bluuebunny/crossref_metadata_2025 huggingface dataset:
STMO-11 CLINICAL EFFICACY OF AWAKE SURGERY: ANALYSIS OF 335 CASE ON EXTENT OF RESECTION AND SURVIVAL TIME
Authors: Fukui Atsushi , Muragaki Yoshihiro , Maruyama Takashi , Saito Taiichi , Nitta Masayuki , Tamura Manabu , Tuzuki Syunsuke , Ikuta Soko , Kawamata Takakazu
Published: December 2019

INTRODUCTION

Awake craniotomy (AS) with intraoperative mapping can be compatible to obtain maximal resection and preserve neurological function for glioma surgery. However, there is less evidence to improve overall survival for glioma patients. We compared the long-term outcome of glioma resection during AS and general anesthesia (GA).

METHODS

Continuous 335 patients with newly diagnosed glioma of WHO grade2 (G2) or higher who underwent surgery with intraoperative MRI between 2000 and 2013 were reviewed. Three-dimensional volumetric tumor measurements before and after operation were made. Multivariate analysis was used to evaluate the effect of awake surgery on overall survival (OS).

RESULTS

The mean age of all cases was 46 years, male: female 199: 136, mean preoperative tumor volume (PTV) 44.5cc, mean extent of resection (EOR) 88.31%, and median survival (MST) 82.6 months. MST of G4 was significantly longer in the AS group (AS 38.9 months vs. GA group 22.0 months: p = 0.03), while multivariate analysis showed that age and KPS was a significant prognostic factor, but AS was not. There was no significant difference in the EOR of G3 (AS group 80.1% vs. general anesthesia 84.2%: p = 0.365), and MST was also not significantly different (AS group 134.8 months vs. GA group 117.9 months: p = 0.338). G2 also had no significant difference in the EOR (AS group 84.6% vs. GA group 86.7%; p = 0.92), and MST was also not significantly different (AS group 152.9 months vs. GA group 135.1 months: p = 0.235). Analysis of G2 or G3 showed no significant differences in PTV, KPS, and age at the surgery between two groups.

CONCLUSION

Even if a glioma is located close to or within the eloquent area, AS can lead to EOR and OS equivalent to the removal of the non-eloquent area under GA.
RT-05 THE RESULTS OF GAMMA KNIFE RADIOSURGERY WITH BEVACIZUMAB (AVAGAMMA THERAPY) FOR RECURRENT GRADE II/III GLIOMAS
Authors: Asanome Taku , Sato Kenichi , Takanashi Masami , Ozaki Yoshimaru , Kinoshita Yusuke , Sugio Hironori , Ishida Yuki , Nakamura Hirohiko
Published: December 2019

BACKGROUND

For primary grade II/III glioma, we usually combine radiation therapy and chemotherapy after surgical resection. However, the treatment of recurrent grade II/III glioma is controversial. For lesions that can be safely resected, the second surgery may be optimal, but grade II/III glioma often occurs in or near the eloquent areas, so partial resection is often performed. In such cases, if a second surgery for the recurrent tumor is performed, total resection is often difficult. We have performed gamma knife radiosurgery with concurrent bevacizumab (GKRS with Bev) as salvage therapy for recurrent grade II/III gliomas, which were considered difficult to resect.

OBJECTIVE

To investigate the outcome of GKRS with Bev for recurrent grade II/III gliomas.  We retrospectively reviewed initial pathological findings, PFS/OS from GKRS with Bev, and OS from initial treatment for 23 cases receiving GKRS with Bev for recurrent grade II/III gliomas at our institution between August 2013 and March 2019.

RESULTS

In the initial pathological findings, grade II were 8 cases (DA: 7, OD: 1), and grade III were 15 cases (AA: 14, AOA: 1). Regarding IDH mutations, in grade II, 3 cases were mutant type, 2 cases were wild type, and 3 cases were unknown. Similarly, in grade III, 5, 6, and 4 cases, respectively. From salvage therapy, PFS was median 6 months in grade II and 8 months in grade III, and OS was median 11 months in grade II and 16 months in grade III. From the initial treatment, OS was median 95 months in grade II, and 38 months in grade III.

CONCLUSION

Because most of our cases were astrocytic tumors, when they relapsed, it seemed that some of them progressed to glioblastoma. Even in these severe cases, GKRS with Bev can play an important role as salvage therapy.
RT-06 PLANNING OF BORON NEUTRON CAPTURE THERAPY (BNCT) USING POSITRON EMISSION TOMOGRAPHY (PET)
Authors: Kawabata Shinji , Takeuchi Koji , Hiramatsu Ryo , Matsushita Yoko , Furuse Motomasa , Wanibuchi Masahiko , Isohashi Kayako , Aihara Teruhito , Ono Koji , Miyatake Shin-Ichi
Published: December 2019

Boron neutron capture therapy (BNCT) is the particle irradiation therapy that the selective radiation for tumor cells is available for theoretically. The role that the amino acid (phenylalanine) PET (18F-BPA-PET) that we used boronophenylalanine (BPA) which is a boron compound for neutron capture reaction as a tracer carries out is major in our BNCT especially for the recent non-craniotomy BNCT, and it covers by treatment, observation from indication. In this report, we introduce this PET as a principal axis about BNCT and a relation of the PET.In our BNCT, we calculated the drug accumulation to the tumor from BPA-PET before neutron irradiation and reflected it for individual treatment. We become able to decide indication of BNCT by using this PET study, and the indication expansion to other systemic cancers including head and neck cancer and lung, liver is now worked on actively. Also, in other irradiation modalities, they make a radiation plan based on PET study, and several reports to try the improvement of results had been present, however, high radiation doses will be “ exposed “ to the lesion showing high accumulation in BPA-PET in BNCT. We determine the neutron exposure time from the dosage for the normal tissue in the actual treatment, but the Lesion / Normal tissue ratio obtained from BPA-PET is reflected by the evaluation of the tumor dose and the following treatment plan. Also, after the treatment, diagnoses of the pathologic condition such as an increase in tumor volume, a recurrence or the radiation necrosis might be difficult, and we found that the PET study was useful in the follow-up stage for the patients with already treated malignant brain tumor.
MPC-12 ACCURACY OF INTRAOPERATIVE SIMPLE FLOW CYTOMETER FOR HIGH GRADE GLIOMA OPERATION COMPARED WITH INTRAOPERATIVE FROZEN DIAGNOSIS
Authors: Asano Kenichiro , Fumoto Toshio , Kamataki Akio , Ogawa Kaoru , Kakuta Kiyohide , Katayama Kosuke , Ohkuma Hiroki , Kurose Akira
Published: December 2019

