bluuebunny/crossref_metadata_2025 huggingface dataset:
NQPC-18 THERAPEUTIC STRATEGY FOCUSING ON COGNITIVE FUNCTION AND QOL IN ELDERLY PATIENTS WITH MALIGNANT BRAIN TUMORS
Authors: Momota Hiroyuki , Saito Tsuyoshi
Published: December 2022

Background

Standard treatments for malignant brain tumors, such as glioblastoma (GBM) and primary CNS lymphoma (PCNSL), are recently established, except for elderly patients with neuro-cognitive impairment. We investigated our experience to adjust possible therapeutic strategy for malignant brain tumors in elderly patients according to cognitive function and QOL.

Methods

We utilized medical record data from 2015 to 2022 in our facility. Fourteen patients (11 patients with GBM and 3 with PCNSL) were retrospectively analyzed for performance status before and after surgery, neuro-cognitive function, treatments, and survival data.

Results

Median age was 76 years old, median preoperative Karnofsky performance status (KPS) was 70, median postoperative KPS was 60, and median score of mini mental state examination (MMSE) was 18/30. Several patients with GBM deteriorated on the MMSE score and KPS after surgery, and the individuals who scored < 10 on the MMSE avoided radiation thrapy, while two patients with PCNSL improved on the MMSE score and KPS. Three patients with GBM and two patients with PCNSL received standard therapies. The rest of patients received alternative therapies; three patients had medical problems for receiving standard treatment, three patients avoided radiation therapy due to cognitive impairment, and three patients declined standard treatment. Median overall survival time in GBM patients was 254 days, and two patients with PCNSL have been still alive.

Conclusions

Treatments for malignant brain tumors in elderly patients are difficult, because of their comorbidities, shorter life expectancy, and cognitive impairment. On the other hand, anticancer drug therapy alone is sometimes effective and prolongs survival of those patients. Development of personalized treatment is needed focusing on cognitive function and QOL in elderly brain tumor patients.
NQPC-21 QOL EVALUATION IN THE TREATMENT COURSE OF CNS LYMPHOMA
Authors: Yamagishi Yuki , Hanayama Naomi , Sasaki Nobuyoshi , Saito Kuniaki , Kobayashi Keiichi , Nakatomi Hirofumi , Shiokawa Yoshiaki , Nagane Motoo
Published: December 2022

Background

Primary central nervous system lymphoma (PCNSL) is the second common primary malignant brain tumor. Compared to glioma, the treatment period is often longer, but there have been few research reports on QOL evaluation during the treatment yet. In this study, we retrospectively examined the QOL scores obtained during and following treatment of PCNSL to determine the association between changes in the QOL score and response to treatment, with particular interest in the issue in the evaluation over time.

Methods

Patients with newly-diagnosed PCNSL who were treated and evaluated for QOL by EORTC QLQ-C30/BN-20 at our facility since April 2016 were included.

Results

A total of 69 patients were included, with a median age of 69, and a male to female ratio of 41:32. The median KPS was 70, and the median MMSE score was 29 points, indicating that a majority of the patients who could undergo the testing retained adequate cognitive function. There were 38 patients (55.1%) who maintained CR during the QOL evaluation period, and their QOL function scores tended to be maintained above the baseline. In contrast, 31 patients (44.9%) who relapsed during the QOL evaluation period showed a tendency to decline in global health at the time of recurrence or evaluation immediately before recurrence, with the worsened symptom score reflecting the localization of recurrence. Any associations of changes in QOL score with therapeutic methods were identified. Changes in QOL scores were rather frequently observed with exacerbation of comorbidities, perhaps due to a high incidence of PCNSL in the elderly patients.

Conclusions

EORTC QLQ-C30/BN-20 enabled QOL evaluation that might reflect treatment effect in PCNSL. The reporting rate to the questionnaire was low in patients with substantial brain dysfunction, and QOL evaluation may also be affected by comorbidities. Further investigation of influencing factors on QOL evaluation is warranted.
ML-4 POLICY CHANGE TO PCNSL TREATMENT LED BY HEMATOLOGY, AND INITIAL TREATMENT RESULTS
Authors: Hashiba Tetsuo , Iwamura Haruka , Naito Nobuaki , Lee Kyo , Miyata Mayuko , Lee Ichi , Kamei Takamasa , Takeda Junichi , Yoshimura Kunikazu , Tenjin Hiroshi , Nonaka Masahiro , Asai Akio
Published: December 2022

In the treatment of PCNSL, chemotherapy is becoming the main treatment, in a while, radiation therapy is becoming to be avoided. In our hospital, hematology leads an initiative to the treatment of PCNSL from 2021. During the 7 years from 2016, there were 32 cases of PCNSL that underwent initial treatment at our hospital, of which 8 cases occurred after 2021. The breakdown was 6:2 male to female, and the average age was 71.3 years. In 5 relatively young patients, remission was induced with 5 to 6 courses of R-MPV therapy, 3 of which received high-dose chemotherapy combined with autologous peripheral blood stem cell transfusion, all of whom avoided RT and have maintained remission. In 3 older patients, only RT was performed in 1 and HD-MTX therapy was performed in 2, of which RT was combined in 1 and BSC was introduced due to treatment related sepsis in another patient. Although the follow-up period was short, there has been no recurrence except for one patient who became BSC. On the other hand, in 24 patients before 2020, HD-MTX therapy combined with RT was performed in all patients, except for 1 patient who underwent RT only due to advanced age and 1 patient who died before treatment due to poor general condition. Recurrence was observed in 8 cases, and additional RT and chemotherapy were performed. Although no recurrence was seen in 16 cases, there are only 4 patients who had been still followed up, 6 died, and 6 had unknown or BSC, with a poor prognosis. One of the reasons was thought to be related to the decrease in ADL due to radiation injury. In the absence of recurrence, ADL may be maintained long-term in young patients. On the other hand, elderly people cannot avoid RT, which is still a problem.
ML-5 THE TRANSITION OF THE TREATMENT OF 60 PCNSL CASES AT OUR INSTITUTION AND CLINICAL CONSIDERATIONS
Authors: Yoshitake Hidenobu , Negoto Tetsuya , Komaki Satoru , Nakamura Hideo , Morioka Motohiro
Published: December 2022

