bluuebunny/crossref_metadata_2025 huggingface dataset:
ACT-21 PRIMARY EXPERIENCE OF NOVOTTF THERAPY FOR THE PATIENTS WITH GBM IN OUR INSTITUTION
Authors: Yamaguchi Shigeru , Motegi Hiroaki , Ishi Yukitomo , Okamoto Michinari , Terasaka Shunsuke
Published: December 2019

BACKGROUND

Based on EF-14 clinical trial, NovoTTF therapy prolong overall survival in the patients with GBM. However, NovoTTF treatment does not become standard therapy because treatment procedures are cumbersome and potentially impose psychological burden on patients who suffer from dismal disease. In our institution, we can choose NovoTTF therapy as one of the treatment options for GBM patients since June 2018. In this report, we summarized primary experience of this novel treatment.

MATERIALS AND METHODS

Adult patients with primary GBM diagnosed after June 2018 were retrospectively reviewed. We investigated the suggestion of NovoTTF, patients’ acceptance, the reason of rejection of NovoTTF, and the condition of NovoTTF treatment.

RESULTS

Among 22 GBM patients, 12 cases were proposed NovoTTF treatment in actual. In 10 cases who were not proposed NovoTTF, the reasons were 1) poor performance status (KPS 50% or less); 7 cases, oldest-old; 1 case, unavailable care person; 2 cases. In 12 cases who were proposed NovoTTF, 5 cases (42%) accepted and performed this therapy. Remaining 7 cases did not accept NovoTTF because rejection of shaving hair; 1 case, troublesome for daily work; 2 cases, refusal due to cumbersome procedure; 2 cases, unavailable cooperation with care person(s); 2 cases. 5 cases treated NovoTTF were 3 males and 2 females, and the median age was 67yo (range 25yo-69yo). All patients were continued NovoTTF for 1–7 months without major complication. In two cases, minor skin trouble was observed, but easy to handle by putting ointment.
PEDT-02 DIAGNOSIS, TREATMENT AND CLINICAL OUTCOME OF ATYPICAL BRAINSTEM TUMOUR IN CHILDHOOD
Authors: Yanagisawa Takaaki , Honda Takaya , Yamaoka Masatada , Akiyama Masaharu , Fukuoka Kohei , Suzuki Tomonari , Adachi Junichi , Mishima Kazuhiko , Nishikawa Ryo , Masumoto Ai , Nonaka Yuichiro , Takei Jun , Mori Ryosuke , Ishi Yudo , Akasaki Yasuharu , Murayama Yuichi
Published: December 2019

BACKGROUND

Brainstem tumours account for 10–15% of brain tumors in childhood. Diffuse intrinsic pontine glioma (DIPG) accounts for 60–80% of them and are diagnosed based on clinical findings and radiologic features. All the rest of tumours excluding DIPG are very rare, heterogeneous group of tumours including low-grade glioma and malignant embryonal tumors. It is often difficult to diagnose and decide treatment strategy for their rarity.

METHODS

To present our experience with atypical brainstem tumours, a retrospective chart review was conducted to identify eligible cases treated over a ten-year period. All tumors involving brainstem, felt not to be DIPGs for absence of clinical/neuroimaging features were included. Demographic information, pathological findings, neuroimaging characteristics, surgical and nonsurgical management plans, and survival data were collected for analysis.

RESULTS

Between April 2007 and March 2017, 16 patients (14 initial and 2 recurrent) aged from 3 to 20 years were identified. 14 of them were symptomatic and 4 of them were asymptomatic at reference. Of 10 symptomatic cases, 10 were biopsied and pathological diagnosis was low-grade glioma in 8, glioblastoma in 2 cases. They had treatment depending on the pathological diagnosis. Of 4 asymptomatic cases, one with small focal tumour, with no findings suggesting malignant tumour with 11C-methioninePET or MRS, progressed to show typical clinical and image findings of DIPG in a year. For other three, they remain asymptomatic without progression with no treatment for 25months, 60months, and 65 months respectively. Malignant transformation was observed in one with biopsy-conformed oligoastrocytoma with no K27M-H3 mutations treated with chemotherapy and another with pilocytic astrocytoma treated with chemotherapy and radiotherapy.

CONCLUSIONS

Though molecular findings such as K27M-H3 mutations can predict clinical outcome in some cases, it still remains difficult to diagnose and find treatment strategy of atypical brainstem tumours. The need and usefulness of nationwide registry study is warranted.
PEDT-04 SIX CASES OF RETINOBLASTOMA WITH CNS INVOLVEMENT
Authors: Kiyotani Chikako , Tsujimoto Shinichi , Isshiki Kyohei , Sugawa Masahiro , Azuma Noriyuki , Usami Kenichi , Ogiwara Hideki , Yosioka Takako , Tsutsumi Yoshiyuki , Fuji Hiroshi , Terashima Keita , Matsumoto Kimikazu
Published: December 2019

Although the survival rate of intraocular retinoblastoma (RB) is nearly 100%, the outcome of central nervous system (CNS) involvement or Trilateral retinoblastoma (TRb: very rare RB which associated with brain tumor) is dismal. We retrospectively reviewed our six cases of these rare tumors. Their ages at diagnosis are 0y3m-1y10m (median 1y3m) (Male 4, Female 2). Only one had RB family history. Their affected eyes were bilateral 2, unilateral 3 and no 1. Their CNS diseases were suprasellar tumor 3, pineal tumor 1 and cerebrospinal fluid (CSF) cytology positive 2. Two of the suprasellar tumor patients had spinal metastasis. Three of the six patients were TRb. One TRb patient was treated with chemotherapy and high-dose chemotherapy without radiotherapy. Although he suffered with secondary osteosarcoma seven years later, he got complete remission and alive 5 years more without any tumor recurrence. The second TRb patient was treated with chemotherapy and local radiotherapy but relapsed 20 months later. The third TRb patient was chemotherapy resistant. Two CSF positive patients had optic nerve invasion. One patient with chiasm invasion died 11 months later because of treatment resistance. The other patient with optic nerve invasion before optic canal had no CNS tumor nor CSF involvement at diagnosis. Chemotherapy before enucleation was given to avoid dissemination. However, CSF cytology became positive after enucleation and remained even with intensified chemotherapy. Finally, he got remission with radiotherapy and high-dose chemotherapy, and alive without disease for 3.8 years. The last patient had suprasellar genetically classified retinoblastoma tumor and cerebrospinal metastasis. This patient showed good chemotherapy response and is still under treatment. Even with "so called° fatal RB cases, some case could survive with intensified therapy. Data accumulation is necessary for better survival of these tumors.
STMO-04 LOCAL CONVECTION-ENHANCED DELIVERY OF CHEMOTHERAPY AS TREATMENT FOR BRAIN TUMORS
Authors: Saito Ryuta , Kanamori Masayuki , Tominaga Teiji
Published: December 2019

