Qualitative MR features to identify non-enhancing tumors within glioblastoma's T2-FLAIR hyperintense lesions.

PURPOSE: To identify qualitative MRI features of non-(contrast)-enhancing tumor (nCET) in glioblastoma's T2-FLAIR hyperintense lesion. METHODS: Thirty-three histologically confirmed glioblastoma patients whose T1-, T2- and contrast-enhanced T1-weighted MRI and 11C-methionine positron emission tomography (Met-PET) were available were included in this study. Met-PET was utilized as a surrogate for tumor burden. Imaging features for identifying nCET were searched by qualitative examination of 156 targets. A new scoring system to identify nCET was established and validated by two independent observers. RESULTS: Three imaging features were found helpful for identifying nCET; "Bulky gray matter involvement", "Around the rim of contrast-enhancement (Around-rim)," and "High-intensity on T1WI and low-intensity on T2WI (HighT1LowT2)" resulting in an nCET score = 2 × Bulky gray matter involvement - 2 × Around-rim + HighT1LowT2 + 2. The nCET score's classification performances of two independent observers measured by AUC were 0.78 and 0.80, with sensitivities and specificities using a threshold of four being 0.443 and 0.771, and 0.916 and 0.768, respectively. The weighted kappa coefficient for the nCET score was 0.946. CONCLUSION: The current investigation demonstrated that qualitative assessments of glioblastoma's MRI might help identify nCET in T2/FLAIR high-intensity lesions. The novel nCET score is expected to aid in expanding treatment targets within the T2/FLAIR high-intensity lesions.

Evaluation of the efficacy and safety of TAS0313 in adults with recurrent glioblastoma.

BACKGROUND: TAS0313 is a multi-epitope long peptide vaccine targeting several cancer-associated antigens highly expressed in multiple cancer types, including glioblastoma (GBM). This cohort of a Phase 2 part evaluated the efficacy and safety of TAS0313 in patients with GBM. METHODS: TAS0313 (27 mg) was administered subcutaneously on Days 1, 8 and 15 of Cycles 1 and 2, and Day 1 of subsequent cycles in 21-day cycles. The primary endpoint was the objective response rate (ORR). The secondary endpoints were the disease control rate, progression-free survival (PFS) and 6- and 12-month progression-free survival rates (PFR) and safety. Immunological response was assessed as an exploratory endpoint. RESULTS: The best overall response was partial response in 1 patient, and the ORR (95% CI) was 11.1% (0.3-48.2%) in the per-protocol set (n = 9). A further 3 patients achieved stable disease, for a disease control rate (95% CI) of 44.4% (13.7-78.8%). Median (95% CI) PFS was 1.7 (1.3-NE) months and 6- and 12-month PFRs (95% CI) were 22.2% (3.4-51.3%) each. Common (≥ 20% incidence) treatment-related adverse events (AEs) were injection site reactions (n = 8, 80.0%), followed by pyrexia (n = 7, 70.0%), and malaise, injection site erythema and injection site pruritus (n = 2, 20.0% each). There were no grade 4 or 5 treatment-related AEs. No deaths occurred during the study. In some patients, TAS0313 treatment was confirmed to increase cytotoxic T lymphocyte and immunoglobulin G levels compared with baseline. CONCLUSION: TAS0313, a multi-epitope long peptide vaccine, demonstrated promising efficacy and acceptable safety in patients with recurrent GBM. CLINICAL TRIAL REGISTRATION: JapicCTI-183824 (Date of registration: Jan 11, 2018).

TERT promoter mutation status is necessary and sufficient to diagnose IDH-wildtype diffuse astrocytic glioma with molecular features of glioblastoma.

The Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) update 3 recommends that histologic grade II and III IDH-wildtype diffuse astrocytic gliomas that harbor EGFR amplification, the combination of whole chromosome 7 gain and whole chromosome 10 loss (7 + /10 -), or TERT promoter (pTERT) mutations should be considered as glioblastomas (GBM), World Health Organization grade IV. In this retrospective study, we examined the utility of molecular classification based on pTERT status and copy-number alterations (CNAs) in IDH-wildtype lower grade gliomas (LGGs, grade II, and III). The impact on survival was evaluated for the pTERT mutation and CNAs, including EGFR gain/amplification, PTEN loss, CDKN2A homozygous deletion, and PDGFRA gain/amplification. We analyzed 46 patients with IDH-wildtype/pTERT-mutant (mut) LGGs and 85 with IDH-wildtype/pTERT-wildtype LGGs. EGFR amplification and a combination of EGFR gain and PTEN loss (EGFR + /PTEN -) were significantly more frequent in pTERT-mut patients (p < 0.0001). Cox regression analysis showed that the pTERT mutation was a significant predictor of poor prognosis (hazard ratio [HR] 2.79, 95% confidence interval [CI] 1.55-4.89, p = 0.0008), but neither EGFR amplification nor EGFR + /PTEN - was an independent prognostic factor in IDH-wildtype LGGs. PDGFRA gain/amplification was a significant poor prognostic factor in IDH-wildtype/pTERT-wildtype LGGs (HR 2.44, 95% CI 1.09-5.27, p = 0.03, Cox regression analysis). The IDH-wildtype LGGs with either pTERT-mut or PDGFRA amplification were mostly clustered with GBM by DNA methylation analysis. Thus, our study suggests that analysis of pTERT mutation status is necessary and sufficient to diagnose IDH-wildtype diffuse astrocytic gliomas with molecular features of glioblastoma. The PDGFRA status may help further delineate IDH-wildtype/pTERT-wildtype LGGs. Methylation profiling showed that IDH-wildtype LGGs without molecular features of GBM were a heterogeneous group of tumors. Some of them did not fall into existing categories and had significantly better prognoses than those clustered with GBM.

Infrequent RAS mutation is not associated with specific histological phenotype in gliomas.

BACKGROUND: Mutations in driver genes such as IDH and BRAF have been identified in gliomas. Meanwhile, dysregulations in the p53, RB1, and MAPK and/or PI3K pathways are involved in the molecular pathogenesis of glioblastoma. RAS family genes activate MAPK through activation of RAF and PI3K to promote cell proliferation. RAS mutations are a well-known driver of mutation in many types of cancers, but knowledge of their significance for glioma is insufficient. The purpose of this study was to reveal the frequency and the clinical phenotype of RAS mutant in gliomas. METHODS: This study analysed RAS mutations and their clinical significance in 242 gliomas that were stored as unfixed or cryopreserved specimens removed at Kyoto University and Osaka National Hospital between May 2006 and October 2017. The hot spots mutation of IDH1/2, H3F3A, HIST1H3B, and TERT promoter and exon 2 and exon 3 of KRAS, HRAS, and NRAS were analysed with Sanger sequencing method, and 1p/19q codeletion was analysed with multiplex ligation-dependent probe amplification. DNA methylation array was performed in some RAS mutant tumours to improve accuracy of diagnosis. RESULTS: RAS mutations were identified in four gliomas with three KRAS mutations and one NRAS mutation in one anaplastic oligodendroglioma, two anaplastic astrocytomas (IDH wild-type in each), and one ganglioglioma. RAS-mutant gliomas were identified with various types of glioma histology. CONCLUSION: RAS mutation appears infrequent, and it is not associated with any specific histological phenotype of glioma.

[Significance of Quality of Life Evaluation for Glioma Patients].

Typically, overall and progression-free survival are used as endpoints in clinical tri-als investigating gliomas, while health-related quality of life(HRQOL)plays a key role in cancer research and may be useful for individual patient care. Previous studies have shown that HRQOL parameters can serve as independent prognostic factors for survival in patients with cancer, while recent studies have highlighted the usefulness of HRQOL in information management and decision-making in cancer treatment. However, a few studies have shown differences between patients' and physicians' perceptions of cancer treatment. In the future, physicians will be expected to recog-nize the importance of the QOL evaluation tool, not only in clinical trials, but also in general practice for gliomas, considering the characteristics of patients with brain tu-mors. In this study, we reviewed the methods of major HRQOL evaluation and sum-marized the first clinical trials incorporating QOL in glioma treatment.

Characteristics and outcomes of elderly patients with diffuse gliomas: a multi-institutional cohort study by Kansai Molecular Diagnosis Network for CNS Tumors.