INTRODUCTION

Intraoperative simple flow cytometer (iFC) was developed in recently, we examined the correlation intraoperative frozen diagnosis (IOFD) and intraoperative frozen section of resection margin (IOFM) to iFC.

METHOD AND MATERIAL

Total 33 cases of high grade glioma patients were underwent operation in April 2017 ~ May 2019, and IOFD and IOFM were compared to iFC. Sample of iFC were retrieved just same parts of IOFM and IOFD. We compared to microscopical findings, MIB-1, malignant index (MI), and MI Level (G0-4).

RESULTS

Accuracy rate of iFC and IOFD in high grade glioma was 84%, and the concordance rate of grading was17.2%. Correlation coefficients between MIB-1 and iFC of IOFD was r=0.5019 P=0.0065. Accuracy rate of IOFM was 46.8%, and concordance rate of grading was 35.5%. Correlation coefficients between MIB-1 and iFC of IOFM was r=0.5899 P=0.0001.

CONCLUSIONS

Although iFC accuracy rates iFC of IOFD and IOFM were high, iFC concordance rates and grade were low. Correlation between MIB-1 and iFC of IOFM was better than that of IOFD. Probably, iFC of IOFD was a little difficult because of sample heterozygosity.
NI-06 MOLECULAR DIAGNOSIS, 11C-METHIONINE UPTAKE AND PROGNOSIS IN GRADE 2 AND 3 GLIOMAS
Authors: Tamura Kaoru , Furuhashi Yaeko , Inaji Motoki , Kobayashi Daisuke , Ogishima Takahiro , Sumita Kazutaka , Tanaka Yoji , Nariai Tadashi , Maehara Taketoshi
Published: December 2019

OBJECT

The revised 2016 WHO Classification of Tumours of the Central Nervous System incorporates genetic alterations into the classification system, with the goal of creating more homogenous disease categories with greater prognostic value. In this study, we reclassified 103 consecutive lower grade gliomas using the revised 2016 WHO classification and examined for 11C-methionine uptake and prognosis.

METHODS

103 consecutive lower grade glioma patients (Grade 2 in 41 patients, Grade 3 in 62 patients) treated at Tokyo Medical and Dental University Hospital from 2000 to 2018 were included in this study. The IDH1/2, ATRX and 1p19q status were analyzed using tumor samples. The tumor-to-normal ratio (T/N) of 11 C-methionine uptake was calculated by dividing the maximum standardized uptake value (SUV) for the tumor by the mean SUV of the normal brain.

RESULT

In the integrated diagnosis, 11 astrocytomas and 17 anaplastic astrocytomas were diagnosed as “IDH-mutant”, while 14 astrocytomas and 29 anaplastic astrocytomas were diagnosed as “IDH-wild”. In the 32 oligodendroglial tumors, 12 oligodendrogliomas and 9 anaplastic oligodendrogliomas were diagnosed as “IDH-mutant and 1p/19q-codeleted”. The concordance rate with 1p19q co-deletion and ATRX retention was 94.7%. The median T/N ratios in oligodendroglial tumors with “IDH-mutant and 1p/19q-codeleted” were 1.83 in Grade 2 and 2.83 in grade 3, which were significantly higher than those in astrocytic tumors with “IDH-mutant” (G2: 1.38, G3:1.62). Kaplan-Meier survival analysis revealed that oligodendroglial tumors with “IDH-mutant and 1p/19q-codeleted” had significantly better outcomes regardless of WHO grade. Overall survival was 90.9% at 5 years and 77.9% at 10 years in oligodendroglial tumors with “IDH-mutant and 1p/19q-codeleted”.

CONCLUSIONS

The results indicated that lower grade glioma categories reclassified with molecular classification correlate with the T/N ratio of methionine and the prognosis.
NI-13 PREDICTION OF PROGNOSIS IN NEWLY DIAGNOSED GLIOBLASTOMA USING MACHINE LEARNING-BASED TEXTURE ANALYSIS OF PREOPERATIVE MRI
Authors: Umehara Toru , Kinoshita Manabu , Sasaki Takahiro , Arita Hideyuki , Yoshioka Ema , Shofuda Tomoko , Hirayama Ryuichi , Kijima Noriyuki , Kagawa Naoki , Okita Yoshiko , Uda Takehiro , Fukai Junnya , Mori Kanji , Kishima Haruhiko , Kanemura Yonehiro
Published: December 2019

INTRODUCTION

Preoperative magnetic resonance imaging (MRI) is a critical modality for the determination of glioblastoma (GBM) treatment strategy, as it is thought to reflect the biology of the tumor to some extent. The authors attempted to predict prognosis of newly diagnosed GBM (nGBM) using machine learning-based texture analysis of preoperative MRI in this study.

METHOD

A total of 160 nGBMs with determined overall survival were collected from Kansai Molecular Diagnosis Network for CNS tumors. Preoperative MRI scans (T1WI, T2WI, and Gd-T1WI) from all cases were semi-quantitatively analyzed leading to acquisition of 489 texture features as explanatory variables using Matlab-based in-house software. Dichotomous overall survival (OS) with a cutoff of 15 months was regarded as the response variable (short or long OS). Lasso regression was employed for feature selection to ensure robustness of the prediction model. One hundred patients were randomly assigned as training dataset (TR), followed by predictive model construction via 5-fold cross-validation. Subsequently, the constructed model was transferred to the remaining 60 patients, which was assigned as test dataset (TD). The survival distribution between populations with predicted short and long OS was compared using log-rank test.