BACKGROUND

Convection-enhanced delivery (CED) of therapeutic agents is a promising local delivery technique that has been extensively studied as a treatment for CNS diseases over the last 2 decades. Applying this technique to treat brain tumors, we have been working to develop novel local chemotherapy against brain tumors. In the meanwhile, clinical trial against diffuse intrinsic brain tumor aiming at Japanese “shonin” approval is recruiting patients. In this study, potential of local CED based chemotherapy against supratentorial brain tumor is discussed.

METHODS

Until today, we have evaluated the safety and efficacy of local CED of nimustine hydrochloride against supratentorial malignant glioma patients in the three prospective, single institute, nonrandomized, open-label studies. Among those, one study recruited the recurrent malignant glioma patients whose enhanced tumor can be surgically resected. After the resection of the tumor, CED of ACNU was performed targeting the surrounding brain. Temozolomide was also given for 5 days during this trial.

RESULTS

Seven patients; 4 male and 3 female, age 33–71 y.o. (median 54 y.o.), were treated in this study. Five patients suffered glioblastoma and two suffered anaplastic astrocytoma. After the treatment, all seven patients lived longer than a year; one survived three years, one survived four and a half years, and one with glioblastoma is still alive after 5 years.

DISCUSSION

Potential efficacy of local chemotherapy delivering nimustine hydrochloride with CED against recurrent malignant glioma was suggested. Further study is required to pave the way for this strategy against supratentorial malignant gliomas.
STMO-14 SURGICAL MANAGEMENT OF DEEP-SEATED GLIOMA AROUND THALAMUS
Authors: Saito Kuniaki , Kobayashi Keiichi , Shimada Daisuke , Iijima Shohei , Shiokawa Yoshiaki , Nagane Motoo
Published: December 2019

BACKGROUND

Higher extent of resection contributes to better prognosis of the patients with glioma. However, resection of deep-seated glioma represents a surgical challenge not only because of the depth but because of adjacent eloquent structures such as pyramidal tract, deep venous system, and brainstem.

METHODS

We performed a retrospective review of patients with deep-seated glioma around thalamus who underwent surgery between March 2014 and February 2019. The tumors were removed with use of neuronavigation, DTI tractography, electrophysiological monitoring and photo dynamics diagnosis using aminolevulinic acid via interhemispheric or transcortical approach. Volumetric analysis of preoperative tumor volume as well as postoperative residual volumes was performed.

RESULTS

A total of 17 patients, ages ranged from 13–79 years (median; 51) were eligible. Twelve patients underwent radical resection and 5 underwent biopsy (2 with craniotomy, 2 with endoscopy, and 1 stereotactic biopsy). Pathological diagnosis consisted of glioblastoma (GBM) in 10, diffuse midline glioma (DMG) in 3, anaplastic astrocytoma in 3, and diffuse astrocytoma in 1. Extent of resection of the patients attempted radical resection was 96.7%±6.4%. Postoperatively, 12 patients developed hemianopsia, 2 had hemiparesis because of corticospinal tract injury, 2 sensory disturbance, and 3 cognitive dysfunction. At 1 month after surgery, Karnofsky performance status (KPS) worsened in 5 GBM patients and 1 DMG patient, while improved or stable in the rest 11 patients.

CONCLUSION

Resection of deep-seated glioma around thalamus accompanies a high risk of neurological deficits. Nevertheless, radical resection without KPS decline can be achieved by preserving the corticospinal tract, deep venous system, and brainstem and minimizing damages of surrounding brain.
MPC-09 THE OPTIMIZATION OF TREATMENTS FOR SO-CALLED PRIMITIVE NEUROECTODERMAL TUMORS WITH MOLECULAR ANALYSIS
Authors: Suzuki Mario , Fujita Naohide , Ogino Ikuko , Fujimura Junya , Kondo Akihide
Published: December 2019

INTRODUCTION

In the previous WHO classification of central nervous tumors, the supratentorial tumors comprise small round blue cells with aggressive clinical features had been defined as primitive neuroectodermal tumor (PNET). Recent molecular analysis revealed that they do not belong to a single entity, but they are re-classified as the tumors of other well-defined tumors and newly defined tumor species. These facts were reflected to the new classifications. While, there are few studies those showed the re-consideration of treatments for tumors diagnosed as so-called PNET. In this study, we propose the optimization of treatments for tumors diagnosed by the new classification to clarify which treatments were effective for the tumors those were diagnosed as PNET.

MATERIALS AND METHODS

The tumor samples diagnosed as so-called PNETs were analyzed. The molecular information was extracted from tumor specimens. We used high throughput analysis with microarray, FISH, and immunohistochemistry. They all had treated in our institution in last 6 years and their clinical courses were followed by medical records. Informed parental consent was obtained from their guardians and this study was approved by the institutional review board of Juntendo university.

RESULTS

Nine tumor samples were able to be analyzed and they are re-classified into high-grade glioma, neuroblastoma, sarcoma, embryonal tumors with multilayered rosettes, C19MC altered (ETMR). They resembled each other closely in morphology, and therefore, it was not able to be classified by histopathological findings. There was a case of pineoblastoma, whose molecular background suggested that the tumor was re-classified into neuroblastoma. In terms of treatments, we have succeeded in neuroblastoma cases so far, ETMRs were required multiple surgeries and radiations to maintain remissions.

