• Radiation Oncology Journal
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• v.37 no.1
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• pp.1-12
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• 2019

Despite recent innovation in treatment techniques and subsequently improved outcomes, the majority of glioblastoma (GBL) have relapses, especially in locoregional areas. Local re-irradiation (re-RT) has been established as a feasible option for recurrent GBL of all ages with safety, tolerability, and effectiveness both in survival and quality of life regardless of fractionation schedule. To keep adverse effects under acceptable range, cumulative dose limit in equivalent dose at 2 Gy fractions by the linear-quadratic model at α/β = 2 for normal brain tissue (EQD2) with narrow margin should be observed and single/hypofractionated re-RT should be undertaken very carefully to recurrent tumor with large volume or adjacent to the brainstem. Promising outcome of re-operation (re-Op) plus re-RT (re-Op/RT) need to be validated and result from re-RT with temozolomide/bevacizumab (TMZ/BV) or new strategy is expected. Development of new-concept prognostic scoring or risk group is required to select patients properly and make use of predictive biomarkers such as O(6)-methylguanine-DNA methyltransferase (MGMT) promotor methylation that influence outcomes of re-RT, re-Op/RT, or re-RT with TMZ/BV.

• Journal of Korean Neurosurgical Society
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• v.51 no.2
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• pp.98-101
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• 2012

We report a patient who underwent gamma knife radiosurgery to treat recurrent meningioma after microsurgery and thereafter developed secondary malignancy adjacent to the original tumor. A 47-year-old woman had underwent resection of the olfactory groove meningioma. Then radiosurgery was done three times over 4 year period for the recurrent tumor. After 58 months from the initial radiosurgery, she presented with headache and progressive mental dullness. Huge tumor in bifrontal location was revealed in MRI. Subsequent operation and pathological examination confirmed diagnosis of glioblastoma. This case fits the criteria of radiation-induced tumor and the clinical implication of the issue is discussed.

• Journal of Korean Neurosurgical Society
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• v.58 no.5
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• pp.426-431
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• 2015

Objective : The purpose of this study was to evaluate the clinical efficacy of continuous low-dose temozolomide (TMZ) chemotherapy for recurrent and TMZ-refractory glioblastoma multiforme (GBM) and to study the relationship between its efficacy and microvessel density within the tumor. Methods : Thirty patients who had recurrent GBM following Stupp's regimen received TMZ daily at $50mg/m^2/day$ until tumor progression between 2007 and 2013. The median duration of continuous low-dose TMZ administration was 8 weeks (range, 2-64). Results : The median progression-free survival (PFS) of continuous low-dose TMZ therapy was 2 months (range, 0.5-16). At 6 months, PFS was 20%. The median overall survival (OS) from the start of this therapy to death was 6 months (95% CI : 5.1-6.9). Microvessel density of recurrent tumor tissues obtained by reoperation of 17 patients was $22.7{\pm}24.1/mm^2$ (mean${\pm}$standard deviation), and this was lower than that of the initial tumor ($61.4{\pm}32.7/mm^2$) (p-value=0.001). It suggests that standard TMZ-chemoradiotherapy reduces the microvessel density within GBM and that recurrences develop in tumor cells with low metabolic burden. The efficacy of continuous low-dose TMZ could not be expected in recurrent GBM cells in poor angiogenic environments. Conclusion : The efficacy of continuous low-dose TMZ chemotherapy is marginal. This study suggests the need to develop further treatment strategies for recurrent and TMZ-refractory GBM.

• Journal of Korean Neurosurgical Society
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• v.50 no.2
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• pp.119-122
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• 2011

We report a case of 70-year-old man with glioblastoma presenting as acute encephalitic illness. The patient exhibited sudden onset of cognitive impairment and headache for 2 days. Initial brain MRI showed left temporal lobe hyperintensity, and cerebrospinal fluid cytology revealed a mild pleocytosis. The patient had initially improved after medical treatment with a presumptive diagnosis of herpes simplex encephalitis (HSE). After 8 months, the patient complained of recurrent seizures. A follow-up brain MRI revealed marked increases in size and surrounding perilesional edema in the left temporal lesion on T2-weighted images and a new contrast-enhancing lesion on gadolinium-enhanced T1-weighted images. Stereotactic brain biopsy revealed a glioblastoma. The atypical encephalitic presentation of glioblastoma should be considered if definitive evidence for the diagnosis of HSE cannot be obtained.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.9
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• pp.4205-4208
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• 2016

