Publications by authors named "Chul-Kee Park"

239 Publications

The Role of Postoperative Radiotherapy in Intracranial Solitary Fibrous Tumor/Hemangiopericytoma: A Multi-Institutional Retrospective Study (KROG 18-11).

Cancer Res Treat 2021 Mar 24. Epub 2021 Mar 24.

Department of Radiation Oncology, Seoul National University Hospital, Seoul National University, College of Medicine, Seoul, Korea.

Purpose: To evaluate the role of postoperative radiotherapy (PORT) in intracranial solitary fibrous tumor/hemangiopericytoma (SFT/HPC).

Methods And Materials: A total of 133 patients with histologically confirmed HPC were included from 8 institutions. Gross total resection (GTR) and subtotal resection (STR) were performed in 86 and 47 patients, respectively. PORT was performed in 85 (64%) patients. The prognostic effects of sex, age, performance, WHO grade, location, size, Ki-67, surgical extent, and PORT on local control (LC), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) were estimated by univariate and multivariate analyses.

Results: The 10-year PFS, and OS rates were 45%, and 71%, respectively. The multivariate analysis suggested that PORT significantly improved LC (p<0.001) and PFS (p<0.001). The PFS benefit of PORT was maintained in the subgroup of GTR (p=0.001), WHO grade II (p=0.001) , or STR (p<0.001). In the favorable subgroup of GTR and WHO grade II, PORT was also significantly related to better PFS (p=0.028). WHO grade III was significantly associated with poor DMFS (p=0.029). In the PORT subgroup, the 0-0.5 cm margin of the target volume showed an inferior LC to a large margin with 1.0-2.0 cm (p=0.021). Time-dependent Cox proportion analysis showed that distant failures were significantly associated with poor OS (p=0.003).

Conclusion: This multicenter study supports the role of PORT in disease control of intracranial SFT/HPC, irrespective of the surgical extent and grade. For LC, PORT should enclose the tumor bed with sufficient margin.
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http://dx.doi.org/10.4143/crt.2021.142DOI Listing
March 2021

Clinical application of patient-specific 3D printing brain tumor model production system for neurosurgery.

Sci Rep 2021 Mar 26;11(1):7005. Epub 2021 Mar 26.

Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, Daehak-ro 101, Jongno-gu, Seoul, 03080, Republic of Korea.

The usefulness of 3-dimensional (3D)-printed disease models has been recognized in various medical fields. This study aims to introduce a production platform for patient-specific 3D-printed brain tumor model in clinical practice and evaluate its effectiveness. A full-cycle platform was created for the clinical application of a 3D-printed brain tumor model (3D-printed model) production system. Essential elements included automated segmentation software, cloud-based interactive communication tools, customized brain models with exquisite expression of brain anatomy in transparent material, adjunctive devices for surgical simulation, and swift process cycles to meet practical needs. A simulated clinical usefulness validation was conducted in which neurosurgeons assessed the usefulness of the 3D-printed models in 10 cases. We successfully produced clinically applicable patient-specific models within 4 days using the established platform. The simulated clinical usefulness validation results revealed the significant superiority of the 3D-printed models in surgical planning regarding surgical posture (p = 0.0147) and craniotomy design (p = 0.0072) compared to conventional magnetic resonance images. The benefit was more noticeable for neurosurgeons with less experience. We established a 3D-printed brain tumor model production system that is ready to use in daily clinical practice for neurosurgery.
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http://dx.doi.org/10.1038/s41598-021-86546-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998007PMC
March 2021

Safety and efficacy of endoscopic dorsum sellar resection for access to retro-infundibular or upper clival tumors (KOSEN-008).

World Neurosurg 2021 Mar 23. Epub 2021 Mar 23.

Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea; Pituitary center, Seoul National University Hospital, Seoul, Republic of Korea. Electronic address:

Objective: The retro-infundibular and upper clival regions are challenging to access using the endoscopic endonasal approach (EEA) because these regions are obstructed by the dorsum sellae and posterior clinoid processes. We evaluated the safety and clinical efficacy of endoscopic dorsum sellar resection (DSR) and identified the optimal indication of endoscopic DSR in patients with craniopharyngioma.

Methods: A retrospective study was conducted in the patients treated with EEA between January 2014 and January 2019. We identified a total of 50 patients who underwent the DSR. Indication for DSR included the following: (1) a tumor involving the upper clivus, (2) a tumor located behind the dorsum sellae, and (3) a tumor involving the interpeduncular or prepontine cistern. We evaluated the clinical outcomes, postoperative endocrinological status, and surgical morbidities.

Results: The patients group included 16 craniopharyngiomas, 30 chordomas, two pituitary adenomas, one schwannoma, and one chondrosarcoma. Extradural approach for DSR with posterior clinoidectomy was performed in 33 patients (66.0%) and interdural transcavernous approach in 17 patients (34.0%). The overall gross total resection rate of the tumor was 92.0 % (46 of 50 patients). Postoperatively, 28 of 33 patients (84.8%) with preoperative normal pituitary function showed preservation of hormonal function.

Conclusion: DSR with/without posterior clinoidectomy is a challenging procedure that requires considerable efforts and advanced surgical techniques, however, it can be safely performed by accumulating experience and thorough knowledge of the surrounding anatomical structures.
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http://dx.doi.org/10.1016/j.wneu.2021.03.085DOI Listing
March 2021

Methylation and molecular profiles of ependymoma: Influence of patient age and tumor anatomic location.

Mol Clin Oncol 2021 May 5;14(5):88. Epub 2021 Mar 5.

Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.