CONCLUSIONS

Re-classification of diagnosis based on the molecular background is necessary to clarify the optimization of treatments for pediatric brain tumors, and the comprehensive methods is required. We present our methods for molecular diagnosis in clinical field and future plans.
MPC-11 IDH1/2 MUTATIONS ARE ASSOCIATED WITH SEIZURE ONSET AND VETRY IMAGING IN PATIENTS WITH DIFFUSE GLIOMA VISUALIZING 2-HYDROXYGLUTARATE BY MASS SPECTRUM
Authors: Ohno Makoto , Hayashi Mitsuhiro , Aikawa Hiroaki , Matsushita Yuko , Miyakita Yasuji , Takahashi Masamichi , Ichimura Koichi , Hamada Akinobu , Narita Yoshitaka
Published: December 2019

BACKGROUND

Mutations in isocitrate dehydrogenase 1 or 2 genes (IDH1/2) frequently occur in lower-grade gliomas. Mutant IDH1/2 proteins gain a new ability to produce 2-hydroxyglutarate (2HG). IDH1/2 mutations have shown to be related with seizure through the structural similarity of 2HG to glutamate. We, therefore, sought to investigate the relationship between seizure and IDH1/2 mutations and to visualize tissue 2HG distribution in patients with diffuse gliomas.

METHODS

We assessed 149 patients with diffuse glioma, and measured tissue 2HG concentrations in 104 patients by using liquid chromatography-tandem mass spectrometry. The matrix-assisted laser desorption/ionization high resolution mass spectrometry imaging (MALDI-HR-MSI) was used to visualize tissue 2HG distribution for 12 tissue samples.

RESULTS

Seizure onset was observed in 34 among 56 (60.7%) patients with IDH1/2 mutant tumor, whereas in 18 among 93 (19.4%) patients with IDH1/2 wild-type tumor (p<0.0001). The tissue 2HG concentration was significantly higher in IDH1/2 mutant tumor than in IDH1/2 wild-type tumor (median: 4862 ng/mg vs 75 ng/mg) (p<0.0001). Multivariate analysis, including tissue 2HG concentration, IDH1/2 status, histology, grade, and location, showed that IDH1/2 mutations was significantly correlated with seizure onset. The MALDI-HR-MSI showed that 2HG spread in various concentration independent of cellularity and also in extracellular space in IDH1/2 mutant tumor tissue.

CONCLUSIONS

We demonstrated the association between IDH1/2 mutations and seizure, and the heterogeneous 2HG distribution not only in cellular area but also in extracellular space. These findings suggest the potential role of 2HG as an intercellular mediator to tumor environment, resulting in epileptogenesis formation.
MPC-14 BRAF V600E MUTANT OLIGODENDROGLIOMA-LIKE TUMORS WITH CHROMOSOMAL INSTABILITY IN ADOLESCENTS AND YOUNG ADULTS
Authors: Fukuoka Kohei , Tabori Uri , Hawkins Cynthia
Published: December 2019

We performed genome-wide methylation analysis on 136 pediatric low grade gliomas, identifying a unique cluster consisting of oligodendroglioma-like BRAF V600E mutant tumors with Recurrent gain of Chromosome 7 and loss of Chromosome 10 (OLIVER). Hierarchical clustering and t-stochastic neighbor embedding analyses cluster them with previously described pediatric-type low grade gliomas, separate from adult gliomas. OLIVERS exhibit distinct clinical behavior as temporal lobe lesions in adolescents and young adults, prolonged history of seizures and all are alive with no recurrence (follow-up 3.2 to 13.2 years). Morphogically, all showed oligodendroglioma-like features, including round nuclei with perinuclear halos, a chicken-wire pattern of branching capillaries and microcalcification. None showed astrocytic features or characteristics suggestive of high-grade tumors including necrosis or mitotic figures. All tumors harbored multiple chromosomal copy number abnormalities (more than 10 chromosomes per OLIVER), but none showed 1p/19q co-deletion or IDH1 mutation. Interestingly, one tumor showed a TERT promoter mutation. Although the series is small, OLIVER may represent a new category of IDH wild-type low grade gliomas which may be confused with molecular GBM. Further, they highlight the heterogeneity of IDH wild-type gliomas and the relatively indolent behavior of pediatric-type gliomas.
NI-14 EVALUATION OF PREOPERATIVE APPARENT DIFFUSION COEFFICIENT (ADC) OF PERITUMORAL LESION FOR PREDICTING SITE PRONE TO RECURRENCE IN PATIENTS WITH GLIOBLASTOMA
Authors: Matsuda Kenichiro , Sakurada Kaori , Kayama Takamasa , Sonoda Yukihiko
Published: December 2019

PURPOSE

In the surgery of glioblastoma (GBM), the maximum safe resection is desired in order to prevent recurrence. The purpose of this study is to make it possible to evaluate the site in which the recurrence after resection of the tumor occur, according to the findings in preoperative MRI, and to avoid the recurrence.

METHOD

The 26 initial cases with GBM treated in our department was investigated. Preoperative MRI, postoperative MRI, and follow-up MRI during the course were analyzed in a retrospective view. In the FLAIR high-signal area around the contrast-enhanced tumor body in preoperative MRI, we investigated the relationship between the site and the ADC value, from the standpoint of whether a recurrence occurred or not.

RESULTS

For preoperative MRI of 26 patients, the FLAIR high-signal region was set to a total of 54 ROI, and several values, such as the ADC values, were measured. In the preoperative images, ADC were higher in the site where the no recurrence occurred during the postoperative course and lower in the site where the recurrence occurred.

