Usefulness of synthetic MRI for differentiation of IDH-mutant diffuse gliomas and its comparison with the T2-FLAIR mismatch sign.

INTRODUCTION: The T2-FLAIR mismatch sign is a characteristic imaging biomarker for astrocytoma, isocitrate dehydrogenase (IDH)-mutant. However, investigators have provided varying interpretations of the positivity/negativity of this sign given for individual cases the nature of qualitative visual assessment. Moreover, MR sequence parameters also influence the appearance of the T2-FLAIR mismatch sign. To resolve these issues, we used synthetic MR technique to quantitatively evaluate and differentiate astrocytoma from oligodendroglioma. METHODS: This study included 20 patients with newly diagnosed non-enhanced IDH-mutant diffuse glioma who underwent preoperative synthetic MRI using the Quantification of Relaxation Times and Proton Density by Multiecho acquisition of a saturation-recovery using Turbo spin-Echo Readout (QRAPMASTER) sequence at our institution. Two independent reviewers evaluated preoperative conventional MR images to determine the presence or absence of the T2-FLAIR mismatch sign. Synthetic MRI was used to measure T1, T2 and proton density (PD) values in the tumor lesion. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance. RESULTS: The pathological diagnoses included astrocytoma, IDH-mutant (n = 12) and oligodendroglioma, IDH-mutant and 1p/19q-codeleted (n = 8). The sensitivity and specificity of T2-FLAIR mismatch sign for astrocytoma were 66.7% and 100% [area under the ROC curve (AUC) = 0.833], respectively. Astrocytoma had significantly higher T1, T2, and PD values than did oligodendroglioma (p < 0.0001, < 0.0001, and 0.0154, respectively). A cutoff lesion T1 value of 1580 ms completely differentiated astrocytoma from oligodendroglioma (AUC = 1.00). CONCLUSION: Quantitative evaluation of non-enhanced IDH-mutant diffuse glioma using synthetic MRI allowed for better differentiation between astrocytoma and oligodendroglioma than did conventional T2-FLAIR mismatch sign. Measurement of T1 and T2 value by synthetic MRI could improve the differentiation of IDH-mutant diffuse gliomas.

Super T2-FLAIR mismatch sign: a prognostic imaging biomarker for non-enhancing astrocytoma, IDH-mutant.

PURPOSE: The T2-FLAIR mismatch sign is a highly specific diagnostic imaging biomarker for astrocytoma, IDH-mutant. However, a definitive prognostic imaging biomarker has yet to be identified. This study investigated imaging prognostic markers, specifically analyzing T2-weighted and FLAIR images of this tumor. METHODS: We retrospectively analyzed 31 cases of non-enhancing astrocytoma, IDH-mutant treated at our institution, and 30 cases from The Cancer Genome Atlas (TCGA)/The Cancer Imaging Archive (TCIA). We defined "super T2-FLAIR mismatch sign" as having a significantly strong low signal comparable to cerebrospinal fluid at non-cystic lesions rather than just a pale FLAIR low-signal tumor lesion as in conventional T2-FLAIR mismatch sign. Cysts were defined as having a round or oval shape and were excluded from the criteria for the super T2-FLAIR mismatch sign. We evaluated the presence or absence of the T2-FLAIR mismatch sign and super T2-FLAIR mismatch sign using preoperative MRI and analyzed the progression-free survival (PFS) and overall survival (OS) by log-rank test. RESULTS: The T2-FLAIR mismatch sign was present in 17 cases (55%) in our institution and 9 cases (30%) within the TCGA-LGG dataset without any correlation with PFS or OS. However, the super T2-FLAIR mismatch sign was detected in 8 cases (26%) at our institution and 13 cases (43%) in the TCGA-LGG dataset. At our institution, patients displaying the super T2-FLAIR mismatch sign showed significantly extended PFS (122.7 vs. 35.9 months, p = 0.0491) and OS (not reached vs. 116.7 months, p = 0.0232). Similarly, in the TCGA-LGG dataset, those with the super T2-FLAIR mismatch sign exhibited notably longer OS (not reached vs. 44.0 months, p = 0.0177). CONCLUSION: The super T2-FLAIR mismatch is a promising prognostic imaging biomarker for non-enhancing astrocytoma, IDH-mutant.

