Soichiro Shibui

Glioblastomas with IDH1/2 mutations have a short clinical history and have a favorable clinical outcome

OBJECTIVEnGlioblastomas with isocitrate dehydrogenase 1/2 mutations comprise a biologically distinct subgroup of glioblastomas. We studied isocitrate dehydrogenase 1/2 mutant glioblastomas at the clinical, molecular and radiological levels to define their clinical features, including the prognostic value of isocitrate dehydrogenase 1/2 mutations compared with isocitrate dehydrogenase 1/2 wild-type glioblastomas.nnnMETHODSnWe investigated 128 newly diagnosed glioblastoma patients who were treated at our institute between January 2005 and May 2013. Isocitrate dehydrogenase 1/2 mutation status was determined using pyrosequencing. O-6-methylguanine deoxyribonucleic acid methyltransferase promoter methylation and 1p/19q co-deletions were also analyzed using pyrosequencing and multiplex ligation-dependent probe amplification, respectively.nnnRESULTSnIsocitrate dehydrogenase 1/2 mutations were detected in 10 of 128 patients (7.8%). Isocitrate dehydrogenase 1/2 mutations were correlated with a younger age, the presence of an oligodendroglial component and 1p/19q co-deletions and a longer survival time. The interval from initial symptom to initial operation did not differ according to isocitrate dehydrogenase 1/2 mutation status (median interval: 2.3 versus 1.2 months; P = 0.13). Two of three isocitrate dehydrogenase 1/2 mutant glioblastomas harboring 1p/19q co-deletions had an oligodendroglial component and were associated with a prolonged survival time. Multivariate analysis of 90 patients treated with temozolomide-based chemoradiotherapy indicated that age, extent of resection, postoperative Karnofsky performance score and O-6-methylguanine deoxyribonucleic acid methyltransferase promoter methylation were correlated with better survival. Isocitrate dehydrogenase 1/2 mutations showed a trend for improved survival (P = 0.068).nnnCONCLUSIONSnMost isocitrate dehydrogenase 1/2 mutant glioblastomas have a short clinical history, and some isocitrate dehydrogenase 1/2 mutant glioblastomas harboring 1p/19q co-deletions behave like oligodendroglial tumors. Isocitrate dehydrogenase 1/2 mutations may have a positive prognostic impact on the Japanese population.

Trends and Outcomes in the Treatment of Gliomas Based on Data during 2001–2004 from the Brain Tumor Registry of Japan.

The committee of Brain Tumor Registry of Japan (BTRJ) was founded in 1973 and conducts surveys and analyses of incidence, therapeutic methods, and treatment outcomes of primary and metastatic brain tumors with the cooperation of the Japan Neurosurgical Society members. Newly diagnosed 3,000–4,000 primary brain tumors and 600–1,000 brain metastases patients were enrolled in each year. This report describes the trends and treatment outcomes of gliomas from BTRJ volume 13, including 13,431 patients with primary brain tumors who newly started treatment from 2001 to 2004. Data from 382 diffuse astrocytomas (DAs), 121 oligodendrogliomas (OLs), 90 oligoastrocytomas (OAs), 513 anaplastic astrocytomas (AAs), 126 anaplastic oligodendrogliomas (AOs), 106 anaplastic oligoastrocytomas (AOAs), and 1,489 glioblastomas (GBMs) were analyzed for overall survival (OS) and progression free survival (PFS) depending on age, symptoms, Karnofsky performance status, location of the tumor, extent of resection (EOR), initial radiotherapy and chemotherapy. The 5-year PFS rates of the patients with DA, OL + OA, AA, AO + AOA, and GBM were 57.0%, 74.6%, 28.7%, 54.0%, and 9.2%, and the 5-year OS rates were 75.0%, 90.0%, 41.1%, 68.2%, and 10.1%, respectively. Higher EOR ≥ 75% in DA and OL + OA and that ≥ 50% in AA, AO + AOA, and GBM significantly prolonged OS. Complications and cause of death were also reported. BTRJ had been edited for all the patients, researchers, and especially for clinicians at bedside to give useful information about brain tumors and to contribute to the advances in brain tumor treatment. This report revealed various clinical problematic issues pertaining to the diagnosis and treatment of gliomas.

Health-related quality of life in long-term survivors with Grade II gliomas: the contribution of disease recurrence and Karnofsky Performance Status

OBJECTIVEnAlthough the number of long-term survivors of glioma has increased, there has been little research on the health-related quality of life of long-term survivors of Grade II glioma following treatment with surgery, radiotherapy and chemotherapy. In this study, we aimed to document the health-related quality of life of people diagnosed with Grade II glioma who had survived >10 years with no evidence of disease at the time of the health-related quality of life survey.nnnMETHODSnTo investigate the health-related quality of life of Grade II glioma survivors without evidence of disease, we surveyed 50 patients 0-20 years after their initial treatments. Each patient completed a multi-part health-related quality of life questionnaire. Based on these surveys, we examined the relationships between health-related quality of life scores and time since initial treatment, Karnofsky Performance Scale scores at the time of the survey, and history of recurrence, radiotherapy and chemotherapy.nnnRESULTSnExcepting bladder control, long-term survivors maintained their quality of life as determined by comparing patients surveyed < 5 and ≥ 10 years after their initial treatment (P < 0.05). Neither radiotherapy nor chemotherapy at the initial treatment was observed to affect health-related quality of life. However, a history of recurrence was significantly associated with deteriorations in many health-related quality of life functional and symptom scores. The Karnofsky Performance Scale scores of patients with a history of recurrence were significantly lower than those without it (P = 0.02). This deterioration was observed in both univariate and multivariate analyses.nnnCONCLUSIONSnOur results indicate that declines in health-related quality of life among long-term survivors of Grade II glioma mainly result from impaired Karnofsky Performance Scale, which is a consequence of disease recurrence.