Background: The aim of this study was to analyse the expression of EGFR in newly diagnosed and recurrent glioblastoma multiforme (GBM). Materials and Methods: Our study included a total of 48 paired samples collected from 24 patients diagnosed with GBM. The intensity of EGFR cytoplasmatic staining was scored on a scale of 1-3+ (weak, intermediate or strong). Results: We found EGFR overexpression in 23 patients (96%) with newly diagnosed GBM, while all recurrent tumours overexpressed EGFR. Ten recurrent tumours (42%) had a lower expression than their new counterpart 13 tumours (54%) had a similar expression, and only one case (2%) had increased expression on recurrence. The expression of EGFR in newly diagnosed GBM was significantly correlated with EGFR expression in recurrent tumour (p = 0.036). In addition, new GBMs with strong EGFR expression had a mean relapse-free interval of 11.5 months (p=0.017). A benefit of combined therapy was observed in the radiotherapy-plus-chemotherapy group where the average time was 11 months (p=0.011), as compared with surgery/radiotherapy alone (average time 6.8 months). Conclusions: The present data show that EGFR is overexpressed in paired GBMs. The discrepancies of EGFR expression between the primary tumour and the recurrence suggest heterogeneity of GBMs but also unity at relapse.

• Radiation Oncology Journal
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• v.20 no.3
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• pp.199-205
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• 2002

Purpose : This study was peformed to determine the optimal radiation therapy field for the treatment of malignant astrocytoma and glioblastoma multiforme. Materials and Methods : From Jan. 1994 to Mar. 2000, 21 patients with malignant astrocytoma and glioblastoma multiforme, confirmed as recurrent by follow up MRI after surgery and radiation therapy, were analyzed. The distance from the margin of the primary lesion to the recurrent lesion was measured. The following factors were analyzed to Investigate the influence of these factors to recurrence pattern; tumor size, degree of edema, surgical extent, gamma knife radiosurgery and multiple lesions. Results : Among the 21 patients, 18 $(86\%)$ were recurred within 2 cm from the primary lesion site. 12 within 1 cm, 6 between 1 and 2 cm. The other 3 patients all with multiple lesions, were recurred at 3, 4, 5 cm, from the primary lesion site. The recurrence pattern was not influenced by the factors of tumor size, extent of edema, surgical extent, or gamma knife radiosurgery. However, patients with multiple lesions showed a tendency of recurrence at sites further from the primary lesion. Conclusions : Most $(86\%)$ of the recurrences of malignant astrocytoma and glioblastoma multiforme occurred within 2 cm from the primary lesion site. The width of treatment field does not need to be changed according to tumor size, degree of edema, surgical extent, or gamma knife radiosurgery. However, the treatment field for multiple lesions appears to be wider than that for a single lesion.

• Journal of Korean Neurosurgical Society
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• v.63 no.6
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• pp.681-688
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• 2020

Glioblastoma (GBM) is one of the most common tumors of the central nervous system, which is the most lethal brain cancer. GBM treatment is based primarily on surgical resection, combined with radiotherapy and chemotherapy. Despite the positive treatment, progression free survival and overall survival were not significantly prolonged because GBM almost always recurs. We are always looking forward to some new and effective treatments. In recent years, a novel treatment method called tumor treating fields (TTFields) for cancer treatment has been proposed. TTFields devices were approved by the Food and Drug Administration (FDA) for adjuvant treatment of recurrent and newly diagnosed GBMs in 2011 and 2015, respectively. This became the first breakthrough treatment for GBM in the past 10 years after the FDA approved bevacizumab for patients with relapsed GBM in 2009. This paper summarized the research results of TTFields in recent years and elaborated the mechanism of action of TTFields on GBM, including cell and animal experimental research, clinical application and social benefits.