Ependymomas are tumors of the central nervous system that can occur in patients of all ages. Guidelines from the World Health Organization (WHO) for the grading of ependymomas consider patient age, tumor resection range, tumor location and histopathological grade. However, recent studies have suggested that a greater focus on both tumor location and patient age in terms of transcriptomic, genetic, and epigenetic analyses may provide a more accurate assessment of clinical prognosis than the grading system proposed by WHO guidelines. The current study identified the differences and similarities in ependymoma characteristics using three different molecular analyses and methylation arrays. Primary intracranial ependymoma tissues were obtained from 13 Korean patients (9 adults and 4 children), after which whole-exome sequencing (WES), ion-proton comprehensive cancer panel (CCP) analysis, RNA sequencing, and Infinium HumanMethylation450 BeadChip array analysis was performed. Somatic mutations, copy number variations, and fusion genes were identified. It was observed that the methylation status and differentially expressed genes were significantly different according to tumor location and patient age. Several novel gene fusions and somatic mutations were identified, including a fusion mutation in a child with a good prognosis. Moreover, the methylation microarray revealed that genes associated with neurogenesis and neuron differentiation were hypermethylated in the adult group, whereas genes in the homeobox gene family were hypermethylated in the supratentorial (ST) group. The results confirmed the existence of significantly differentially expressed tumor-specific genes based on tumor location and patient age. These results provided valuable insight into the epigenetic and genetic profiles of intracranial ependymomas and uncovered potential strategies for the identification of location- and age-based ependymoma-related prognostic factors.
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http://dx.doi.org/10.3892/mco.2021.2250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7976387PMC
May 2021

Adjuvant radiotherapy versus observation following gross total resection for atypical meningioma: a systematic review and meta-analysis.

Radiat Oncol 2021 Feb 17;16(1):34. Epub 2021 Feb 17.

Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea.

Background: The impact of adjuvant radiotherapy (RT) on atypical meningioma (AM) underwent a gross total resection (GTR) remains unclear, showing conflicting results from various studies. The objective of this study was to perform an updated meta-analysis for observational studies to determine the effect of adjuvant RT after GTR on local recurrence and survival outcomes compared to observation after GTR.

Methods: PubMed, Embase, and Web of Science were searched to identify comparative studies that reported outcomes of adjuvant RT versus observation for AM patients after GTR. Local recurrence rate, progression-free survival (PFS), overall survival (OS), and toxicities related to RT were considered as outcomes of interest. Differences between two cohorts were estimated by calculating odds ratios (OR) for LR rate and hazard ratios (HR) for survival outcomes with 95% confidence intervals (CIs) for meta-analysis, using R version 4.0.3 software. Included studies were appraised with the Risk of Bias Assessment tool for Non-Randomized Studies. Outcome ratios were combined with the Mantel-Haenszel method and the inverse variance-weighted method, appropriately.

Results: Data from 30 studies involving 2904 patients (adjuvant RT: n = 737; observation: n = 2167) were eventually included. Significant reduction of local recurrence rate was seen in the adjuvant RT cohort compare to that in the observation cohort (OR 0.50; 95% CI 0.36-0.68; p < 0.0001). Pooled HRs of PFS at 1-year, 3-year, 5-year, and > 5-year revealed that adjuvant RT was superior to observation. There was no significant difference in OS between the two cohorts during any period. Most toxicities were tolerable with grade 1 or 2. There was no documented grade 5 toxicity.

Conclusions: For AM patients who underwent GTR, evidence suggested that adjuvant RT could potentially decrease local recurrence and improve PFS better than observation.
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http://dx.doi.org/10.1186/s13014-021-01759-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890913PMC
February 2021

Long-Term Outcomes and Sequelae Analysis of Intracranial Germinoma: Need to Reduce the Extended-Field Radiotherapy Volume and Dose to Minimize Late Sequelae.

Cancer Res Treat 2021 Jan 13. Epub 2021 Jan 13.

Department of Radiation Oncology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.

Purpose: We aimed to refine the radiotherapy (RT) volume and dose for intracranial germinoma considering recurrences and long-term toxicities.

Materials And Methods: Total 189 patients with intracranial germinoma were treated with RT alone (n=50) and RT with upfront chemotherapy (CRT) (n=139). All cases were confirmed histologically. RT fields comprised the extended-field and involved-field only for primary site. The extended-field, including craniospinal, whole-brain (WB), and whole-ventricle (WV) for cranial field, is followed by involved-field boost. The median follow-up duration was 115 months.

Results: The relapses developed in 13 patients (6.9%). For the extended-field, cranial RT dose down to 18 Gy exhibited no cranial recurrence in 34 patients. In CRT, 74 patients (56.5%) showed complete response to chemotherapy and no involved-field recurrence with low-dose RT of 30 Gy. WV RT with chemotherapy for the basal ganglia or thalamus germinoma showed no recurrence. Secondary malignancy developed in ten patients (5.3 %) with a latency of 20 years (range, 4-26) and caused mortalities in six. WB or craniospinal field rather than WV or involved-field significantly increased the rate of hormone deficiencies, and secondary malignancy. RT dose for extended-field correlated significantly with the rate of hormone deficiencies, secondary malignancy, and neurocognitive dysfunction.

Conclusion: Reduced dose and volume of extended-field rather than total dose or involved-field will be critical to decrease the late toxicities. Upfront chemotherapy could be beneficial for the patients with complete response to minimize the RT dose down to 30 Gy. Prospective trials focused on de-intensification of the extended-field RT are warranted.
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http://dx.doi.org/10.4143/crt.2020.1052DOI Listing
January 2021

Modulation of Nogo receptor 1 expression orchestrates myelin-associated infiltration of glioblastoma.

Brain 2021 Mar;144(2):636-654

Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.

As the clinical failure of glioblastoma treatment is attributed by multiple components, including myelin-associated infiltration, assessment of the molecular mechanisms underlying such process and identification of the infiltrating cells have been the primary objectives in glioblastoma research. Here, we adopted radiogenomic analysis to screen for functionally relevant genes that orchestrate the process of glioma cell infiltration through myelin and promote glioblastoma aggressiveness. The receptor of the Nogo ligand (NgR1) was selected as the top candidate through Differentially Expressed Genes (DEG) and Gene Ontology (GO) enrichment analysis. Gain and loss of function studies on NgR1 elucidated its underlying molecular importance in suppressing myelin-associated infiltration in vitro and in vivo. The migratory ability of glioblastoma cells on myelin is reversibly modulated by NgR1 during differentiation and dedifferentiation process through deubiquitinating activity of USP1, which inhibits the degradation of ID1 to downregulate NgR1 expression. Furthermore, pimozide, a well-known antipsychotic drug, upregulates NgR1 by post-translational targeting of USP1, which sensitizes glioma stem cells to myelin inhibition and suppresses myelin-associated infiltration in vivo. In primary human glioblastoma, downregulation of NgR1 expression is associated with highly infiltrative characteristics and poor survival. Together, our findings reveal that loss of NgR1 drives myelin-associated infiltration of glioblastoma and suggest that novel therapeutic strategies aimed at reactivating expression of NgR1 will improve the clinical outcome of glioblastoma patients.
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http://dx.doi.org/10.1093/brain/awaa408DOI Listing
March 2021

Editorial Statistics and Best Reviewer Awards 2020 for the Journal of Korean Neurosurgical Society.