RESULTS

Distributions of the analyzed data were as follows; 53 short OS cases in the TR (53.0%) and 27 cases in the TD (45.0%). As for the result of transfer analysis in TD, 38 cases out of 60 (63.3%) were predicted to be short OS (76.3 % of recall, 54.3% of precision, and 63.5% of F-measure). The population of predicted short OS significantly showed poorer prognosis (median OS 14.0 vs 19.1 months) (p=0.02, log-rank test).

CONCLUSION

Short OS was successfully identified from preoperative MRI with high recall rates with our algorithm. The presented result ensures the potential of machine learning-based texture analysis for prognostic stratification of nGBM.
NI-17 T2-FLAIR MISMATCH SIGN IN DIFFUSE GLIOMA AND DYSEMBRYOPLASTIC NEUROEPITHELIAL TUMOR
Authors: Onishi Shumpei , Yamasaki Fumiyuki , Takano Motoki , Yonezawa Ushio , Sugiyama Kazuhiko , Kurisu Kaoru
Published: December 2019

BACKGROUND

T2-FLAIR mismatch sign was reported as a specific imaging marker for diffuse astrocytoma with IDH-mutant and 1p/19q non-codeletion. However, most of the previous studies for T2-FLAIR mismatch were confirmed only among low grade glioma. The purpose of this study is to assess the T2-FLAIR mismatch sign in supratentorial diffuse glioma, diffuse midline glioma and dysembryoplastic neuroepithelial tumor (DNT) to unveil the exception rules of the sign.

METHODS

In total, 51 patients were included in this study; 33 supratentorial diffuse glioma (18 diffuse astrocytoma with IDH mutant (IDHmut-Noncodel), 12 oligodendroglioma with IDH-mutant and 1p19q codeletion (IDHmut-Codel), 3 diffuse astrocytoma with IDH wildtype (IDHwt)), 18 diffuse midline glioma and 11 DNT. The tumors were evaluated by 2 independent reviewers to assess presence or absence of T2-FLAIR mismatch sign.

RESULT

Ten out of 18 cases of IDHmut-Noncodel presented T2-FLAIR mismatch sign. None of the other supratentorial diffuse glioma (IDHmut-Codel and IDHwt) presented T2-FLAIR mismatch. The T2-FLAIR mismatch sign for IDHmut-Noncodel presented 100% positive predictive values among supratentorial diffuse glioma. However, 8 out of 18 cases of diffuse midline glioma and 8 out of 11 cases of DNT also presented the T2-FLAIR mismatch.

CONCLUSION

The T2-FLAIR mismatch sign was specific marker for IDHmut-NonCodel among supratentorial diffuse glioma. Physicians need to be aware that diffuse midline glioma and DNT could present the T2-FLAIR mismatch sign.
NI-19 USEFULNESS OF AMIDE PROTON TRANSFER IMAGE IN IMAGING DIAGNOSIS OF GLIOMA
Authors: Shirota Masami , Nitta Masayuki , Maruyama Takashi , Saitou Taiichi , Tsuduki Syunsuke , Ikuta Souko , Yoshida Ayako , Abe Kayoko , Abe Kouichirou , Muragaki Yoshihiro , Kawamata Takakazu
Published: December 2019

INTRODUCTION

APT image is one of the imaging methods in MRI, and it is a molecular image that images the concentration of an amide group having an amino acid increasing in a tumor, and is expected to be clinically applied in the imaging diagnosis of glioma. on the other hand, MET-PET is useful for diagnosis of glioma because it is well accumulated in tumor cells. Based on the results of pathological diagnosis, we compared the two and verified that APT image is useful.

METHOD

The study included 36 patients who underwent APT image and MET-PET. (Glioma WHO2016 Grade:GII/III/IV,and Pseudoprogression). MET-PET was administered 370MBq/kg, and the accumulation ratio (TNR) of the tumor part to the normal part was measured. APT image measured APT signal with the region of interest at the tumor site.

RESULTS

APT signal in all 36 cases was correlated with 2.19±0.94 and TNR with 2.61±1.55 (r=0.67,p<0.001).The discrimination accuracy between GII/III/IV and Pseudoprogression by APT signal was 84% sensitivity and 100% specificity at threshold 2.0.GII APT signal 2.30±0.43, TNR 4.02±2.12, GIII APT signal 2.67±0.69, TNR 2.81±0.72, GIV APT signal 2.78±0.61, TNR 3.37±1.28 in grade diagnosis At high grade, APT signal and TNR were high. The APT signal of the oligodendroglioma line (GII/III) was 2.44±0.7, the TNR was 3.78±1.51, the APT signal of the astrocytoma line (GII/III) was 2.69±0.51, and the TNR was 2.43±0.98.The oligodendroglioma lineage was lower in APT signal than the astrocytoma lineage, and the TNR was higher.