Cost of medical care for malignant brain tumors at hospitals in the Japan Clinical Oncology Group brain-tumor study group.

BACKGROUND: This study aimed to investigate what treatment are selected for malignant brain tumors, particularly glioblastoma (GBM) and primary central nervous system lymphoma (PCNSL), in real-world Japan and the costs involved. METHODS: We conducted a questionnaire survey regarding treatment selections for newly diagnosed GBM and PCNSL treated between July 2021 and June 2022 among 47 institutions in the Japan Clinical Oncology Group-Brain Tumor Study Group. We calculated the total cost and cost per month of the initial therapy for newly diagnosed GBM or PCNSL. RESULTS: The most used regimen (46.8%) for GBM in patients aged ≤74 years was 'Surgery + radiotherapy concomitant with temozolomide'. This regimen's total cost was 7.50 million JPY (Japanese yen). Adding carmustine wafer implantation (used in 15.0%), TTFields (used in 14.1%), and bevacizumab (BEV) (used in 14.5%) to the standard treatment of GBM increased the cost by 1.24 million JPY for initial treatment, and 1.44 and 0.22 million JPY per month, respectively. Regarding PCNSL, 'Surgery (biopsy) + rituximab, methotrexate, procarbazine, and vincristine (R-MPV) therapy' was the most used regimen (42.5%) for patients of all ages. This regimen incurred 1.07 million JPY per month. The three PCNSL regimens based on R-MPV therapy were in ultra-high-cost medical care (exceeding 1 million JPY per month). CONCLUSIONS: Treatment of malignant brain tumors is generally expensive, and cost-ineffective treatments such as BEV are frequently used. We believe that the results of this study can be used to design future economic health studies examining the cost-effectiveness of malignant brain tumors.

T2-FLAIR mismatch sign, an imaging biomarker for CDKN2A-intact in non-enhancing astrocytoma, IDH-mutant.

INTRODUCTION: The WHO classification of central nervous system tumors (5th edition) classified astrocytoma, IDH-mutant accompanied with CDKN2A/B homozygous deletion as WHO grade 4. Loss of immunohistochemical (IHC) staining for methylthioadenosine phosphorylase (MTAP) was developed as a surrogate marker for CDKN2A-HD. Identification of imaging biomarkers for CDKN2A status is of immense clinical relevance. In this study, we explored the association between radiological characteristics of non-enhancing astrocytoma, IDH-mutant to the CDKN2A/B status. METHODS: Thirty-one cases of astrocytoma, IDH-mutant with MTAP results by IHC were included in this study. The status of CDKN2A was diagnosed by IHC staining for MTAP in all cases, which was further confirmed by comprehensive genomic analysis in 12 cases. The T2-FLAIR mismatch sign, cystic component, calcification, and intratumoral microbleeding were evaluated. The relationship between the radiological features and molecular pathological diagnosis was analyzed. RESULTS: Twenty-six cases were identified as CDKN2A-intact while 5 cases were CDKN2A-HD. The presence of > 33% and > 50% T2-FLAIR mismatch was observed in 23 cases (74.2%) and 14 cases (45.2%), respectively, and was associated with CDKN2A-intact astrocytoma (p = 0.0001, 0.0482). None of the astrocytoma, IDH-mutant with CDKN2A-HD showed T2-FLAIR mismatch sign. Cystic component, calcification, and intratumoral microbleeding were not associated with CDKN2A status. CONCLUSION: In patients with non-enhancing astrocytoma, IDH-mutant, the T2-FLAIR mismatch sign is a potential imaging biomarker for the CDKN2A-intact subtype. This imaging biomarker may enable preoperative prediction of CDKN2A status among astrocytoma, IDH-mutant.

Residual diffusion-weighted imaging hyperintense signal in primary central nervous system lymphoma can predict early recurrence.