J Korean Neurosurg Soc 2021 Jan 1;64(1):1-3. Epub 2021 Jan 1.

Editor in Chief, Journal of Korean Neurosurgical Society; Department of Neurosurgery, Seoul National University Boramae Hospital, Seoul, Korea.

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http://dx.doi.org/10.3340/jkns.2020.0364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819797PMC
January 2021

Absolute quantification of tumor-infiltrating immune cells in high-grade glioma identifies prognostic and radiomics values.

Cancer Immunol Immunother 2021 Jan 8. Epub 2021 Jan 8.

Department of Neurosurgery, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea.

Purpose: To understand the tumor immune microenvironment precisely, it is important to secure the quantified data of tumor-infiltrating immune cells, since the immune cells are true working unit. We analyzed unit immune cell number per unit volume of core tumor tissue of high-grade gliomas (HGG) to correlate their immune microenvironment characteristics with clinical prognosis and radiomic signatures.

Methods: The number of tumor-infiltrating immune cells from 64 HGG core tissue were analyzed using flow cytometry and standardized. After sorting out patient groups according to diverse immune characteristics, the groups were tested if they have any clinical prognostic relevance and specific radiomic signature relationships. Sparse partial least square with discriminant analysis using multimodal magnetic resonance images was employed for all radiomic classifications.

Results: The median number of CD45 + cells per one gram of HGG core tissue counted 865,770 cells which was equivalent to 8.0% of total cells including tumor cells. There was heterogeneity in the distribution of immune cell subpopulations among patients. Overall survival was significantly better in T cell-deficient group than T cell-enriched group (p = 0.019), and T8 dominant group than T4 dominant group (p = 0.023). The number of tumor-associated macrophages (TAM) and M2-TAM was significantly decreased in isocitrate dehydrogenase mutated HGG. Radiomic signature classification showed good performance in predicting immune phenotypes especially with features extracted from apparent diffusion coefficient maps.

Conclusions: Absolute quantification of tumor-infiltrating immune cells confirmed the heterogeneity of immune microenvironment in HGG which harbors prognostic impact. This immune microenvironment could be predicted by radiomic signatures non-invasively.
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http://dx.doi.org/10.1007/s00262-020-02836-wDOI Listing
January 2021

The prognostic significance of p16 expression pattern in diffuse gliomas.

J Pathol Transl Med 2021 Mar 23;55(2):102-111. Epub 2020 Dec 23.

Department of Pathology, Seoul National University Hospital, Seoul, Korea.

Background: CDKN2A is a tumor suppressor gene that encodes the cell cycle inhibitor protein p16. Homozygous deletion of the CDKN2A gene has been associated with shortened survival in isocitrate dehydrogenase (IDH)-mutant gliomas. This study aimed to analyze the prognostic value of p16 and to evaluate whether p16 immunohistochemical staining could be used as a prognostic marker to replace CDKN2A genotyping in diffuse gliomas.

Methods: p16 immunohistochemistry was performed on tissue microarrays of 326 diffuse gliomas with diagnoses that reflected IDH-mutations and 1p/19q codeletion status. The results were divided into three groups (negative, focal expression, overexpression) according to the presence and degree of p16 expression. Survival analysis was performed to assess the prognostic value of p16 expression.

Results: A loss of p16 expression predicted a significantly worse outcome in all glioma patients (n=326, p<.001), in the IDH-mutant glioma patients (n=103, p=.010), and in the IDH-mutant astrocytoma patients (n=73, p=.032). However, loss of p16 expression did not predict the outcome in the IDH-wildtype glioma patients (n=223, p=.121) or in the oligodendroglial tumor patients with the IDH-mutation and 1p/19q codeletion (n=30, p=.457). Multivariate analysis showed the association was still significant in the IDH-mutant glioma patients (p=.008; hazard ratio [HR], 2.637; 95% confidence interval [CI], 1.295 to 5.372) and in the IDH-mutant astrocytoma patients (p=.001; HR, 3.586; 95% CI, 1.649 to 7.801). Interestingly, patients who presented with tumors with p16 overexpression also had shorter survival times than did patients with tumors with p16 focal expression in the whole glioma (p< .001) and in IDH-mutant glioma groups. (p=.046).

Conclusions: This study suggests that detection of p16 expression by immunohistochemistry can be used as a useful surrogate test to predict prognosis, especially in IDH-mutant astrocytoma patients.
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http://dx.doi.org/10.4132/jptm.2020.10.22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987518PMC
March 2021

Superselective pseudocontinuous arterial spin labeling in patients with meningioma: utility in prediction of feeding arteries and preoperative embolization feasibility.

J Neurosurg 2020 Nov 13:1-7. Epub 2020 Nov 13.

3Department of Radiology, Seoul National University Bundang Hospital, Gyeonggi-do, Republic of Korea.

Objective: Superselective pseudocontinuous arterial spin labeling (ss-pCASL) is an MRI technique in which individual vessels are labeled to trace their perfusion territories. In this study, the authors assessed its merit in defining feeding vessels and gauging preoperative embolization feasibility for patients with meningioma, using digital subtraction angiography (DSA) as the reference method.