DISCUSSION

APT images are non-invasive, can easily provide important information, and have the same diagnostic potential as MET-PET. Although TNR of oligodendroglioma (GII/III) tends to be high, the APT signal which is not affected by the blood-brain barrier is consistent in measurement value and is useful for diagnostic imaging of glioma.
NQPC-05 BEVACIZUMAB AFTER PROGRESSION OF GLIOBLASTOMA PROLONGS PATIENT’S LIVING TIME AT HOME IN THE LAST 90 DAYS
Authors: Matsutani Tomoo , Hirono Seiichiro , Iwadate Yasuo
Published: December 2019

Bevacizumab (Bev) is currently available for recurrent glioblastoma to improve a patient’s quality of life (QoL). To maintain a patient’s daily life activity, Bev is sometimes continued beyond radiographical progression until neurological deteriorations. However, the benefit of continuous use of Bev in its terminal stage is not clarified. To clarify the benefit, we retrospectively analyzed clinical data of glioblastoma patients in the terminal stage. Ninety-five patients, who died by supra-tentorial newly-diagnosed glioblastoma progression from 2008 to 2018, were included. Bevacizumab use in the last 90 days, living time at home or final place of death were retrospectively analyzed. Of 95, twenty-six received Bevacizumab beyond progression in the last 90 days (Bev-group), and 49 did not (non-Bev group). The median overall survival time is not different between both, and the number of patients, who died at home, is seven (26.9%) and six (12.2%), respectively. Mean final administration day from death is 49.2 days and the mean living time at home in the last 90 days is 49.2 days in the Bev group, which is statistically longer than 24.0 days of the non-Bev group (p=0.0016).To continue Bev beyond progression prolongs the living time at home in the last 90 days in glioblastoma patients, and Bev should be considered in its palliative care.
ML-04 PROGNOSTIC SIGNIFICANCE OF IMMUNOHISTOCHEMICAL SUBTYPES BASED ON THE STAGE OF B-CELL DIFFERENTIATION IN PRIMARY CNS LYMPHOMA
Authors: Inoue Akihiro , Kohno Shohei , Matsumoto Shirabe , Suehiro Satoshi , Nishikawa Masahiro , Ozaki Saya , Watanabe Hideaki , Ohnishi Takanori , Kunieda Takeharu
Published: December 2019

PURPOSE

Primary central nervous system lymphoma (PCNSL) has been immunohistochemically classified into two subtypes, germinal center (GC) B-cell and non-GC B-cell, but prognostic impact of these subtypes remains debated. We investigated clinical features and prognostic significance of newly defined immunohistochemical subtypes that were identified by expression patterns of three B-cell differentiation markers in PCNSL. In addition, we analyzed a factor related to responsiveness to high-dose methotrexate (HD-MTX) chemotherapy.

METHODS

Tumors from 32 PCNSL patients were immunohistochemically evaluated regarding expression of CD10, BCL-6, and MUM-1 and classified into subtypes according to the expression patterns of these markers. Clinical features and prognostic outcome of these subtypes were investigated.

RESULTS

Twenty-three patients were treated with HD-MTX-based chemotherapy followed by whole-brain radiation therapy (WBRT), and nine were treated with WBRT alone. Three immunohistochemical subtypes were identified, including A-type expressing CD10, BCL-6, and MUM-1 (12 patients), B-type expressing BCL-6 and MUM-1 (12 patients) and C-type expressing MUM-1 only (8 patients). Response rate in the HD-MTX therapy group was 57.1% (4/7) in A-type, 87.5% (7/8) in B-type, and 75% (6/8) in C-type. C-type with the lowest metabolic activity showed significantly longer overall survival than A-type with the higher uptake of methionine (71.6 versus 39.6 months).

CONCLUSIONS

Immunohistochemical identification of PCNSL based on the B-cell differentiation stage revealed three types of tumors, showing different metabolic activity and survival time. Refined immunohistochemical classification of PCNSL subtypes may become a useful tool for predicting more accurate prognosis and accessing the sensitivity to HD-MTX therapy.
ML-07 R-MPV-A THERAPY FOR PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA IN THE ELDERLY: OUTCOME AND PROBLEM
Authors: Fudaba Hirotaka , Momii Yasutomo , Onishi Kouhei , Asou Daigo , Fujiki Minoru
Published: December 2019

PURPOSE

R-MPV-A therapy has recently been reported to improve the outcomes of primary central nervous system lymphoma (PCNSL). Our patients have received R-MPV-A therapy since 2017 and elderly patients have only been treated with whole brain radiotherapy when they do not show a complete response after induction chemotherapy. We report the therapeutic outcomes and problems of elderly PCNSL patients treated with R-PMV-A.

MATERIALS & METHODS

Eight newly diagnosed PCNSL patients received R-MPV therapy from September 2017 to June 2019. We retrospectively reviewed the cycles of R-MPV therapy, radiotherapy, consolidation high-dose Ara-C (HD-Ara-C) therapy, and the G8 score (a geriatric assessment).

RESULTS

Patients were divided into three groups: Group A (71–75 years; n=2), Group B (76–80 years; n=4), and Group C (>81 years; n=2). All Group A patients finished 5 cycles of R-MPV therapy, showed a complete response, and underwent consolidation HD-Ara-C therapy. Two Group B patients showed a complete response on R-MPV therapy. One of the other patients showed a partial response after 3 cycles of R-MPV therapy, and a >3 kg reduction in body weight. The patient’s G8 score was 12 points. Whole brain radiotherapy (23.4 Gy) was administered followed by local radiotherapy (21.6 Gy). One patient showed a partial response after 7 cycles of R-MPV therapy and started radiotherapy. One Group C patient received radiotherapy after 3 cycles of R-MPV because of a new lesion. The other Group C patient showed acute renal damage after 3 cycles of R-MPV.

CONCLUSION

R-MPV-A therapy was relatively safe for our elderly PCNSL patients. Notably, patients >76 years of age sometimes had severe adverse effect with increased R-MPV cycles. A promising therapeutic strategy based on age and geriatric assessment is needed.
ML-11 DETECTION OF MYD88 MUTATIONS FROM CELL FREE DNA AIDS IN THE DIAGNOSIS OF CENTRAL NERVOUS SYSTEM LYMPHOMAS
Authors: Natsumeda Manabu , Watanabe Jun , Kanemaru Yu , Tsukamoto Yoshihiro , Okada Masayasu , Oishi Makoto , Fujii Yukihiko
Published: December 2019

BACKGROUND

Diagnosis of primary central nervous system lymphomas (PCNSL) can be challenging. We have shown that the detection of MYD88 mutation in cell free DNA (cfDNA) taken from cerebrospinal fluid (CSF) is reliable (JCO Precision Oncology, 2019; Leukemia and Lymphoma, 2019). We report four cases in which detection of MYD88 mutation aided in the diagnosis.