Genome-wide DNA methylation profiling identifies primary central nervous system lymphoma as a distinct entity different from systemic diffuse large B-cell lymphoma

Taishi Nakamura1,2 · Satoshi Yamashita3 · Kazutaka Fukumura4 · Jun Nakabayashi5 · Kazuhiro Tanaka6 · Kaoru Tamura7 · Kensuke Tateishi2 · Manabu Kinoshita8 · Shintaro Fukushima1 · Hirokazu Takami1 · Kohei Fukuoka1 · Kai Yamazaki1 · Yuko Matsushita9 · Makoto Ohno9 · Yasuji Miyakita9 · Soichiro Shibui10 · Atsuhiko Kubo11 · Takashi Shuto12 · Sylvia Kocialkowski13 · Shoji Yamanaka14 · Akitake Mukasa15 · Takashi Sasayama6 · Kazuhiko Mishima16 · Taketoshi Maehara7 · Nobutaka Kawahara2 · Motoo Nagane17 · Yoshitaka Narita9 · Hiroyuki Mano4 · Toshikazu Ushijima3 · Koichi Ichimura2

A Case of Breast Cancer Brain Metastasis with a 16-Year Time Interval without Evidence of Cancer Recurrence

The median time of brain metastasis from the diagnosis of breast cancer is approximately 3 years. In this case report, a 69-year-old woman demonstrated cerebellar ataxia. Brain magnetic resonance imaging revealed enhanced lesions in bilateral cerebellar hemispheres. She had undergone surgery, radiation, and chemotherapy for uterine and breast cancer 24 years prior and 16 years prior, respectively. Although she had not received any anticancer treatment for 10 years, no recurrences were identified using whole body scans. A partial tumor resection was performed and the histological diagnosis was an adenocarcinoma from breast cancer. As no extracranial lesions were found, gamma-knife irradiation was performed, without additional systemic chemotherapy. One month posttreatment, the tumors dramatically reduced in size and the patient completely recovered from cerebellar ataxia. Systemic chemotherapy is not always required for brain metastasis from breast cancer with a long interval period, as long as no evidence of extracranial recurrence is detected.

Glioblastoma multiforme versus pleomorphic xanthoastrocytoma with anaplastic features in the pathological diagnosis: a case report

BackgroundPleomorphic xanthoastrocytoma (PXA) with anaplastic features should be strictly distinguished from glioblastoma multiforme (GBM).Case presentationA case of PXA that was initially diagnosed as GBM is presented. A 42-year-old man visited our clinic because of right hemiparesis and total aphasia. Head magnetic resonance imaging demonstrated enhanced multiple cystic lesions in the left temporal lobe suggesting an intra-parenchymal brain tumor. The lesion was partially removed and GBM with a Ki-67 index of 20xa0% was diagnosed by pathological examination of the resected specimen. Despite receiving radiation and chemotherapy, the patient died 6xa0months after the first admission. At autopsy, the boundary between the tumor and normal brain tissue was clear. Large parts of the tumor demonstrated typical features of PXA, including pleomorphism, clear xanthomatous cells with foamy cytoplasm, positive silver staining, and a Ki-67 index of less than 1xa0%.Discussion and conclusionsGBM should be diagnosed only when the majority of the tumor cells are undifferentiated. Although the operative specimen appeared typical GBM histologically, the diagnosis of GBM was subsequently excluded by the autopsy finding that much of the tumor had the characteristic features of a benign PXA. Therefore, the final diagnosis in this case was PXA with anaplastic features. PXA with anaplastic features should be carefully distinguished from GBM to facilitate appropriate decisions concerning treatment.

Reactivation of cytomegalovirus following treatment of malignant glioma with temozolomide

Temozolomide is a standard chemotherapeutic agent in the treatment of malignant gliomas. Lymphocytopenia is reported to be the most frequent and severe adverse effect, which causes opportunistic infections such as pneumocystis pneumonia (PCP) and increases the risk of the reactivation of viruses such as hepatitis B virus (HBV) and cytomegalovirus (CMV). However, the incidence of temozolomide-induced CMV reactivation remains unclear. We report on a case of a 62-year-old female with gliomatosis cerebri who had severe lymphocytopenia and pneumonia following concurrent temozolomide treatment and prophylaxis for PCP. She presented cough, fever, and severe lymphocytopenia 1xa0month after chemoradiotherapy with temozolomide. Her serum β-d-glucan levels remained within the normal range, which was helpful to rule out a diagnosis of PCP. Other opportunistic infections were ruled out, and a blood test for the CMV antigen was positive for pp65 antigenemia. The patient was diagnosed as having CMV pneumonia. She was treated with ganciclovir and recovered. It was very difficult to distinguish between PCP and CMV pneumonia with only the clinical presentation and radiological findings. When a patient receives temozolomide, it is important to be aware of the potential for a CMV reactivation. The serum β-d-glucan levels and pp65 antigenemia are very useful for diagnosis of CMV pneumonia.