Methods: Thirty-one consecutive patients with meningiomas were prospectively recruited, each undergoing DSA (and embolization, if feasible) before resection. All ss-pCASL imaging studies were performed 1 day prior to DSA. Two neuroradiologists independently reviewed ss-pCASL images, rating the contribution of each labeled vessel to tumor blood supply as none, minor, or major. Two neuroradiologists also gauged the feasibility of embolization in each patient, based on ss-pCASL images. Interobserver and intermodality agreement were determined using Cohen's kappa statistic. The diagnostic performance of ss-pCASL was assessed in terms of discerning tumor blood supply and the potential for embolization.

Results: Interobserver agreement in the rating of blood supply by ss-pCASL was very good (κ = 0.817, 95% CI 0.771-0.863), and intermodality agreement (consensus ss-pCASL readings vs DSA findings) was good (κ = 0.688, 95% CI 0.632-0.744). In delineating tumor blood supply, ss-pCASL showed high sensitivity (87.1%) and specificity (87.2%). The positive and negative predictive values for embolization feasibility were 85.2% and 100%, respectively.

Conclusions: In patients with meningiomas, feeding vessels are reliably predicted by ss-pCASL. This noninvasive approach, involving no iodinated contrast or radiation exposure, is particularly beneficial if there are no prospects of embolization.
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http://dx.doi.org/10.3171/2020.7.JNS201915DOI Listing
November 2020

Clinical and Genomic Characteristics of Adult Diffuse Midline Glioma.

Cancer Res Treat 2020 Nov 9. Epub 2020 Nov 9.

Department of Neurosurgery, Seoul National University Hospital, Seoul, Korea.

Purpose: The treatment outcomes and genomic profiles of diffuse midline glioma (DMG) in adult patients are rarely characterized. We performed a retrospective study to evaluate the clinicogenomic profiles of adult patients with brain DMG.

Materials And Methods: Patients aged ≥ 18 years diagnosed with brain DMG at Seoul National University Hospital were included. The clinicopathological parameters, treatment outcomes, survival, and genomic profiles using 82-gene targeted next-generation sequencing (NGS) were analyzed. The 6-month progression-free survival (PFS6) after radiotherapy and overall survival (OS) were evaluated.

Results: Thirty-three patients with H3-mutant brain DMG were identified. The median OS from diagnosis was 21.8 months (95% confidence interval [CI], 13.2 to not available [NA]) and involvement of the ponto-medullary area tended to have poor OS (median OS, 20.4 months [95% CI, 9.3 to NA] vs. 43.6 months [95% CI, 18.2 to NA]; p=0.07). Twenty-four patients (72.7%) received radiotherapy with or without temozolomide. The PFS6 rate was 83.3% (n=20). Patients without progression at 6 months showed significantly prolonged OS compared with those with progression at 6 months (median OS, 24.9 months [95% CI, 20.4 to NA] vs. 10.8 months [95% CI, 4.0 to NA]; p=0.02, respectively). Targeted NGS was performed in 13 patients with DMG, among whom nine (69.2%) harbored concurrent TP53 mutation. Two patients (DMG14 and DMG23) with PIK3CAR38S+E545K and KRASG12A mutations received matched therapies. Patient DMG14 received sirolimus with a PFS of 8.4 months.

Conclusion: PFS6 after radiotherapy was associated with prolonged survival in adult patients with DMG. Genome-based matched therapy may be an encouraging approach for progressive adult patients with DMG.
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http://dx.doi.org/10.4143/crt.2020.694DOI Listing
November 2020

Radiological assessment schedule for high-grade glioma patients during the surveillance period using parametric modeling.

Neuro Oncol 2020 Nov 1. Epub 2020 Nov 1.

Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine.

Background: An optimal radiological surveillance plan is crucial for high-grade glioma (HGG) patients, which is determined arbitrarily in daily clinical practice. We propose the radiological assessment schedule using a parametric model of standardized progression-free survival (PFS) curves.

Methods: A total of 277 HGG patients (178 glioblastoma (GBM) and 99 anaplastic astrocytoma (AA)) from a single institute who completed the standard treatment protocol were enrolled in this cohort study and retrospectively analyzed. The patients were stratified into each layered risk group by genetic signatures and residual mass or through recursive partitioning analysis. PFS curves were estimated using the piecewise exponential survival model. The criterion of a 10% progression rate among the remaining patients at each observation period was used to determine the optimal radiological assessment time point.

Results: The optimal follow-up intervals for MRI evaluations of the isocitrate dehydrogenase (IDH) wild-type GBM was every 7.4 weeks until 120 weeks after the end of standard treatment, followed by a 22-week inflection period and every 27.6 weeks thereafter. For the IDH mutated GBM, scans every 13.2 weeks until 151 weeks are recommended. The optimal follow-up intervals were every 22.8 weeks for the IDH wild-type AA, and 41.2 weeks for the IDH mutated AA until 241 weeks. Tailored radiological assessment schedules were suggested for each layered risk groups of the GBM and the AA patients.

Conclusions: The optimal schedule of radiological assessments for each layered risk group of patients with HGG could be determined from the parametric model of PFS.
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http://dx.doi.org/10.1093/neuonc/noaa250DOI Listing
November 2020

Inhibition of MUC1 exerts cell-cycle arrest and telomerase suppression in glioblastoma cells.

Sci Rep 2020 10 26;10(1):18238. Epub 2020 Oct 26.

Department of Neurosurgery, Seoul National University College of Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Korea.

Mucin 1 (MUC1) is a transmembrane glycoprotein involved in tumorigenesis of diverse cancers. However, the role of MUC1 in glioblastoma (GBM) has not yet been fully explored. In this study, the anticancer mechanism of MUC1 suppression in GBM was investigated. The expression level of MUC1 was analyzed in human glioma and paired normal brain tissues. MUC1 was overexpressed in GBM and was negatively associated with overall survival. Moreover, we silenced MUC1 to investigate its effect in GBM cell lines and found that knockdown of MUC1 inhibited cell proliferation and resulted in cell cycle arrest at G1 phase. MUC1 silencing decreased the phosphorylation of RB1 and increased the expression of CDKN1B. Gene set enrichment analysis showed that a series of genes related to cell cycle, telomere maintenance and transforming growth factor Beta (TGF-β) signaling in epithelial mesenchymal transition (EMT) were influenced by MUC1 knockdown. Notably, the reduced TERT expression levels combined with impaired telomerase activity and the switching of telomere maintenance mechanism to alternative lengthening of telomeres (ALT) were observed after MUC1 knockdown. Our results support the role of MUC1 in oncological process in GBM which can be developed as a therapeutic target for cell cycle control and telomere maintenance mechanism.
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http://dx.doi.org/10.1038/s41598-020-75457-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589558PMC
October 2020

A Nationwide, Population-Based Epidemiology Study of Primary Central Nervous System Tumors in Korea, 2007-2016: A Comparison with United States Data.