CASE 1

A 67-year-old man with a history of systemic B-cell lymphoma, experienced right hemiparesis. MRI showed a slightly enhancing lesion located in the midbrain. MYD88 L265P mutation was found by digital droplet PCR analysis of cfDNA extracted from CSF. The patient underwent a needle biopsy, and was diagnosed as diffuse large B-cell lymphoma.

CASE 2

A 32-year-old man was diagnosed as having a demyelinating lesion after experiencing severe headaches. A small enhancing lesion was found in the right frontal lobe, and the patient was treated with steroids. The lesions repeatedly disappeared and reappeared and finally, stopped responding to steroids. MYD88 mutation was detected. A biopsy was performed, and the diagnosis was PCNSL.

CASE 3

A 49-year-old man underwent a biopsy for a right frontal lesion after experiencing memory loss; the pathology showed broad T-cell infiltration but only some perivascular B-cells with slight atypia. The patient was tapered off steroids, and the lesion spread rapidly. An open biopsy was performed, but the pathology was not typical for B-cell lymphoma. The patient’s symptoms rapidly worsened, and whole brain irradiation was performed. At recurrence, MYD88 mutation was detected.

CASE 4

An 82-year-old man presented with blurred vision. Vitreous humor biopsy was inconclusive for ocular lymphoma. A head MRI showed an intracranial lesion which spontaneously regressed. MYD88 was detected, and the patient is being closely observed.

CONCLUSION

Detection of MYD88 mutation from cfDNA extracted from CSF can aid in the diagnosis of CNS lymphoma, especially in atypical cases.
ML-14 LOW INVASIVE APPROACH FOR PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA TREATMENT INVOLVING RITUXIMAB–METHOTREXATE + PROCARBAZINE + VINCRISTINE AND TRIPLE INTRATHECAL INJECTION
Authors: Ogawa Takahiro , Oowada Kei , Tanba Kazuna , Hirakawa Kouichi
Published: December 2019

INTRODUCTION

Although the treatment outcomes of primary central nervous system lymphoma (PCNSL) with multiple treatment regimens involving high–dose methotrexate (MTX)–based multiagent chemotherapy have improved compared with the outcomes with high–dose methotrexate therapy in recent years, its regimen has not been established. Additionally, it is controversial whether intrathecal (IT) MTX injection can be included in a regimen. Our facilities treat PCNSL with R–MPV (rituximab–methotrexate + procarbazine + vincristine) and triple IT injection (methotrexate + Ara C + prednisolone). Here we report a low invasive approach for PCNSL treatment involving R–MPV therapy and triple IT injection.

CASE DESCRIPTION

A 58–year–old woman complained of prolonged headache and had undergone a medical checkup at our department. Head computed tomography revealed a mass lesion with edema near the right anterior horn of the lateral ventricle. After being hospitalized, biopsy was performed via a small craniotomy for the mass lesion near the right anterior horn of the lateral ventricle, which was suspected to be PCNSL. Multipurpose Head Frame 2 (Mizuho Co., Ltd.) was used for four points of head fixation. Vertek Biopsy Kit (Medtronic Co., Ltd.) was attached to it, and needle biopsy guided by neuronavigation was performed. Finally, biopsy samples were obtained from the lesion. Changes in the entry and target points could be easily made through the operative procedure, which was performed uneventfully. The diagnosis was B–cell–related lymphoma. Subsequently, an Ommaya reservoir was placed via lumbar puncture on postoperative day 7. Finally, the patient was successfully treated with R–MPV therapy and triple IT injection, thereby avoiding repeated lumbar puncture and reduced pain associated with IT injection.

CONCLUSION

We have reported the diagnosis of PCNSL with needle biopsy guided by neuronavigation and its treatment with R–MPV therapy and triple IT injection after lumbar Ommaya reservoir placement. This approach was associated with reduced invasion and pain in the patient.
MNG-01 NATURAL HISTORY OF ASYMPTOMATIC MENINGIOMAS: REVIEW WITH META-ANALYSES
Authors: Nakasu Satoshi , Nakasu Yoko
Published: December 2019

Frequency of meningioma as an incidental finding in neuroimaging study is increasing. It is important to characterize tumors that will grow to be symptomatic in order to select appropriate treatment and radiological follow-up because long-term observation may increase the risk of surgery due to enlargement of the tumors and aging of patients. [Methods]We reviewed 26 studies that analyzed natural courses in asymptomatic or untreated meningiomas. RESULTS: In time-growth rate analysis, nearly 70% of meningiomas showed radiological progression defined by a volume criteria and the rate approached plateau at 5–6 years. About half of incidental meningiomas presented a decelerating growth pattern or no growth while less than one-fourth of them grew exponentially. Growth pattern change could be affected by the length of follow-up period. Radiological progression, growth speed (annual volume change (AVC) or relative growth rate (RGR)) and symptomatic progression had each different factor related to their progression. Younger age, non-calcification and high intensity on T2 weighted image related to radiological progression and rapid growth speed but not to symptomatic progression. Tumors in men and lager size were likely to be symptomatic in meta-analysis. AVC (>= 2.1cm3/year) was the strongest indicator for symptom development. In the group of AVC >=2.1cm3/year, progression free rate was 69.3% at 3 years, and reached to 55.4% at 6 years whereas 100% in slower growth group. [Conclusion]Radiological features may not be useful for prediction of symptom development except for perifocal edema in a long term. This may be due to dynamic change of these radiological markers in a long term. Quantitative tumor size and growth speed especially AVC were important factors for decision of treatment.
MNG-07 A CASE OF TRANSFORMED ANAPLASTIC MENINGIOMA IN 18 YEARS
Authors: Fujii Yu , Ogiwara Toshihiro , Yamazaki Daisuke , Nagamine Kohei , Horiuchi Tetsuyoshi
Published: December 2019

INTRODUCTION

Although 95% of meningiomas are benign tumor (WHO grade I), they rarely exist malignant transformation. It is well known that WHO II or III meningiomas rapidly grow and recurrent frequently. However, there are no common sense about duration of malignant transformation between previous reports. Here we report a case of anaplastic meningioma which showed malignant transformation in 18 years.

