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

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

BACKGROUND: Optimal treatment for recurrent primary central nervous system lymphomas (PCNSLs) has not been defined yet and there is no general consensus about the salvage chemotherapy after high-dose methotrexate (HD-MTX)-based chemotherapy. The purpose of the present study was to evaluate the efficacy and safety of procarbazine, lomustine, and vincristine (PCV) chemotherapy for recurrent PCNSLs. METHODS: We reviewed eight immunocompetent patients (five males/three females, mean age: 56 years) who received salvage PCV chemotherapy (procarbazine 60 mg/m2, days 8 through 21: CCNU 110 mg/m2, day 1: vincristine 2 mg, days 8 and 28) for recurrent PCNSL and two patients switched to PCV chemotherapy due to severe adverse effects of HD-MTX chemotherapy. Radiologic responses, survival, and adverse effects were analyzed. RESULTS: Of the eight recurrent PCNSLs, three patients (37.5%) showed radiologic complete response, one patient (12.5%) showed partial response, and four patients (50%) showed progressive disease after PCV chemotherapy. Median progression free survival (PFS) from the first administration of PCV to relapse or last follow-up was 7 months (range 5-32 months) and median overall survival was 8 months (range 2-41 months). The two patients who switched to PCV chemotherapy showed PFS of 9 and 5 months from the beginning of PCV to relapse. The common side effects were thrombocytopenia, neutropenia, and peripheral neuropathy. There were 4 grade III or IV myelo-suppression, but no fatal complications, including severe hemorrhage or infection, were observed. CONCLUSION: Salvage PCV chemotherapy has a moderate anti-lymphoma activity for recurrent PCNSLs after the HD-MTX-based chemotherapy with tolerable toxicity.
Central Nervous System* ; Consensus ; Disease-Free Survival ; Drug Therapy* ; Female ; Follow-Up Studies ; Hemorrhage ; Humans ; Lomustine* ; Lymphoma* ; Methotrexate ; Neutropenia ; Peripheral Nervous System Diseases ; Procarbazine* ; Recurrence ; Salvage Therapy ; Thrombocytopenia ; Vincristine*

A 49-year-old female patient was admitted due to memory disturbances. Magnetic resonance (MR) imaging suggested gliomatosis cerebri (GC), which had spread to both insular lobes, both frontal and basal ganglia and the brain stem. A stereotactic biopsy was performed at the high signal intensity area of the T2-weighted MR image, and the revealed a diffuse astrocytoma. Radiation therapy was judged not to be an appropriate treatment for the patient because of her cognitive impairment. A combinatorial chemotherapy regiment consisting of Procarbazine, CCNU, and Vincristine (PCV) was agreed upon after discussion. The patient underwent six cycles of PCV chemotherapy (a full dose was applied until the 3rd cycle, and dose then was reduced to 75% for the remaining cycles). Although the patient exhibited side effects such as bone marrow suppression and gastrointestinal symptoms, these were managed by medication. Over the 28 months following initiation of treatment, the high signal area in the right frontal and temporal lobes in the T2-weighted MR image decreased, and the patient's cognitive function [global deterioration scale (GDS) 4 points, mini-mental state examination (MMSE) 25 point] also improved (GDS 1 points, MMSE 29 points). PCV chemotherapy can therefore be an alternative therapeutic option for patients with GC who cannot be treated with radiation therapy or other chemotherapies.
Astrocytoma ; Basal Ganglia ; Biopsy ; Bone Marrow ; Brain Stem ; Drug Therapy* ; Female ; Humans ; Lomustine* ; Memory ; Middle Aged ; Neoplasms, Neuroepithelial* ; Procarbazine* ; Temporal Lobe ; Vincristine*

