (≥ 60 years), poor Karnofsky performance score (70), and uncontrolled ICP were found to be unfavorable prognostic factors for patient survival. A greater amount of intraventricular chemotherapy, which was evaluated as time-dependent covariate, and concurrent systemic chemotherapy significantly improved overall survival in the multivariable analysis.Intraventricular chemotherapy for patients with LMC from non-small-cell lung cancer could palliate associated symptoms and prolong patients' survival. Careful selection of patients for intraventricular chemotherapy is recommended with aggressive ICP control and concurrent systemic chemotherapy.

Sellar arachnoid cysts are rare; an infected arachnoid cyst is extremely rare as only one case has been reported to date in the literature. Here, we report a patient with an infected or inflamed sellar arachnoid cyst that was successfully treated with transsphenoidal surgery (TSA). A 53-year-old female with a history of chronic sinusitis developed a headache 5 months ago, and one month before admission polyuria, polydipsia, and abnormal vaginal bleeding occurred. The magnetic resonance imaging (MRI) showed a sellar cystic mass with a thickened pituitary stalk. Preoperative hormonal study revealed normal pituitary hormone levels except for a moderate elevation of prolactin. She was diagnosed with diabetes insipidus of the central nervous system origin based on a water-deprivation test. TSA was performed under an impression of symptomatic Rathke's cleft cyst according to the MRI findings. Intraoperative findings showed confirmation of turbid intracystic contents, but micro-organisms were unidentified on microbial culture. Pathology of the cyst wall revealed inflamed meningoepithelial lining cells compatible with an arachnoid cyst.

Objectives: To evaluate the feasibility, sensitivity and specificity of IOM for IDEM and ED metastatic spinal tumours, and to assess usefulness of SSEP for patients in whom MEP was not measurable. Methods and materials: One hundred and one consecutive patients with IDEM and ED metastatic spinal tumours at the cord level (C1 to L1) received surgery under SSEP and/or MEP was included. Feasibility of IOM was defined to be negative in case of no measurable MEP or SSEP under general anaesthesia after confirmation of reversal of neuromuscular block. More than 50% change of MEP or SSEP amplitude and more than 10% delay of SSEP latency were evaluated as positive signs of IOM change. Results: MEP was measurable in 74 out of 101 trials, thus feasibility is 73%. Patient with normal motor power showed higher feasibility than those with motor power 3 or less. (93% vs. 39%) Among 74 patients with measurable MEP, 19 patients showed positive MEP change and 14 patients got worse of their motor power postoperatively.

Object Surgical spillage has been one of the causative factors for the development of leptomeningeal seeding (LMS) after resection of brain metastases. In this paper, the authors' goal was to define the factors related to the development of LMS and to evaluate the difference according to tumor location. Methods The authors retrospectively analyzed 242 patients who had undergone resection for brain metastases. The factors investigated included tumor location with proximity to the CSF pathway (that is, contacting, involved with, or separated from the CSF pathway), the method of resection, and the use of the Cavitron Ultrasonic Surgical Aspirator (CUSA). Results A total of 39 patients (16%) developed LMS at a median of 6.0 months (range 1–42 months) after resection. The risk of developing LMS was significantly higher in patients whose tumors were resected piecemeal than in those whose tumors were removed en bloc, with a hazard ratio (HR) of 4.08 (p < 0.01). The incidence of LMS was significantly higher in patients in whom the CUSA was used, and the HR was 2.64 (p < 0.01). The proximity of tumor to the CSF pathway in the involved group conferred an increased risk of LMS compared with the separated group (HR 11.36, p < 0.01). The risk of piecemeal resection for LMS was significant only in involved lesions (p < 0.01), and the use of the CUSA in both contact and involved lesions increased the incidence of LMS (p < 0.01 and p < 0.03, respectively). Conclusions The authors suggest that piecemeal resection using the CUSA should be limited because of the risk of postsurgical LMS, especially when the tumor is in contact with the CSF pathway.

Purpose Hemorrhagic metastatic brain tumors are not rare, but little is known about the surgical outcome following treatment. We conducted this study to determine the result of the surgical outcome of hemorrhagic metastatic brain tumors. Materials and methods From July 2001 to December 2008, 21 patients underwent surgery for hemorrhagic metastatic brain tumors at our institution. 15 patients had lung cancer, 3 had hepatocellular carcinoma, and the rest had rectal cancer, renal cell carcinoma, and sarcoma. 20 patients had macroscopic hemorrhage in the tumors, and one patient had intracerebral hemorrhage surrounding the tumor. A retrospective clinical review was conducted focusing on the patterns of presenting symptoms and signs, as well as local recurrence following surgery. Results Among 21 hemorrhagic brain metastases, local recurrence developed in two patients. The 12 month progression free survival rate was 86.1%. Mean time to progression was 20.8 months and median survival time after surgery was 11.7 months. Conclusion The results of our study showed that hemorrhagic metastatic brain tumors rarely recurred after surgery. Surgery should be considered as a good treatment option for hemorrhagic brain metastasis, especially in cases with increased intracranial pressure or severe neurologic deficits.