CASE

The patient was 77-year-old man. He was pointed out as having a 20-mm mass in the left occipital convexity at brain checkup 19 years before. After 6 months, the mass was totally removed (Simpson grade I) at previous hospital. Histopathological diagnosis revealed meningioma with psammoma body, whose Ki-67 index was below 1 %. Postoperative course was good and periodic follow up was abandoned. The patient presented with consciousness disturbance and right hemiparesis after 18 years from the first operation. CT scan showed a 30-mm mass with intratumoral hemorrhage and perifocal edema in the left occipital lesion. Tumor removal was performed. The border of the tumor was clear and the macroscopic view was compatible with meningioma at intraoperative findings. The tumor was removed as much as possible, but partially remained which were extended to superior sagittal sinus (Simpson grade III). Histopathological findings were anaplastic meningioma with sarcoid change, whose Ki-67 index was 70%. His neurological abnormality improved postoperatively.

DISCUSSION

In the previous report, anaplastic meningioma is a rare tumor, which is 1% of whole meningioma. The rate of malignant transformation is reported 12–38%. The cause of malignant transformation is reported to be radiation therapy, mechanical stimulation by surgical manipulation, viral infection, and loss of chromosome. Although recurrence rate is low at total resection of meningioma, there rarely exists malignant transformation after a long period of time like our case.
BT-05 A CASE OF GLIOMATOSIS CEREBRI WITH TOTAL SPINAL CORD EXTENSION
Authors: Chiba Yasuyoshi , Takemoto Osamu , Yamada Junji , Matsumura Takaki
Published: December 2019

INTRODUCTION

Although gliomatosis cerebri is no longer a pathological diagnostic name, it is still an important disease state as a gliomatosis cerebri growth pattern. Here we report a case of gliomatosis cerebri originating from the left cerebral hemisphere that developed whole spinal cord.

CASE

A 10-year-old boy. He has a history of 13q-syndrome and left retinoblastoma. Left eye enucleation and chemotherapy (modified 98A1) have been performed. MRI in July 2017 showed no abnormalities, but in September 2018, he developed epilepsy. MRI revealed a gliomatosis cerebri that spreads extensively in the left cerebral hemisphere. Biopsy revealed anaplastic astrocytoma (MIB-1 LI; 22%, IDH1 / 2; WT, TERT C228T mutation positive) and IMRT (59.4Gy) and temozolomide (Stupp regimen) were performed in December 2018. In June 2019, neck pain developed. Head and neck MRI revealed that the tumor in the head increased lightly, and there was no suspicion of tumor growth in the brainstem, but the tumor progressed to the entire spinal cord. Therefore, radiation therapy was started from the lower brainstem that had not been irradiated last time to the entire spinal cord, and administration of bevacizumab was started.

DISCUSSION

Based on the single cell origin theory, the left hemisphere tumor and spinal cord tumor should be continuous. Since gliomatosis cerebri is visualized on MRI only after the tumor volume has increased and edema has occurred, it may appear as if there is no tumor in between. The spinal cord MRI was not taken, so it is only speculation, but it seems that tumor cells had probably infiltrated the spinal cord from the beginning, and it seems that it gradually increased because it was not irradiated. Considering the possibility of remote invasion as in this case, it is necessary to consider taking MRI of spinal cord at the first occurrence.
BT-09 CLINICAL AND MOLECULAR GENETIC FEATURE OF CEREBELLAR GLIOBLASTOMA
Authors: Iijima Shohei , Saito Kuniaki , Shimizu Saki , Kobayashi Keiichi , Shimada Daisuke , Matsumoto Yoshie , Shiokawa Yoshiaki , Nagane Motoo
Published: December 2019

INTRODUCTION

Cerebellar glioblastoma (cGBM) is extremely rare, accounting for 0.7–0.9% of all gliomas. Few studies have reported on clinical course, histopathology, and prognosis. In this report, we discussed cases which were diagnosed as cGBM, and were treated in our institute.

Materials and Methods

We retrospectively analyzed 9 cGBMs (age ranged 41 to 85 years, median 69), operated at our institute after 2010 January, and evaluated their  promoter methylation,  mutation, and Copy Number Variation status detected by methylation-specific PCR (MSP), DNA sequencing or immunohistochemistry, and Multiplex Ligation-dependent Probe Amplification (MLPA), respectively.

RESULTS

All patients underwent resection; 3 gross total resections (GTRs, 33%), 2 subtotal resections, 4 partial resections, with relatively low achievement of GTR. The tumor location predominated in the cerebellar hemisphere (7 patients, 78%) over vermis (2). One patient had brain stem invasion. After surgery, 8 patients received temozolomide (TMZ) and radiotherapy (RT), while did only one RT alone. After recurrence, three patients were treated with bevacizumab monotherapy, and other three received either TMZ and RT, TMZ and ACNU, or TMZ monotherapy. The median progression-free survival (PFS) was 12.0 months, and the median overall survival (OS) was 17.1 months. Five patients (56%) were  methylated, whereas all were wild-type.  deletion was negative in all patients.  amplification and combined  amplification and  deletion were found in one patient each.

DISCUSSION

Despite the lower rate of GTR, there was a tendency of longer PFS compared to supratentorial GBM (sGBM). The clinical course after recurrence was unfavorable, and OS thereafter was similar to that of sGBM. cGBMs appeared to lack the typical genetic mutations occurred in sGBM, suggesting that cGBMs might be stimulated with different regulatory cellular signals.
CS-02 CLINICAL AND MOLECULAR ANALYSIS OF ASTROBLASTOMAS
Authors: Ichikawa Tomotsugu , Mino Satoshi , Kenmotsu Naoya , Kuramoto Satoshi , Ono Yasuhiro , Kawauchi Masamitsu , Kurozumi Kazuhiko , Date Isao , Shimada Akira , Nakamura Satoko , Yanai Hiroyuki , Hirato Junko , Yokoo Hideaki
Published: December 2019

Astroblastoma is extremely rare brain tumor which mostly arise in cerebral hemisphere of children and young adult. Limited data exists on its clinical feature and molecular analysis. We recently experienced two female patients with astroblastoma in the cerebrum.