OBJECTIVE: To evaluate the efficacy of temozolomide (TMZ) chemotherapy for recurrent anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA). METHODS: A multi-center retrospective trial enrolled seventy-two patients with histologically proven AO/AOA who underwent TMZ chemotherapy for their recurrent tumors from 2006 to 2010. TMZ was administered orally (150 to 200 mg/m2/day) for 5 days per 28 days until unacceptable toxicity occurred or tumor progression was observed. RESULTS: TMZ chemotherapy cycles administered was median 5.3 (range, 1-41). The objective response rate was 24% including 8 cases (11%) of complete response and another 23 patients (32%) were remained as stable disease. Severe side effects (> or =grade 3) occurred only in 9 patients (13%). Progression-free survival (PFS) of all patients was a median 8.0 months (95% confidence interval, 6.0-10.0). The time to recurrence of a year or after was a favorable prognostic factor for PFS (p<0.05). Overall survival (OS) was apparently differed by the patient's histology, as AOA patients survived a median OS of 18.0 months while AO patients did not reach median OS at median follow-up of 11.5 months (range 2.7-65 months). Good performance status of Eastern Cooperative Oncology Group 0 and 1 showed prolonged OS (p<0.01). CONCLUSION: For recurrent AO/AOA after surgery followed by radiation therapy, TMZ could be recommended as a salvage therapy at the estimated efficacy equal to procarbazine, lomustine, and vincristine (PCV) chemotherapy at first relapse. For patients previously treated with PCV, TMZ is a favorable therapeutic option as 2nd line salvage chemotherapy with an acceptable toxicity rate.
Disease-Free Survival ; Drug Therapy* ; Follow-Up Studies ; Humans ; Lomustine ; Oligodendroglioma* ; Procarbazine ; Recurrence ; Retrospective Studies ; Salvage Therapy ; Vincristine

A 37-year-old male presented with a mass measuring 2.5 cm in size in the midbrain and obstructive hydrocephalus, which had manifested as a headache and dizziness. Magnetic resonance (MR) imaging of the brain showed intermediate enhancement on T1-weighted MR imaging and a high intensity of enhancement on T2-weighted MR. Neurosurgeons performed an occipital craniotomy with partial removal of the tumor and the postoperative diagnosis was a pineal parenchymal tumor with intermediate differentiation. He had undergone irradiation with 54 Gy of radiation on 27 fractions for removal of the remaining tumor approximately one month after surgery. However, in follow-up imaging performed four months after radiotherapy, a remnant mass in the superoposterior aspect of the midbrain was found to have extended to the hypothalamus and the third ventricle. He was treated with six cycles of procarbazine, lomustine, vincristine chemotherapy. At five months since the completion of chemotherapy, the brain MR imaging showed no evidence of any remaining tumor and he no longer displayed any of his initial symptoms.
Adult ; Brain ; Craniotomy ; Dizziness ; Follow-Up Studies ; Headache ; Humans ; Hydrocephalus ; Hypothalamus ; Lomustine ; Magnetics ; Magnets ; Male ; Mesencephalon ; Pinealoma ; Procarbazine ; Third Ventricle ; Vincristine

OBJECTIVE: This retrospective study was performed to evaluate the role of chemotherapy in the management of patients with anaplastic astrocytoma (AA). METHODS: We compared the survival outcome among the 3 different treatment protocol groups in a single institution. A total of 86 patients (39 men and 47 women) with newly diagnosed AA after surgery were analyzed. Among them, 31 patients (36.0%) were treated with radiotherapy only (RT Group), 30 patients (34.9%) were treated with nimustine-cisplatin chemotherapy before RT (ACNU-CDDP group), and 25 patients (29.1%) were treated with procarbazine, lomustine and vincristine (PCV) chemotherapy after radiotherapy (PCV group). RESULTS: The median survival was 14.0, 30.0 and 72.0 months in RT, ACNU-CDDP, and PCV group, respectively and showed significant differences (RT vs. ACNU-CDDP; p=0.039, RT vs. PCV; 0.002, ACNU-CDDP vs. PCV; 0.045). PCV group showed less toxicity rate (5 patients; 20%) than ACNU-CDDP group (12 patients; 40%), while only 3 patients (9.6%) in RT group experienced grade 3 or 4 toxicities. CONCLUSION: An application of chemotherapy before or after radiotherapy is beneficial in prolonging the survival of patients with AA. Adjuvant PCV chemotherapy after radiotherapy is recommendable.
Astrocytoma ; Clinical Protocols ; Humans ; Lomustine ; Male ; Procarbazine ; Retrospective Studies ; Vincristine