The efficacy of RMPV-A (rituximab, methotrexate, procarbazine, vincristine, and cytarabine) and whole brain irradiation for primary central nervous system lymphoma (PCNSL) have recently been reported. Our institution also introduced RMPV therapy in 2020 after an era of conventional HD-MTX to cytarabine and rituximab combination. In this report, we analyzed 60 PCNSL cases treated from 2013 to 2021.There were 32 female patients (53%) with a median age of 70 years (30-87). Five patients (8%) received radiotherapy alone as initial treatment, 30 (50%) received HD-MTX (including radiation), 17 (28%) received HD-MTX plus rituximab or cytarabine, and 9 (13%) received RMPV therapy. The response rate (CR, CRu, PR) in the HD-MTX group was 88%, and the complete response rate (CR, CRu) was 51%. In contrast, the RMPV arm had a response rate of 100% and a complete response rate of 6 patients (66.7%). 7 patients (14%) in the HD-MTX arm and 2 patients (22%) in the RMPV arm were unable to continue treatment due to adverse events. The treatment of PCNSL has undergone significant changes in recent years, with the availability of RMPV-A, thiotepa, and tirabrutinib, and it is now possible to construct treatment that avoids leukoencephalopathy caused by radiation therapy as much as possible, which had been a major problem of conventional therapy. However, because of the use of strong drugs, caution must be exercised when treating patients in poor general conditions, especially the elderly. However, the present analysis indicates that many elderly patients can be successfully treated with careful observation. In the future, it is essential to accumulate cases treated with RMPV therapy and tilabrutinib and conduct further data analysis to establish a new generation of treatment for PCNSL.
ML-8 HIGH-DOSE CHEMOTHERAPY SUPPORTED BY AN AUTOLOGOUS STEM CELL TRANSPLANT IN RELAPSED PRIMARY CNS LYMPHOMA
Authors: Mishima Kazuhiko , Tkahashi Naoki , Shirahata Mitsuaki , Suzuki Tomonari , Mizuno Reina , Adachi Junichi , Ozawa Tastuya
Published: December 2022

Background

Many patients with primary CNS lymphoma (PCNSL) relapse despite complete response (CR) after initial therapy. Relapsed PCNSL (rPCNSL) has a poor prognosis, and no adequate standard of treatment has been established. Autologous stem cell transplant (ASCT)-assisted high-dose chemotherapy (HDC) for rPCNSL is a promising treatment option, as is thiotepa (TT), which has been used in malignant lymphoma as a treatment option for PCNSL. In March 2020, TT was approved in Japan as a pre-treatment for ASCT in malignant lymphoma. TBC, TT with busulfan and cyclophosphamide, and BCNU+TT are used in Europe and the US, but treatment-related mortality (TRM) has been reported in about 10% of patients. The regimen approved in Japan is Buslufan-TT(BuTT) therapy in combination with busulfan, which differs from TBC in dosage, and there is little information on efficacy and safety for rPCNSL. In our hospital, we have introduced BuTT therapy for rPCNSL in patients under 65 years of age. In this report, we describe our experience with this treatment. Subjects: Five patients with rPCNSL since May 2021, age <66 years, PS 0-2, are included in this study.

Methods

After obtaining CR with (R)MPV therapy after relapse, peripheral blood stem cells were harvested after administration of G-CSF and plerixafor, pretreated with BuTT therapy (Bu: 3.2 mg/kg, Day-8, -7, -6, -5: TT: 5 mg/kg, Day-4, -3) and transplanted on Day 0.

Results

Adverse events of Grade 3 or higher were abdominal pain in 2 cases, diarrhea in 1 case, pharyngitis in 2 cases, sepsis in 1 case, and pleuritis in 1 case, but all recovered, and no TRM was observed. All five patients are currently alive without recurrence.

Conclusion

HDC/ASCT is expected to be a curative treatment for rPCNSL. Future issues include the establishment of an upper age limit for the indication.
ML-9 TREATMENT OUTCOMES OF TIRABRUTINIB FOR RELAPSED AND REFRACTORY PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA IN A SINGLE INSTITUTE
Authors: Ohka Fumiharu , Yamaguchi Junya , Motomura Kazuya , Takeuchi Kazuhito , Nagata Yuichi , Maeda Sachi , Nishikawa Tomohide , Kibe Yuji , Shimizu Hiroki , Saito Ryuta
Published: December 2022

Recent clinical studies improved prognosis of primary central nervous system lymphoma (PCNSL) using multiple treatment reagents combined with radiation therapy. However, for recurrent and refractory cases after treatment with regimen consisting of multiple reagents, potent effective treatment has not been established yet. Tirabrutinib, Bruton's tyrosine kinase inhibitor was introduced for treatment of recurrent and refractory PCNSL in Japan. However, case series study investigating the clinical outcome of PCNSL cases treated with tirabrutinib have not been reported yet excepting for phase I/II study of tirabrutinib. We treated nine recurrent and two refractory cases. In all of these cases, except for one case exhibiting severe skin rash in spite of cessation of administration of tirabrutinib, we obtained favorable overall response rate (CR or Cru=5 and PR=5) together with favorable progression free survival (median; 339 days). Five cases exhibited skin rash (CTCAE grade 3; n=2 and grade 2; n=3). Grade 3 or 2 skin rash were found on day 9 or 75 of tirabrutinib treatment, respectively. In one case, MYD88 mutations in ctDNA derived from blood plasma were turned to be negative after one week administration of tirabrutinib. Although adverse effects such as skin rash was frequently found, tirabrutinib is effective for recurrent or refractory PCNSL cases. Our data suggested that treatment response of tirabrutinib could be evaluated via evaluation of copy number analysis of MYD88 mutations in ctDNA of blood plasma.
MET-4 ANALYSIS OF METASTATIC BRAIN TUMORS DISCOVERED AT THE SAME TIME AS THE PRIMARY LESION
Authors: Yamamoto Yohei , Nawate Syohei , Nakamura Aya , Ishii Takuya , Tanaka Toshihide , Akasaki Yasuharu , Murayama Yuichi
Published: December 2022