• Journal of Korean Neurosurgical Society
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• v.55 no.1
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• pp.54-56
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• 2014

Intracranial tumors secondary to radiotherapy are rare. In this group gliomas are the rarest. Only 6 cases of glioblastoma multiforme (GBM) have been reported in patients undergoing radiotherapy (RT) for craniopharyngiomas of which only 4 have been in children less than 18 years of age. In recent years RT has become a mainstay of adjuvant therapy for recurrent or partially excised craniopharyngiomas. We report a child of 12 years who had previously undergone RT for a suprasellar craniopharyngioma and presented 10 years later with a GBM. This is the 5th pediatric case in literature demonstrating a GBM after RT for a craniopharyngioma. The implications of subjecting the pediatric population to RT for a benign lesion versus the outcome of gross total removal and management of RT induced tumors is discussed and the need to avail of safer alternatives such as stereotactic radiosurgery is stressed.

• Korean Journal of Radiology
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• v.21 no.4
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• pp.471-482
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• 2020

Objective: We aimed to determine the optimized image-based surrogate endpoints (IBSEs) in targeted therapies for glioblastoma through a systematic review and meta-analysis of phase III randomized controlled trials (RCTs). Materials and Methods: A systematic search of OVID-MEDLINE and EMBASE for phase III RCTs on glioblastoma was performed in December 2017. Data on overall survival (OS) and IBSEs, including progression-free survival (PFS), 6-month PFS (6moPFS), 12-month PFS (12moPFS), median PFS, and objective response rate (ORR) were extracted. Weighted linear regression analysis for the hazard ratio for OS and the hazard ratios or odds ratios for IBSEs was performed. The associations between IBSEs and OS were evaluated. Subgroup analyses according to disease stage (newly diagnosed glioblastoma versus recurrent glioblastoma), types of test treatment, and types of response assessment criteria were performed. Results: Twenty-three phase III RCTs published between 2000 and 2017, including 8387 patients, met the inclusion criteria. OS showed strong correlations with PFS (standardized β coefficient [R] = 0.719), 6moPFS (R = 0.647), and 12moPFS (R = 0.638). OS showed no correlations with median PFS and ORR. In subgroup analysis according to types of therapies, PFS showed the highest correlations with OS in targeted therapies for cell cycle pathways (R = 0.913) and growth factor receptors and their downstream pathways (R = 0.962). 12moPFS showed the highest correlation with OS in antiangiogenic therapy (R = 0.821). The response assessment in neuro-oncology criteria provided higher correlation coefficients between OS and IBSEs than the Macdonald criteria. Conclusion: Overall, PFS is an optimized IBSE in targeted therapies for glioblastoma; however, 12moPFS is optimal in antiangiogenic therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.10
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• pp.4609-4614
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• 2016

Purpose: To evaluate the therapeutic effects of copper reduction on angiogenesis-related factors in patients with glioblastoma multiforme treated by gamma knife radiosurgery. Materials and Methods: In the present block randomized, placebo-controlled trial, fifty eligible patients with a diagnosis of glioblastoma multiforme who were candidates for gamma knife radiosurgery were randomly assigned into two groups to receive daily either 1gr penicillamine and a low copper diet or placebo for three months. The intervention started on the same day as gamma knife radiosurgery. Serum interleukin-6 (IL-6), tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), vascular endothelial growth factor (VEGF) and copper levels were measured at baseline and after the intervention. The serum copper level was used as the final index of compliance with the diet. In order to control probable side effects of intervention, laboratory tests were conducted at the beginning, middle and end of the study. Results: The patients had a mean age and Karnofsky Performance Scale of 43.7 years and 75 respectively. Mean serum copper levels were significantly reduced in intervention group. Mean survival time was 18.5 months in intervention group vs. 14.9 in placebo group. VEGF and IL-6 levels in the intervention group were also significantly reduced compared to the placebo group and $TNF-{\alpha}$ increased less. Conclusions: It seems that reducing the level of copper in the diet and dosing with penicillamine leads to decline of angiogenesis-related factors such as VEGF, IL-6 and $TNF-{\alpha}$. Approaches targeting angiogenesis may improve survival and can be used as a future therapeutic strategy.