bluuebunny/crossref_metadata_2025_split huggingface dataset:
ACT-5 Prognosis of IDH-mut lower-grade gliomas in Hokkaido University Hospital
Authors: Yamaguchi Shigeru , Ishi Yukitomo , Okamoto Michinari , Sawaya Ryousuke , Motegi Hiroaki , Kobayashi Hiroyuki , Terasaka Shunsuke , Fujimura Miki 
Published: December 2021

Abstract
Background: WHO grade 2 and 3 adult gliomas are nowadays getting together as lower-grade gliomas (LrGGs), but we had been recognized grade 3 (G3) tumors as high-grade and grade 2 (G2) tumors as low-grade. In this report, we investigate the treatment and prognosis of the patients with LrGG harboring IDH mutations in our institutions. Methods:We retrospectively review primary treatments and their prognosis for LrGG patients with IDH mutation since 2003. They categorized as astrocytomas and oligodendrogliomas according to 1p/19q loss-of-heterozygosity status. Prognosis were evaluated by overall survival. Postoperative primary treatments applied chemo-radiotherapy (CRT), radiotherapy only (RT), chemotherapy only (CT), and observation (Ob). Results: 36 astrocytomas and 60 oligodendrogliomas were identified. In astrocytomas, the patients with G3 (N=16) were treated by CRT (N=14) or CT (N=2), and the patients with G2 (N=20) were treated by CRT (N=2), RT (N=3), CT (N=3), or Ob (N=12). In oligodendrogliomas, the patients with G3 (N=34) were treated by CRT (N=32) or CT (N=2), and the patients with G2 (N=26) were treated by CRT (N=3), RT (N=1), CT (N=5), or Ob (N=17). 10-year survival rate (10yOS) of astrocytomas and oligodendrogliomas are 54% and 90%, respectively (p=0.002). According to histological malignancy, 10yOS of G3 and G2 astrocytomas were 54% and 54%, respectively (p=0.97) and that of G3 and G2 oligodendrogliomas were 86% and 100%, respectively (p=0.64). In both group, there are no different of prognosis according to histological malignancy. Discussion: There was no prognostic different between G2 and G3 astrocytomas in our institution. Since the treatment intensity for G2 and G3 astrocytomas were clearly different, the primary treatment for G2 astrocytomas might be insufficient. On the other hand, there were no prognostic different between G2 and G3 oligodendrogliomas in our institution, as with recent reports, so the primary treatment intensity for oligodendrogliomas should be appropriate.
STMO-6 Impact of the extent of resection on the survival of patients with lower grade gliomas using awake brain mapping
Authors: Motomura Kazuya , Chalise Lushun , Ohka Fumiharu , Aoki Kosuke , Nishikawa Tomohide , Yamaguchi Junya , Shimizu Hiroyuki , Kibe Yuji , Natsume Atsushi , Wakabayashi Toshihiko , Saito Ryuta 
Published: December 2021