Introduction

Among metastatic brain tumors, especially in cases where the primary tumor and metastatic brain tumor are found at the same time, it is necessary to consider the priority of treatment for intracranial lesions and the means to obtain a definitive diagnosis. In this study, we performed a statistical analysis on the factors affecting mean survival (mOS) in patients with concurrent primary and metastatic brain tumors.

Subjects and Methods

A total of 252 patients with metastatic brain tumors treated at our hospital since 2014 were divided into two groups: simul-meta (58 patients) and non-simul-meta (194 patients). Age, sex, primary tumor, number of tumors, presence or absence of metastasis to other organs, localization of intracranial lesions, presence or absence of carcinomatous meningitis, performance status (PS), details of therapeutic intervention (radiation therapy, chemotherapy, surgery). The background factors between the two groups were analyzed using the chi-square test. Factors affecting mOS were evaluated by univariate analysis with log-rank test and multivariate analysis with Cox proportional hazards test.

Results

In simul-meta and non-simul-meta, mOS was 328 and 295 days, respectively (p=0.864). As a background, lung cancer (76%: 59%; p = 0.02) and surgical intervention group (28%: 11%; p <0.01) were numerous in simul-meta. Good prognostic factors in the simul-meta group extracted by multivariate analysis were surgical intervention and cases of chemotherapy. Chemotherapy cases were stratified into conventional chemotherapy and molecular-targeted drug use, and the prognosis of molecular-targeted cases was better than that of conventional chemotherapy (p=0.01).

Discussion

In patients with concurrent disease, it is important to complete treatment for intracranial lesions, including surgical treatment, and maintain a general condition that allows chemotherapy to be administered. In addition, considering the frequent occurrence of lung cancer, it is necessary to develop a treatment plan with molecular target therapy in mind.
MET-8 EFFECT OF VEGF-TARGETED THERAPY FOR SYMPTOMATIC/REFRACTORY BRAIN EDEMA CAUSED BY METASTATIC BRAIN TUMORS
Authors: Fumiyuki Yamasaj , Takayasu Takeshi , Yonezawa Ushio , Taguchi Akira , Onishi Shumpei , Novita Ikbar , Sugiyama Kazuhiko , Horie Nobutaka
Published: December 2022

Background

Molecular target therapy with EGFR and ALK inhibitors greatly improved the prognosis of lung cancer patients with driver mutation-positive metastatic brain tumors. Inhibitors of VEGF are also useful for treating brain edema induced by brain metastases. In this study, we examined the impact of VEGF inhibitors on symptomatic/refractory edema in metastatic brain tumors.

Materials and Methods

This retrospective study included the patients with metastatic brain tumors who received VEGF-targeted therapy for symptomatic/refractory brain edema. The primary cancer site, radiation therapy for metastatic brain tumors, corticosteroid administration, symptoms, Karnofsky performance status, and MR imagings before and after VEGF-targeted therapy were all gathered from the patient's medical records.

Results

19 patients with symptomatic/refractory cerebral edema [NSCLC(15), LCNEC(1), SCLC(1), breast cancer(2), colorectal cancer (2)] were treated with anti-VEGF medication. Nine patients were treated with bevacizumab as a monotherapy, and 12 patients were treated with bevacizumab or ramucirumab in combination as a multi-drug therapy. Prior brain irradiation was administered to 17 patients. Corticosteroids were used to treat brain edema in 8 patients. VEGF inhibitors were effective in all patients, improving symptoms by reducing brain edema.

Conclusion

We recommend VEGF inhibitor for symptomatic/refractory edema of metastatic brain tumors. This treatment may be successful independent of the primary cancer site.
MET-10 A SINGLE CENTER RETROSPECTIVE ANALYSIS OF AWAKE CRANIOTOMY FOR METASTATIC BRAIN TUMOR
Authors: Yanagisawa Shunsuke , Ohno Makoto , Takahashi Masamichi , Mukai Takayasu , Kawaguhci Yuki , Sakurai Takuro , Oki Mami , Matsuoka Aiko , Miyakita Yasuji , Narita Yoshitaka
Published: December 2022

Background/purpose

Recent advances in cancer treatment provide surgical indication chances of metastatic brain tumors, and awake craniotomy for them is increasing. However, a small number of hospitals can perform awake craniotomy by limitation of hospital capacity. Here we show a single center retrospective analysis of awake craniotomy for metastatic brain tumor.

Materials and Methods

we analyzed consecutive 35 cases from January 2016 to January 2022 in our hospital. Rehabilitation staff evaluated them before surgery and after within a week.

Result

Patients characteristic were as follows. Mean and median age 57.0 (16-81) and median 62 respectively. Left side tumor were 31(88.6%). Frontal lobe was 26(74.3%), temporal lobe 5(14.3%), parietal lobe 3(8.6%), occipital lobe 1. Origin of cancer was lung 17(48.6%), gastrointestinal lesion 5(14.3%), breast 4(11.4%), soft tissues 3(8.6%), radiation necrosis 4(11.4%), uterus and malignant melanoma 1 respectively. KPS was 100-90 18(51.4%), KPS 80 6(8.6%) and KPS70 11(31.4%). Gross total removal was 30, partial removal was 5. MMSE of before and after surgery was mean 27.1 and median 29. Trail Making Test (TMT) of 24 cases test showed improvement in 11 (45.8%) cases. Median OS was 18.8 months (95%CI: 11.2-526).