CONCLUSION

In the FLAIR high-signal area around the tumor in preoperative images, ADC value is useful in evaluating whether it has tendency to develop the recurrence in the future course or not. It was suggested that significant recurrence occurs at part with low-ADC value. It is considered useful for the planning of the extent of resection in the surgery and the irradiation range in radiation treatment.
NQPC-07 IMMEDIATE POSTOPERATIVE REHABILITATION FOR PATIENTS WITH NEWLY-DIAGNOSED GLIOMA
Authors: Ikeda Mitsuyo , Yamada Shin , Okajima Yasutomo , Saito Kuniaki , Kobayashi Keiichi , Shiokawa Yoshiaki , Nagane Motoo
Published: December 2019

BACKGROUNDS

Importance of early intensive rehabilitation is recently emphasized not only for Stroke Unit but for Intensive Care Unit. We have started such early comprehensive rehabilitation for patients after brain tumor surgery. Rehabilitation therapists were specially assigned to our brain surgery unit as members of the ward staffers. The purpose of this study is to show how this rehabilitation trial works for post-surgery patients with glioma.

METHODS

Thirty-two patients with glioma (20 males and 12 females) who were admitted to our institution in the year of 2018 were included. Mean age was 61.8±13.3 years; glioblastoma was the major tumor type (24 patients). We retrospectively analyzed rehabilitation outcome focusing on improvement of the Functional Independence Measure (FIM) scores during hospitalization.

RESULTS

Mean duration from surgery to the first rehabilitation intervention was 2.4±1.2 days, and mean hospital stay was 74.4±31.4days. Twenty patients were discharged to home (62 %) and 12 were transferred to other hospitals for convalescence. Motor, cognitive and total FIM scores were 41.0±22.2, 18.0±7.5, and 59.1±27.3 before surgery, whereas they were 61.4±28.6, 21.8±9.4, and 83.2±36.9, respectively, at discharge. Motor FIM items revealed more remarkable improvement than those of cognitive ones. Since starting the early intensive rehabilitation trial, patients with brain tumor have been systematically rehabilitated with an organized manner before and after surgery.

CONCLUSION

Early intensive rehabilitation for patients with brain tumor is recommended to be done by on-ward therapists who are assigned to work specially as members of the ward. Both motor and cognitive improvement is expected during hospitalization even in patients with malignant brain tumor.
NQPC-10 END-OF-LIFE PHASE OF GLIOBLASTOMA
Authors: Omura Tomoko , Miyakita Yasuji , Omura Takaki , Ohno Makoto , Takahashi Masamichi , Satomi Natsuko , Fujimoto Kenji , Narita Yoshitaka
Published: December 2019

BACKGROUND

Despite aggressive treatment with surgery and chemo-radiation therapy, it is difficult to cure patients with glioblastoma (GBM). The end-of-life (EOL) phase of patients with GBM, and related problems, have not yet been adequately studied. Most cancer patients died in the hospital (84%) in 2017, but the Japanese government has recommended palliative home-care and the number of deaths at home has recently been increasing. This study explores the current situation of EOL care for GBM patients in our hospital.

METHODS

We retrospectively examined the clinical course and EOL phase of 166 consecutive patients who were treated in our hospital between 2010 and 2017.

RESULT

In total, 107 patients died; 28 (26%) at home, 25 (23%) in hospice care, 9(9%) in nursing homes, 21(20%) in long-term care hospitals (LTCH), 13(12%) in our hospital, and 11(10%) in other neurosurgical hospitals. The median survival time and length of EOL phase for patients who died at home were 596 and 77 days; 469 and 103 days in hospice care; 528 days and 149 days in LTCH; 388 days and 52 days in our hospital; 802 and 91 days in other neurosurgical hospital; and 565 days and 55 days in nursing homes, respectively. The KPS of patients who transferred to LTCH or was started palliative care in other neurological hospital was 60. That of other patients was 50.The patients who died at home entered deep coma in the last 3.5 days (n=24) of life and could not take oral feeds for 7 days (n=26).

CONCLUSION

According to cancer patient study, the home-based palliative time of longer prognosis group were 59 days. EOL phase of GBM may be longer than other cancer. We must consider the problems of the EOL phase and improve the quality of EOL care.
ML-02 MULTIAGENT IMMUNOCHEMOTHERAPY, R-MPV-A, FOR PATIENTS WITH SECONDARY CENTRAL NERVOUS SYSTEM LYMPHOMA
Authors: Nagane Motoo , Kobayashi Keiichi , Saito Kuniaki , Shimada Daisuke , Matsumoto Yoshie , Iijima Shohei , Sasaki Nobuyoshi , Yamagishi Yuki , Takayama Nobuyuki , Shiokawa Yoshiaki
Published: December 2019

BACKGROUNDS

Standard of care (SOC) for primary central nervous system lymphoma (PCNSL) has been induction therapy with high-dose methotrexate (MTX)-based multiagent immunochemotherapies followed by consolidation, and we have shown that one such regimen, R-MPV-A have superior efficacy over HD-MTX alone with whole brain radiotherapy (WBRT). While SOC for secondary CNS involvement of systemic diffuse large B-cell lymphoma (DLBCL)(SCNSL) has not been established. Here we report the outcome of R-MPV-A for patients with SCNSL.

PATIENTS AND METHODS

Fifteen patients with SCNSL treated with R-MPV-A from January 2014 to January 2019 in Kyorin University Hospital were eligible. Prior treatment for systemic DLBCL was mostly R-CHOP. Response and survival outcomes were evaluated.

RESULTS

Median age was 68.0 y (55–84), male/female 6/9, median KPS 70 (40–90), histopathological confirmation was achieved in 12 patients (80%; biopsy 11). RMPV (rituximab+MTX+procarbazine+vincristine) 3 cycles in 3, 4–7 cycles in 6, 8 cycles in 5. WBRT and cytarabine were delivered in 6 and 9 patients, respectively. R-MPV resulted in 6 CRs/CRus, 5 PRs, 1 SD, and 2 PDs (Response rate 73%). R-MPV-A including consolidation led to 9 CRs/CRus, 2 PRs, 1 SD, and 2 PDs (complete response rate 60%). With median F/U period of 11.2 m (0.1–51.5), 1y-PFS and 2y-PFS of R-MPV-A were 66.0% and 56.6%, 1y-OS and 2y-OS were 72.2% and 72.2%, respectively. Median PFS/OS were not reached. Consolidation cytarabine was associated with better outcome. Three deaths occurred during the treatment (20%; two during R-MPV with aged 70s, KPS 40 and 50; one presented MTX clearance delay). No other serious adverse events were observed.