BACKGROUND: The treatment response of primary central nervous system lymphomas (PCNSLs) is mainly evaluated using postcontrast T1-weighted imaging (T1WI). Because poorly enhanced lesions may contain residual tumors, the combination of evaluation methods will potentially improve the accuracy of determining treatment effectiveness. In this study, we evaluated the usefulness of diffusion-weighted imaging (DWI) in predicting recurrence among patients with PCNSL who achieved complete response (CR)/unconfirmed CR (CRu). METHODS: Fifty-four patients newly diagnosed with PCNSL who were treated at our institution and achieved CR/CRu at the end of treatment were included in this study. The patients were divided into two groups according to the presence or absence of residual DWI hyperintense signal at the tumor site at the end of treatment. Kaplan-Meier analysis was performed to analyze the median overall survival (OS) and progression-free survival (PFS). RESULTS: The mean age of the 54 patients was 66.4 ± 13.3 years. The induction therapies were HD-MTX in 20 patients, R-MPV in 29 patients, and other chemotherapies in five patients. Radiotherapy was performed in 35 patients, high-dose cytarabine therapy in 14 patients, and autologous hematopoietic stem cell transplantation in one patient, and of the 54 patients, 10 had no consolidation therapy. The residual DWI hyperintense signal sign was observed in 18 patients. The R-MPV regimen was statistically associated with a lower rate of residual DWI hyperintense signal (p = 0.0453). The median PFS was statistically shorter in the residual DWI hyperintense signal group than in the non-residual DWI hyperintense signal group (14.0 months vs. 85.1 months) (p < 0.0001, log-rank test). CONCLUSION: A residual DWI hyperintense signal at the end of treatment was statistically associated with shorter PFS. Among patients who achieved CR/CRu evaluated based on postcontrast T1WI, DWI could be a valuable additional sequence to predict the early recurrence of PCNSL.

Secondary meningioma after cranial irradiation: case series and comprehensive literature review.

BACKGROUND: Secondary meningioma after cranial irradiation, so-called radiation-induced meningioma, is one of the important late effects after cranial radiation therapy. In this report, we analyzed our case series of secondary meningioma after cranial irradiation and conducted a critical review of literature to reveal the characteristics of secondary meningioma. MATERIALS AND METHODS: We performed a comprehensive literature review by using Pubmed, MEDLINE and Google scholar databases and investigated pathologically confirmed individual cases. In our institute, we found pathologically diagnosed seven cases with secondary meningioma between 2000 and 2018. Totally, 364 cases were analyzed based on gender, WHO grade, radiation dose, chemotherapy. The latency years from irradiation to development of secondary meningioma were analyzed with Kaplan-Meier analysis. Spearman's correlation test was used to determine the relationship between age at irradiation and the latency years. RESULTS: The mean age at secondary meningioma development was 35.6 ± 15.7 years and the mean latency periods were 22.6 ± 12.1 years. The latency periods from irradiation to the development of secondary meningioma are significantly shorter in higher WHO grade group (P = 0.0026, generalized Wilcoxon test), higher radiation dose group (P < 0.0001) and concomitant systemic chemotherapy group (P = 0.0003). Age at irradiation was negatively associated with the latency periods (r = -0.23231, P < 0.0001, Spearman's correlation test). CONCLUSION: Cranial irradiation at older ages, at higher doses and concomitant chemotherapy was associated with a shorter latency period to develop secondary meningiomas. However, even low-dose irradiation can cause secondary meningiomas after a long latency period. Long-term follow-up is necessary to minimize the morbidity and mortality caused by secondary meningioma after cranial irradiation.

Characteristics and therapeutic strategies of brain and cranial radiation-induced sarcoma: analysis of 165 cases from our case experience and comprehensive review.

BACKGROUND: Radiation-induced sarcoma (RIS) is among the neoplasms potentially caused by radiation therapy (RT) for brain tumors. However, the clinical characteristics of and ideal treatment for RIS are unclear. We analysed our case experience and conducted a comprehensive literature review to reveal the characteristics of brain and cranial RIS. METHODS: We analysed 165 cases of RIS from the literature together with the RIS case treated at our institution. In each case, the latency period from irradiation to the development of each RIS and the median overall survival (OS) of the patients was analysed by Kaplan-Meier analysis. Spearman's correlation test was used to determine the relationship between the latency period and radiation dose or age at irradiation. RESULTS: The mean age at the development of RIS was 39.63 ± 17.84 years. The mean latency period was 11.79 ± 8.09 years. No factors associated with early development of RIS were detected. The median OS was 11 months, with fibrosarcoma showing significantly shorter OS compared with osteosarcoma and other sarcomas (p = 0.0021), and intracranial RIS showing a worse prognosis than extracranial RIS (p < 0.0001). Patients treated with surgery (p < 0.0001) and postoperative chemotherapy (p = 0.0157) for RIS presented significantly longer OS, whereas RT for RIS was not associated with a survival benefit. CONCLUSIONS: Although prognosis for RIS is universally poor, pathological characteristics and locations are associated with worse prognosis. Surgery and chemotherapy may be the ideal treatment strategies for RIS.