Case 1 is three-year-old girl. She developed left hemiparesis. CT and MRI revealed large supratentorial mass with cystic component and calcification. Gross total removal was achieved. She is well without recurrence on MRI one year after surgery. Case 2 is 42-year-old lady. She developed partial seizure. CT and MRI revealed a mass with ring-enhancement in the left temporal lobe. Gross total removal was achieved under awake craniotomy. She is well without recurrence on MRI six months after surgery. Pathologic examination of both patients showed pseudorosette formation of tumor cells around vasculature. Molecular analysis revealed rearrangement of MN-1 in case 1 but not in case 2. Case 2 showed BRAF V600E mutation and loss of CDKN2A/2B. Both patients received no adjuvant therapy.

Prognosis of astroblastoma varies and standard of treatment is not established. Gross total resection is associated with increased survival, but the role of adjuvant chemotherapy and radiation therapy are controversial. Advances in molecular analysis will lead to establish molecular classification and risk-adapted treatment strategy.
CS-09 PROPOSAL OF A NEW CLASSIFICATION FOR DETERMINING THERAPEUTIC STRATEGY ACCORDING TO THE PROGRESSION OF OLFACTORY NEUROBLASTOMA
Authors: Motegi Hiroaki , Yamaguchi Shigeru , Ishi Yukitomo , Endo Shogo , Kobayashi Hiroyuki , Terasaka Shunsuke , Suzuki Masanobu , Nakamaru Yuji , Homma Akihiro , Houkin Kiyohiro
Published: December 2019

INTRODUCTION

Olfactory neuroblastoma (ONB) is a rare type of malignancy that infiltrates and propagates from the nasal cavity to the anterior skull base and into the cranium. Various treatment strategies have been used at different institutions and time of treatment. Although the staging system proposed by Kadish is commonly adopted has not proven useful for predicting prognosis or choosing among treatment strategies. Factors to be considered have increased accordingly, for example, whether to perform ESS alone or in combination with craniotomy, whether to try preserving the olfactory sense and whether to use neoadjuvant chemotherapy. In this study, we reviewed ONB cases treated at our institution to propose a new classification system to help determine treatment strategies.

METHODS

Thirty-four patients treated at Hokkaido University were included. Stages of craniocaudal progression were defined as Nasally/Paranasally localized (NP), Frontal Base progression (FB), and Brain invasion (BI). Stages of lateral progression were defined as Midline (M) or Lateral extension (L), and Unilateral (U) or Bilateral (B).

RESULTS

Between 2008 and 2016, patients at the BI stage were proactively treated with neoadjuvant chemotherapy and achieved long-term survival (mean overall survival, 64.2 months). However, no standard way of choosing among treatment options was established. M-stage patients underwent concurrent craniotomy. From 2017 onwards, 5 patients were treated according to the new classification system. All were FB-M cases, including 4 cases of B disease, in which ESS alone followed by radiotherapy was used. One patient in the FB-M-U category underwent unilateral resection and the olfactory sense was preserved. In general, the treatment with ESS alone appeared to be preferred for M disease, and surgery after neoadjuvant chemotherapy was advisable for BI cases.

CONCLUSION

The result suggests that the new classification system is helpful to decide the treatment strategy according to the progression of ONB.
COT-02 TREATMENT EXPERIENCE OF PAZOPANIB FOR A CASE OF VON-HIPPEL LINDAU DISEASE
Authors: Hayashi Nobuhide , Koyama Yoshiki , Tsuji Eisaku , Okada Hideo , Kuwata Toshikazu
Published: December 2019

INTRODUCTION

von Hippel-Lindau (VHL) disease is an autosomal dominant genetic disorder associated with neoplastic lesions in multiple organs. Here, we report our experience with a patient with VHL disease presenting with complications of renal tumors, wherein pancreatic cystic lesions and renal neoplastic lesions were reduced in size with the administration of pazopanib at our department.

PATIENT

The patient was a 26-year-old man who presented with hiccups and was diagnosed with medullary hemangioblastoma with a cyst that was resected. The other central nervous system lesions were located in the right optic nerve sheath, cervical and thoracic spinal cord, with multiple cystic type tumors in the pancreas, renal tumors, and epididymal tumors. Although the family history was unclear, the clinical diagnostic criteria for VHL disease were met, and mutations were found in the VHL gene analysis. Six months after the initiation of pazopanib therapy at a dose of 800 mg/day, there was no remarkable change in the hemangioblastoma on imaging; however, the pancreatic and renal lesions had shrunk. In addition, new lesions did not appear. Adverse events included diarrhea, graying of hair.

DISCUSSION

Pazopanib is a multi-tyrosine kinase inhibitor that inhibits angiogenesis and inhibits tumor growth. In VHL disease, pancreatic and renal tumors influence the survival prognosis, and for hemangioblastoma, the lesions increase in number and size and the corresponding surgery affects the functional prognosis. Although there was a poor tumor-reduction effect on the hemangioblastoma, there was a supposed inhibitory effect on the appearance of new lesions and the enlargement of the existing lesions.