OBJECTIVE: This retrospective study was performed to evaluate the role of chemotherapy in the management of patients with anaplastic astrocytoma (AA). METHODS: We compared the survival outcome among the 3 different treatment protocol groups in a single institution. A total of 86 patients (39 men and 47 women) with newly diagnosed AA after surgery were analyzed. Among them, 31 patients (36.0%) were treated with radiotherapy only (RT Group), 30 patients (34.9%) were treated with nimustine-cisplatin chemotherapy before RT (ACNU-CDDP group), and 25 patients (29.1%) were treated with procarbazine, lomustine and vincristine (PCV) chemotherapy after radiotherapy (PCV group). RESULTS: The median survival was 14.0, 30.0 and 72.0 months in RT, ACNU-CDDP, and PCV group, respectively and showed significant differences (RT vs. ACNU-CDDP; p=0.039, RT vs. PCV; 0.002, ACNU-CDDP vs. PCV; 0.045). PCV group showed less toxicity rate (5 patients; 20%) than ACNU-CDDP group (12 patients; 40%), while only 3 patients (9.6%) in RT group experienced grade 3 or 4 toxicities. CONCLUSION: An application of chemotherapy before or after radiotherapy is beneficial in prolonging the survival of patients with AA. Adjuvant PCV chemotherapy after radiotherapy is recommendable.
Astrocytoma ; Clinical Protocols ; Humans ; Lomustine ; Male ; Procarbazine ; Retrospective Studies ; Vincristine

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Brain Neoplasms ; drug therapy ; genetics ; Chromosomes, Human, Pair 1 ; Chromosomes, Human, Pair 10 ; Chromosomes, Human, Pair 19 ; Chromosomes, Human, Pair 9 ; Humans ; Lomustine ; therapeutic use ; Loss of Heterozygosity ; Oligodendroglioma ; drug therapy ; genetics ; Procarbazine ; therapeutic use ; Prognosis ; Vincristine ; therapeutic use

OBJECTIVETo investigate the effect of nitric oxide (NO) on cytotoxicity of Lomustine (CCNU) in vitro.

METHODSCCNU was used to treat human glioma cell line BT-325 with different concentration of cytokines or NO donors, NO levels was measured by Griess assay and cell survival was evaluated by MTT assay.

RESULT(1) Pretreatment with IL-1 beta and LPS markedly suppressed CCNU cytotoxicity in BT-325 cells with a significant increase in NO production (P<0.05). This function could be inhibited by L-NAME. (2) DETA NONOate suppressed cytotoxicity of CCNU to BT -325 cells in a dose-dependent manner (P<0.05). (3) CCNU co-cultured with SNAP for 24 h showed higher cytotoxic to BT-325 cells(P<0.05).

CONCLUSIONNO partly suppresses cytotoxicity of Lomustine, which might be associated with chemoresistance of BT-325 cells against CCNU in vitro. NO can also slow the degradation of CCNU in water solution.

Antineoplastic Agents, Alkylating ; pharmacology ; Cell Line, Tumor ; Drug Resistance, Neoplasm ; Glioma ; drug therapy ; pathology ; Humans ; Interleukin-1 ; pharmacology ; Lipopolysaccharides ; pharmacology ; Lomustine ; pharmacology ; NG-Nitroarginine Methyl Ester ; pharmacology ; Nitric Oxide ; physiology