Abstract
Purpose: The aim of this study was to assess the effect of the extent of resection (EOR) of tumors on survival in a series of patients with lower-grade gliomas (LGGs) who underwent awake brain mapping.
Methods: We retrospectively analyzed 126 patients with LGGs in the dominant and non-dominant hemisphere who underwent awake brain surgery at the same institution between December 2012 and May 2020.
Results: The median progression-free survival (PFS) rate of patients with LGGs in the group with an EOR &gt;100 %, including supratotal resection (n = 47; median survival [MS], not reached), was significantly higher than that in the group with an EOR &lt;100% (n = 79; MS, 43.1 months; 95% CI: 37.8–48.4 months; p = 0.04). In patients with diffuse astrocytomas and anaplastic astrocytomas, the group with EOR &gt;100 %, including supratotal resection (n = 25; MS, not reached), demonstrated a significantly better PFS rate than did the group with an EOR &lt;100% (n = 45; MS, 35.8 months; 95% CI: 19.9–51.6 months; p = 0.03). Supratotal or gross total resection was correlated with better PFS in IDH-mutant type of diffuse astrocytomas and anaplastic astrocytomas (n = 19; MS, not reached vs. n = 35; MS, 40.6 months; 95% CI: 22.3–59.0 months; p = 0.02). By contrast, supratotal or gross total resection was not associated with longer PFS rates in patients with IDH-wild type of diffuse astrocytomas and anaplastic astrocytomas.
Conclusions: It is noteworthy that supratotal or gross total resection significantly correlated with better PFS in IDH-mutant type of WHO grade II and III astrocytic tumors. In light of our finding that EOR did not correlate with PFS in patients with aggressive IDH-wild type of diffuse astrocytomas and anaplastic astrocytomas, we suggest treatments that are more intensive will be needed for the control of these tumors.
STMO-17 Treatment outcome of photodynamic therapy using talaporfin sodium for recurrent high-grade glioma
Authors: Ohno Makoto , Kawauchi Daisuke , Hayashi Yoshiharu , Satomi Kaishi , Miyakita Yasuji , Takahashi Masamichi , Yanagisawa Shunsuke , Tamura Yukie , Kikuchi Miyu , Hamada Akinobu , Narita Yoshitaka 
Published: December 2021

Abstract
Objective: Photodynamic therapy (PDT) using Talaporfin Sodium (TS) is a novel therapeutic strategy to improve local tumor control in high-grade glioma. TS is a photosensitizer that accumulates in tumor cells and produces highly toxic free radicals by intraoperative irradiation of laser with a 664nm wavelength. However, little is known about the treatment outcomes of PDT in recurrent high-grade gliomas (rHGG). In this study, we investigated the treatment outcome of PDT in rHGG and evaluated the correlation between intratumoral TS accumulation and outcomes. Methods: We included 21 patients with rHGG and 22 tumors, who were treated by PDT between June 2016 and March 2021. TS was transvenously administered 22–26 hours before PDT. Intratumoral TS concentrations were measured by liquid chromatography using frozen tissue. Results: The rHGGs included 10 glioblastoma, IDH1/2-wildtype (GBM, IDH1/2-WT: 45.5%), 3 GBM, IDH1/2-mutant (GBM, IDH1/2-Mut: 13.6%), 7 anaplastic oligodendroglioma, IDH1/2-Mut/codel (AO, IDH1/2-Mut/codel: 31.8%), 1 anaplastic astrocytoma, IDH1/2-WT (AA, IDH1/2-WT: 4.5%), 1 high-grade astrocytoma, IDH1/2-WT (4.5%). The median local progression free survival (PFS) time after PDT was 3.6 months and the median survival time from PDT was 19.4 months. The intratumoral TS concentrations of 7 tumors (TS(-): 31.8%) were below the limit of quantification, and the intratumoral TS concentrations of the remaining 15 tumors (TS(+)) were 43.5 ng/mg-protein (14.7–132 ng/mg-protein). The intratumoral TS concentrations were not significantly associated with IDH1/2 mutation status, cellularity, tumor grade, and pattern of enhancement. The median PFS from PDT tended to be longer in TS(+) than in TS(-) (TS(+): 6.3 vs TS(-): 1.4 months, p = 0.054). Conclusions: We found that the intratumoral TS concentrations were heterogeneous and 31.8% were below the limit of quantification. TS(+) tended to have better local tumor control than TS(-), suggesting the intratumoral TS accumulation have an impact of treatment outcomes of PDT.
STMO-19 Impact of aggressive resection for glioblastoma of the thalamus with histone H3-K27M mutation
Authors: Nonaka Masahiro , Hashiba Tetsuo , Asai Akio 
Published: December 2021