Cancer Res Treat 2020 Oct 7. Epub 2020 Oct 7.

Division of Cancer Registration and Surveillance, National cancer center, Goyang, Korea.

Purpose: The purpose of this study was to determine the epidemiologic characteristics and survival of patients with primary brain and other central nervous system (CNS) tumors in Korea and to compare our findings with those from the United States.

Materials And Methods: We collected data on primary brain and CNS tumors diagnosed between 2007 and 2016 from the Korea Central Cancer Registry. The age-standardized incidence rates (ASRs) and 5-year relative survival rates (RSRs) were evaluated. We applied the classification and definitions of the Central Brain Tumor Registry of the United States to our analysis for direct comparison with United States data.

Results: A total of 115,050 primary brain and CNS tumors were identified, and the ASR of all tumors was 22.01 per 100,000 individuals, which was lower than the 23.41 in the United States. However, the ASR of malignant tumors was significantly lower herein (4.27) than in the United States (7.08). Meningeal tumors were the most common histologic group among all tumors (ASR, 8.32). The 5-year RSR of all primary brain and other CNS tumors was 86.4%, and that of all malignant tumors was 44.1%, which was higher than the 35.8% observed in the United States. Among malignant tumors, glioblastomas had the lowest 5-year RSR (12.1%).

Conclusion: In Korea, malignant brain and other CNS tumors have a lower incidence and better survival outcome.
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http://dx.doi.org/10.4143/crt.2020.847DOI Listing
October 2020

H3 G34-mutant high-grade glioma.

Brain Tumor Pathol 2021 Jan 29;38(1):4-13. Epub 2020 Sep 29.

Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.

H3F3A G34 (H3.3 G34)-mutant high-grade gliomas (HGG) are rare, and newly recognized infiltrating gliomas of the cerebral hemisphere. Here, we report the clinicopathological and molecular characteristics of four H3.3 G34-mutant gliomas in terms of its biological behavior compared to those of glioblastomas (GBMs) and H3 K27M-mutant diffuse midline gliomas (DMGs) of our hospital. The median age of the four patients with H3.3 G34 HGG was 44.5 years (14-66 years). Three patients had tumors in the cerebral hemisphere, whereas one patient had synchronous double tumors in the cerebral hemisphere and posterior fossa. All these tumors were high-grade glioma, but neither microvascular proliferation nor necrosis. They displayed uniform genetic and epigenetic signatures; ATRX-mutant, MGMT promoter-methylated, Olig2-negative, but IDH- and TERT promoter-wildtype. The median survival rate of H3.3 G34-mutant HGGs, IDH-was 23.5 months. In conclusion, H3.3 G34-mutant gliomas were unique HGGs with uniform genetic and epigenetic abnormalities, which suggested a single phylogenic origin. The median survival of H3.3 G34-mutant HGGs was better than those of IDH-wildtype GBMs and H3 K27M-mutant DMGs, but worse than that of IDH-mutant GBM. The tumor-infiltrating area and resectability may be the crucial parameters for the prognosis of the patients.
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http://dx.doi.org/10.1007/s10014-020-00378-8DOI Listing
January 2021

Comparison of Genetic Profiles and Prognosis of High-Grade Gliomas Using Quantitative and Qualitative MRI Features: A Focus on G3 Gliomas.

Korean J Radiol 2021 02 10;22(2):233-242. Epub 2020 Sep 10.

Department of Neurology, Seoul National University College of Medicine, Seoul, Korea.

Objective: To evaluate the association of MRI features with the major genomic profiles and prognosis of World Health Organization grade III (G3) gliomas compared with those of glioblastomas (GBMs).

Materials And Methods: We enrolled 76 G3 glioma and 155 GBM patients with pathologically confirmed disease who had pretreatment brain MRI and major genetic information of tumors. Qualitative and quantitative imaging features, including volumetrics and histogram parameters, such as normalized cerebral blood volume (nCBV), cerebral blood flow (nCBF), and apparent diffusion coefficient (nADC) were evaluated. The G3 gliomas were divided into three groups for the analysis: with this isocitrate dehydrogenase ()-mutation, mutation and a -codeleted (IDHmut1p/19qdel), mutation, -nondeleted (IDHmut1p/19qnondel), and wildtype (IDHwt). A prediction model for the genetic profiles of G3 gliomas was developed and validated on a separate cohort. Both the quantitative and qualitative imaging parameters and progression-free survival (PFS) of G3 gliomas were compared and survival analysis was performed. Moreover, the imaging parameters and PFS between IDHwt G3 gliomas and GBMs were compared.

Results: IDHmut G3 gliomas showed a larger volume ( = 0.017), lower nCBF ( = 0.048), and higher nADC ( = 0.007) than IDHwt. Between the IDHmut tumors, IDHmut1p/19qdel G3 gliomas had higher nCBV ( = 0.024) and lower nADC ( = 0.002) than IDHmut1p/19qnondel G3 gliomas. Moreover, IDHmut1p/19qdel tumors had the best prognosis and IDHwt tumors had the worst prognosis among G3 gliomas ( < 0.001). PFS was significantly associated with the 95th percentile values of nCBV and nCBF in G3 gliomas. There was no significant difference in neither PFS nor imaging features between IDHwt G3 gliomas and IDHwt GBMs.

Conclusion: We found significant differences in MRI features, including volumetrics, CBV, and ADC, in G3 gliomas, according to mutation and codeletion status, which can be utilized for the prediction of genomic profiles and the prognosis of G3 glioma patients. The MRI signatures and prognosis of IDHwt G3 gliomas tend to follow those of IDHwt GBMs.
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http://dx.doi.org/10.3348/kjr.2020.0011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817637PMC
February 2021

Intracranial Metaplastic Meningioma : Clinical and Radiological Characteristics of 11 Cases.