CONCLUSIONS

These results suggest the certain efficacy of R-MPV-A for SCNSL. Being heavily pretreated frequently, precautions should be taken to identify high risk cases.
ML-05 A CASE OF NEUROLYMPHOMATOSIS ARISED SECONDARILY FROM PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA
Authors: Horiguchi Keishi , Asano Hirofumi , Osawa Tadashi , Tosaka Masahiko , Yoshimoto Yuhei
Published: December 2019

A woman in her 40s. A biopsy of multiple intracranial lesions was performed, and the patient was diagnosed with DLBCL. As an initial treatment, 6 courses of high dose MTX therapy were performed and CR was achieved. Radiation therapy was not desired by the patient. On the 19th month after initial treatment, tumor recurrence was confirmed by MRI and added 2 courses of HD-MTX. On the 23rd month, second recurrence around the left basal ganglia were observed. One additional course of HD-MTX was performed, but due to the appearance of renal damage that was thought to be acute tubular necrosis, additional HD-MTX was not performed and whole brain irradiation was performed. She began complaining of pain in the trunk and extremities during radiation. When MRI and FDG-PET were performed in the 25th month, multiple lesions were found in the ganglia, plexus, and peripheral nerves from the cervical spinal cord to the sacral spinal cord. Cerebrospinal fluid cytology revealed atypical lymphocytes and lymphoma dissemination in the spinal cord. When intrathecal administration of the anticancer agent was performed nine times weekly, the CSF cytology was negative. Imaging findings showed that the lesions relapsed, although the lesions were temporarily reduced. After confirming that the renal function had recovered, two additional courses of HD-MTX were performed. Accumulation of FDG-PET in the lesion disappeared in the 29th month. However, peripheral neuropathic pain and paraplegia remained. Discussion: Neurolymphomatosis is considered to be a clinically rare disease that presents invasion of lymphoma into peripheral nerves including the cranial nerves, nerve roots or plexus. Diagnosis of NL has been required to be proved by nerve biopsy or autopsy, but noninvasive FDG-PET has been reported to be effective. In this case, CR was not obtained with anticancer drug intrathecal injection, and HD-MTX therapy was successful.
ML-09 DIAGNOSIS AND TREATMENT OF PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA IN HIV POSITIVE PATIENTS
Authors: Takano Koji , Nishimoto Keisuke , Yamazaki Hiroki , Murakami Koki , Tachi Tetsuro , Kidani Tomoki , Kanemura Yonehiro , Nakajima Shin , Masuda Tomohito , Kurusu Tomomi , Hirota Kazuyuki , Uechi Takashi , Watanabe Dai , Nishida Yasuharu , Uehira Tomoko , Fujinaka Toshiyuki
Published: December 2019

INTRODUCTION

HIV infection is known to cause a variety of central nervous system complications, such as malignant lymphoma (ML), toxoplasma encephalopathy, cryptococcal encephalopathy, progressive multifocal leukoencephalopathy (PML), brain tuberculosis and HIV encephalopathy. In our hospital, we performed brain biopsy for HIV-positive patients with central nervous system lesions suspected malignant lymphoma, or cases difficult to diagnose with blood, cerebrospinal fluid, and imaging alone. In this study, we retrospectively examined HIV-positive patients who underwent brain biopsy at our hospital, and analyzed diagnosis and treatment of patients with ML.

Methods HIV-positive patients who underwent brain biopsy in our hospital from January 2010 to April 2019 were examined in this study. We analyzed background factors, preoperative examination results, pathological diagnosis, treatment and prognosis.

RESULTS

There were 1,894 HIV-positive patients who were treated at our hospital during the period, of which 16 cases underwent a total of 18 brain biopsies. The final diagnosis was 7 ML (6 PCNSL, 1 brain metastasis), 3 toxoplasma encephalopathy, 1 PML, 1 brain tuberculosis, 1 immune reconstitution syndrome, 1 Penicillium marneffei infection, 1 hematoma and one case that could not be diagnosed. In patients with ML, preoperative sIL-2 receptor was higher and EBV positive cases in cerebrospinal fluid tended to be more common (p=0.051, p=0.086, respectively). Five of the six patients with PCNSL were treated at our hospital, four of which were treated with highly active antiretroviral treatment (HAART) and whole-brain irradiation and one with HAARA alone, resulting four with CR and one with SD. Four patients, except one who had sudden death of unknown cause, were still alive without recurrence (median observation period 44.5 months).

CONCLUSION

At the moment, it is difficult to diagnose ML without brain biopsy. HIV-positive status has been regarded as a poor prognosis factor in PCNSL patients, but the prognosis seems to have improved with HAART.
MET-01 INDICATION AND OUTCOME OF SALVAGE SURGERY FOR LOCAL PROGRESSION OF BRAIN METASTASIS PREVIOUSLY TREATED WITH STEREOTACTIC IRRADIATION
Authors: Mitsuya Koichi , Deguchi Shoichi , Nakasu Yoko , Hayashi Nakamasa
Published: December 2019

PURPOSE

To determine treatment outcome following salvage surgery (SS) for local progression of brain metastasis treated by stereotactic irradiation (STI).

METHODS

The clinical records of patients who underwent SS of local progression of brain metastases after STI at our institute between October 2002 and July 2019 were retrospectively reviewed. Kaplan-Meier curves were used for the assessment of overall survival (OS). The decision to perform SS was based on findings of magnetic resonance imaging and/or clinical evidence of local progression of the brain metastases and status of systemic disease. Prognostic factors for survival were analyzed; age, sex, primary cancer, RPA classification at surgery, extent of resection, radiotherapy after salvage surgery, and pre-surgical neutrophil-to-lymphocyte ratio (NLR).