Surgery, anticoagulation therapy, pregnancy, and hormone treatments, such as bromocriptine, are well-characterized precipitating factors for pituitary apoplexy. However, whether cytotoxic chemotherapy for systemic cancer could cause pituitary apoplexy has not been investigated. Here, we present a case of a 41-year-old woman who developed a severe headache with decreased visual acuity after intravenous cytotoxic chemotherapy to treat metastatic breast cancer. Preoperative neuroimaging revealed pituitary adenoma with necrosis. Operative findings and pathologic examination concluded extensive necrosis with a small intratumoral hemorrhage in a pre-existing pituitary adenoma. We reviewed two additional previously published cases of pituitary apoplexy after systemic chemotherapy and suggest that cytotoxic chemotherapy may induce pituitary apoplexy.

One of difficulties in intra-CSF chemotherapy for leptomeningeal carcinomatosis (LMC) is a lack of quantitative measure for the treatment response. Previous studies evaluated CSF profiles to predict treatment response or to correlate with prognosis. However, the results were inconsistent mainly due to small number of patients and heterogeneous treatment. We analyzed 283 patients with LMC from solid cancer, who underwent intraventricular chemotherapy at National Cancer Center from 2003 to 2013. CSF parameters were cytology, cell count and protein level. Control of intracranial pressure (ICP) was reviewed as an objective indicator of symptom improvement. CSF profiles before the treatment were significantly different according to sample sites (p < 0.001) in both cell count (lumbar vs. ventricular is mean 23 ± 44 vs. 8 ± 30) and protein level (mean 124 ± 168 vs. 33 ± 66 mg/dL). Initial lumbar CSF protein level was correlated with development of increased ICP (p = 0.059), hydrocephalus (HCP) (p = 0.049), and cauda equine syndrome (CES) (p< 0.001). But, initial ventricular CSF profiles did not reflect LMC disease activity. Decrease of CSF protein level after treatment was associated with increased ICP control (p = 0.017) while cell count change or cytology conversion is not predictive. Patients with low initial protein level (≤ 50mg/dL), or cell count (≤15) show prolonged survival (p = 0.001 and 0.015, respectively). But, decrease of either protein level or cell count after the treatment and cytology response did not significantly affect the patients OS. We suggest that CSF cell count is too low to reflect disease activity or treatment response especially those from ventricle. Initial CSF protein is in accordance with LMC symptoms and the decrease of protein level after the treatment is predictive of treatment response. We need new quantitative pharmacodynamic markers for LMC treatment to improve efficacy of intraventricular chemotherapy.

Vertebroplasty (VP), including balloon kyphoplasty (BKP), has long been accepted as a minimally invasive surgical intervention for the stabilization of painful vertebral compression fractures. In metastatic compression fracture (MCF), cancer often invades the paravertebral structure and involves the posterior column of the vertebrae.In the present study, we first analyzed how clinical features of MCF affect functional outcomes after VP. Second, we evaluated whether BKP is more beneficial than simple VP (SVP) in MCF.This is a retrospective observational study.Three hundred forty-two patients who underwent VP for painful MCF from solid cancer were included. We excluded MCF from hematopoietic cancer, such as leukemia or multiple myeloma.Pain improvement was evaluated using the visual analog scale (VAS; range: 0-10), and if the VAS score decreased by at least three points the treatment was considered effective. Postoperative change in Karnofsky performance status (KPS) and drug requirement for pain control were also measured as functional outcomes.An institutional database at the National Cancer Center of Korea was searched to identify all patients who underwent VP for painful MCF between March 2002 and September 2013. Demographic data, as well as preoperative and postoperative clinical factors, were collected from patients' medical records. Radiological features, including paravertebral extension of tumors and the extent of three-column involvement, were reviewed from pretreatment magnetic resonance imaging (MRIs). These clinical and radiological factors were then analyzed for their influence on functional outcomes.The mean preoperative VAS score was 5.8; this improved to a mean of 2.7 after VP. Effective improvement in VAS score (≥3) was achieved in 206 patients (60%). Patients with radiculopathy, as well as those with involvement of (1) the posterior column or (2) more than four out of six columns, presented with significantly higher pretreatment VAS scores and experienced more effective improvement after treatment (p.05). Two hundred thirty-eight patients (70%) underwent SVP, whereas the remaining 104 patients underwent BKP. The pretreatment degree of compression was significantly higher in BKP (mean: 47%) than in SVP patients (mean: 30%) (p.001). However, preoperative VAS scores were not significantly different between the two groups, and the resultant VAS score improvement was also not significantly different. Although BKP patients reported to have a greater chance of more than 3 mL of cement injection (p=.01), the mean amount of cement injected was not different between the two groups. Patients with other bone metastases showed a significantly poorer KPS improvement rate (p=.015). Patients having moderately or slowly growing cancer according to the Tomita classification had a greater chance of reduced drug requirements 1 month after the procedure (p=.004).Paravertebral extension and posterior column involvement of MCF did not preclude pain improvement after VP. Balloon kyphoplasty for MCF failed to show enhanced pain improvement relative to SVP. Metastatic compression fracture patients with other bone metastases or rapidly growing tumors had a lower chance of performance improvement and reduced drug requirements, respectively.