Discussion/conclusion

We selected most awake craniotomy on left frontal lobe and each evaluating scales showed no deterioration. Awake craniotomy for metastatic brain tumor is effective procedure for saving function.
MET-11 NEAR-INFRATED OPTICAL CONTRAST OF INDOCYANINE GREEN CAN LOCALIZE METASTATIC BRAIN TUMORS
Authors: Muto Jun , Mine Yutaka , Joko Masahiro , Oba Shigeo , Hirose Yuichi
Published: December 2022

Introduction

The utility of intraoperative real-time fluorescent navigation of indocyanine green (ICG) for cerebrospinal tumors has been demonstrated in gliomas, schwannomas, and meningiomas. We reported the usefulness of the existing Second window ICG (SWIG) for metastatic brain tumors, in which 5 mg/kg is administered 24 hours before the day before surgery. Subsequently, we developed a Delayed window ICG (DWIG) administered 1 hour before observation intraoperatively and report our experience.

Methods

The subjects were 28 patients from August 2019 to March 2022, with an average age of 67 years, diagnosed with metastatic brain tumors. Eighteen patients were in the SWIG group and 10 in the DWIG group. Iridium (Visionsense) and KINEVO (Carl Zeiss) were used for near-infrared irradiation and observation.

Results

Near-infrared light was irradiated during surgery, and in all cases, fluorescence from the tumor was confirmed. Fluorescence emission could be confirmed as far as 10 mm from the brain surface. The Signal Background Ratio (SBR) of tumor to brain parenchyma was 3.4 in SWIG and 4.2 in DWIG. There is no significant difference between them.(P=0.15) All patients had contrast areas on preoperative contrast MRI, and the ratio of contrast area to brain parenchyma (T1BR) was 2.5. After intraoperative resection, all resected patients showed no contrast lesions on immediate postoperative MRI. No perioperative complications due to I CG administration were noted.

Conclusions

Metastatic tumors may be difficult to distinguish from the normal brain visually due to the inaccuracy of the navigation system caused by intraoperative brainshift and blurring of the boundaries under an optical microscope. Intraoperative fluorescence angiography is useful in such cases because it allows tumor localization and removal in real time. DWIG is useful for metastatic brain tumors because it is simple and easy to use, with no significant difference compared to existing SWIG.
MET-14 OUTCOME OF METASTATIC CEREBELLAR TUMOR: A SINGLE-CENTER STUDY
Authors: Nakano Tomoyuki , Miyakita Yasuji , Ohno Makoto , Takahashi Masamichi , Yanagisawa Shunsuke , Omura Takaki , Tamura Yukie , Kikuchi Miyu , Hosoya Tomohiro , Narita Yoshitaka
Published: December 2022

Background

Brain metastases (BM) to the cerebellum account for approximately 20% of all of BM. From the results of JCOG0504 clinical trial, observation with salvage SRS (stereotactic radiosurgery) has been established as a standard therapy for a patient after complete resection of BM. However, we often experience early local recurrence after resection of cerebellar BM, therefore, we retrospectively analyzed them to consider the appropriate timing of SRS.

Methods

We extracted surgical cases with cerebellar BM from January 2015 to March 2022 and analyzed the patient characteristics, treatment content, postoperative intracranial progression-free survival (IC-PFS) and postoperative overall survival (OS).

Results

A total of 57 cases were enrolled (male: female = 43.9%: 56.1%) in this study. The median age was 61.9 years (51.9-68.2). The common primary lesions were NSCLC (31.6%), colorectal cancer (19.3%), and breast cancer (17.5%). The IC-PFS was 4.5 months (2.6-5.7) and the OS was 11.6 months (9.1-21.8), but the local recurrent rate within 3 months was 43.4%. The rate of patients with leptomeningeal metastases (LMM) at the first recurrence was 26.3%, significantly higher than 7.7% in JCOG0504 (p=0.000224). In the postoperative observation group (no SRS within a month), the OS was 25.3 months (11.6-NA), which was longer than the 15.6 months (11.4-20.8) of JCOG0504. RT was performed in 18 patients at the recurrence (SRS: 15, WBRT (whole-brain radiotherapy): 9). SRS was the only factor that prolonged the OS (25.2 vs. 6.1 months (p=0.0212)). Furthermore, in the patients who underwent radiotherapy within 1 month after surgery, postoperative SRS (10.2 vs. 3.1 months, p=0.00437), and postoperative SRS to the resection cavity (11.0 vs. 3.7mo, p=0.0012) significantly prolonged the OS.

Conclusion

Since cerebellar BM has high recurrence and frequent LMM, early SRS for a resected cavity after surgery might lead to more favorable outcomes in cerebellar BM patients.
MNG-2 AN ANAPLASTIC MENINGIOMA WITH THE DIFFERENTIATION INTO OSTEOSARCOMA TISSUE
Authors: Adachi Junichi , Komine Hiroyuki , Sasaki Atsushi
Published: December 2022