INTRODUCTION: This study investigates the current state of clinical practice and molecular analysis for elderly patients with diffuse gliomas and aims to elucidate treatment outcomes and prognostic factors of patients with glioblastomas. METHODS: We collected elderly cases (≥ 70 years) diagnosed with primary diffuse gliomas and enrolled in Kansai Molecular Diagnosis Network for CNS Tumors. Clinical and pathological characteristics were analyzed retrospectively. Various factors were evaluated in univariate and multivariate models to examine their effects on overall survival. RESULTS: Included in the study were 140 elderly patients (WHO grade II: 7, III: 19, IV: 114), median age was 75 years. Sixty-seven patients (47.9%) had preoperative Karnofsky Performance Status score of ≥ 80. All patients underwent resection (gross-total: 20.0%, subtotal: 14.3%, partial: 39.3%, biopsy: 26.4%). Ninety-six of the patients (68.6%) received adjuvant treatment consisting of radiotherapy (RT) with temozolomide (TMZ). Seventy-eight of the patients (75.0%) received radiation dose of ≥ 50 Gy. MGMT promoter was methylated in 68 tumors (48.6%), IDH1/2 was wild-type in 129 tumors (92.1%), and TERT promoter was mutated in 78 of 128 tumors (60.9%). Median progression-free and overall survival of grade IV cases was 8.2 and 13.6 months, respectively. Higher age (≥ 80 years) and TERT promoter mutated were associated with shorter survival. Resection and adjuvant RT + TMZ were identified as independent factors for good prognosis. CONCLUSIONS: This community-based study reveals characteristics and outcomes of elderly glioma patients in a real-world setting. Elderly patients have several potential factors for poor prognosis, but resection followed by RT + TMZ could lengthen duration of survival.

Clinical outcomes of brain metastases from hepatocellular carcinoma: a multicenter retrospective study and a literature review.

INTRODUCTION: The introduction of systemic chemotherapy for advanced hepatocellular carcinoma in recent years has led to the prediction that cases of brain metastases from hepatocellular carcinoma will increase. However, because brain metastases from hepatocellular carcinoma are relatively rare, the characteristics of this pathology are poorly understood. METHODS: We carried out a multicenter retrospective study to verify the characteristics of brain metastases from hepatocellular carcinoma in Japan. RESULTS: A total of 38 patients were enrolled and patient characteristics were poor general condition in many patients due to the progression of primary cancers. Stereotactic radiosurgery/stereotactic radiotherapy alone was the most common treatment (39.5%), with best supportive care provided for 10.5%. Median survival was 6 months, the neurological death rate was 28%, and the rate of brain hemorrhage was high (39.5%). Overall survival was analyzed for correlations with age, etiology of chronic liver disease, albumin-bilirubin (ALBI) grade, RPA classification, control of the primary tumor, number of brain metastases, brain hemorrhage, surgical resection, and radiotherapy. In multivariate analysis, ALBI grade, number of brain metastases and brain hemorrhage showed statistically significant correlation. CONCLUSIONS: A multivariate analysis extracted three items-ALBI grade, number of brain metastases, and brain hemorrhage-as prognostic factors for survival of brain metastases from hepatocellular carcinoma.

A nationwide multi-institutional retrospective study to identify prognostic factors and develop a graded prognostic assessment system for patients with brain metastases from uterine corpus and cervical cancer.

BACKGROUND: The prevalence of brain metastases (BM) from uterine cancer has recently increased because of the improvement of overall survival (OS) of patients with uterine cancer due to its early detection and improved local control as a result of new effective treatments. However, little information is available regarding their clinical characteristics and prognosis, because oncologists have encountered BM from uterine cancer on rare occasions. METHODS: Records from 81 patients with uterine BM were collected from 10 institutes in Japan. These were used in a multi-institutional study to identify prognostic factors and develop a graded prognostic assessment (GPA) for patients with BM from uterine cancer. RESULTS: Median OS after the development of BM was 7 months (95% confidence interval, 4 to 10 months). Multivariate analysis revealed that there were survival differences according to the existence of extracranial metastases and number of BM. In the present uterine-GPA, a score of 0 was assigned to those patients with ≥5 BM and extracranial metastasis, a score of 2 was assigned to those patients with one to four BM or without extracranial metastasis, and a score of 4 was assigned to those patients with one to four BM and without extracranial metastasis. The median OS for patients with a uterine-GPA scores of 0, 2, and 4 was 3, 7, and 22 months, respectively. A survival analysis confirmed the presence of statistically significant differences between these groups (p < 0.05). The results were validated by data obtained from the National Report of Brain Tumor Registry of Japan. CONCLUSION: Uterine GPA incorporates two simple clinical parameters of high prognostic significance and can be used to predict the expected survival times in patients with BM from uterine cancer. Its use may help in determining an appropriate treatment for individual patients with BM.