Characteristics and therapeutic strategies of radiation-induced glioma: case series and comprehensive literature review.

INTRODUCTION: The so-called radiation-induced glioma (RIG, a secondary glioma after cranial irradiation), is a serious late effect after cranial radiation therapy. The clinical characteristics of and ideal treatment for these tumors are unclear. We analyzed our case series and conducted a comprehensive literature review to reveal the precise characteristics of RIGs. METHODS: We analyzed the cases of six patients with RIGs treated at our institution and 354 patients with RIGs from the literature. The latency period from irradiation to the development of each RIG and the median overall survival of the patients were subjected to Kaplan-Meier analyses. Spearman's correlation test was used to determine the relationship between age at irradiation and the latency period. RESULTS: The mean age of the 360 patients at the development of RIG was 27.42 ± 17.87 years. The mean latency period was 11.35 ± 8.58 years. Multiple gliomas were observed in 28.4%. WHO grade 3 and 4 RIGs accounted for 93.3%. The latency periods were significant shorter in the higher WHO grade group (p = 0.0366) and the concomitant systemic chemotherapy group (p < 0.0001). Age at irradiation was negatively associated with the latency period (r =- 0.2287, p = 0.0219). The patients treated with radiotherapy achieved significantly longer survival compared to those treated without radiotherapy (p = 0.0011). CONCLUSIONS: Development in younger age, multiplicity, and high incidence of grade 3 and 4 are the clinical characteristics of RIGs. Cranial irradiation at older ages and concomitant chemotherapy were associated with shorter latency for the development of RIG. Radiation therapy may be the feasible treatment option despite radiation-induced gliomas.

Influence of growth hormone therapy on germinoma survivors.

PURPOSE: Due to the effectiveness of growth hormone therapy (GHT), the number of cancer survivors receiving GHT has increased. Previous studies had indicated that GHT was not associated with the increasing risks of tumor recurrence and development with second neoplasm (SN) in cancer survivors. However, to date, research on those risks in germinoma survivors is still limited. The aim of this study is to evaluate the impact of GHT in relation to tumor recurrence and development with SN in pure germinoma survivors. METHODS: This retrospective cohort study was approved by the Ethical Committee for Epidemiology of our institution. Seventy-three consecutive patients who underwent a biopsy of the lesion and were diagnosed with pure germinoma were retrospectively studied. They (median age, 15.0 years) were followed up more than 1 year after biopsy (median follow-up period, 14.3 years). The following data was obtained from the medical records of the patients: age, sex, preoperative magnetic resonance imaging findings, hormonal replacement, and events including tumor recurrence and/or SN. RESULTS: In our patient series, 16 patients (21.9%) who were more likely to have neurohypophysial lesion and receive multiple hormonal therapies had received GHT. No significant differences in the rates of tumor recurrence and development with SN were observed between the patients who had and had not received GHT. Moreover, the recurrence-free survival and overall survival rates were not different between the patients who had and had not received GHT. CONCLUSIONS: GHT did not increase the risks of tumor recurrence and development with SN in pure germinoma survivors.

T2-FLAIR Mismatch Sign and Response to Radiotherapy in Diffuse Intrinsic Pontine Glioma.