RESULTS

Fifty-four SS of 48 patients were performed. The median age of the patients was 63 years (range 36–79). The median interval from STI to SS was 12 months. The median overall survival was 20.2 months from SS. Primary cancer were lung 34, breast 10, and other 10. Fourteen of 54 lesions (26%) developed local recurrence. Leptomeningeal dissemination occurred after the SS in 3 patients (5.7%). RPA classification (1 vs 3, HR:0.16, 95%CI: 0.03–0.59) (2 vs 3, HR:0.44, 95%CI:0.19–0.97) and primary cancer (breast vs lung, HR:0.21, 95%CI:0.05–0.64) (breast vs others, HR:0.08, 95%CI:0.015–0.32) (lung vs others, HR:0.38, 95%CI:0.16–0.94)) were identified as good prognostic factors of overall survival in multivariate analysis. The optimum NLR threshold value was identified as 3.65 for 1-year survival from SS (AUC0.62, sensitivity:71%).

CONCLUSIONS

Salvage surgery for local progression of brain metastases after STI in selected cases leads to a meaningful improvement in survival.
CS-04 INTEGRATED CLINICAL, HISTOPATHOLOGICAL, AND MOLECULAR DATA ANALYSIS OF 190 CENTRAL NERVOUS SYSTEM GERM CELL TUMORS FROM THE IGCT CONSORTIUM
Authors: Takami Hirokazu , Fukuoka Kohei , Mukasa Akitake , Saito Nobuhito , Shibui Soichiro , Nakazato Yoichi , Nishikawa Ryo , Matsutani Masao , Ichimura Koichi
Published: December 2019

BACKGROUND

We integrated clinical, histopathological, and molecular data of central nervous system germ cell tumors to provide insights into their management.

METHODS

Data from the Intracranial Germ Cell Tumor Genome Analysis Consortium were reviewed. A total of 190 cases were classified as primary GCTs based on central pathological reviews.

RESULTS

All but one of the cases that were bifocal (neurohypophysis and pineal glands) and cases with multiple lesions including neurohypophysis or pineal gland were germinomas (34 of 35). Age was significantly higher in patients with germinoma than other histologies. Comparison between tumor marker and histopathological diagnoses showed that 18.2% of histopathologically diagnosed germinomas were marker-positive and 6.1% of non-germinomatous GCTs were marker-negative, suggesting a limitation in the utility of markers or histopathology alone using small specimens for diagnosis. Comparison between local and central histopathological diagnoses revealed a discordance of 12.7%. Discordance was significantly less frequent in biopsy cases, implying difficulty in detecting all histopathological components of heterogeneous GCTs. Germinomas at the typical sites (neurohypophysis or pineal gland) showed a better PFS than those at atypical sites (p=0.03). A molecular-clinical association study revealed frequent MAPK pathway mutations in males (51.4 vs 14.3 %, p=0.007), and PI3K/mTOR pathway mutations in basal ganglia cases (p=0.004). Basal ganglia cases also had frequent chromosomal losses. Some chromosomal aberrations (2q, 8q gain, 5q, 9p/q, 13q, 15q loss) showed potential prognostic significance.

CONCLUSIONS

These in-depth findings of this study regarding the clinical and molecular heterogeneity will increase our understanding of the pathogenesis of this enigmatic tumor.
CS-12 IDH-1 MUTANT GLIOMA IN BROTHER AND SISTER, ONSET AT AGE OF 30s
Authors: Kitai Ryuhei , Yamauchi Takahiro , Neishi Hiroyuki , Isozaki Makoto , Tsunetoshi Kenzo , Matsuda Ken , Arishima Hidetaka , Kodera Toshiaki , Kikuta Ken-ichiro
Published: December 2019

A 38-year-old man consulted with our neurosurgery group at University of Fukui hospital, due to tonic-clonic seizures. An MRI revealed a non-enhanced intra-axial tumor at the left frontal lobe. CT showed no calcification in the tumor. The tumor was removed by awake brain surgery. The pathological specimen was diagnosed as a diffuse astrocytoma with IDH-mutant. Immunohistochemical staining and DNA sequencing confirmed a R132H mutation at IDH-1. Telomerase Reverse Transcriptase (TERT) promoter mutation and 1p 19q codeletion was not evident. Four years later, his sister, a 40-year-old woman, had an MRI as a routine medical check that found a right frontal tumor at the mirror site of her brother’s tumor, and with identical radiological findings. The tumor was completely removed. The specimen revealed oligodendrocytoma, with mutant IDH and 1p/19q co-deleted. DNA sequencing showed also R132H at IDH-1. TERT promoter mutation was evident at C228T, which is a surrogate marker for oligodendroglioma. IDH-mutant astrocytoma and oligodendroglioma in siblings; and germline mutation of IDH have not been reported. However, the respective incidences of astrocytoma and oligodendroglioma are 0.55/100,000/year and 0.26/100,000/year according to United State statistics, which indicates that merely coincidental occurrence of these tumors is extremely unlikely. A trigger for IDH mutation that runs in rare families could warrant whole-genome sequencing.
CS-14 A CASE OF CIC-REARRANGED INTRACRANIAL SARCOMA
Authors: Tanaka Shota , Sato Daisuke , Ikemura Masako , Takayanagi Shunsaku , Tsutsumi Kazuo , Saito Nobuhito
Published: December 2019

INTRODUCTION

Intracranial sarcoma is extremely rare among primary brain tumors and often misdiagnosed. Its standard treatment is yet to be established, and treatment options are discussed on a case-by-case basis. Here we report our recent case of intracranial sarcoma review the relevant literature.

CASE ILLUSTRATION

A 57-year-old right-handed man presented with headache and was found to have a 5cm mass in the right frontal lobe. Gross total resection was achieved without complications. Given the local pathological diagnosis being glioblastoma, adjuvant radiotherapy with concurrent temozolomide was administered. Further pathological examination revealed Capicua (CIC) rearrangement on FISH, which lead to the diagnosis of sarcoma. No further treatment was pursued at that time. However, he noticed rapid decline in the right visual acuity 7 months from the initial diagnosis. MRI demonstrated a rapidly-growing mass in the right optic nerve sized 1.5cm, which was depicted as a high uptake area on FDG-PET, suggestive of recurrence. Two cycles of chemotherapy with vincristine, ifosfamide, doxorubicin, and etoposide as well as GammaKnife stereotactic radiosurgery were performed with partial response. Sustained myelosuppression and debilitating constitutional symptoms precluded additional chemotherapy. No further recurrence was noted 1 year after diagnosis.