Ipsilateral hemiparesis caused by putaminal hemorrhage in a patient with horizontal gaze palsy with progressive scoliosis: a case report.

BACKGROUND: Horizontal gaze palsy with progressive scoliosis (HGPPS) is an autosomal recessive disorder caused by mutations in the ROBO3 gene, resulting in a critical absence of crossing fibers in the brainstem. CASE PRESENTATION: We present a patient with ipsilateral hemiparesis caused by putaminal hemorrhage who had a history of horizontal gaze paralysis and scoliosis since childhood. Diffusion tensor imaging (DTI) tractography confirmed the presence of uncrossed corticospinal tracts. Sequence analysis of the entire ROBO3 coding regions revealed a novel nonsense mutation. CONCLUSION: We report the first known HGPPS case with intracranial hemorrhage and ROBO3 mutation showing an absence of major crossing pathways by DTI.

Health-related quality of life in long-term survivors with Grade II gliomas: the contribution of disease recurrence and Karnofsky Performance Status.

OBJECTIVE: Although the number of long-term survivors of glioma has increased, there has been little research on the health-related quality of life of long-term survivors of Grade II glioma following treatment with surgery, radiotherapy and chemotherapy. In this study, we aimed to document the health-related quality of life of people diagnosed with Grade II glioma who had survived >10 years with no evidence of disease at the time of the health-related quality of life survey. METHODS: To investigate the health-related quality of life of Grade II glioma survivors without evidence of disease, we surveyed 50 patients 0-20 years after their initial treatments. Each patient completed a multi-part health-related quality of life questionnaire. Based on these surveys, we examined the relationships between health-related quality of life scores and time since initial treatment, Karnofsky Performance Scale scores at the time of the survey, and history of recurrence, radiotherapy and chemotherapy. RESULTS: Excepting bladder control, long-term survivors maintained their quality of life as determined by comparing patients surveyed < 5 and ≥ 10 years after their initial treatment (P < 0.05). Neither radiotherapy nor chemotherapy at the initial treatment was observed to affect health-related quality of life. However, a history of recurrence was significantly associated with deteriorations in many health-related quality of life functional and symptom scores. The Karnofsky Performance Scale scores of patients with a history of recurrence were significantly lower than those without it (P = 0.02). This deterioration was observed in both univariate and multivariate analyses. CONCLUSIONS: Our results indicate that declines in health-related quality of life among long-term survivors of Grade II glioma mainly result from impaired Karnofsky Performance Scale, which is a consequence of disease recurrence.

Automated volumetry of meningiomas in contrast-enhanced T1-Weighted MRI using deep learning.

BACKGROUND: Meningiomas are among the most common intracranial tumors. In these tumors, volumetric assessment is not only important for planning therapeutic intervention but also for follow-up examination.However, a highly accurate automated volumetric method for meningiomas using single-modality magnetic resonance imaging (MRI) has not yet been reported. Here, we aimed to develop a deep learning-based automated volumetry method for meningiomas in MRI and investigate its accuracy and potential clinical applications. METHODS: For deep learning, we used MRI images of patients with meningioma who were referred to Osaka University Hospital between January 2007 and October 2020. Imaging data of eligible patients were divided into three non-overlapping groups: training, validation, and testing. The model was trained and tested using the leave-oneout cross-validation method. Dice index (DI) and root mean squared percentage error (RMSPE) were measured to evaluate the model accuracy. Result: A total of 178 patients (64.6 ± 12.3 years [standard deviation]; 147 women) were evaluated. Comparison of the deep learning model and manual segmentation revealed a mean DI of 0.923 ± 0.051 for tumor lesions. For total tumor volume, RMSPE was 9.5 ± 1.2%, and Mann-Whitney U test did not show a significant difference between manual and algorithm-based measurement of the tumor volume (p = 0.96). CONCLUSION: The automatic tumor volumetry algorithm developed in this study provides a potential volume-based imaging biomarker for tumor evaluation in the field of neuroradiological imaging, which will contribute to the optimization and personalization of treatment for central nervous system tumors in the near future.