Abstract
Glioblastoma of the thalamus occurs predominantly in childhood and young adulthood, and cases with histone mutations are thought to have a particularly poor prognosis. We studied tumor resection rate, age, type of adjuvant therapy, and histone gene mutations on progression-free survival (PFS) and overall survival (OS) in patients who underwent aggressive removal. Eight cases of thalamic glioblastoma were included in the study. The mean age at surgery was 36.1 years (10–74 years, 3 cases under 18 years). Tumor removal was performed from the parieto-occipital lobe to the thalamus via the lateral ventricles in all cases. In all cases, more than 90% of the contrast-enhancing lesions were removed. Postoperatively, one patient had sensory disturbance of the left upper limb, and the other had incomplete paralysis of the left upper and lower limbs, but both were able to walk with a cane. In the case of the patient with postoperative complications, the tumor was located in the vicinity of the internal capsule. All patients were treated with radiation therapy and temozolomide, and bevacizumab and Novo-TTF were used in cases after approval. All patients were able to return home and return to school or work after initial treatment. The mean progression-free survival (PFS) was 0.87 years, and overall survival (OS) was 1.95 years. Five patients had histone H3-K27M mutations, and three patients had no mutations. PFS and OS were 1.02 years and 0.62 years, respectively, and 2.53 years and 1.20 years, respectively, both of which were longer in patients with mutations (PFS; p=0.16, OS; p=0.23).Aggressive removal of glioblastoma of the thalamus may improve prognosis, especially in patients with histone H3-K27M mutations. In patients with tumors extending to the vicinity of the internal capsule, total removal may cause paralysis and sensory disturbance.
MPC-5 Characteristics of H3 G34-mutant gliomas
Authors: Kibe Yuji , Ohka Fumiharu , Motomura Kazuya , Aoki Kosuke , Maeda Sachi , Hirano Masaki , Nishikawa Tomohide , Yamaguchi Junya , Yamazaki Shintaro , Natsume Atsushi , Saito Ryuta 
Published: December 2021

Abstract
Introduction: Diffuse hemispheric gliomas, H3 G34-mutant (DHG H3G34-mutant) are newly recognized infiltrating gliomas of the cerebral hemispheres of pediatric and young adult patients. We experienced 6 DHG H3G34-mutant cases. In this study, we describe the clinical, radiological and pathological characteristics of these cases.
Result: Mean age at diagnosis was 16.8 years (range:10–26). Three patients were male. Among six cases, tumors located in cerebral cortex in five cases and multiple sites including basal ganglia and cortex in a case. All tumors showed no or only a faint contrast-enhancement and harbored restriction of diffusion. One patient underwent total resection, four underwent partial resection and one underwent biopsy. Pathological diagnosis were CNS embryonal tumors (n=3/6), glioblastoma, IDH-wildtype (n=2/6) and anaplastic astrocytoma, IDH-wildtype (n=1/5). All cases were negative for Olig2 and positive for GFAP in immunohistochemistry. Mean Ki-67 index was 38% (range: 10–60%). All cases revealed at least one of mitosis, necrosis or microvascular proliferation. Especially, mitosis was the most frequently found (n=5/6). The H3F3A mutations were G34R mutations in all cases. One case revealed a characteristic mutation pattern, therefore now we are performing further examination. Adjuvant chemoradiotherapies were performed for all cases. Mean progression free survival was 10.1 months (range: 1.6–33.1).
Discussion: As published literatures reported, all cases exhibited restriction of diffusion and negative for Olig2. For a cerebral hemispheric tumor of pediatric or young adult patient which shows restriction of diffusion and no contrast-enhancement, and of which pathological findings is malignant and olig2 is negative, genetic analysis of H3F3A gene might be essential.
MPC-10 Prognostic analysis in IDH mutant astrocytoma patient with CDKN2A/B homozygous deletion
Authors: Yanagisawa Shunsuke , Satomi Kaishi , Miyakita Yasuji , Ohno Makoto , Takahashi Masamichi , Tamura Yukie , Kawachi Daisuke , Kikuchi Miyu , Kitahara Mai , Matushita Yuko , Yoshida Akihiko , Ichimura Koichi , Narita Yoshitaka 
Published: December 2021

