bluuebunny/crossref_metadata_2025_split huggingface dataset:
NI-10 T2/FLAIR mismatch sign and methionine PET uptake in grade II and III gliomas
Authors: Ebiko Yusuke , Tamura Kaoru , Hara Shoko , Inaji Motoki , Tanaka Yoji , Nariai Tadashi , Ishii Kenji , Maehara Taketoshi 
Published: November 2020

Abstract
Background: Recent study suggests that “T2/FLAIR mismatch” sign is specific MRI finding for isocitrate dehydrogenase mutated (IDH-mut) 1p19q non-codeleted gliomas (Grade II and III astrocytic tumors). T2/FLAIR mismatch sign may be useful for predicting the histological type of glioma before surgery. However, it is not known what this finding reflects. Therefore, we examined the correlation between T2/FLAIR mismatch sign and uptake of methionine with positron emission tomography (MET-PET), and molecular classification of glioma.
Methods: 74 glioma patients (grade II: 30 cases, grade III: 44 cases) with preoperative MRI and MET-PET who underwent surgical resection during 2000–2019 were included in this study. MR scans were evaluated by 3 independent reviewers to assess presence/absence of T2/FLAIR mismatch sign. The tumor-to-normal (T/N) ratio of methionine uptake was calculated by dividing the maximum standardized uptake value (SUV) for the tumor by the mean SUV of the normal brain. We examined the relationship between IDH mutation, 1p/19q codeletion, mismatch, and T/N ratio of MET-PET.
Results: Out of the 74 cases, astrocytic tumors (A group: IDH-mutant, 1p19q non-codeleted) were 21 (28%), oligodendroglial tumors (O group: IDH-mutant, 1p19q codeleted) were 19 (26%), and IDH wild tumors (W group) were 34 (46%). The T2/FLAIR mismatch sign was present in 16 cases (22%). The T/N ratio of MET-PET in the tumor with T2/FLAIR mismatch sign was 1.56, which was significantly lower than that in the tumor without mismatch sign (2.01, p=0.016). T2/FLAIR mismatch sign was found in 7 (33%) cases in the A group, 0 (0%) case in the O group and 9 (26%) cases in the W group, and the positive rate was significantly higher in the A group (p=0.013).
Conclusions: “T2/FLAIR mismatch” sign was a specific finding for astrocytic tumor, and the cases with positive “T2/FLAIR mismatch” sign had significantly lower MET-PET uptake than that with negative cases.
NI-11 Clinical significance of intracystic diffusion hyperintensity lesions remaining after treatment of intracranial germ cell tumor
Authors: Takano Motoki , Takayasu Takeshi , Yonezawa Ushio , Taguchi Akira , Sugiyama Kazuhiko , Yamasaki Fumiyuki 
Published: November 2020

Abstract
Background and purpose: About 30% of intracranial germ cell tumors are mixed germ cell tumors and teratomas are often found as those components. Intense chemoradiotherapy is performed according to the malignancy of the histopathology, but high-intensity lesion inside the cystic tumor on diffusion weighted imaging (DWI) sometimes remains after completion of the chemoradiotherapy. In this study, we examined the clinical significance of the DWI high-intensity lesion remaining in the cyst. METHODS: Five patients after initial chemoradiotherapy were resected residual tumor by craniotomy at our hospital from 2009 to 2019. Preoperative gadolinium-enhanced MRI defined the non-contrast-enhanced part of the tumor as intracystic, and DWI intensity was classified by its look as low-intensity, equal-intensity, and high-intensity compared to the cortex of the same slice. DWI signals in the solid area, cyst wall, and cyst were evaluated. Results: All cases were mature teratoma in histopathology, and no other tumor components were observed. On DWI, the cyst wall and solid part were visualized with low signal. High-intensity lesions and equal-intensity lesions in the cyst cavity were found in 3 and 1 cases, respectively. In these cases, pathological findings revealed a keratin-like substance in the cyst. Discussion: The intracystic high and equal intensity lesions on DWI removed after completion of chemoradiotherapy are considered to reflect the keratin-like component of mature teratoma. If DWI- high intensity and equal intensity lesions remain in the cyst of the tumor after the completion of chemoradiotherapy, tumor shrinkage cannot be expected even if the chemotherapy is strengthened. In such cases, we should consider to removing them by surgery. Conclusion: When DWI high and equal intensity lesions are found in the cysts of tumors remaining after chemoradiotherapy for intracranial germ tumors, it is possible that mature teratoma remains.
NI-13 The effectiveness and limitation of survival prediction in primary glioblastoma using machine learning-based texture analysis
Authors: Umehara Toru , Kinoshita Manabu , Sasaki Takahiro , Arita Hideyuki , Yoshioka Ema , Shofuda Tomoko , Kodama Yoshinori , Hirayama Ryuichi , Kijima Noriyuki , Kagawa Naoki , Okita Yoshiko , Takano Koji , Uda Takehiro , Fukai Junya , Sakamoto Daisuke , Mori Kanji , Kanemura Yonehiro 
Published: November 2020

