Brain Tumors In Japan Research Articles

First Clinical Report of the Intraoperative Macro- and Micro-Photodiagnosis and Photodynamic Therapy Using Talaporfin Sodium for a Patient with Disseminated Lumbar Medulloblastoma.

Photodiagnosis (PD) and photodynamic therapy (PDT) using the second-generation photosensitizer talaporfin sodium together with an exciting laser for primary intracranial malignant tumors is well recognized in Japan, and many medical institutions are introducing this new therapeutic option. In particular, intraoperative PDT using talaporfin sodium for infiltrating tumor cells in the cavity walls after the resection of malignant glioma is now covered by health insurance after receiving governmental approvement, and this method has been recommended in therapeutic guidelines for primary malignant brain tumors in Japan. On the other hand, experimental and clinical studies on the development of novel therapeutic strategies for malignant spinal cord tumors have not been reported to date, although their histological features are almost identical to those of intracranial malignant tumors. Therefore, the clinical outcomes of malignant spinal cord tumors have been less favorable than those of malignant brain tumors. In this report, we performed the PD and PDT using talaporfin sodium on a patient with a metastatic lumbar lesion that was detected on magnetic resonance image (MRI) 50 months after the resection of cerebellar medulloblastoma who presented with lumbago and sciatica. We were able to detect the target lesion in the conus medullaris using a surgical microscope, and detected the disseminated medulloblastoma cells floating in the cerebrospinal fluid using a compact fluorescence microscope. Furthermore, we performed PDT to the resected lumbar lesion with the adjuvant platinum-based chemotherapy, and the patient survived a meaningful life for more than 2 years after the lumbar surgery. This report describes the first case of a human patient in whom the efficacy of PD and PDT was demonstrated for a malignant spinal cord tumor.

Next-Generation Sequencing Tests for Malignant Brain Tumors

The cancer genome-profiling test is performed to analyze exome gene mutations, amplifications, deletions, fusion gene expression, etc. in tumor tissues with a next-generation sequencer to identify tumor-specific driver genes. The cancer genome-profiling test is covered by medical insurance for patients with malignant brain tumors in Japan, but it is limited to patients with good PS(performance status), considering the conditions for participation in clinical trials. The findings of the expert panel will create more opportunities to administer new therapeutic agents for clinical trials for malignant brain tumors.

EPID-09. THE INCIDENCE OF PRIMARY BRAIN TUMORS IN CHILDREN IN JAPAN BASED ON 2016 NATIONAL CANCER REGISTRY IN JAPAN

The national cancer registries began in January 2016 and the actual number of cancer patients in 2016 including primary brain tumors in Japan was released as a preliminary report in January 2019. According to the report, 667 incidence of pediatric brain tumors were reported in aged 0–14 years (boy: 382; girl: 285), of them 537 patients underwent surgery, chemotherapy, or radiation therapy (diagnosis: 516, undiagnosed: 21), and 130 patients were followed up without any treatments. The breakdown of tumor types was 279 Neuroepithelial tumors, 73 Embryonal tumors (61 Medulloblastomas), and 63 Germ Cell Tumors (GCTs). The crude rate per 100,000 population in 2016 was 4.23 for all pediatric brain tumors, 1.77 for Neuroepithelial tumor, 0.39 for Medulloblastoma, and 0.40 for GCTs. In comparison, the United States CBTRUS2019 (2012–2016) reported that the age-adjusted incidence rates per 100,000 population in the United States was 5.74 for all pediatric brain tumors, 4.15 for Neuroepithelial tumors, 0.48 for Medulloblastoma, and 0.22 for GCTs. The age-adjusted incidence in Japan based on the US population in 2000 was 4.21 for all pediatric brain tumors, Neuroepithelial tumor 1.77, Medulloblastoma 0.39, and GCTs 0.39, suggesting that the incidence of Neuroepithelial tumor and Medulloblastoma is lower whereas that of GCTs is approximately twice comparing to the US. By taking advantage of the national cancer registry data, which was publicly opened to researchers in 2019, we report the incidence of primary brain tumors and its comparison worldwide based on the re-classification criteria of primary brain tumors including benign tumor.