Abstract
background: IDH mutant astrocytoma has good prognosis compared with IDH wildtype one. In IDH mutant astrocytoma, However, patients with CDKN2A/B homozygous deletion (HD) are worse prognosis than non CDKN2A/B HD. Here we analyzed the prognosis of glioma patients identified with CDKN2A/B HD in our hospital. method: There were 62 cases, and female was 26. Mean age of all cases was 41.2 and median age was 38. In IDH gene status, R132H was 59 cases (95.2%), R172K 2 (3.2%) and R132S 1 (1.6%). All 62 cases were TERT wildtype. CDKN2A/B HD were 12 cases (19.4%). In log-rank test, the group of CDKN2A/B HD was poor prognosis than non HD. In astrocytoma grade 3, CDKN2A/B HD had significantly poor prognosis (p=0.002). In Cox proportional hazard model analysis, CDKN2A/B HD was effective predictive prognostic factor as well as age and grading (p=0.03). discussion/conclusion: We showed that CDKN2A/B HD was good predictive prognostic factor in IDH mutant astrocytoma.
NI-2 Use of neurite orientation dispersion and density imaging(NODDI)for early distinction between infiltrating tumor and vasogenic edema in non-enhancing lesions with glioblastoma patients
Authors: Okita Yoshiko , Takano Koji , Tateishi Soichiro , Hayashi Motohisa , Sakai Mio , Kinoshita Manabu , Kishima Haruhiko , Nakanishi Katsuyuki 
Published: December 2021

Abstract
Background: Glioblastoma is a highly infiltrative tumor. In the non-enhancing T2-weighted hyperintense area, differentiating between non-enhancing tumors (NETs) and vasogenic edema is challenging. Neurite orientation dispersion and density imaging (NODDI) is a new diffusion MRI technique that reveals the inhomogeneity of the brain microstructure. The aim of this study is to differentiate between NETs and edema in glioblastomas using NODDI. Methods: Data were collected from 20 patients with glioblastoma as well as three patients with metastasis and two with meningioma (control), who underwent MRI as part of pre-surgical examination. The MRI data included T2- and T1-weighted contrast-enhanced images and NODDI images. Three neurosurgeons manually placed the volume of interest (VOI) on the NETs and edema based on the previous reports. ICVF, ODI, ISOVF, FA, and ADC were calculated for each VOI. Results: Fifteen and 13 VOIs were placed on NETs and edema, respectively. Each parameter was measured and the unpaired t-test revealed a significant difference between NETs and edema (p &lt;0.0001). The ROC curve analysis revealed a large difference in the ADC, FA, and ISOVF between NETs and edema compared to ICVF and ODI. Principal component analysis of the five parameters showed that ADC, ISOVF, and FA contributed to the differentiation between NETs and edema. Multiple logistic regression analysis was performed with the three aforementioned parameters. A predictive formula could be created to discriminate between NETs and edema, following the use of which, the ROC curve revealed an AUC value of 0.8891. Furthermore, this formula was applied to the edematous regions of the images of the negative control group, and the prediction degree of the tumor was well below 0.5, thus enabling differentiation as edema.Conclusions: NODDI may prove to be a useful tool to discriminate between NETs and edema in the non-contrast T2 hyperintensity region of glioblastoma.
NI-11 Usefulness of the magnetic resonance imaging arterial spin labeling method for diagnosing posterior fossa hemangioblastoma
Authors: Hiu Takeshi , Ishiyama Ayano , Morikawa Minoru , Baba Shiro , Ujifuku Kenta , Yoshida Koichi , Izumo Tsuyoshi , Matsuo Takayuki 
Published: December 2021