Eighty-two year old woman developed motor aphasia. A brain MRI revealed an (1) extramedullary tumor adhering to the dura mater which enhanced almost uniformly and (2) an intramedullary tumor in the left frontal lobe. She underwent surgery in which we removed both tumors. Pathological examination revealed that (1) was meningothelial meningioma, WHO grade 1, without malignant findings. (2) had a high cell density, many mitosis (about 15 in 10 high-power fields), and a high MIB-1 index, leading to atypical meningioma, WHO grade 2. In addition, osteosarcoma component was found in part of (2), MIB-1 was further elevated, and the same site was diagnosed as anaplastic meningioma, equivalent to WHO garde 3. As a result of genetic analysis,tumor (1) had hemi-deletion and tumor (2) had homozygous deletion of the CDKN2A/2B gene. A case of anaplastic meningioma with osteosarcoma tissue has not been reported in the past as far as we could find, and it seems to be an extremely rare case. In this case, it is presumed that the other allele was deleted in the CDKN2A/2B hemi-deficient cells with benign morphology, and the homozygous deletion cells transformed into malignant transformation.
MNG-3 STRATIFICATION OF TUMOR GROWTH BY RISK FACTORS AND PREDICTED TUMOR VOLUME CURVES FOR SUPRATENTORIAL MENINGIOMAS
Authors: Hirayama Ryuichi , Yamada Shuhei , Iwata Takamitsu , Utsugi Reina , Tachi Tetsuro , Kuroda Hideki , Kijima Noriyuki , Okita Yoshiko , Kagawa Naoki , Kishima Haruhiko
Published: December 2022

Background

The natural history of meningiomas is still unclear, and no guidelines have been established based on objective indices regarding the necessity and timing of therapeutic intervention.Objective: We attempted to provide statistics on the characteristics of tumor volume change, stratify tumor growth by risk factors, and generate a predictive tumor volume curve based on the statistics, with the aim of describing the natural history of meningiomas.

Methods

313 cases were included in the study, with the origin of meningioma being the circumflex and parasagittal sinus areas and the cerebral sickle region, and with multiple MRI scans performed at intervals of at least 3 months. Relative growth rate (RGR) and annual volume change (AVC) were calculated by measuring tumor volume, and the patients were classified into three groups according to the combination of gender, age, and MRI T2WI signal intensity, and compared.

Results

The median RGR and AVC of the entire cohort were 6.1% and 0.20 cm3/year, respectively, and there were significant differences between groups in gender (p=0.018) and MRI T2WI (p < 0.001) for RGR and tumor location (p=0.025) and initial tumor volume (p < 0.001)for AVC. The median RGR and AVC in the classification were 17.5% and 1.05 cm3/year for the very high growth group, 8.2% and 0.33 cm3/year for the high growth group, and 3.4% and 0.04 cm3/year for the low growth group, showing significant differences between the groups (p < 0.001). The predicted tumor volume curve showed an average 2.24-fold or 5.24 cm3 increase in volume over 5 years in the very high-growth group, while little tumor volume change was observed in the low-growth group.

Conclusion

The combination of growth risk factors allowed stratification of tumor growth and provided a predictive tumor volume curve for each county. The results may assist in the treatment of meningiomas.
BT-5 LONG-TERM OUTCOME OF CLIVAL CHORDOMAS AT A SINGLE INSTITUTION
Authors: Shinojima Naoki , Uekawa Ken , Mukasa Akitake
Published: December 2022

Purpose

Chordoma is a rare malignant tumor, about 30% of which occurs in the clivus. The purpose of this study is to investigate the outcome after treatment of clival chordoma in our institute.

Methods

Nineteen patients {M/F=11/8, mean age: 50.4 (15-72) years} who were treated between 1987 and 2021 and followed for at least 6 months were retrospectively evaluated for survival and local control rate.

Results

The cumulative survival rate was 89.2% at 5 years, 82.3% at 10 years, and 54.9% at 25 years, and the median OS was 107 (6-359) months. 4 deaths: 2 tumor deaths (1 from poorly differentiated chordoma), 2 non-tumor deaths (1 from IC rupture after heavy ion radiotherapy). The cumulative local control rate was 47.3% at 5 years and 35.5% at 10 years, with a median progression-free survival (PFS) of 41 (0-278) months. There was no difference in OS (p=0.85) or PFS (p=0.90) between the two groups, with 6 cases of gross total resection, GTR (all transsphenoidal) and 13 cases of non-GTR (9 transsphenoidal, 4 transcranial) at first surgery. In the 4 patients without irradiation (1 GTR, 3 non-GTR), no disease progression (PD) was observed, and the mean OS was 170 (69-278) months. Of the 15 patients irradiated, 6 were irradiated before PD and 9 were irradiated after PD, and there was no difference in OS or PFS between the two groups, i.e., the timing of irradiation. One patient with refractory chordoma was found to have elevated TMB levels by cancer genome testing and is currently receiving pembrolizumab, which has resulted in significant tumor shrinkage.

Conclusion

The patients with clival chordoma have a varied course, which may be due to differences in molecular biology. Cancer genome testing may provide new treatment options, such as molecularly targeted drugs and immune checkpoint inhibitors, for refractory cases.
BT-6 CLINICO-RADIO-PATHOLOGICAL FEATURES OF 1ST RELAPSE OF GLIOBLASTOMA AFTER PHOTODYNAMIC THERAPY
Authors: Yoshioka Yamato , Akimoto Jiro , Fukami Shinjiro , Nagai Kenta , Saitou Yuuki , Kohno Michihiro
Published: December 2022

Introduction

We describe the clinicopathological picture of patients who underwent surgery at the time of initial recurrence after photodynamic therapy (PDT) for first-episode glioblastoma.

Subjects and Methods

We examined the clinicopathological picture of 12 patients who had undergone PDT in a sub-total or greater resected luminal wall at the time of initial surgery, and who were able to undergo repeat resection because a new contrast-enhancing lesion was detected during follow-up.

