OBJECTIVE: To establish a mouse model bearing orthotopic temozolomide (TMZ)-resistant glioma that mimics the development of drug resistance in gliomas METHODS: Seventy-eight adult C57BL/6 mice were randomly divided into 6 groups ( RESULTS: The mouse models bearing TMZresistant glioma was successfully established. The cells from the high-dose induced group showed a significantly higher colony-forming rate than those from the high-dose control group ( CONCLUSIONS Progressive increase of TMZ doses in mice bearing orthotopic gliomas can effectively induce TMZ resistance of the gliomas.
Animals ; Antineoplastic Agents, Alkylating/pharmacology* ; Brain Neoplasms/drug therapy* ; Cell Line, Tumor ; Disease Models, Animal ; Drug Resistance, Neoplasm ; Glioma/drug therapy* ; Mice ; Mice, Inbred C57BL ; Temozolomide/therapeutic use*

Glioma is the most common lethal tumor of the human brain. The median survival of patients with primary World Health Organization grade IV glioma is only 14.6 months. The World Health Organization classification of tumors of the central nervous system categorized gliomas into lower-grade gliomas and glioblastomas. Unlike primary glioblastoma that usually develop de novo in the elderly, secondary glioblastoma enriched with an isocitrate dehydrogenase mutant typically progresses from lower-grade glioma within 5-10 years from the time of diagnosis. Based on various evolutional trajectories brought on by clonal and subclonal alterations, the evolution patterns of glioma vary according to different theories. Some important features distinguish the normal brain from other tissues, e.g., the composition of the microenvironment around the tumor cells, the presence of the blood-brain barrier, and others. The underlying mechanism of glioma recurrence and evolution patterns of glioma are different from those of other types of cancer. Several studies correlated tumor recurrence with tumor heterogeneity and the immune microenvironment. However, the detailed reasons for the progression and recurrence of glioma remain controversial. In this review, we introduce the different mechanisms involved in glioma progression, including tumor heterogeneity, the tumor microenvironment and drug resistance, and their pre-clinical implements in clinical trials. This review aimed to provide new insights into further clinical strategies for the treatment of patients with recurrent and secondary glioma.
Aged ; Brain Neoplasms/genetics* ; Drug Resistance ; Glioblastoma ; Glioma/genetics* ; Humans ; Mutation ; Neoplasm Recurrence, Local/drug therapy* ; Tumor Microenvironment

Treating adult low-grade gliomas (LGGs) is particularly challenging due to the highly infiltrative nature of this type of brain cancer. Although surgery, radiotherapy, and chemotherapy are the mainstay treatment modalities for LGGs, the optimal combination management plan for a particular patient based on individual symptoms and the risk of treatment-induced toxicity remains unclear. This review highlights the competency and limitations of standard treatment options while providing an essential therapeutic update regarding current clinical trials aimed at implementing targeted therapies with morbidity rates lower than those for current LGG treatments and also augmenting the killing of cancerous cells while maintaining an improved quality of life.
Adult* ; Brain Neoplasms ; Drug Therapy ; Glioma* ; Homicide ; Humans ; Quality of Life ; Radiotherapy

Glioma is the most common brain tumor with a dismal prognosis. While temozolomide (TMZ) based chemotherapy significantly improves survival in glioma patients, resistance against this compound commonly leads to glioma treatment failure. Overexpression of long-noncoding RNA (LncRNA) FoxD2 adjacent opposite strand RNA 1 (FoxD2-AS1) was identified to promote glioma development, but the role in TMZ resistance remains unclear. In this paper, we found that FoxD2-AS1 was overexpressed in recurrent glioma, high FoxD2-AS1 expression was significantly correlated with poor patient outcome. Methylation of O⁶-methylguanine-DNA methyltransferase (MGMT) is significantly less frequent in high FoxD2-AS1 expression patients. Knockdown of FoxD2-AS1 decreased the proliferation, metastatic ability of glioma cells and promote the sensitivity to TMZ in glioma cells. Furthermore, knockdown of FoxD2-AS1 induced hypermethylation of the promoter region of MGMT. Our data suggested that FoxD2-AS1 is a clinical relevance LncRNA and mediates TMZ resistance by regulating the methylation status of the MGMT promoter region.
Brain Neoplasms ; Drug Resistance ; Drug Therapy ; Glioma ; Humans ; Methylation ; Prognosis ; Promoter Regions, Genetic ; RNA ; RNA, Long Noncoding ; Treatment Failure