J Korean Neurosurg Soc 2020 Sep 1;63(5):657-663. Epub 2020 Sep 1.

Department of Pathology, Seoul National University Hospital, Seoul, Korea.

Objective: Metaplastic meningioma is an extremely rare subtype of World Health Organization (WHO) grade I meningioma. It has distinctive histological subtypes according to its own mesenchymal components. Owing to its scarcity, clinical or radiological features of a metaplastic meningioma are poorly described.

Methods: Between 2004 and 2018, we analyzed total 1814 cases surgically proven meningioma for 15 years. Among them, metaplastic meningioma was diagnosed in 11 cases. Magnetic resonance images were taken for all patients, and computed tomography scan was taken for 10 patients.

Results: WHO grade I meningiomas were 1376 cases (75.9%), 354 cases (19.5%) in WHO grade II, and 84 cases (4.6%) in WHO grade III meningiomas. Metaplastic meningioma was 11 cases as 0.8% of WHO grade I meningioma and 0.6% of entire meningiomas for 15 years. Among the entire 11 metaplastic meningiomas, five tumors (45%) were diagnosed as a lipomatous subtype with rich fat components, four (36%) as an osseous subtype with extensive bone formation and two (18%) as a xanthomatous subtype. There was no cartilaginous subtype metaplastic meningioma in our study. Lipomatous and osseous metaplastic meningioma have peculiar radiological characteristics according to mesenchymal components.

Conclusion: We investigated a rare metaplastic meningioma subtype based on our 15-year surgical experience with meningiomas. Further investigation will be necessary for the clear clarification of tumor nature of this rare tumor.
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http://dx.doi.org/10.3340/jkns.2020.0151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7477148PMC
September 2020

Penta-fluorophenol: a Smiles rearrangement-inspired cysteine-selective fluorescent probe for imaging of human glioblastoma.

Chem Sci 2020 Jun 11;11(22):5658-5668. Epub 2020 May 11.

Department of Biomedical Science , Graduate School , Kyung Hee University , Seoul 02447 , Korea . Email:

Two of the most critical factors for the survival of glioblastoma (GBM) patients are precision diagnosis and the tracking of treatment progress. At the moment, various sophisticated and specific diagnostic procedures are being used, but there are relatively few simple diagnosis methods. This work introduces a sensing probe based on a turn-on type fluorescence response that can measure the cysteine (Cys) level, which is recognized as a new biomarker of GBM, in human-derived cells and within on-site human clinical biopsy samples. The Cys-initiated chemical reactions of the probe cause a significant fluorescence response with high selectivity, high sensitivity, a fast response time, and a two-photon excitable excitation pathway, which allows the imaging of GBM in both mouse models and human tissue samples. The probe can distinguish the GBM cells and disease sites in clinical samples from individual patients. Besides, the probe has no short or long-term toxicity and immune response. The present findings hold promise for application of the probe to a relatively simple and straightforward following of GBM at clinical sites.
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http://dx.doi.org/10.1039/d0sc01085eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449700PMC
June 2020

A glioneuronal tumor with fusion.

NPJ Genom Med 2020 3;5:24. Epub 2020 Jun 3.

Department of Pathology, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, 03080 Korea.

We report a case of glioneuronal tumor (GNT) with a discovery of novel gene fusion of resulting from aberrant chromosome 7 abnormalities. We executed an elaborate genomic study on this case including whole-exome sequencing and RNA sequencing. Genomic analysis of the tumor revealed aberrations in chromosomes 1 and 7 and a fusion. Further analysis of the upregulated genes revealed substantial connections with MAPK pathway activation. We concluded that the chromosome 7 abnormalities prompted gene fusion which successively leads to MAPK pathway activation. We deliberated that MAPK pathway activation is one of the driver pathways responsible for the oncogenesis of GNT.
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http://dx.doi.org/10.1038/s41525-020-0131-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270112PMC
June 2020

Postoperative radiotherapy for WHO grade II-III intracranial ependymoma in adults: An intergroup collaborative study (KROG 18-06/KNOG 18-01).

Radiother Oncol 2020 09 2;150:4-11. Epub 2020 Jun 2.

Department of Radiation Oncology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea. Electronic address:

Background And Purpose: To evaluate the impact of adjuvant postoperative radiotherapy (PORT) in adult WHO grade II-III intracranial ependymoma (IEPN).

Materials And 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.
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http://dx.doi.org/10.1016/j.radonc.2020.05.045DOI Listing
September 2020

Correction to: Chemoradiation in elderly patients with glioblastoma from the multi‑institutional GBM‑molRPA cohort: is short‑course radiotherapy enough or is it a matter of selection?

J Neurooncol 2020 05;148(1):67

Department of Radiation Oncology, St. Vincent's Hospital, The Catholic University of Korea School of Medicine, Suwon, 16247, South Korea.

The name of author Do Hoon Lim was incorrect in the initial online publication. The original article has been corrected.
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http://dx.doi.org/10.1007/s11060-020-03532-6DOI Listing
May 2020

A National Consensus Survey for Current Practice in Brain Tumor Management III: Brain Metastasis and Primary Central Nervous System Lymphoma.

Brain Tumor Res Treat 2020 Apr;8(1):20-28

Department of Cancer Control, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.

Background: The Guideline Working Group of the Korean Society for Neuro-Oncology (KSNO) conducted the nationwide questionnaire survey for diverse queries facing to treat patients with brain tumor. As part III of the survey, the aim of this study is to evaluate the national patterns of clinical practice for patients with brain metastasis and primary central nervous system lymphoma (PCNSL).

Methods: A web-based survey was sent to all members of the KSNO by email. The survey included 7 questions of brain metastasis and 5 questions of PCNSL, focused on the management strategies in specific situations. All questions were developed by consensus of the Guideline Working Group.