Abstract
Introduction: Clinical application of survival prediction of primary glioblastoma (pGBM) using preoperative images remains challenging due to a lack of robustness and standardization of the method. This research focused on validating a machine learning-based texture analysis model for this purpose using internal and external cohorts. Method: We included all cases of IDH wild-type pGBM available of preoperative MRI (T1WI, T2WI, and Gd-T1WI) from the databases of Kansai Molecular Diagnosis Network for CNS tumors (KN) and The Cancer Genome Atlas (TCGA). Of 242 cases from KN, we assigned 137 cases as a training dataset (D1), and the remaining 105 cases as an internal validation dataset (D2). Furthermore, we extracted 96 cases from TCGA as an external validation dataset (D3). Preoperative MRI scans were semi-quantitatively analyzed, leading to the acquisition of 489 texture features as explanatory variables. Dichotomous overall survival (OS) with a 16.6 months cutoff was regarded as the response variable (short/long OS). We employed Lasso regression for feature selection, and a survival prediction model constructed for D1 via cross-validation (M1) was applied to D2 and D3 to ensure the model robustness. Results: The population of predicted short OS by M1 significantly showed poorer prognosis in D2 (median OS 11.1 vs. 19.4 months; log-rank test, p=0.03), while there was no significant difference in D3 (median OS 14.2 vs. 11.9 months; p=0.61). In the comparative analysis using t-SNE, there was little variation in the feature distribution among three datasets. Conclusion: We were able to validate the prediction model in the internal but not in the external cohort. The presented result supports the use of machine learning-based texture analysis for survival prediction of pGBM in a localized population or country. However, further consideration is required to achieve a universal prediction model for pGBM, irrespective of regional difference.
NI-17 Evaluation of preoperative apparent diffusion coefficient (ADC) of peritumoral FLAIR high lesion and histopathological features in patients with glioblastoma
Authors: Matsuda Kenichiro , Oe Rintaro , Sonoda Yukihiko 
Published: November 2020

Abstract
Objective: In removal of the glioblastoma, maximum and safe removal is desired for recurrence prevention with functional preservation. In recent years, the setting of the removal range has also been studied not only the contrast enhanced lesions, but also the surrounding FLAIR high signal lesion. We are studying the prediction of the site that is likely to occur recurrence in the FLAIR high signal lesion of glioblastoma, and we are focusing on the ADC of pre-operative MRI as an index. The purpose of this study is to evaluate the ADC and the actual pathological tissue image in the FAIR high signal lesion around the contrast enhanced lesion of glioblastoma. Method: We examined the case of removal of the glioblastoma treated in our department. Analysis was performed using a pathological tissue specimen of excised tumors and their surrounding tissues in each case, and the ADC value of pre-operative MRI. Pathological tissue image and ADC values of FAIR high signal lesion were compared. Results: 19 tissue samples which were taken from the FLAIR high signal lesion around the contrast enhanced tumor from 10 cases. For a total of 19 locations, it was compared with the histopathological features of the site. As a result, in the low part of the ADC value in the preoperative MRI relatively had high cell density of atypical cells, it was often exhibited findings that infiltration of tumor cells is suspected. Conclusion: In general, ADC is said to suggest an increase in cell density and thus infiltration of tumor cells. However, the same findings were obtained in the pre-operative MRI examined this time. Since ADC also suggests cell density and tumor infiltration in pre-operative MRI, ADC of pre-operative MRI was considered useful for examination of the removal range and radiation therapy planning in surgery for glioblastoma.
NQPC-02 Long-term survival in patients with primary intracranial germ cell tumors treated with surgery, platinum-based chemotherapy, and radiotherapy: a single-institution study
Authors: Motomura Kazuya , Shimizu Hiroyuki , Ohka Fumiharu , Aoki Kosuke , Tanahashi Kuniaki , Hirano Masaki , Chalise Lushun , Nishikawa Tomohide , Yamaguchi Junya , Yoshida Jun , Natsume Atsushi , Wakabayashi Toshihiko 
Published: November 2020