Bilateral thalamic gliomas (BTGs) are rare brain tumors. In general, the prognosis is poor because of the involvement of bilateral thalami and limitations of surgical excision. Consequently, patients with symptoms of personality changes and memory impairment must be differentiated from others. Magnetic resonance imaging (MRI) is essential for the diagnosis of BTGs and reveals a hypo-intense lesion on T1-weighted images and a hyper-intense lesion on T2 images. We report a case of a 17-year-old female patient suffering from progressive cognitive dysfunction and personality changes and subsequent rehabilitation treatment. Brain MRI showed an enlarged bilateral thalamus, with hyperintensity on T2-weighted images and iso-intensity on T1-weighted images. A biopsy was performed, and the pathology revealed a high-grade glioma. The patient was referred for radiotherapy and chemotherapy. She also underwent rehabilitation treatment for 5 weeks and showed improvement in standing balance, endurance, and speech fluency. The patient's Modified Barthel Index scores also improved. Cancer rehabilitation is important in brain tumor patients because they have a higher incidence of neurological sequelae than others. Rehabilitation of patients with a malignant brain tumor is also important for improving health-related quality of life by maintaining the general condition and preventing complications during and after cancer treatment.
Adolescent ; Biopsy ; Brain ; Brain Neoplasms ; Diagnosis ; Drug Therapy ; Female ; Glioma ; Humans ; Incidence ; Magnetic Resonance Imaging ; Memory ; Memory Disorders ; Neurobehavioral Manifestations ; Pathology ; Prognosis ; Quality of Life ; Radiotherapy ; Rehabilitation ; Thalamus

BACKGROUND: Pilocytic astrocytoma (PA) is a brain tumor that is relatively more common in children and young adults. METHODS: We retrospectively reviewed the medical records of patients with PA treated at a single center between 1988 and 2018. RESULTS: We included 31 subjects with PA. The median age at diagnosis was 13.4 years, and the median follow-up duration was 9.9 years. The total PA group had a 10-year disease-specific survival (DSS) rate of 92.6% [95% confidence interval (CI), 82.6–100] and 10-year progression-free survival (PFS) rate of 52.8% (95% CI, 32.0–73.6). In patients aged <20 years, tumors were more likely to be located in sites in which gross total tumor resection (GTR) was impossible. No statistically significant difference in 10-year DSS was found between the GTR (100%) and non-GTR (89.7%; 95% CI, 76.2–100; p=0.374) groups. However, a statistically significant difference in 10-year PFS was found between the GTR (100%) and non-GTR groups (30.7%; 95% CI, 8.6–52.8; p=0.012). In the non-GTR group, no statistically significant difference in 10-year DSS was found between the patients who received immediate additional chemotherapy and/or radiotherapy (Add-Tx group, 92.9%; 95% CI, 79.4–100) and the non-Add-Tx group (83.3%; 95% CI, 53.5–100; p=0.577). No statistically significant difference in 10-year PFS was found between the Add-Tx group (28.9%; 95% CI, 1.7–56.1) and non-Add-Tx group (33.3%; 95% CI, 0–70.9; p=0.706). CONCLUSION: The PFS of the patients with PA in our study depended only on the degree of surgical excision associated with tumor location. This study is limited by its small number of patients and retrospective nature. A multicenter and prospective study is necessary to confirm these findings.
Adolescent ; Astrocytoma ; Brain Neoplasms ; Child ; Diagnosis ; Disease-Free Survival ; Drug Therapy ; Follow-Up Studies ; Glioma ; Humans ; Medical Records ; Prognosis ; Prospective Studies ; Radiotherapy ; Retrospective Studies ; Survivors ; Young Adult

BACKGROUND: There was no practical guideline for the management of patients with central nervous system tumor in Korea for many years. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has developed the guideline for glioblastoma. Subsequently, the KSNO guideline for World Health Organization (WHO) grade II cerebral glioma in adults is established. METHODS: The Working Group was composed of 35 multidisciplinary medical experts in Korea. References were identified by searching PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL databases using specific and sensitive keywords as well as combinations of keywords regarding diffuse astrocytoma and oligodendroglioma of brain in adults. RESULTS: Whenever radiological feature suggests lower grade glioma, the maximal safe resection if feasible is recommended globally. After molecular and histological examinations, patients with diffuse astrocytoma, isocitrate dehydrogenase (IDH)-wildtype without molecular feature of glioblastoma should be primarily treated by standard brain radiotherapy and adjuvant temozolomide chemotherapy (Level III) while those with molecular feature of glioblastoma should be treated following the protocol for glioblastomas. In terms of patients with diffuse astrocytoma, IDH-mutant and oligodendroglioma (IDH-mutant and 1p19q codeletion), standard brain radiotherapy and adjuvant PCV (procarbazine+lomustine+vincristine) combination chemotherapy should be considered primarily for the high-risk group while observation with regular follow up should be considered for the low-risk group. CONCLUSION: The KSNO's guideline recommends that WHO grade II gliomas should be treated by maximal safe resection, if feasible, followed by radiotherapy and/or chemotherapy according to molecular and histological features of tumors and clinical characteristics of patients.
Adult ; Astrocytoma ; Brain ; Central Nervous System ; Drug Therapy ; Drug Therapy, Combination ; Follow-Up Studies ; Glioblastoma ; Glioma ; Humans ; Isocitrate Dehydrogenase ; Korea ; Oligodendroglioma ; Radiotherapy ; World Health Organization