Results: In the survey about brain metastasis, respondents preferred surgical resection with adjuvant treatment for patients with a surgically accessible single brain metastatic lesion less than 3 cm in size without extracranial systemic lesions. However, most respondents considered radiosurgery for surgically inaccessible lesions. As the preferred treatment of multiple brain metastases according to the number of brain lesions, respondents tended to choose radiotherapy with increasing number of lesions. Radiosurgery was mostly chosen for the brain metastases of less than or equal to 4. In the survey about PCNSL, a half of respondents choose high-dose methotrexate-based polychemotherapy as the first-line induction therapy for PCNSL. The consolidation and salvage therapy showed a little variation among respondents. For PCNSL patients with cerebrospinal fluid dissemination, intrathecal chemotherapy was most preferred.

Conclusion: The survey demonstrates the prevailing clinical practice patterns for patients with brain metastasis and PCNSL among members of the KSNO. This information provides a point of reference for establishing a practical guideline in the management of brain metastasis and PCNSL.
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http://dx.doi.org/10.14791/btrt.2020.8.e7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221464PMC
April 2020

A National Consensus Survey for Current Practice in Brain Tumor Management II: Diffuse Midline Glioma and Meningioma.

Brain Tumor Res Treat 2020 04;8(1):11-19

Department of Cancer Control, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.

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 II of the survey, the aim of this study is to evaluate the national patterns of clinical practice for patients with diffuse midline glioma and meningioma.

Methods: A web-based survey was sent to all members of the KSNO by email. The survey included 4 questions of diffuse midline glioma and 6 questions of meningioma (including 2 case scenarios). All questions were developed by consensus of the Guideline Working Group.

Results: In the survey about diffuse midline glioma, 76% respondents performed histologic confirmation to identify H3K27M mutation on immunohistochemical staining or sequencing methods. For treatment of diffuse midline glioma, respondents preferred concurrent chemoradiotherapy with temozolomide (TMZ) and adjuvant TMZ (63.8%) than radiotherapy alone (34.0%). In the survey about meningioma, respondents prefer wait-and-see policy for the asymptomatic small meningioma without peritumoral edema. However, a greater number of respondents had chosen surgical resection as the first choice for all large size meningiomas without exception, and small size meningiomas with either peritumoral edema or eloquent location. There was no single opinion with major consensus on long-term follow-up plans for asymptomatic meningioma with observation policy. As many as 68.1% of respondents answered that they would not add any adjuvant therapies for World Health Organization grade II meningiomas if the tumor was totally resected including dura.

Conclusion: The survey demonstrates the prevailing clinical practice patterns for patients with diffuse midline glioma and meningioma among members of the KSNO. This information provides a point of reference for establishing a practical guideline in the management of diffuse midline glioma and meningioma.
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http://dx.doi.org/10.14791/btrt.2020.8.e6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221470PMC
April 2020

A National Consensus Survey for Current Practice in Brain Tumor Management I: Antiepileptic Drug and Steroid Usage.

Brain Tumor Res Treat 2020 Apr;8(1):1-10

Department of Cancer Control, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.

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.
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http://dx.doi.org/10.14791/btrt.2020.8.e5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221462PMC
April 2020

Chemoradiation in elderly patients with glioblastoma from the multi-institutional GBM-molRPA cohort: is short-course radiotherapy enough or is it a matter of selection?

J Neurooncol 2020 May 2;148(1):57-65. Epub 2020 May 2.

Department of Radiation Oncology, St. Vincent's Hospital, The Catholic University of Korea School of Medicine, Suwon, 16247, South Korea.

Background: The optimal radiotherapy regimen in elderly patients with glioblastoma treated by chemoradiation needs to be addressed. We provide the results of a comparison between conventionally fractionated standard radiotherapy (CRT) and short-course radiotherapy (SRT) in those patients treated by temozolomide-based chemoradiation.

Methods: Patients aged 65 years or older from the GBM-molRPA cohort were included. Patients who were planned for a ≥ 6-week or ≤ 4-week radiotherapy were regarded as being treated by CRT or SRT, respectively. The median RT dose in the CRT and SRT group was 60 Gy in 30 fractions and 45 Gy in 15 fractions, respectively.

Results: A total of 260 and 134 patients aged older than 65 and 70 years were identified, respectively. CRT- and SRT-based chemoradiation was applied for 192 (73.8%) and 68 (26.2%) patients, respectively. Compared to SRT, CRT significantly improved MS from 13.2 to 17.6 months and 13.3 to 16.4 months in patients older than 65 years (P < 0.001) and 70 years (P = 0.002), respectively. Statistical significance remained after adjusting for age, performance status, surgical extent, and MGMT promoter methylation in both age groups. The benefit was clear in all subgroup analyses for patients with Karnofsky performance score 70-100, Karnofsky performance score ≤ 60, gross total resection, biopsy, methylated MGMT promoter, and unmethylated MGMT promoter (all P < 0.05).

Conclusion: CRT significantly improved survival compared to SRT in elderly glioblastoma patients treated with chemoradiation in selected patients amenable for chemoradiation. This study is hypothesis-generating and a prospective randomized trial is urgently warranted.
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http://dx.doi.org/10.1007/s11060-020-03468-xDOI Listing
May 2020

Reduced-dose whole-brain radiotherapy with tumor bed boost after upfront high-dose methotrexate for primary central nervous system lymphoma.

Radiat Oncol J 2020 Mar 25;38(1):35-43. Epub 2020 Mar 25.

Department of Radiation Oncology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea.

Purpose: This retrospective study compares higher-dose whole-brain radiotherapy (hdWBRT) with reduced-dose WBRT (rdWBRT) in terms of clinical efficacy and toxicity profile in patients treated for primary central nervous system lymphoma (PCNSL).

Materials And Methods: Radiotherapy followed by high-dose methotrexate (HD-MTX)-based chemotherapy was administered to immunocompetent patients with histologically confirmed PCNSL between 2000 and 2016. Response to chemotherapy was taken into account when prescribing the radiation dose to the whole brain and primary tumor bed. The whole brain dose was ≤23.4 Gy for rdWBRT (n = 20) and >23.4 Gy for hdWBRT (n = 68). Patients manifesting cognitive disturbance, memory impairment and dysarthria were considered to have neurotoxicity. A median follow-up was 3.62 years.