Awake surgery for a deaf patient using sign language: A case report.

Background: Although awake surgery is the gold standard for resecting brain tumors in eloquent regions, patients with hearing impairment require special consideration during intraoperative tasks. Case Description: We present a case of awake surgery using sign language in a 45-year-old right-handed native male patient with hearing impairment and a neoplastic lesion in the left frontal lobe, pars triangularis (suspected to be a low-grade glioma). The patient primarily communicated through sign language and writing but was able to speak at a sufficiently audible level through childhood training. Although the patient remained asymptomatic, the tumors gradually grew in size. Awake surgery was performed for tumors resection. After the craniotomy, the patient was awake, and brain function mapping was performed using tasks such as counting, picture naming, and reading. A sign language-proficient nurse facilitated communication using sign language and the patient vocally responded. Intraoperative tasks proceeded smoothly without speech arrest or verbal comprehension difficulties during electrical stimulation of the tumor-adjacent areas. Gross total tumor resection was achieved, and the patient exhibited no apparent complications. Pathological examination revealed a World Health Organization grade II oligodendroglioma with an isocitrate dehydrogenase one mutant and 1p 19q codeletion. Conclusion: Since the patient in this case had no dysphonia due to training from childhood, the task was presented in sign language, and the patient responded vocally, which enabled a safe operation. Regarding awake surgery in patients with hearing impairment, safe tumor resection can be achieved by performing intraoperative tasks depending on the degree of hearing impairment and dysphonia.

Prediction of MGMT promotor methylation status in glioblastoma by contrast-enhanced T1-weighted intensity image.

Background: The study aims to explore MRI phenotypes that predict glioblastoma's (GBM) methylation status of the promoter region of MGMT gene (pMGMT) by qualitatively assessing contrast-enhanced T1-weighted intensity images. Methods: A total of 193 histologically and molecularly confirmed GBMs at the Kansai Network for Molecular Diagnosis of Central Nervous Tumors (KANSAI) were used as an exploratory cohort. From the Cancer Imaging Archive/Cancer Genome Atlas (TCGA) 93 patients were used as validation cohorts. "Thickened structure" was defined as the solid tumor component presenting circumferential extension or occupying >50% of the tumor volume. "Methylated contrast phenotype" was defined as indistinct enhancing circumferential border, heterogenous enhancement, or nodular enhancement. Inter-rater agreement was assessed, followed by an investigation of the relationship between radiological findings and pMGMT methylation status. Results: Fleiss's Kappa coefficient for "Thickened structure" was 0.68 for the exploratory and 0.55 for the validation cohort, and for "Methylated contrast phenotype," 0.30 and 0.39, respectively. The imaging feature, the presence of "Thickened structure" and absence of "Methylated contrast phenotype," was significantly predictive of pMGMT unmethylation both for the exploratory (p = .015, odds ratio = 2.44) and for the validation cohort (p = .006, odds ratio = 7.83). The sensitivities and specificities of the imaging feature, the presence of "Thickened structure," and the absence of "Methylated contrast phenotype" for predicting pMGMT unmethylation were 0.29 and 0.86 for the exploratory and 0.25 and 0.96 for the validation cohort. Conclusions: The present study showed that qualitative assessment of contrast-enhanced T1-weighted intensity images helps predict GBM's pMGMT methylation status.

Management of glioblastoma in an NF1 patient with moyamoya syndrome: a case report.

INTRODUCTION: Glioma and moyamoya syndrome are both potential complications of neurofibromatosis type 1 (NF1). Here, we report the first case of NF1 concomitantly presenting with glioblastoma 10 years after surgical treatment of moyamoya syndrome. CASE REPORT: A 14-year-old boy with NF1 was incidentally diagnosed by magnetic resonance imaging (MRI) with a thalamic tumor during a follow-up for moyamoya syndrome, which had been treated with surgery 10 years earlier. After observation for 36 months, he developed left hemiparesis, and MRI revealed an increase in tumor size and obstructive hydrocephalus due to the tumor. Needle biopsy was performed through small craniotomy, and the histological diagnosis was glioblastoma. After concurrent chemoradiotherapy with 23 cycles of temozolomide, partial response of the tumor was observed. However, 24 months after the start of the initial therapy, the tumor showed regrowth, and the patient died 30 months after the initial therapy. No cerebrovascular events associated with moyamoya syndrome and chemoradiotherapy were observed during the clinical course of glioblastoma. DISCUSSION: Glioblastoma is a fatal disease in children, and our patient successfully received chemoradiotherapy with temozolomide despite the diagnoses of NF1 and moyamoya syndrome. Although radiotherapy or chemotherapy potentially causes cerebrovascular complications, chemoradiotherapy might be feasible for glioblastoma treatment in patients with moyamoya syndrome and NF1. The following issues are discussed in the management of the present case: the indication of biopsy in NF1 cases, the method of surgery, and the treatment protocol for tumors concomitant with moyamoya disease or syndrome.