Results

The age at onset ranged from 43 to 80 years, with a male-to-female ratio of 9:3. PDT was applied to the wall of the resected lumen 4-13 times using a reflector as needed. Initial pathology showed IDH wild-type glioblastoma in all patients. Postoperatively, only the Stupp regimen was performed, but local recurrence on imaging was observed 9-24 months (median 11.5 months) postoperatively. Contrast-enhanced lesions were seen throughout or deeper into the luminal wall on imaging, but they were irregular and necrotic and were not well characterized by DWI/ADC due to strong perineural edema. Most of the patients had low density (around 15%) of tumor cells, but abundant T lymphocytes and foam cell infiltrate. 2 patients (9 and 20 months after the first surgery) showed no tumor cells, only necrosis, endothelial degeneration, and lymphocytic infiltrate, and were judged to have pseudoprogression. 1 patient (9 and 20 months after the first surgery) showed no tumor cells and was judged to have pseudoprogression. In one case (11.7 months after initial surgery), tumor-like dysplastic cells were found in less than 10% of the tissue.

Discussion/Conclusion

When the first recurrence of glioblastoma after PDT is diagnosed, the possibility of late pseudo-progression should be taken into account, and the pathological search using various modalities such as MRS, perfusion study, PET/SPECT, etc. should be performed. Short-term wait and scan are important.
CS-10 POLYMORPHOUS LOW-GRADE NEUROEPITHELIAL TUMOR OF THE YOUNG: OUR CASE AND REVIEW OF THE LITERATURE
Authors: Kakuta Kiyohide , Asano Kenichiro , Ueno Kouta , Watanabe Ryouta , Saito Atsushi , Kurose Akira
Published: December 2022

Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a new tumor that was officially listed in the WHO 5th edition in 2021. It is clinically and pathologically oligodendroglioma-like, but can be distinguished by CD34 positivity. Although this case was initially thought to be an oligodendroglioma-like low grade glioma, it was clinically and pathologically considered to be a typical case, so we report it here.14 year old female. No special notes, including growth and development. The patient suddenly developed a generalized tonic convulsion and was taken to the emergency room. A CT scan revealed a lesion with strong calcification in her left temporal lobe, and she was referred to our department. She had no neurological findings and underwent total resection under awake surgery. She was difficult to diagnose with intraoperative frozen section. diagnosis.The pathological findings are medium-sized oval to oblong nuclei, diffuse proliferation of tumor cells with delicate cell projections, and oligodendroglioma-like areas with perinuclear halos. A very large number of fine calcifications are observed, but necrosis and microvascular hyperplasia are not observed. GFAP, olig2, and nestin were positive, and synaptophysin, Nf, Hu C/D, MAP2, and chromograninA were negative. MIB-1 was less than 5%. The sequence was IDH1/2, TERTwild, and the BRAF-V600E mutation was recognized. Tumor cells were CD34-positive, leading to a final diagnosis of PLNTY. PLNTY is a new concept of tumor and accumulation is still small. Although this case has typical clinical and pathological features, preoperative diagnosis was difficult because it is a rare tumor. Intraoperative diagnosis is also difficult, suggesting the difficulty of diagnosing this tumor. Based on past cases, we report preoperative diagnostic imaging, intraoperative findings, and histopathological findings, including literature considerations.
COT-2 MALIGNANT BRAIN TUMOR DIAGNOSED AS SUBDURAL HEMATOMA DURING A BRAIN CHECKUP: CASE REPORT
Authors: Ogawa Takahiro , Kotani Saki , Doi Tomoyuki , Nagai Toshiki , Murakami Nobukuni
Published: December 2022

Case description

65-year-old female. One month before the checkup, she had a bruise on the parietal region of her head. The patient was referred to our department because a subdural hematoma was suspected on the MRI scan of the head taken at a brain checkup. However, a few months after the initial visit, headache localized around the bruised area began to appear. Since the headache symptoms did not improve, he returned to our department and contrast-enhanced MRI was performed again. Contrast-enhanced MRI showed a tumor lesion of more than 6 cm in size, which infiltrated subcutaneously, epidurally, intradurally, and contralaterally. Other mass lesions were also found in the left frontal region and left neck. The patient underwent subcutaneous mastectomy to remove the left parietal subcutaneous mass and confirm the diagnosis. The scalp tumor had a soft and elastic subcutaneous mass, which was easily detached from the scalp and bone, removed in one lump. The pathological diagnosis was malignant lymphoma. The patient was transferred to the Department of Hematology and started R-MPV therapy.

Conclusion

No case has been reported in the literature that led to the diagnosis of malignant lymphoma during a brain checkup. In the present case, a subdural hematoma was diagnosed at the brain checkup because of the origin of the tumor and the history of head injury at the same site. However, there is a report that it was a subcutaneous mass and an epidural mass caused by malignant lymphoma mimicking epidural hematoma. This should be kept in mind. Although the brain scan was not sufficient to screen the patient, the fact that the patient was symptomatic confirmed the diagnosis, and the patient had an outcome that led to subsequent treatment.
COT-8 DEVELOPMENT OF TARGETED GENE PANEL FOR RAPID MOLECULAR DIAGNOSIS OF BRAIN TUMORS
Authors: Nakashima Takuma , Funakoshi Yusuke , Uneda Atsuhito , Nambu Shohei , Kitahara Mai , Yanagisawa Shunsuke , Ohno Makoto , Takahashi Masamichi , Miyakita Yasuji , Narita Yoshitaka , Suzuki Hiromichi
Published: December 2022

Background

Brain tumors are diagnosed based on pathological and genetic features defined by WHO classification. Although targeted gene panels are clinically available, most of them do not cover all the necessary genes for the diagnosis of brain tumors. Moreover, broad copy number analysis, which the current WHO classification requires, usually lacks in the gene panel. Another problem is that those panels demand a high burden of time and cost, which disturbs rapid diagnosis and broad application. To overcome those problems, we developed a rapid and cost-effective workflow of molecular diagnosis for brain tumors.

Methods

Our panel contains 109 genes of which 68 are necessary for fundamental molecular diagnosis and 41 are other common driver genes. To detect copy number changes and structural variants, which generate a fused gene, additional probes are placed on common SNPs and introns containing common breakpoints. MGMT methylation status is examined at the same time using bisulfite-converted DNA amplification. Sequencing data is analyzed using a supercomputer.