CONCLUSION

We have recently experienced a case of CIC-rearranged intracranial sarcoma. FISH was useful in detecting CIC rearrangement and reaching the correct pathological diagnosis. Rapid recurrence of the tumor was noted, but well controlled with radiochemotherapy.
COT-06 HBV REACTIVATION DURING AND AFTER THE TREATMENT OF MALIGNANT GLIOMA WITH TEMOZOLOMIDE
Authors: Kanamori Masayuki , Saito Ryuta , Uenohara Hiroshi , Tominaga Teiji
Published: December 2019

BACKGROUND

It has been reported that temozolomide treatment for malignant glioma can lead to the reactivation of Hepatitis B virus (HBV) and fulminant hepatitis. However, the frequency of HBV reactivation and the preventative effect of entecavir remains unclear. In this study, we retrospectively reviewed clinical features of the cases treated by temozolomide for malignant glioma, focusing on the reactivation of HBV and the effect of entecavir.

METHODS

We screened 129 cases with newly diagnosed and recurrent malignant glioma for HBs antigen, HBs antibody and HBc antibody before the administration of temozolomide. HBV-DNA were quantified by real-time PCR in the HBV carrier and the cases with occult HBV infection. HBV- DNA were monitored every 1–3 months by real-time PCR during temozolomide treatment and 12 months after completion of temozolomide. Entecavir were started before temozolomide treatment to the HB carrier, and if HBV-DNA became detectable at follow-up to the cases with occult HBV infection. Results 2 (1.5%) and 20 (15%) of 129 cases were HB carrier and had occult HBV infection, respectively. HBV- DNA in both of HB carrier turned negative after administration of entecavir, but transiently turned positive again during temozolomide treatment. In the cases with occult HBV infection, 4 (20%) patients had HBV reactivation. HBV- DNA turned negative after starting entecavir without liver dysfunction.

CONCLUSION

HBV carrier and the cases with occult HBV infection were not rare in Japan, and HBV reactivation developed frequently during temozolomide treatment. Because pharmacological prevention of HBV reactivation with entecavir was effective, the screening and monitoring is indispensable in the treatment of malignant glioma with temozolomide.
COT-12 CLINICAL MANAGEMENT AND TIMING OF SURGICAL TREATMENT FOR ASYMPTOMATIC GLIOMA
Authors: Matsuda Ryosuke , Morimoto Takayuki , Takeshima Yasuhiro , Tamura Kentaro , Yamada Shuichi , Nishimura Fumihiko , Nakagawa Ichiro , Motoyama Yasushi , Park Young-Su , Nakamura Mitsutoshi , Nakase Hiroyuki
Published: December 2019

BACKGROUND

In Japan, there are many cases where intracranial diseases are found accidentally due to the widespread use of MRI and brain check-up. Unruptured cerebral aneurysms and asymptomatic cerebral infarctions are often diagnosed, but asymptomatic glioma is rarely diagnosed. We analyzed the asymptomatic gliomas retrospectively among grade 2 or higher gliomas that had undergone diagnostic imaging or surgical treatment in our institution.

MATERIAL AND METHODS

Of 166 adults with grade 2 or higher grade glioma treated in our institution between 2007 and 2018, 15 cases were asymptomatic. Twelve cases were males and 3 were females, with an average age of 55.1 years (34–79 years). There were 7 cases found in brain check-up, 6 cases in the follow-up of other intracranial diseases, and 2 cases in migraine. Twelve patients, except 3 patients, have undergone surgical treatment, and the average time from an initial imaging to surgical treatment was 51.1 weeks (2 to 329 weeks). Eight patients were treated after radiological follow-up and 4 cases are treated within 2 months after the tumor was discovered. The pathological diagnosis was grade 2: 5 cases, grade 3: 2 cases, and grade 4: 5 cases. Three patients without surgical treatment were diagnosed as grade 2 on MRI. Six patients died during follow-up. The median survival time from the first surgical treatment for grade 3 and 4 glioma was 17 months.

CONCLUSION

Incidence of asymptomatic glioma is very rare. Even for asymptomatic gliomas, the prognosis is not so good due to malignant transformation and disease progression. It is important to explain the natural course of disease and treatment strategy accurately.
COT-14 CLINICAL FEATURES OF PEDIATRIC CENTRAL NERVOUS SYSTEM TUMORS
Authors: Higa Nayuta , Yonezawa Hajime , Uchida Hiroyuki , Oyoshi Tatsuki , Yoshimoto Koji
Published: December 2019

INTRODUCTION

Here,we discuss the presentation,histology,therapy,and outcome of central nervous system tumors in children.

METHODS

Treatment outcome and management was assessed for children diagnosed with central nervous tumors from 2007 to 2017 at Kagoshima University.

RESULTS

Eight-eight patients (56 boys,32 girls) with a mean age of 10.3 years were included in this study. Patient tumor types included: germ cell tumor (n = 26); medulloblastoma (n = 16); pilocytic astrocytoma (n = 8); glioblastoma (n = 8); ependymoma (n = 6,1 with grade 2,5 with grade 3); hemangioblastoma,schwannoma,and ganglioglioma (n = 3 each); SEGA,pilomyxoid astrocytoma,and diffuse astrocytoma (n = 2 each),and anaplastic astrocytoma,PPTID,PNET,PXA,DIA,central neurocytoma,astroblastoma,meningioma,and choroid plexus papilloma (n = 1 each). The most common patient clinical features were headache and vomiting associated with hydrocephalus. The median follow-up period was 61 months. All patients with germ cell tumors underwent adjuvant chemotherapy and radiation therapy (RT); patients with germinoma or immature teratoma were still alive,while patients with embryonal carcinoma,yolk sac tumor,or choriocarcinoma had poor prognosis with a median survival of 16 months. For cases of ependymoma,three patients received ICE chemotherapy and RT,and two patients received RT alone; median survival time was 31 months. For high grade glioma,seven patients received temozolomide and RT,and two patients received temozolomide alone; median survival time was 13 months.