Optic nerve sheath meningioma presenting as progressive visual disturbance during pregnancy: A case report.

Meningiomas are often reported to be sensitive to progesterone, but it is not clear how pregnancy and childbirth affect this. A 41-year-old woman experienced two pregnancies and two deliveries. During the first pregnancy, her right visual acuity was impaired, but it recovered after delivery. However, during the second pregnancy, the right visual acuity was impaired again and did not recover after the second delivery. The magnetic resonance imaging revealed a right optic nerve sheath meningioma (ONSM). Surgical resection of the intracranial extension of the tumor was performed to prevent tumor invasion of the left optic nerve and optic chiasm. Pathological examination diagnosed meningioma with positive immunostaining for progesterone receptor. The present study provided clinical features of ONSM associated with pregnancy. ONSM may present with increased tumor growth and impaired vision with pregnancy.

Surgical resection of glioblastoma in basal ganglia and utility of exoscope: Technical case reports.

Background: Due to the presence of many perforating arteries and the deep location of basal ganglia tumors, dissection of the perforating arteries is critical during tumor resection. However, this is challenging as these arteries are deeply embedded in the cerebrum. Surgeons need to bend their heads for a long time using operative microscope and it is uncomfortable for the operating surgeon. A high-definition (4K-HD) 3D exoscope system can significantly improve the surgeon's posture during resection and widen the operating view field considerably by adjusting the camera angle. Methods: We report two cases of glioblastoma (GBM) involving basal ganglia. We used a 4K-HD 3D exoscope system for resecting the tumor and analyzed the intraoperative visualization of the operative fields. Results: We could approach the deeply located feeding arteries before successfully resecting the tumor using a 4K-HD 3D exoscope system which would have been difficult with the sole use of an operative microscope. The postoperative recoveries were uneventful in both cases. However, postoperative magnetic resonance imaging showed infarction around the caudate head and corona radiata in one of the cases. Conclusion: This study has highlighted using a 4K-HD 3D exoscope system in dissecting GBM involving basal ganglia. Although postoperative infarction is a risk, we could successfully visualize and dissect the tumors with minimal neurological deficits.

Neurite orientation dispersion and density imaging and diffusion tensor imaging to facilitate distinction between infiltrating tumors and edemas in glioblastoma.

BACKGROUND: Glioblastomas are highly infiltrative tumors, and differentiating between non-enhancing tumors (NETs) and vasogenic edema (Edemas) occurring in the non-enhancing T2-weighted hyperintense area is challenging. Here, we differentiated between NETs and Edemas in glioblastomas using neurite orientation dispersion and density imaging (NODDI) and diffusion tensor imaging (DTI). MATERIALS AND METHODS: Data were collected retrospectively from 21 patients with primary glioblastomas, three with metastasis, and two with meningioma as controls. MRI data included T2 weighted images and contrast enhanced T1 weighted images, NODDI, and DTI. Three neurosurgeons manually assigned volumes of interest (VOIs) to the NETs and Edemas. The DTI and NODDI-derived parameters calculated for each VOI were fractional anisotropy (FA), apparent diffusion coefficient (ADC), intracellular volume fraction (ICVF), isotropic volume fraction (ISOVF), and orientation dispersion index. RESULTS: Sixteen and 14 VOIs were placed on NETs and Edemas, respectively. The ICVF, ISOVF, FA, and ADC values of NETs and Edemas differed significantly (p < 0.01). Receiver operating characteristic curve analysis revealed that using all parameters allowed for improved differentiation of NETs from Edemas (area under the curve = 0.918) from the use of NODDI parameters (0.910) or DTI parameters (0.899). Multiple logistic regression was performed with all parameters, and a predictive formula to differentiate between NETs and Edemas could be created and applied to the edematous regions of the negative control-group images; the tumor prediction degree was well below 0.5, confirming differentiation as edema. CONCLUSIONS: Using NODDI and DTI may prove useful in differentiating NETs from Edemas in the non-contrast T2 hyperintensity region of glioblastomas.