Abstract
Purpose: In the present study, we performed a retrospective review of patients receiving carboplatin based chemotherapy followed by radiotherapy for newly diagnosed primary intracranial germ cell tumors. In order to identify an optimal germ cell tumor treatment strategy, we evaluated treatment outcomes and toxicity and compliance.
Methodology: This study included 110 consecutive patients with newly diagnosed primary intracranial germ cell tumors. The drug doses and administration schedule of carboplatin-etoposide (CARB-VP) were as follows: carboplatin (300 mg/m2 daily for 1 days), and etoposide (100 mg/m2 on days 1 to 3). Ifosfamide-carboplatin-etoposide (ICE) treatment comprised ifosfamide (1500 mg/m2 daily for 3 days), carboplatin (300 mg/m2 daily for 1 days), and etoposide (100 mg/m2 daily for 3 days). Patients with germinomatous germ cell tumors (pure germinoma or germinoma with STGC) basically receive three cycles of CARB-VP and a total dose of 30Gy whole ventricular radiotherapy. We delivered combination therapy consisting of combined ICE chemotherapy and craniospinal irradiation followed by the complete resection of the residual tumor for nongerminomatous malignant germ cell tumors.
Results: The median follow-up time was 11.0 years (range, 0.5–37.8 years). The 5-year total survival rates of germinomatous and nongerminomatous germ cell tumors were 97.2% and 66.7%, respectively. The 10-year and 20-year total survival rates of germinomatous germ cell tumors were 95.7% and 90.0%, respectively. Adverse events related to carboplatin based chemotherapy are not detected. Furthermore, no treatment-related deaths were observed.
Conclusions: Our treatment with surgery, carboplatin based chemotherapy followed by radiotherapy is effective in treating primary intracranial germ cell tumors, especially in germinomatous group.
ML-01 Pathological characteristics of primary central nervous system lymphoma with atypical radiological finding
Authors: Inukai Madoka , Shibahara Ichiyo , Handa Hajime , Saruta Wakiko , Sato Sumito , Hide Takuichiro , Kumabe Toshihiro 
Published: November 2020

Abstract
Background: If the brain tumor is suspected to be a primary central nervous system lymphoma (PCNSL) on radiological findings, it is general to perform biopsy to obtain the pathological diagnosis. Glioblastomas (GBs) must be distinguished from PCNSLs. In addition to commonly used contrast-enhanced T1-weighted imaging, diffusion-weighted image (DWI), and apparent diffusion coefficient (ADC) value, the following characteristics of PCNSLs were reported to be essential for this purpose: 1) no increase in blood flow on perfusion images obtained by the arterial spin labeling (ASL) method; 2) less microbleeding on T2*-weighted images (T2*). However, we experienced some exceptional cases. Purpose: To clarify the histopathological features of PCNSLs those had atypical radiological findings. Method: 62 consecutive PCNSL cases (40 males, 22 females, mean age 65.4 years, range 35–84) treated in our department from April 2013 to March 2020 were retrospectively analyzed. We compared the following features between 47 biopsy cases showing typical image findings as PCNSLs (Group A) and 15 surgically resected cases with atypical findings (Group B), 1) number of blood vessels per hyper 10 fields, 2) occupying area of blood vessels per unit area, 3) immunoreactivity of vascular endothelial growth factor (VEGF), and 4) germinal center B-cell (GCB) subtype. Results: In Group A, the number of blood vessels in the tumor was 39.3 on average, and the area occupied by blood vessels was 3.8%. In Group B, the former was 133.2, and the latter was 9.9%. There was no significant difference in VEGF expression and GCB subtype. Conclusion: In PCNSLs showing with high blood flow and microbleeds, the blood vessels were rich and partial bleeding was confirmed histologically. We should analyze much more cases to set the threshold both of the ADC value and the absolute value of blood flow calculated by the ASL method to distinguish between PCNSLs and GBs.
ML-05 One-year follow-up data of phase I/II study of tirabrutinib in patients with relapsed or refractory primary central nervous system lymphoma
Authors: Mishima Kazuhiko , Narita Yoshitaka , Nagane Motoo , Terui Yasuhito , Arakawa Yoshiki , Yonezawa Hajime , Asai Katsunori , Fukuhara Noriko , Sugiyama Kazuhiko , Shinojima Naoki , Aoi Arata , Nishikawa Ryo 
Published: November 2020