CONCLUSION

Pazopanib administration resulted in the shrinkage or regression of pancreatic and renal lesions. In addition, it inhibited the increase in number and size of hemangioblastomas. Further, prolonging the surgical treatment interval may help maintain the patient’s quality of life.
COT-07 HEREDITARY BRAIN TUMOR DISEASE MEDICINE IN THE CANCER GENOME MEDICAL AGE-IMPORTANCE OF MULTIDISCIPLINARY COLLABORATION AND GENETIC COUNSELING
Authors: Takayanagi Shunsaku , Tanaka Shota , Shin Masahiro , Nakatomi Hirofumi , Oseto Kumiko , Sato Atsushi , Saito Nobuhito
Published: December 2019

INTRODUCTION

Recently, the cancer genome medical system has been rapidly promoted in Japan, such as cancer related gene panel test as NCC oncopanel and Fonduation One being covered by insurance. At the same time, there is a great deal of attention now on hereditary tumor diseases caused by abnormalities in cancer-related genes and their medical treatment. Von Hippel-Lindau (VHL) disease and tuberous sclerosis (TSC) are one such hereditary tumor disease, and develop tumors in multiple organs such as kidney tumors and lung tumors as well as brain tumors. The University of Tokyo Hospital has been developing an in-hospital medical care system for VHL disease and TSC. [VHL disease] If VHL disease is diagnosed at an early stage and strives for early detection and treatment of tumor, it is said that the prognosis is not largely different from normal people. Therefore, our hospital opened a specialized outpatient for VHL disease from 2012, and has carried out genetic diagnosis of VHL disease and medical treatment based on it. [TSC] Recently, the use of Afinitor for SEGA was covered by insurance in Japan, and a system in which multiple departments involved in our hospital cooperated was established, and regular meetings were held to determine treatment policies.

DISCUSSION

It was the development of genetic counseling system and multidisciplinary cooperation system that was important in any disease. Genetic counseling helps patients with illness and their families to genetically understand and adapt to illness. In the case of hereditary diseases, the practice of genetic counseling was very useful. In addition, since it is a disease involving multiple organs, close cooperation with other in-hospital clinics has been extremely useful for early detection and treatment of patient’s lesions.
COT-15 LITERATURE REVIEW ON THE DECISION MAKING OF THE BRAIN TUMOR PATIENT
Authors: Kishi Tatsuya , Sakurada Naoya , Horikawa Mayumi , Ohkubo Haruaki , Ishii Kazumi , Miyakita Yasuji , Ohno Makoto , Takahashi Masamichi , Narita Yoshitaka
Published: December 2019

BACKGROUND

Patients with primary brain tumors find it difficult to make decisions during the advanced disease stage and experience decreased consciousness. It is important for patients to receive supported decision-making early. Medical staff should know what to do and when to do it,but there are no clear guidelines. Therefore,we reviewed the literature for supported decision-making for primary brain tumor patients,particularly to provide information for understanding trends reported in previous research.

METHOD

On January 1,2019,we conducted a search using keywords,such as “brain tumor”and “decision-making,” via PubMed and “Igakuchuo-zashi” in Japan. We extracted literature about treatment decision support and end-of-life care for patients with primary brain tumors. Furthermore,we studied and chose the documents for information provision.

RESULT

Upon observing 7 studies,we found: 1) about 50% of the patients want more prognostic information; 2) patients with brain tumor tend to be anxious,but they want more information to develop a good understanding of the disease and to lower their anxiety; 3) about half of the brain tumor patients in end-of-life care are unable to make decisions sooner owing to impaired consciousness,and hence are unable to share treatment preferences with their doctors; 4) when medical professionals provide information,such as adding video tools about end-of-life care to oral explanations,it facilitates supported decision-making; and 5) when the caregiver intends to notify patients,the family feels conflicted.

DISCUSSION

The results suggested that if the timing of the end-of-life conversation is late,it becomes difficult for the patient to make decisions and the burden of decision-making falls on the family. It is necessary to examine effective supported decision-making tools for patients by assessing and comprehending information needs and anxiety levels of primary brain tumor patients.
COT-23 INITIAL EXPERIENCE OF TREATMENT FOR GLIOBLASTOMA BY NOVO-TTF
Authors: Omura Takaki , Miyakita Yasuji , Ohno Makoto , Takahashi Masamichi , Satomi Natsuko , Fujimoto Kenji , Omura Tomoko , Narita Yoshitaka
Published: December 2019

PURPOSE

In 2018,Optune (TTF) became available covered by public insurance for patients with glioblastoma,based on the effectiveness of the US EF-14 study (TTF + TMZ (temozolomide) vs. TMZ). There are problems such as use of at least 18 hours a day,behavior restrictions,expensive medical expenses,etc. From the initial use experience of optune in our hospital,we examined the problems of effectiveness and treatment of TTF.

METHOD

We examined patient approval rate of TTF use and treatment problems in patients with glioblastoma who started treatment in our department from 2017.11 when TTF became covered by insurance.

RESULT

There were 41 patients with primary glioblastoma during the study period (male: female = 25: 16,median age 60 years (22–77)). There are 10 patients with KPS <70 that are not TTF indications (male: female = 7: 3,median age 45.5 (29–64),consent rate 38.5%). For 26 people (63% of the total) excluding 5 patients who participated in clinical trial,we explained that TTF indications,clinical trial results,adverse events,wearing rate should be 75% or more,and that full shaving is required. 10 people wanted to undergo TTF treatment. The consent rate of women is lower than that of men (46.7% vs. 27.3%),there was a tendency to take TTF treatment in young patients. Average wear rates of 5 patients who continued for more than 6 months were 55%,76%,84%,85%,91%,respectively. Use of TTF for 6 months or longer with residual tumor was CR 1 case,PR 1 case,SD 2 cases. Our department policy is to continue for 12 months. One person ends in 12 months,the other continues to use TTF. So far,no adverse events caused by TTF have been observed,though,there were complaints about the weight of the equipment,feeling of binding,restrictions on bathing,etc.,and one person stopped using it in the fifth month.

DISCUSSION

The consent rate for TTF use was about 40% as expected,and 80% of patients with an average wearing rate of 75% or more. TTF can generally continue once the patient is convinced and begins to use,but seems to be severely restricted in behavior in patients with paralysis. There is no profound data on TTF in Japan,and it is necessary to collect data at multiple facilities and clarify the effectiveness and safety in the future.