CONCLUSIONS

Patients with germ cell tumors had a relatively good prognosis,while patients with ependymoma or high grade glioma had a poor prognosis. As treatment strategies for ependymoma and high grade glioma are currently limited,it is necessary to evaluate treatment options in consideration of clinical course and quality of life,in addition to histologic and genetic findings.
COT-16 INDICATION OF SYSTEMIC THERAPY FOR ELDER PATIENTS WITH BRAIN TUMORS: A SYSTEMATIC REVIEW AND PERSPECTIVE
Authors: Nakasu Yoko , Mitsuya Koichi , Nakasu Satoshi , Nozaki Kazuhiko
Published: December 2019

BACKGROUND

Little is known about indications and outcome prediction of systemic therapy for elderly patients with brain tumours. Clinical conditions of individuals are heterogenous from healthy to frail or diseased,moreover,are often reversible.

METHOD

We retrieved the literature of brain tumour,systemic therapy,chemotherapy,immunotherapy,in randomized controlled trials (RCTs) and reviews on PubMed database from 2008 to 2018.

RESULTS

1) Definition of elderly by age in years: Depending on each protocol,the definition is arbitrary. Patients older than 60 or 70 years are usually in the elderly group. 2) Systemic evaluation: Performance status (PS) and visceral function are not sufficient to assess elderly patients. Assessment tools specifically developed for the geriatric population are recommended to evaluate individual patients. 3) Effects and toxicity of systemic therapy: Only a few RCT showed no inferiority of outcome in patients older than 60 or 65 years. There are only few evidences about the senile fragility of blood-brain barrier or distribution of drugs in the elderly brain. Molecular subtyping of brain tumours might predict the effects and toxicities of therapies for elderly patients.

CONCLUSION

Feasibility of modern systemic therapies are not well studied for elderly patients with brain tumours. Clinical condition varies in individual elderly patients. We need prospective studies of systemic therapy in elderly patients based on an eligibility with not only chronologic age but comprehensive geriatric assessments.
COT-17 EFFECT OF BEVACIZUMAB AGAINST CYSTIC COMPONENT OF PRIMARY/METASTATIC BRAIN TUMORS
Authors: Yamasaki Fumiyuki , Takano Motoki , Yonezawa Ushio , Taguchi Akira , Onishi Shumpei , Kurisu Kaoru , Sugiyama Kazuhiko
Published: December 2019

BACKGROUND

Bevacizumab (BEV) improves the symptom via reducing the peritumoral edema and sometimes via reducing the size of brain tumor. However,the effect of BEV against cystic part of brain tumor has not been documented yet. In this report,we investigated the effect of BEV on cystic component of brain tumors.

MATERIALS AND METHODS

Our institutional review board approved this retrospective study. Between 2008 and 2018,139 patients with primary or metastatic brain tumor were treated with BEV in our Hospital. We defined cystic lesions as high intense lesion of size 1 cm or bigger on T2WI,and excluded necrotizing cysts and cystic changes in surgical resection cavity. The symptoms and images before and after administration of bevacizumab were evaluated. Changes in cyst size of brain tumor was evaluated as follows: CR (complete response=disappearance),PR (reduction by 50% or more),MR (reduction by 25–50%),SD (size change less than 25%),PD (increase by 25% or more). The effect of bevacizumab on tumor itself was determined according to RANO criteria.

RESULTS

Of the 139 patients,21 (15.1%) brain tumors had cystic component. The best response of cyst to BEV were as follows: CR 6,PR 7,MR 4,SD 4. The group of patients with progressively increasing cysts prior to BEV administration had significant cyst size reduction compared to stable cyst size groups at best response timing (mean 76.3% vs. 32.8%,P<0.01). Patients with cyst showed significant improvement of symptoms after the treatment with BEV compared to patients without cyst (P<0.01). However,response rate against tumor itself was not different between patients with or without cyst. Overall survival of glioblastoma patients after starting BEV was not different between tumor with cyst and without cyst.

CONCLUSION

BEV may be effective for patients who are symptomatic due to cystic enlargement.
Use of Ultraviolet Irradiation in Addition to Commonly Used Hospital Disinfectants or Cleaners Further Reduces the Bioburden on High-Touch Surfaces
Authors: Zeber John E , Coppin John D , Villamaria Frank C , Williams Marjory D , Copeland Laurel A , Chatterjee Piyali , Choi Hosoon , Jinadatha Chetan
Published: December 2019

Background

The reduction in microbial bioburden achieved by terminal disinfection in a hospital may vary considerably by type of disinfectant or cleaner and by environmental service (EVS) personnel. This study estimated whether supplemental ultraviolet (UV) irradiation after disinfection or cleaning reduced bioburden and whether the supplemental effect persisted after adjusting for disinfectant or cleaner type and EVS personnel.

Methods

Environmental samples for aerobic bacterial colonies (ABC) and methicillin-resistant Staphylococcus aureus (MRSA) were obtained from 5 high-touch surfaces in patient rooms at 3 time points: before manual cleaning, after manual cleaning using 1 of 3 disinfectants or 1 cleaner, and after UV irradiation.

Results

For ABC, the model-estimated mean (95% uncertainty interval) counts were 56% (48%–63%) lower for postmanual + UV compared with manual clean alone, and for MRSA they were 93% (62%–99%) lower for postmanual + UV vs manual clean alone.

Conclusions

Although UV supplementation provides incremental benefit in bioburden reduction across all cleaners or disinfectants tested, it provides the greatest benefit when supplementing cleaners or disinfectants with the lowest disinfection properties. UV irradiation provides additional bioburden reduction to manual cleaning or disinfection, even when accounting for variability introduced by different disinfectants and EVS personnel.