Abstract
In March 2020, Tirabrutinib (TIR), a second-generation oral Bruton’s tyrosine kinase inhibitor, was approved for the indication of relapsed or refractory PCNSL (r/rPCNSL) based on the results of a phase I/II study in Japan. In this study, 44 Japanese patients with r/rPCNSL were treated with TIR QD at 320 mg, 480 mg, or 480 mg in the fasted condition (480 mg fasted QD). The primary endpoint was overall response rate (ORR) assessed by an independent review committee according to International PCNSL Collaborative Group criteria. We previously reported the results of this study with data cutoff in June 2019 (Narita et al. Neuro Oncol. 2020). In the report, 17 of 44 patients were treated with TIR at 480 mg fasted QD which is an approved dose, and had ORR of 52.9%, median progression-free survival of 5.8 months, and median overall survival of not reached (median follow-up: 3.8 months). In 44 patients, ORR was similar among patients harboring either of the oncogenic mutants CARD11, MYD88, CD79B, or wild type. Throughout the whole patients, most common adverse events (AEs) at any grade were rash (31.8%), neutropenia (22.7%), leukopenia (18.2%), and lymphopenia (15.9%), and grade ≥3 AEs were neutropenia (9.1%), lymphopenia, leukopenia, and erythema multiforme (6.8% each). One patient with 480 mg QD had grade 5 AEs (pneumocystis jirovecii pneumonia and interstitial lung disease). We will present one-year follow-up data of this study at the meeting. As of data cutoff (February 2020), 11 of 44 patients continued to receive TIR, including 6 patients with 480 mg fasted QD. Updated data for overall survival, duration of response, and time to onset of AEs will also be presented. TIR is a promising new treatment for r/rPCNSL.
ML-08 Safety and efficacy of consolidation cytarabine for newly-diagnosed primary central nervous system lymphoma
Authors: Sasaki Nobuyoshi , Kobayashi Keiichi , Saito Kuniaki , Sasaki Yuta , Okamura Yuma , Yamagishi Yuki , Shimizu Saki , Shiokawa Yoshiaki , Nagane Motoo 
Published: November 2020

Abstract
Backgrounds: While consolidation therapies which incorporate whole brain radiotherapy (WBRT) and/ or chemotherapies such as high dose (HD)- cytarabine are commonly applied following induction chemotherapies in primary central nervous system lymphoma (PCNSL), the optimal treatment for consolidation therapy has not been established. We aimed to investigate the safety and efficacy of consolidation cytarabine with a dose modification policy in PCNSL. Patients and methods: PCNSL patients initially treated by R-MPV (rituximab, methotrexate, procarbazine and vincristine) and subsequently treated either by WBRT of 24Gy followed by cytarabine (WBRT-AraC group), or cytarabine alone (AraC group) were identified. WBRT was deferred in patients 71 years old or younger who had obtained a complete response (CR) after R-MPV. Cytarabine was dose-modified according to age groups (3 g/m2 in patients 70 years old or younger, 2 g/m2 in patients aged 71–75 years, 1 g/m2 in patients aged 76–80 years). Toxicity profiles, progression-free survival (PFS), overall survival (OS) were analyzed. Results: Twenty-five patients were identified (median age: 69 [range: 34–80], median KPS:70 [range: 40–90]), including 11 patients from the WBRT-AraC group, and 14 patients from the AraC group. Median PFS was unreached in the WBRT-AraC group, and 41.8 months in the AraC group. Median OS was unreached in both groups. The overall rate of grade 3/4 hematologic toxicities was high (92%), but mostly manageable without major complications. Fourteen patients received 3 g/m2, 4 patients received 2 g/m2, 7 patients received 1 g/m2 of cytarabine, and the rate of grade 4 leukopenia/ thrombocytopenia was 64%/57%, 25%/50%, and 29%/29%, respectively. Discussion: HD-cytarabine consolidation therapy with dose modification according to age groups for PCNSL was feasible and well-tolerated in patients 80 years of age or younger. The efficacy of HD-cytarabine was undetermined and further investigation is warranted.
ML-15 The future direction of treatment development for primary central nervous system lymphoma (PCNSL)
Authors: Shinojima Naoki , Fujimoto Kenji , Yamamoto Takahiro , Ohta Kazutaka , Takezaki Tatsuya , Kuroda Jun-ichiro , Makino Keishi , Mukasa Akitake 
Published: November 2020