BACKGROUND: There was no practical guideline for the management of patients with central nervous system tumor in Korea in the past. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, developed the guideline for glioblastoma successfully and published it in Brain Tumor Research and Treatment, the official journal of KSNO, in April 2019. Recently, the KSNO guideline for World Health Organization (WHO) grade III cerebral glioma in adults has been established. METHODS: The Working Group was composed of 35 multidisciplinary medical experts in Korea. References were identified by searches in PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL databases using specific and sensitive keywords as well as combinations of keywords. Scope of the disease was confined to cerebral anaplastic astrocytoma and oligodendroglioma in adults. RESULTS: Whenever radiological feature suggests high grade glioma, maximal safe resection if feasible is globally recommended. After molecular and histological examinations, patients with anaplastic astrocytoma, isocitrate dehydrogenase (IDH)-mutant should be primary treated by standard brain radiotherapy and adjuvant temozolomide chemotherapy whereas those with anaplastic astrocytoma, NOS, and anaplastic astrocytoma, IDH-wildtype should be treated following the protocol for glioblastomas. In terms of anaplastic oligodendroglioma, IDH-mutant and 1p19q-codeletion, and anaplastic oligodendroglioma, NOS should be primary treated by standard brain radiotherapy and neoadjuvant or adjuvant PCV (procarbazine, lomustine, and vincristine) combination chemotherapy. CONCLUSION: The KSNO's guideline recommends that WHO grade III cerebral glioma of adults should be treated by maximal safe resection if feasible, followed by radiotherapy and/or chemotherapy according to molecular and histological features of tumors.
Adult ; Astrocytoma ; Brain ; Brain Neoplasms ; Central Nervous System ; Drug Therapy ; Drug Therapy, Combination ; Glioblastoma ; Glioma ; Humans ; Isocitrate Dehydrogenase ; Korea ; Lomustine ; Oligodendroglioma ; Radiotherapy ; World Health Organization

Choroid plexus tumors are uncommon brain tumors that primarily occur in children. Most of these tumors originate from the intraventricular area, and the most common clinicalpresentation is increased intracranial pressure. Dissemination through the cerebrospinal fluid space is the inevitable natural course of the disease. Here, we present 2 rare cases of adult choroid plexus carcinoma (CPC), each with distinct clinical presentation and progression. The first case was a 40-year-old male who presented with multiple intraventricular masses. After surgical biopsy, radiation and intrathecal chemotherapy failed to elicit any response. The patient progressed with spinal cord dissemination and expired 1 year later. The second case presented with visual disturbance, and brain MRI revealed a large ovoid juxtaventricular mass with peritumoral edema. This 49-year-old female patient underwent craniotomy for what was thought to be a high-grade glioma; however, the mass was connected to the choroid plexus at the operative field. Her pathology specimen was diagnosed as CPC, and adjuvant systemic chemotherapy was administered. She has now been free of recurrence for 10 months. The description of the presentation and progression of these rare adult-onset CPC provides insight for the diagnosis and treatment of other rare instances of choroid plexus tumors.
Adult ; Biopsy ; Brain ; Brain Neoplasms ; Cerebrospinal Fluid ; Child ; Choroid Plexus Neoplasms ; Choroid Plexus ; Choroid ; Craniotomy ; Diagnosis ; Drug Therapy ; Edema ; Female ; Fourth Ventricle ; Glioma ; Humans ; Intracranial Pressure ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Pathology ; Recurrence ; Spinal Cord

BACKGROUND: While procarbazine, CCNU (lomustine), and vincristine (PCV) has been an alternative chemotherapy option for malignant gliomas, it is worth investigating whether the combination of only procarbazine and CCNU is comparable because vincristine adds toxicity with uncertain benefit. The purpose of this study was to evaluate the feasibility of procarbazine and CCNU chemotherapy for recurrent glioblastoma multiforme (GBM) with O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation. METHODS: Eight patients with recurrent GBM following concurrent chemoradiotherapy and temozolomide (TMZ) adjuvant therapy were enrolled in this trial; they received no other chemotherapeutic agents or target therapy. They received CCNU (75 mg/m²) on day 1 and procarbazine (60 mg/m²) through days 11 and 24 every 4 weeks. The median cycle of CCNU and procarbazine was 3.5 (range: 2–6). RESULTS: One patient achieved stable disease. The median progression-free survival (PFS) with procarbazine and CCNU chemotherapy was eight weeks (range: 5–73), and the PFS rates were 25% and 12.5% at 16 and 30 weeks, respectively. The median overall survival (OS) from the initial diagnosis to death was 40 months, and the median OS from the administration of procarbazine and CCNU chemotherapy to death was 9.7 months (95% confidence interval: 6.7–12.7). Serious adverse events were found at six visits, and two cases were considered to be grade 3 toxicities. CONCLUSION: The efficacy of procarbazine and CCNU chemotherapy is not satisfactory. This study suggests the need to develop other treatment strategies for recurrent and TMZ-refractory GBM. Trial registry at ClinicalTrials.gov, NCT017337346.
Chemoradiotherapy ; Diagnosis ; Disease-Free Survival ; Drug Therapy* ; Glioblastoma* ; Glioma ; Humans ; Lomustine* ; Methylation* ; Procarbazine* ; Vincristine