Results

The analysis time is within 4 days: 2 days for library preparation, 1 day for sequencing, and 12 hours for analysis. Detected driver alterations were validated by whole genome sequencing data. MGMT methylation status was correlated between the results of our workflow and pyrosequencing.

Conclusions

We have developed a rapid comprehensive molecular analysis workflow that detects genetic alterations and MGMT methylation. Our method allows a cost-effective molecular diagnosis with high accuracy, which would improve molecular diagnosis for brain tumors.
COT-12 ANALYSIS OF 5-ALA STRONGLY POSITIVE FINDINGS USING IMAGE J FOR MALIGNANT BRAIN TUMOR
Authors: Kon Takashi , Kobayashi Yusuke , Sato Yosuke , Shimizu Katsuyoshi , Mizutani Tohru
Published: December 2022

For brain tumor surgery using 5-ALA during surgery, we analyze the brightness using image analysis software Image J, we report the results to date for strongly positive findings. Thirty-nine patients who were suspected of having malignant glioma before surgery and who were strongly positive for 5-ALA during surgery were included. (21 malignant glioma, 14 metastatic brain tumor, 3 meningioma, and 1 germ cell tumor.) Intraoperative 5-ALA-positive findings were analyzed with image analysis software Image J (Wayne Rasband: NIH), brightness was measured with histograms, and maximum brightness was compared. The average maximum brightness titer was 106.38 (50-225) in 21 cases of malignant glioma. The brightness titer was 84.5 (28-121) in 14 cases of metastatic brain tumor, 80 (59-97) in meningioma, and 43 in 1 case of germ cell tumor. No clear correlation was found between brightness, tumor grading, and MIB-1 LI. In addition, a clear difference in luminance was observed between the tumor and the ventricle in one case.By analyzing brightness with Image J, it will be possible to obtain informations about tumors from different perspectives.
COT-13 OUTCOMES OF MEDULLOBLASTOMA IN KOBE CHILDREN,S HOSPITAL OVER THE RECENT 11 YEARS
Authors: Kawamura Atsufumi , Koyama Junji , Akutsu Nobuyuki , Enami Haryka , Hayashi Hideya
Published: December 2022

Introduction

Medulloblastoma is the most frequent malignant brain tumor in children, which 5-year survival rate have improved to 70-85%. In this study, we retrospectively reviewed outcomes and late complications of 31 medulloblastoma cases treated at our institute from 2010 to 2021.

Cases

The mean age of the cases was 6.5 years. 22 cases were total resection and 17 were judged to be in the high-risk group. With respect to histopathological diagnosis, 23 cases were classified as classic type, 2 as desmoplastic/nodular type, 2 as with extensive nodularity type, and 4 as anaplastic/large cell type. As for molecular analysis, WNT was 2, SHH was 3 , Group 3 was 3, Group 4 was 8 cases. One case was lost due to relocation.

Results

21 patients have no recurrence of medulloblastoma, but two were victims of second cancers. The remaining 19 cases were all in the standard-risk group and survived with a complete reaction (CR). There were 9 cases of recurrence (including disseminated disease) and the survived case after retreatment was only one in the high-risk group which indicated CR.

Discussion

The 5-year survival rate for patients in standard-risk group at our institution was 92.3%, indicating improved outcomes. The poor prognosis group could be divided in group who developed recurrence or second cancers after 5 years or more and group who indicated insufficient reaction to multimodality treatment and died around 2 years after diagnosis. As late complications, there were 5 cases of higher functional impairment, who were 16.7% of whole cases and almost in the high-risk group. It is necessary to pursue further treatment for the high-risk group and to recognize that the number of survivors of medulloblastoma cases is increasing, and to support for the AYA generation.
COT-14 OUTCOMES OF MEDULLOBLASTOMA IN KOBE CHILDREN,S HOSPITAL OVER THE RECENT 11 YEARS
Authors: Kawamura Atsufumi , Koyama Junji , Akutsu Nobuyuki , Enami Haryka , Hayashi Hideya
Published: December 2022

Introduction

Medulloblastoma is the most frequent malignant brain tumor in children, which 5-year survival rate have improved to 70-85%. In this study, we retrospectively reviewed outcomes and late complications of 31 medulloblastoma cases treated at our institute from 2010 to 2021.

Cases

The mean age of the cases was 6.5 years. 22 cases were total resection and 17 were judged to be in the high-risk group. With respect to histopathological diagnosis, 23 cases were classified as Classic type, 2 as Desmoplastic/nodular type, 2 as With extensive nodularity type, and 4 as Anaplastic/Large cell type. As for molecular analysis, WNT was 2, SHH was 3 , Group 3 was 3, Group 4 was 8 cases. One case was lost due to relocation.

Results

21 patients have no recurrence of medulloblastoma, but two were victims of second cancers. The remaining 19 cases were all in the standard-risk group and survived with a complete reaction (CR). There were 9 cases of recurrence (including disseminated disease) and the survived case after retreatment was only one in the high-risk group which indicated CR.