Abstract
Purpose: We found that the combination of high-dose Methotrexate (HD-MTX)-based therapy and histone deacetylase inhibitor (HDACI) had a therapeutic effect on PCNSL. In addition, this year, tirabrutinib, a Bruton’s tyrosine kinase inhibitor, was approved for marketing as a single agent for relapsed/refractory PCNSL, and new therapeutic development is expected. We will examine the treatment results of PCNSL in our department retrospectively and discuss the future direction of treatment development. METHODS: From 2001 to 2014, 82 newly diagnosed PCNSL patients treated with HD-MTX/Procarbazine (MP) as initial remission induction chemotherapy were retrospectively analyzed. RESULTS: Complete response (CR) was obtained in 38 patients (46.3%) after initial chemotherapy, and the median overall survival (OS) in the CR and non-CR groups was 2636 days and 728 days, respectively, and significantly shorter in the non-CR group (p&lt;0.01). In the CR group, 27 cases (71.1%) recurred and 12 cases received HD-MTX re-challenge (M-re), 14 cases received treatment other than M-re (1 case did not receive treatment), the median OS after relapse was 590 days. The median post-relapse progression-free survival (PFS) of the 10 patients undergoing M-re at the first relapse was 116 days, the median OS after relapse was 590 days. The median post-relapse PFS of 16 patients receiving other treatments was 428 days, the median OS after relapse was 532 days. There was no difference in PFS and OS after recurrence in treatment at the first recurrence (p=0.15, p=0.55). Conclusion: The OS of non-CR patients in the initial chemotherapy and the OS after recurrence after CR were short. The possible directions of PCNSL treatment development include 1) increasing the CR rate with initial chemotherapy and maintaining CR for a long time for newly diagnosed PCNSL, and 2) finding an effective treatment for recurrence. New drugs such as tirabrutinib and HDACIs may be breakthroughs.
MET-01 Linac-based fractionated stereotactic radiotherapy with micro-multileaf collimeter for large brain metastasis unsuitable for surgical resection
Authors: Matsuda Ryosuke , Tamamoto Tetsuro , Morimoto Takayuki , Takeshima Yasuhiro , Tamura Kentaro , Yamada Shuichi , Nishimura Fumihiko , Nakagawa Ichiro , Motoyama Yasushi , Park Young-Su , Nakase Hiroyuki 
Published: November 2020

Abstract
To assess clinical outcomes using linac-based, fractionated, stereotactic radiotherapy (fSRT) with a micro-multileaf collimator for large brain metastasis (LBM) unsuitable for surgical resection. Between January 2009 and October 2018, we treated 21 patients with LBM using linac-based fSRT. LBM was defined as a tumor &gt;30mm maximal diameter in gadolinium-enhanced magnetic resonance images. LBMs originated from the lung (n=17, 81%), ovary (n=2, 9.5%), rectum (n =1, 4.8%), and esophagus (n=1, 4.8%). The median pretreatment Karnofsky Performance Status was 50 (range: 50~80). Recursive partition analysis (RPA) was as follows: Classes 2 and 3 were 7 and 14 patients, respectively. The median follow-up was 5 months (range: 1~86 months). The range of tumor volume was 8.7~26.5 cm3 (median: 17.1 cm3). All patients were basically treated with fSRT ranged from 35 Gy with 7 Gy daily fractions, except in three cases. The progression-free survival was 3.0 months. The median survival time was 7.0 months. There was no permanent radiation injury in any of the patients. Radiation-caused central nervous system necrosis, according to the Common Terminology Criteria for Adverse Events version 4.0, occurred in one patient (grade 3). One patients received bevacizumab for radiation necrosis. Two patients underwent additional surgical resection due to local progression and cyst formation. For patients with LBM unsuitable for surgical resection, linac-based fSRT is a promising therapeutic alternative.