Introduction: Chordoma and chondrosarcoma are rare tumors of the base of the skull and are difficult candidates for surgical treatment. They are also usually resistant to conventional radiation therapy. We report preliminary results of hypofractionated stereotactic radia- tion therapy (SRT) using the Cyberknife system (Accuray Inc., Sunnyvale, Calif., USA) for primary and recurrent chordomas and chondrosarcomas of the skull base and upper cervical region. Material and Methods: Nine pathologically proven chordoma/chondrosarcoma patients underwent Cyberknife treatment, and in 4 patients Cyberknife was performed as a primary adjuvant treatment after operation. Remainder of the patients had previously received conventional radiotherapy except 1 who had received Gamma Knife treatment. The prescribed tumor dose ranged from 21 to 43.6 Gy in three to five fractions. The dosimetric characteristics were evaluated for conformity and coverage indices. Dose volume histograms of both the tumor and the critical structure were obtained, and the dose delivered to a specific volume (25, 50 and 100%) of the critical structure was calculated in each case. Mass response was measured on follow-up MRI scans. Total tumor doses of different fractionation numbers were converted into single session equivalent doses and linear quadratic equivalent doses of conventional radiation for comparison among patient groups. Result: Nosignificant complications were observed during the treatment and early follow-up periods except one instance of transient esophagitis and one instance of otitis. All treatment plans met the criteria for standard protocol of radiosurgery suggested by the Radiation Therapy Oncology Group, specifically in terms of conformity index, which ranged from 1.01 to 1.83. Three plans had a coverage index that was rated as a minor acceptable deviation. All patients were followed from 11 to 30 (median 24) months following the treatment with regular magnetic resonance images, and 4 patients showed mass reduction. Disease progression was not noted in any patient during the above follow-up period except 1 patient who showed asymptomatic recurrence on 27-month follow-up MRI. Dose volume histograms revealed that the relative dose to volume percent of critical structure, measured at 25, 50 and 100%, was apparently lower in the pretreatment surgical decompression group than in the nondecompression group. Two patients developed radiation-induced myelopathy. The delivered radiation dose to the critical structure calculated using the linear-quadratic formula was within the acceptable range in one case and exceeded 70 Gy at 50% volume of the spinal cord in the other. Conclusion: The hypofractionated Cyberknife SRT is effective in generating therapeutic response in these radioresistant tumors, with minimal toxicity during the procedure and early follow-up period. Repeated radiosurgical treatment may also be feasible for tumor recurrences but deserves great caution with respect to the biological effects of the accumulated dose on the adjacent critical structures. Cyberknife SRT may be a potentially valuable treatment option once the long-term results and appropriate dose calculators are optimally defined.

CD95/Fas is a cell surface protein that belongs to the tumor necrosis factor receptor family. Signals through CD95/Fas are able to induce apoptosis in sensitive cells. Therefore, modalities to regulate the CD95/Fas expression level in tumor cells are called for. In the present study, we show that sublethal doses of arsenic trioxide (As2O3) sensitized CD95/Fas-induced apoptosis in human cervical cancer cells, and the sensitizing effects resulted from As2O3-mediated increase in the expression of the CD95/Fas. N-acetyl-L-cysteine, a specific scavenger of reactive oxygen species, abrogated As2O3-induced upregulation of CD95/Fas and enhancement of CD95/Fas-mediated apoptosis. Furthermore, inhibition of NF-κB by transient transfection of IκBα supersuppressor blocked the increase of CD95/Fas expression following As2O3 treatment. Antisense oligonucleotide of CD95/Fas and ZB4, an antibody that blocks the binding of CD95/Fas ligand to CD95/Fas, reduced the amount of As2O3-sensitized CD95/Fas-induced apoptosis, demonstrating the specificity of CD95/Fas-binding ligands in the As2O3-sensitized CD95/Fas-induced apoptosis. These findings demonstrate that sensitization of human cervical cancer cells to CD95/Fas-mediated apoptosis by As2O3 can be partly due to induction of ROS and subsequent upregulation of CD95/Fas gene expression by NF-κB activation. © 2004 Wiley-Liss, Inc.