Retrospective Multicenter Study of Stereotactic Irradiation for Metastatic Brain Tumors in Japan

Stereotactic Irradiation (STI) has been increasingly utilized in the management for metastatic brain tumor. However, many studies show combined therapy with surgery or whole brain radiation therapy (WBRT). The purpose of this study is to report the multicenter outcome of metastatic brain tumors treated only by STIs in Japan. This was a retrospective multicenter analysis to review a total of 686 patients with 918 lesions which had diameter > 10 mm. STIs were performed among 26 institutions participated in Japanese Radiation Oncology Study Group (JROSG) from January 2013 to December 2015 treated with linear accelerators. Previous WBRT or surgery cases were all excluded. Local control (LC), overall survival (OS), and brain necrosis followed with diagnostic MRI were analyzed by Kaplan-Meier method. Patient characteristics were as follows. Median age was 67 years (range: 26-91). Median follow-up was 12.1 months (range: 0.5-55.5), Median KPS score/ tumor size/ number of lesion were 90/ 17mm/ 2, respectively. Primary sites were lung/ breast/ GI/ others = 527/ 106/ 114/ 171 cases, respectively. Median dose delivered was 31.5 Gy in 3 fractions (range 13.4-55 Gy). Treatment outcome was CR/ PR/ SD/ PR = 151/ 349/ 167/ 145 and death/ survive = 510/ 280, respectively. 1-year LC was 80.5%. Median survival was 15.8 months. 1-year OS was 58.9%. 1-year LC for tumor size of 3-4 cm was 59.2%. There was no difference in LC between single fraction and multiple fractions. Brain necrosis occurred at 6 months/ 1-year = 4.8%/ 10.6%. The incidence was linearly correlated with the time after treatment. Positive outcome of STI for brain metastases without WBRT or surgery was achieved. LC was a little poor with the tumor diameter > 3 cm. Brain necrosis occurred regardless of a tumor size and a delivered dose, and long-term follow-up is mandatory.

Initial symptoms and diagnostic delay in children with brain tumors at a single institution in Japan.

A prolonged interval between onset of symptoms and diagnosis of childhood brain tumor is associated with worse neurological outcomes. The objectives of this study are to determine factors contributing to diagnostic delay and to find an interventional focus for further reduction in the interval between symptom onset and diagnosis in Japan. We retrospectively analyzed 154 patients younger than 18 years with newly diagnosed brain tumors who visited our institution from January 2002 to March 2013. The median age at diagnosis was 6.2 years and the median total diagnostic interval (TDI) was 30 days. Patients with low-grade tumors and cerebral midline tumor location had significantly long TDI. Durations between the first medical consultation and diagnosis (diagnostic interval, DI) were exceedingly longer for patients with visual, hearing, or smelling abnormalities as the first symptom (median, 303 days). TDI and DI of patients who visited ophthalmologists or otolaryngologist for the first medical consultation were significantly longer. Among these patients, longer DI was associated with worse visual outcome. Raising awareness of brain tumor diagnosis among ophthalmologists and otolaryngologists may reduce diagnostic delay and may improve the neurological impairment of children with brain tumors in Japan.

Current Status of Palliative and Terminal Care for Patients with Primary Malignant Brain Tumors in Japan.

Palliative care and advance care planning (ACP) from the first diagnosis of glioblastoma are important. This questionnaire survey was conducted to understand the current status of palliative care for brain tumors in Japan. Representative characteristics of Japan in comparison with Western countries (P <0.01) are described below: (1) Gender ratio of male in physicians who treat brain tumors in Europe and the United States/Canada are about 70%, but 94% in Japan. (2) The specialty is predominantly neurosurgeon (93%) in Japan. The ratio of neurologists is predominantly 40% in Europe. In the United States/Canada, neurologist (27%) and neurosurgeon (29%) are main parts. (3) Years of medical experience over 15 in physicians is 73% in Japan. Proportions of those with over 15 years are 45% in Europe and 30% in the United States/Canada. (4) In practicing setting, the rate of academic medical centers is about 80% in Europe and the United States/Canada, and ~60% in Japan. Representative differences compared with past domestic data (2007) (P <0.01): (1) In glioblastoma, the rate of explaining about median survival time increases from 39% (2007) to 80% (2018). Explanation about medical conditions to the patient himself with his family increases from 20% (2007) to 39% (2018). (2) Place of death: The rate at hospital is decreasing from 96% (2007) to 79% (2018) and at home is increasing from 3% (2007) to 10% (2018) (3) The rate of ventilator in adult has decreased from 74% (2007) to 54% (2018), but nasal tube feeding has remained unchanged from 62% (2007) to 60% (2018). These results will be shared with physicians to make better care systems for patients with brain tumors.