Results: The 3-year overall survival (OS) and progression-free survival (PFS) were 70.0% and 48.9% with rdWBRT, and 63.2% and 43.2% with hdWBRT. The 3-year OS and PFS among patients with partial response (n = 45) after chemotherapy were 77.8% and 53.3% with rdWBRT, and 58.3% and 45.8% with hdWBRT (p > 0.05). Among patients with complete response achieved during follow-up, the 3-year freedom from neurotoxicity (FFNT) rate was 94.1% with rdWBRT and 62.4% with hdWBRT. Among patients aged ≥60 years, the 3-year FFNT rate was 87.5% with rdWBRT and 39.1% with hdWBRT (p = 0.49). Neurotoxicity was not observed after rdWBRT in patients aged below 60 years.

Conclusion: rdWBRT with tumor bed boost combined with upfront HD-MTX is less neurotoxic and results in effective survival as higher-dose radiotherapy even in partial response after chemotherapy.
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http://dx.doi.org/10.3857/roj.2020.00052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113152PMC
March 2020

Prognostication of anaplastic astrocytoma patients: application of contrast leakage information of dynamic susceptibility contrast-enhanced MRI and dynamic contrast-enhanced MRI.

Eur Radiol 2020 Apr 17;30(4):2171-2181. Epub 2020 Jan 17.

Department of Neurology, College of Medicine, Seoul National University, Seoul, South Korea.

Purpose: To examine the applicability of contrast leakage information from dynamic susceptibility contrast-enhanced (DSC) MRI and dynamic contrast-enhanced (DCE) MRI to determine which one is the most valuable surrogate imaging biomarker for predicting disease progression in anaplastic astrocytoma (AA) patients.

Materials And Methods: This study was approved by the institutional review board (IRB), which waived informed consent. A total of seventy-three AA patients who had undergone preoperative DCE and DSC MRI and received standard treatment, including partial resection or biopsy followed by radiation therapy, were included in this retrospective study. Based on Response Assessment in Neuro-Oncology (RANO), patients were sorted into progression (n = 21) and non-progression (n = 52) groups. Tumor boundaries were defined as high-signal intensity (SI) lesions on fluid-attenuated inversion recovery (FLAIR) imaging, where we analyzed mean pharmacokinetic parameters (K, V, and V) from DCE MRI and contrast leakage information (mean extraction fraction (EF)) from DSC MRI.

Results: Mean V and mean EF were significantly higher in patients with progression-free survival (PFS) < 18 months than in those with PFS ≥ 18 months. For distinguishing the group with PFS < 18 months, AUC values were calculated using the mean V value (AUC = 0.716). The Kaplan-Meier survival analysis revealed that mean V value was significantly correlated with PFS. In Cox proportional-hazards regression, only the mean V value was found to be significantly associated with PFS.

Conclusion: We found that the mean V value based on high-SI tumor lesions on FLAIR imaging was capable of predicting outcomes of AA patients as a potential surrogate imaging biomarker.

Key Points: • Mean V(2.152 ± 1.857 vs. 1.173 ± 1.408) was significantly higher in anaplastic astrocytoma patients with PFS < 18 months that in those with PFS ≥ 18 months (p = 0.02). • Cox proportional-hazards regression showed that only mean V(p = 0.034) was significantly associated with PFS, regardless of IDH mutation status, in anaplastic astrocytoma patients.
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http://dx.doi.org/10.1007/s00330-019-06598-7DOI Listing
April 2020

Longitudinal molecular trajectories of diffuse glioma in adults.

Nature 2019 12 20;576(7785):112-120. Epub 2019 Nov 20.

The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.

The evolutionary processes that drive universal therapeutic resistance in adult patients with diffuse glioma remain unclear. Here we analysed temporally separated DNA-sequencing data and matched clinical annotation from 222 adult patients with glioma. By analysing mutations and copy numbers across the three major subtypes of diffuse glioma, we found that driver genes detected at the initial stage of disease were retained at recurrence, whereas there was little evidence of recurrence-specific gene alterations. Treatment with alkylating agents resulted in a hypermutator phenotype at different rates across the glioma subtypes, and hypermutation was not associated with differences in overall survival. Acquired aneuploidy was frequently detected in recurrent gliomas and was characterized by IDH mutation but without co-deletion of chromosome arms 1p/19q, and further converged with acquired alterations in the cell cycle and poor outcomes. The clonal architecture of each tumour remained similar over time, but the presence of subclonal selection was associated with decreased survival. Finally, there were no differences in the levels of immunoediting between initial and recurrent gliomas. Collectively, our results suggest that the strongest selective pressures occur during early glioma development and that current therapies shape this evolution in a largely stochastic manner.
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http://dx.doi.org/10.1038/s41586-019-1775-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6897368PMC
December 2019

Flexible, sticky, and biodegradable wireless device for drug delivery to brain tumors.

Nat Commun 2019 11 15;10(1):5205. Epub 2019 Nov 15.

Center for Nanoparticle Research, Institute for Basic Science (IBS), Seoul, 08826, Republic of Korea.

Implantation of biodegradable wafers near the brain surgery site to deliver anti-cancer agents which target residual tumor cells by bypassing the blood-brain barrier has been a promising method for brain tumor treatment. However, further improvement in the prognosis is still necessary. We herein present novel materials and device technologies for drug delivery to brain tumors, i.e., a flexible, sticky, and biodegradable drug-loaded patch integrated with wireless electronics for controlled intracranial drug delivery through mild-thermic actuation. The flexible and bifacially-designed sticky/hydrophobic device allows conformal adhesion on the brain surgery site and provides spatially-controlled and temporarily-extended drug delivery to brain tumors while minimizing unintended drug leakage to the cerebrospinal fluid. Biodegradation of the entire device minimizes potential neurological side-effects. Application of the device to the mouse model confirms tumor volume suppression and improved survival rate. Demonstration in a large animal model (canine model) exhibited its potential for human application.
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http://dx.doi.org/10.1038/s41467-019-13198-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858362PMC
November 2019