Growth risk classification and typical growth speed of convexity, parasagittal, and falx meningiomas: a retrospective cohort study.

OBJECTIVE: Meningiomas are the most common primary intracranial tumors, and their clinical and biological characteristics vary by location. Convexity, parasagittal, and falx meningiomas account for approximately 50%-65% of intracranial meningiomas. Focusing only on these locations, the aim of this study was to determine the typical speed of tumor growth, to assess the growth risk, and to show the possible tumor volume that many lesions can reach after 5 years. METHODS: Patients with radiologically suspected convexity, parasagittal, or falx meningiomas at the authors' institution were studied retrospectively. The relative growth rate (RGR) and annual volume change (AVC) were calculated from MRI at more than 3-month intervals. Based on sex, age, and signal intensity on T2-weighted MRI, the cases were classified into three groups: extremely high-growth, high-growth, and low-growth groups. RESULTS: The data of 313 cases were analyzed. The median RGR and AVC for this entire cohort were 6.1% (interquartile range [IQR] 2.4%-16.0%) and 0.20 (IQR 0.04-1.18) cm3/year, respectively. There were significant differences in sex (p = 0.018) and T2-weighted MRI signal intensity (p < 0.001) for RGR, and T2-weighted MRI signal intensity (p < 0.001), tumor location (p = 0.025), and initial tumor volume (p < 0.001) for AVC. The median RGR and AVC were 17.5% (IQR 8.3%-44.1%) and 1.05 (IQR 0.18-3.53) cm3/year, 8.2% (IQR 2.9%-18.6%) and 0.33 (IQR 0.06-1.66) cm3/year, and 3.4% (IQR 1.2%-5.8%) and 0.04 (IQR 0.02-0.21) cm3/year for the extremely high-growth, high-growth, and low-growth groups, respectively, with a significant difference among the groups (p < 0.001). A 2.24-times, or 5.24 cm3, increase in tumor volume over 5 years was typical in the extremely high-growth group, whereas the low-growth group showed little change in tumor volume even over a 5-year follow-up period. CONCLUSIONS: For the first time, the typical speed of tumor growth was calculated, focusing only on patients with convexity, parasagittal, and falx meningiomas. In addition, the possible tumor volume that many lesions in these locations can reach after 5 years was shown based on objective indicators. These results may allow clinicians to easily detect lesions that require frequent follow-up or early treatment by determining whether they deviate from the typical range of the growth rate, similar to a growth chart for children.

Identification of glioblastoma-specific antigens expressed in patient-derived tumor cells as candidate targets for chimeric antigen receptor T cell therapy.

Background: New therapies for glioblastoma (GBM) are urgently needed because the disease prognosis is poor. Chimeric antigen receptor (CAR)-T cell therapy that targets GBM-specific cell surface antigens is a promising therapeutic strategy. However, extensive transcriptome analyses have uncovered few GBM-specific target antigens. Methods: We established a library of monoclonal antibodies (mAbs) against a tumor cell line derived from a patient with GBM. We identified mAbs that reacted with tumor cell lines from patients with GBM but not with nonmalignant human brain cells. We then detected the antigens they recognized using expression cloning. CAR-T cells derived from a candidate mAb were generated and tested in vitro and in vivo. Results: We detected 507 mAbs that bound to tumor cell lines from patients with GBM. Among them, E61 and A13 reacted with tumor cell lines from most patients with GBM, but not with nonmalignant human brain cells. We found that B7-H3 was the antigen recognized but E61. CAR-T cells were established using the antigen-recognition domain of E61-secreted cytokines and exerted cytotoxicity in co-culture with tumor cells from patients with GBM. Conclusions: Cancer-specific targets for CAR-T cells were identified using a mAb library raised against primary GBM tumor cells from a patient. We identified a GBM-specific mAb and its antigen. More mAbs against various GBM samples and novel target antigens are expected to be identified using this strategy.