Abstract
Purpose: It is sometimes challenging to diagnose hemangioblastoma by MRI when the tumor is a solid mass in the posterior fossa. We therefore evaluated perfusion images and diffusion-weighted images to diagnose hemangioblastoma in order to obtain the most useful quantitative features. Methods: Thirty-one posterior fossa tumors whose pathological diagnosis was confirmed by surgery were included in groups A (12 hemangioblastomas) and B (non-hemangioblastoma 19 cases: metastatic tumor 6 cases, pilocytic astrocytoma 3 cases, malignant lymphoma 3 cases, glioblastoma 2 cases, medulloblastoma 2 cases, and other 3 cases). All cases were imaged by 3.0-Tesla MRI, with the apparent diffusion coefficient (ADC) on diffusion-weighted imaging as the parameter, arterial spin labeling (ASL) as the relative value from the CBF map to the region of interest (ROI) in the contralateral hemisphere as perfusion image, dynamic susceptibility contrast (DSC) as rCBF, rCBV, corrected CBV, and K2. The ROI was set to match the contrast-enhanced part, and the two groups were compared and examined. Results: The relative ASL value of group A and the corrected CBV in DSC were significantly higher than group B (p&lt;0.001). In contrast, the ADC showed no marked difference between the two groups. In the distinction between the two groups, the receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) of the relative ASL value was significantly higher than the other parameters (AUC 0.995, cut-off value 2.34, sensitivity 100%, specificity 99.5%). Discussion/Conclusion: The non-contrast ASL method was extremely useful for diagnosing hemangioblastoma in posterior fossa tumors. The ASL method has been reported helpful for the follow-up of residual tumors or recurrence after surgery. Contrast-enhanced DSC is not always essential for diagnosing posterior fossa hemangioblastoma. It should be noted that measuring the ROI by ASL is difficult when the size of the mural nodule is small.
ML-4 A case of primary CNS lymphoma diagnosed 5 years after stereotactic radiosurgery
Authors: Tabei Yusuke , Nakazato Ichirou , Ooyama Kenichi , Kawashima Masatou , Matsuno Akira , Nomura Ryutarou 
Published: December 2021

Abstract
Central nervous system primary malignant lymphoma (PCNSL) is rarely diagnosed as multiple metastatic brain tumors. Almost tumors recure early after receiving stereotactic radiosurgery (SRS). Regardless of the fact, the following case report displays PCNSL, diagnosed five years after the initial treatment with SRS as brain metastases of unknown primary origin. This extraordinal case suggests long-term follow-up regarding PCNCL. The case was a 55-year-old woman with a history of a total hysterectomy for cervical cancer. She developed left paralysis. Brain MRI confirmed a 27 mm contrast-enhanced lesion in the right frontal lobe and three other lesions. SRS was performed as a diagnosis of multiple brain metastases for urgent symptom relief. No extra-cranial cancerous lesions were found. Unknown primary cancer was a probable diagnosis at that time. Two years after SRS, local regrowth of tumor of the right frontal primary motor area was discovered. Re-irradiation was performed. Cerebral edema, contrast enhancement, and left paralysis progressed following five months, taking an oral corticosteroid. Craniotomy and debulk. The pathological diagnosis was brain radiation necrosis due to no viable tumor cells. New lesions in the left temporal lobe and basal ganglia appeared three years after surgery. Awake craniotomy was performed for the left temporal lobe lesion. Histopathology showed diffuse growth of tumor cells with a high nucleo-cytoplasmic ratio and irregular nuclear shape. Immunohistochemistry revealed positive CD10, CD20, CD45 (LCA), MUM1, and negative CD3, CD5. The Ki- 67 labeling rate was as high as almost 100% to diagnose diffuse large B-cell lymphoma, PCNSL. Multidrug chemotherapy consisting of rituximab, high-dose methotrexate, procarbazine, and vincristine were performed. Complete remission was obtained without any serious adverse events. Considering the residual radiation necrosis, whole-brain irradiation was avoided. Moreover, consolidation therapy was performed only with high-dose cytarabine therapy.
ML-7 Liquid biopsy for MYD88 mutation in cerebrospinal fluid in patients with suspected primary CNS lymphoma
Authors: Yuki Yamagishi , Sasaki Nobuyoshi , Matsushita Yuko , Shimizu Saki , Matsumoto Yoshie , Saito Kuniaki , Kobayashi Keiichi , Nakatomi Hirofumi , Shiokawa Yoshiaki , Ichimura Koichi , Nagane Motoo 
Published: December 2021