Discussion

The 5-year survival rate for patients in standard-risk group at our institution was 92.3%, indicating improved outcomes. The poor prognosis group could be divided in group who developed recurrence or second cancers after 5 years or more and group who indicated insufficient reaction to multimodality treatment and died around 2 years after diagnosis. As late complications, there were 5 cases of higher functional impairment, who were 16.7% of whole cases and almost in the high-risk group. It is necessary to pursue further treatment for the high-risk group and to recognize that the number of survivors of medulloblastoma cases is increasing, and to support for the AYA generation.
COT-15 PATHOLOGICAL ANALYSIS OF MALIGNANT GLIOMA IN THE END STAGE
Authors: Hirai Nozomi , Saito Norihiko , Sato Sho , Kushida Naoki , Hiramoto Yu , Fujita Satoshi , Nakayama Haruo , Hayashi Morito , Ito Keisuke , Sakurai Takatoshi , Oharazeki Toshiaki , Iwabuchi Satoshi
Published: December 2022

Background

Malignant gliomas have an extremely high rate of recurrence and brain invasion despite standard treatment, ultimately leading to tumor death. Tumor death is generally thought to be caused by brain herniation due to mass effect, as confirmed by studies of malignant glioma brain autopsies performed in the 1960s and 1980s. However, there have been few studies of brain autopsies of malignant gliomas after the introduction of chemotherapy with temozolomide, and the pathological characteristics of the end stage of the disease have not been clarified in recent years. In this study, we report the clinical and pathological characteristics of the end stages of malignant glioma cases treated at our hospital from the initial treatment to the confirmation of death.

Methods

10 cases of malignant glioma that were treated from initial treatment to pathological autopsy at our hospital from 2007 to 2018 were included in this study. We analyzed the pathology, neuroradiological changes, and clinical course of these cases at the end stage.

Results

The mean age of the 10 patients was 59 (15-77) years, and the median overall survival was 16.5 months. The primary tumor sites were 2 frontal lobes, 3 parietal lobes, 3 temporal lobes, 1 cerebellum, and 1 multiple lesions. The direct cause of death in all cases was neurological death due to tumor progression. Gross findings of pathological autopsy specimens showed that tumor excision sites were cavitated or recurrent, but mass effect was poor and there were few cases of brain herniation. On the other hand, microscopic findings showed infiltration of tumor cells into the brain stem through the brain parenchyma.

Conclusion

This study suggests that tumor invasion into the brainstem is involved as a cause of tumor death. It is possible that the new treatment may change the recurrence pattern or alter the morphology of glioma cells.
COT-16 NATION-WIDE LANDSCAPE OF GENOMIC ANALYSIS OF ADULT CENTRAL NERVOUS SYSTEM TUMORS IN JAPAN
Authors: Takahashi Masamichi , Watanabe Yuko , Koyama Takafumi , Sunami Kuniko , Kubo Takashi , Cho Hourin , Hirata Makoto , Tao Kayoko , Sudo Kazuki , Kohsaka Shinji , Yanagisawa Shunsuke , Ohno Makoto , Miyakita Yasuji , Yamamoto Noboru , Narita Yoshitaka
Published: December 2022

Background

Comprehensive genomic profiling (CGP) testing has been covered by public health insurance and its clinical application has started in Japan since June 2019. All the results of CGP testing are sent to the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) and shared with clinicians after discussion at the Expert Panel (EP). Here we report the results of analysis of adult central nervous system (CNS) tumors registered in Japan.

Methods

C-CAT registry data as of April 2022 (ver. 20220406) was used. Patient background, diagnosis, type of CGP testing, genetic alterations and treatment status after EP were analyzed.

Results

1042 patients with CNS tumors were enrolled, 338 (32.4%) were younger than 20 years old and 704 (67.6%) were older. Among 704 adult patients, mean age was 47.6 years and median ECOG PS was 1. Top tumor diagnosis included glioblastoma (42.8%), anaplastic astrocytoma (11.8%) and anaplastic oligodendroglioma (5.0%), and 634 (90.0%) were tested with FoundationOne CDx(R). Regarding genomic alterations, 278 had TP53 mutation, 242 had CDKN2A deletion, 221 had TERT mutation, 218 had CDKN2B deletion, 136 had IDH1 mutation, and 39 had TMB high (>10Mb) and no NTRK gene fusion was observed. EP recommended treatment options in 187 cases (26.6%) and 60 cases (8.5%) reached therapeutic agents, including 25 Patient-Proposed Healthcare Services, 16 approved drugs, 8 pharmaceutical clinical trials, 7 investigator-initiated clinical trials and 4 others.

Conclusion

This is the first report of nation-wide results of CNS tumors analyzed by CGP in Japan. Although some patients were able to reach therapeutic agents under the Patient-Proposed Healthcare Services system, little number of patients reached clinical trial. Development of new drugs is urgently warranted.
LW-1 MY LIFE WORK : MY RESEARCH WORK FOCUSING ON TUMOR-ASSOCIATED ENDOTHELIAL CELLS ALONG WITH VEGF FOR 30 YEARS
Authors: Tanaka Toshihide
Published: December 2022

When I was a medical student, I happened to see the typical histopathology of glioblatoma (GBM) containing expanding necrosis surrounded by enormous glomerulous microvasculature with endothelial proliferation resembling glomeruli in the kidney. It looks like tumor cells starving out due to lack of blood supply with accelerating growth. Since then, I have been fascinated by tumor angiogenesis that might be an attractive therapeutic target.In 1989, vascular endothelial growth factor (VEGF) and vascular permeability factor (VPF) turned out to be identical. In 1992, VEGF expression was distributed surrounding necrosis area in GBM. In 1993, anti-tumor effect of monoclonal antibody for VEGF via inhibition of angiogenesis on various tumor models including glioma was verified in vivo. In 1996, VEGF was found to inhibit the functional maturation of dendritic cells, suggesting that therapeutic blockade of VEGF may improve prospect for immunotherapy as well as inhibition of angiogenesis. Those findings made me excited with visionary idea that combination therapy of anti-VEGF therapy and dendritic cell-based immunotherapy might be a potential therapeutic approach for GBM. Currently, I am dedicated in clinical study of dendritic cell-based immunotherapy and bevacizumab for GBM.Since graduating from medical school and discovery of VEGF in the same era, my clinic and research have been supported by serendipity of a vast of experiences and many people. I would give take-home message to next generation that originality and creativity were cultivated in real-world, and that serendipity and integration were precious for development of basic and clinical research.