NQPC-01 CURRENT STATUS AND PROBLEMS OF ADVANCE CARE PLANNING AND PALLIATIVE CARE FOR MALIGNANT BRAIN TUMOR

Purpose Genomic medicine is in progress, but the median survival of glioblastoma is 14–16 months. It seems to have the same life prognosis as stage 4 like unresectable pancreatic cancer, lung cancer and colon cancer. Palliative care including Advance care planning (ACP) at first diagnosis of glioblastoma is important We conducted a questionnaire survey to understand the current status of Japanese oncologists. Method In July 2018, a questionnaire of 37 items was sent by e-mail to 767 members of Japanese Society of Neuro Oncology, and in August replies were received from 154 persons (20%). The same 22-item questionnaire in 2012–2013 was compared internationally with a report (Walbert T., et al., 2015) by Society of NeuroOncology and the European Association of NeuroOncology. In addition, we compared domestically with a 30-item questionnaire (Narita et al. 2009) in 2007. The Nonparametric Mann-Whitney’s U test was mainly used. Result 1 Characteristics of Japan in comparison with Western countries(p<0.01): 1. The number of doctors in charge is overwhelmingly male. 2. The specialty is predominantly neurosurgeons. 3. Aging of NeuroOncologists. 4, medical treatment place: the proportion of university is low. 5, frequent regular examination of the patient. Result 2Changes compared with domestic(Japan) data 11 years ago(p<0.01): 1 Explaining the condition in more detail. 2. Explaining to not only the family but also the patient. 3. Continuing chemotherapy more aggressively. 4. The place of death: decreasing at hospitals and increasing at home. 5, Frequency with a respirator decreased. 6, About 70% at the end of the period, nasal injection and gastrostomy are applied. Conclusion In the treatment of malignant brain tumors in Japan, a male neurosurgeon who has over 15 years of experience actively continues chemotherapy and appears to see it with nasal injection.

Present clinical practices of stereotactic irradiation for metastatic brain tumors in Japan: results of questionnaire survey of the Japanese Radiation Oncology Study Group (JROSG) working subgroup for neurological tumors.

To determine the current practice of stereotactic irradiation (STI) for brain metastases in Japan by a questionnaire survey. A questionnaire was distributed to 313 institutions performing STI with one of the following machines: Gamma Knife (GK), CyberKnife (CK), Novalis (Nov), or other linear accelerator (LINAC)-based systems (OLS). The participation was voluntary. There were 163 responding institutions. The total number of STI treatments between April 2013 and March 2014 was 10,684. Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (SRT) were performed in 8624 (80.7%) and 2060 (19.3%) cases, respectively. Whole-brain radiation therapy (WBRT) was performed for a total of 3515 cases. For a case model of a 1.5-cm solitary brain metastasis in a non-eloquent area, the most common GTV-PTV margin was 2mm (22 of 114 institutions), and an institutional standard fraction was 1 (75 of 114 institutions). The doses for the model case also varied from 13.0 to 26.0Gy (Median 20Gy) when converted to SRS (α/β = 10). A prescription point was at the PTV margin the most. The median dose constraints which were converted to SRS (α/β = 3) to organs at risk were 12.2, 12.7, and 13.7Gy for optic nerves, cavernous sinus, and brainstem, respectively. STI for brain metastases in current practice varied significantly among institutions. These different strategies relied mostly on the type of treatment machine used. It is thus necessary to establish a common guideline to express dose prescriptions and plan qualities for different STI machines.

Overview of treatment for adult malignant brain tumors in Japan

Overview of treatment for adult malignant brain tumors in Japan

Response to the comments on "Analysis of Mobile Phone Use Among Young Patients with Brain Tumors in Japan".

Response to the comments on "Analysis of Mobile Phone Use Among Young Patients with Brain Tumors in Japan".

Comments on analysis of mobile phone use among young patients with brain tumors in Japan

Comments on analysis of mobile phone use among young patients with brain tumors in Japan

Analysis of mobile phone use among young patients with brain tumors in Japan.

The purpose of this study was to clarify ownership and usage of mobile phones among young patients with brain tumors in Japan. The subjects of this study were patients with brain tumors diagnosed between 2006 and 2010 who were between the ages of 6 and 18 years. The target population for the analysis was 82 patients. Patients were divided into two groups: 16 patients who were mobile phone owners 1 year before diagnosis, and 66 patients who did not own mobile phones (non-owners). Using data on the mobile phone ownership rate obtained from three general-population surveys, we calculated the expected number of mobile phone owners. The three age-adjusted standardized ownership ratios were 0.83 (95% confidence interval [CI]: 0.56-1.22), 0.51 (95% CI: 0.24-1.04), and 0.75 (95% CI: 0.42-1.32). The mobile phone ownership prevalence among the young Japanese patients with brain tumors in the current study does not differ from available estimates for the general population of corresponding age. However, since the use of mobile phones among children is increasing annually, investigations into the health effects of mobile phone use among children should continue. Bioelectromagnetics. 38:349-355, 2017. © 2017 Wiley Periodicals, Inc.