Abstract
Background: Treatment intervention for central nervous system lymphoma (CNSL) requires pathological diagnosis by surgical biopsy. However, there are some cases in which the risk of surgery is high due to age, comorbidities, localization of lesions, etc. We are developing a CNSL diagnostic method based on the detection of MYD88 L265P mutation by digital PCR (dPCR) using CSF-DNA, and a high accuracy with a sensitivity of 92.9% and a specificity of 100% has been reported. Here, we report two cases with suspected brain stem CNSL, whose treatment strategy was determined by integrated clinico-laboratory information including neurological presentations, imaging, and the result of liquid biopsy. Result: Case 1. A 63-year-old woman visited our hospital with a complaint of right hemiplegia, which deteriorated in two months. MR images revealed a contrast-enhancing lesion in the left midbrain-ventral pons, suggesting CNSL. Biopsy was not considered because of its location, while dPCR using CSF-DNA showed a cluster of MYD88 mutation signals. Based on these work-ups, she was treated with high-dose methotrexate-based chemotherapy, resulting in a complete response with marked improvement of symptoms. Case 2. An 83-year-old man was referred for a history of diplopia and ataxic gait lasting for a month. MR images revealed an invasive lesion on his right midbrain-dorsal pons. Biopsy was declined due to the location, and liquid biopsy using CSF-DNA was performed to assist the diagnosis. In the first test, the CSF-DNA yield was too insufficient to determine the mutation signal by dPCR. The second dPCR using sufficient amount of CSF-DNA resulted in the Target/Total value of 0.049% which was lower than the threshold, suggesting the absence of MYD88 mutation. The patient underwent radiation therapy accordingly.Conclusions: CSF MYD88 mutation analysis by dPCR may have clinical utility and requires sufficient amount of CSF-DNA for exclusion of noise signals.
ML-10 Tirabrutinib, a second-generation BTK inhibitor in relapsed and refractory primary CNS lymphoma: A single institute study
Authors: Mishima Kazuhiko , Mitsuaki Shirahata , Adachi Junichi , Suzuki Tomonari , Uchida Eita , Nishikawa Ryo 
Published: December 2021

Abstract
BACKGROUND: The prognosis of relapsed and refractory (r/r) primary CNS lymphoma (PCNSL) is poor, and the development of new therapeutic agents is desirable. Comprehensive genetic analysis of PCNSL has shown that MYD88 and CD79B are frequently mutated and are oncogenic drivers, suggesting that Bruton’s tyrosine kinase (BTK), which is located downstream of MYD88 and CD79B, may be a reasonable therapeutic target. Tirabrutinib is a second-generation oral BTK inhibitor recently approved in Japan for the treatment of r/r PCNSL. In this study, we evaluated the efficacy and safety of tiraburtinib treatment of r/r PCNSL at Saitama Medical University. MATERIAL AND METHODS: Eighteen patients with r/r PCNSL to HD-MTX-based regimens were treated with 480 mg tiraburtinib daily under fasting conditions until disease progression. RESULTS: The median age was 63.5 years, and the median KPS was 70. Nine patients (50%) achieved a CR, 2 (11%) had a partial response, 3 (17%) had stable disease, and 4 (22%) had progressive disease. After a median follow-up of 17.3 months, the median progression-free survival was 7.9 months, and the median overall survival was 23.6 months. There were four cases of long-term treatment lasting more than one year. Grade 3 or higher adverse events were observed in 1 case of maculopapular rash, 1 case of cardiac failure, 1 case of neutropenia, and 1 case of lymphopenia. CONCLUSION: Tiraburtinib can be administered relatively safely to patients with relapsed or refractory PCNSL, and a certain degree of efficacy can be expected. Which patients can be treated with tiraburtinib over the long term, when can stop tirabrutinib treatment for patients with long-term CR, and the mechanism of tiraburtinib resistance needs to be determined.