Overview of treatment for adult malignant brain tumors in Japan

Overview of treatment for adult malignant brain tumors in Japan

Parent’s Perceived Provision of Information Regarding Diagnosis to Children with Brain Tumors

Background: The aim of this study was to clarify the degree of information provision to children with brain tumors, factors influencing this provision, and the relationship between this provision and psychosocial consequences. Methods: A total of 157 parents completed a questionnaire on the degree of information provision to their children and sociodemographic and medical characteristics. Parents and their children completed subscales of the Pediatric Quality of Life Inventory (PedsQL) Cancer Module. Relevant factors were investigated using ordinal logistic regression analysis and compared with PedsQL scores by degree of information provision with adjustment for age. Results: The majority of children aged 2 - 4 years received a low level of information only in regard to medical procedure and preparation. The majority of children aged 5 - 11 years were provided information regarding disease symptoms and treatment, but not actual diagnosis. Approximately half of children aged 12 - 18 years were provided detailed information including their actual diagnosis. Older children generally received more information regarding their disease (odds ratio [OR] = 1.3 per 1 year old, P < 0.001), while children with intellectual disability received less (OR = 0.2, P = 0.006). The provision of information did not worsen scores for Procedural Anxiety, Treatment Anxiety, Worry, or Communication. Conclusions: To our knowledge, this is the first report on the degree of information provision to children with brain tumors. Parents of children with brain tumors in Japan provide information dependent on age and intellectual level. The disclosure of information to children regarding their disease might affect their trust of medical and health care professionals.

GE-16 * JAPANESE PEDIATRIC MOLECULAR NEURO-ONCOLOGY GROUP (JPMNG): ESTABLISHMENT OF A NATIONWIDE MOLECULAR DIAGNOSTIC NETWORK FOR PEDIATRIC MALIGNANT BRAIN TUMORS IN JAPAN

Recent intensive molecular biological analyses revealed that pediatric brain tumors can be subclassified into multiple distinct molecular subgroups. The current consensus is that medulloblastomas consist of four core subgroups, and the sub-grouping of ependymomas is being proposed. This molecular sub-grouping system will not only improve our understanding of the biology of these tumors, but may also contribute for the development of novel therapeutic targets and strategies in the future. We have formed the Japanese Pediatric Molecular Neuro-oncology Group (JPMNG) and initiated a new clinical research project to establish a nationwide network of a molecular diagnosis system for pediatric brain tumors in Japan with the aim to provide a standardized molecular diagnosis according to the international consensus. We initially focus on medulloblastomas and ependymomas. Fresh, fresh-frozen and/or formalin-fixed paraffin-embedded archived tissue specimens are collected. Optimal diagnostic methods are being set up to reliably and reproducibly classify them into molecular subgroups according to the consensus criteria. These include gene expression analysis using the NanoString nCounter system, immunohistochemistry, RT-PCR, DNA sequencing, fluorescence in situ hybridization, and DNA methylation analysis. We have so far collected a total of 85 tissue samples including 30 medulloblastomas and 55 ependymomas. Preliminary study using 17 meduloblastomas indicated that proportions of four core subgroups were WNT (12%), SHH (35%), Group 3 (0%) and Group 4 (53%), respectively. Driver gene analysis showed that two WNT medulloblastomas had CTNNB1 mutations and TP53 mutations were found in one WNT and one SHH tumors. Mutation of TERT promoter was also found in one adult SHH tumors. We expect that this research will provide a highly accurate molecular diagnosis of medulloblastoma and ependymoma comparable to the international standard, leading to form a basis for better clinical management and outcomes and to develop new therapeutic strategies of the pediatric brain tumors in Japan.

ED-21 * INCIDENCE AND OUTCOMES IN BRAIN TUMORS OF JAPAN 2001-2004

BACKGROUND: The Brain Tumor Registry of Japan (BTRJ) was founded to investigate the statistical characteristics of brain tumors in Japan from 1975. The 13th edition of the BTRJ is published in 2014 (Neurologia medico-chirurgica Vol. 54 (2014) Supplement). METHODS: Data on primary or metastatic brain tumor cases that were newly diagnosed from 2001 to 2004 were collected from 2009 until the end of 2012. Approximately 330 neurosurgeons, medical doctors, and staff from 109 institutions collected 16,338 data from clinical records. These institutions included most universities, colleges, and hospitals with Japan Neurosurgical Society-authorized boards. These data were collected via the Internet Data and Information Center for Medical Research. Data, including the birthplace, age, tumor sites, diagnostic method, therapy (surgery, radiation, or chemotherapy), and the outcome of these treatments, according to the World Health Organization (WHO) 2007 brain tumor classification were collected. Survival data were analyzed using the Kaplan-Meier method. RESULTS: 5-year overall survival (OS) and 5-year progression free survival (PFS) of major brain tumors are as follows; grade II diffuse astrocytoma: 75%, 57%, grade II oligodendroglial tumor: 90%, 74.6%, grade III anaplastic astrocytoma: 41.1%, 28.7%, grade III anaplastic oligodendroglial tumor: 68.2%, 54%, glioblastoma: 10.1%, 9.2%, primary CNS lymphoma: 64.4%, 34.7%, null cell pituitary adenoma: 98.3%, 85.1%, neurinoma: 98.8%, 89.5%, grade I meningioma: 97.9%, 90.5%, grade II meningioma: 91.2%, 60.6%, grade III meningioma: 86.6%, 53.4%, chordoma: 89.1%,48.1%. CONCLUSIONS: Trends and problems in the treatment and outcomes of brain tumors of Japan in 2001-2004 will be presented and discussed.

転移性脳腫瘍の疫学

転移性脳腫瘍の疫学

Epidemiology of childhood brain tumors in Japan.

Using the vital statistics issued annually by the Japanese Government from 1960 to 1994, the mortality of brain tumors during childhood (0-14 years of age) in Japan was estimated. Since there are few nationwide registries of childhood cancers with a sufficiently high registration rate, the incidence of brain tumors was calculated using the Registry of Childhood Malignancies in Hokkaido Prefecture from 1969 to 1996. Though the mortality due to malignant diseases as a whole during childhood has been decreasing, and though there should be progress in therapeutic methods, the mortality due to brain tumors in children has been increasing. The incidence of brain tumors in Hokkaido Prefecture has been increasing as well. There was no tendency for the incidence of medulloblastoma to decrease. The incidence of childhood brain tumors has been increasing in Japan, though the cause is unknown. The period of the present study corresponded to a period of high economic growth. Thus, a study on environmental factors would be interesting.

Congenital brain tumors in Japan (ISPN Cooperative Study): specific clinical features in neonates

The authors present specific clinical features of brain tumors occurring in immature brain in comparison with those of older infants and children. Twenty-six neonatal brain tumors, which accounted for 11.3% of 231 brain tumors diagnosed in the 1st year of life collected in a cooperative study in Japan, were analyzed. Although astrocytomas were invariably common tumors in each age group, comprising 25.0% for all pediatric brain tumors, teratomas were the most common type of neonatal brain tumors and accounted for 33.4% in this age group. Location of tumors in the immature brain was more striking, involving the posterior fossa region less commonly, as in 11.1% in neonatal, 29.5% in infantile, and 41.4% in all pediatric age groups. Surgical intervention was performed in 97.4% of the infantile and 79.1% of the neonatal cases, but total or subtotal resection of the mass was achieved only in 58.9% in the infants and 73.7% in the neonates. There was more strict limitation in performing the adjuvant therapies in the immature age groups. Radiation therapy and chemotherapy were given only in 32.0% and 27.6%, respectively, in the neonatal cases. The prognosis was extremely poor in the immature cases: 1-year, 5-year, and 10-year survival rates were 59.3%, 26.1%, 11.5% in the infants, and 43.5%, 23.8%, 7.1% in the neonates, respectively. Of the neonates, 76% and of the infants 73.1% were retarded. The present study delineates the characteristic clinical features of tumors involving immature brain and emphasized that establishment of more specific therapeutic modalities is urgent.

聴神経腫よう診断への耳鼻咽喉科医の寄与 全国大学附属病院調査

In order to find out how otologists contribute to the diagnosis of acoustic neurinoma, a questionnaire was sent to 80 neurosurgical departments of university hospitals. Answers were obtained from 71 departments.1) Acoustic neurinomas represented 7.8% of all brain tumors in Japan. The rate varied from 0% to 24% in university hospitals. 2) 48.8% of acoustic neurinomas were diagnosed by otologists. The rate varied from 0% to 100% in university hospitals.Since in most cases, the first symptom of acoustic neurinoma is unilateal progressive hearing loss, it was presumed that more than 48.8% of acoustic neurinoma patients had visited an otologist's clinic.In order to prevent wrong diagnosis, problems which frequently rise in diagnosing acoustic neurinomas are discussed.