PURPOSE: The T2-fluid-attenuated inversion recovery (FLAIR) mismatch sign was previously reported as a diagnostic indicator of diffuse astrocytoma, isocitrate dehydrogenase-mutant, and 1p/19q noncodeletion. Subsequently, it was reported that the same findings were observed in diffuse intrinsic pontine glioma (DIPG). We investigated the clinical significance of T2-FLAIR mismatch sign in DIPG. METHODS: Twenty-one patients with DIPG (Male: Female = 12:9) were treated at our institute between 2004 and 2019. All patients were treated with local radiotherapy of 54 Gy/30 fractions. The positive T2-FLAIR mismatch sign was defined if it fulfilled the following criteria: (1) T2-FLAIR mismatch volume was >50% of T2 high volume at nonenhanced area, (2) the FLAIR low lesion is not associated with gadolinium enhancement (inside of enhancement or just outside of enhancement defined as edema), and (3) signal-intensity of FLAIR lowest lesion at tumor is lower than the normal cerebellar cortex. RESULTS: In our patient series, T2-FLAIR mismatch sign was found in 5 out of 21 patients. Objective response rate of radiotherapy was 100% in patients positive for T2-FLAIR mismatch, while it was 25.0% in patients negative for T2-FLAIR mismatch, and this difference was statistically significant (p < 0.01, Fisher's exact test). In patients under the age of 18-years, T2-FLAIR mismatch positive had a slightly better prognosis (p < 0.05, Wilcoxon test). CONCLUSION: T2-FLAIR mismatch sign in DIPG may be an indicator for better response to radiotherapy and a better prognostic factor.

Bevacizumab for optic pathway glioma with worsening visual field in absence of imaging progression: 2 case reports and literature review.

Children with optic pathway gliomas (OPGs) frequently suffer from problems of visual function resulting from tumors. Previous reports showed that bevacizumab improved visual function in patients with OPG via tumor response to treatment. In these two case reports, we show that bevacizumab improved visual field without tumor response as seen in imaging. Both, a 10-year-old girl and a 6-year-old boy, had previous history of treatment with platinum-based chemotherapy. They had visual deterioration without tumor progression on MR imaging. Bevacizumab effectively and immediately improved visual field in both patients without imaging response of OPG. We emphasize that bevacizumab should be considered for patients with OPGs having visual deterioration without tumor progression.

Immunostaining of Increased Expression of Enhancer of Zeste Homolog 2 (EZH2) in Diffuse Midline Glioma H3K27M-Mutant Patients with Poor Survival.

INTRODUCTION: The interaction of K27M mutation in histone H3 (H3K27M mutation) with polycomb repressive complex 2 (PRC2) is facilitated by the enhancer of zeste homolog 2 (EZH2). Subsequently, this interaction leads to the global reduction level of H3K27me3. We analyzed the EZH2 expression level in H3K27M mutation-positive tumors and revealed the association of high EZH2 expression with poor survival. METHODS: Our study included 12 patients, with an age range of 6-56 years and treated between 2007 and 2016. All patients underwent MRI study for nonenhanced T1, T2, diffusion, gadolinium-enhanced T1-weighted imaging, and fluid-attenuated inversion recovery (FLAIR). Immunohistochemical staining was performed against H3K27M, H3K27me3, EZH2, EED, mutant isocitrate dehydrogenase 1 (IDH1), α-thalassemia X-linked intellectual disability (ATRX), p53, O6-methylguanine-DNA methyltransferase (MGMT), and Ki-67 antibodies. RESULTS: All patients were negative for IDH1R132H and H3K27me3, but H3K27M-positive. Staining against EZH2 was negative in all histological features of grade II cases (3/12) and positive in grade III and IV cases; EZH2 positivity is associated with poor prognosis (p = 0.0082). EZH2 positivity was not associated with EED positivity. Retained ATRX staining was found mostly in grade III and IV cases (6/12). P53 was predominantly positive in cases of astrocytoma and glioblastoma (8/12). The labeling index of Ki-67 was 1.2-31.4% for grade II and III histological features and 11.2-24.8% for grade IV. CONCLUSION: We suggest that the expression of EZH2 is not associated with the PRC2 pathway and increases in patients with H3K27M-mutant diffuse midline glioma and a poor prognosis. Further studies are necessary to understand the mechanism involved.

[Weekly Vinblastine in Pediatric Optic Pathway/Hypothalamic Glioma:2 Cases Report].

It is reported that vinblastine monotherapy has promising activity in patients with pediatric optic pathway/hypothalamic glioma(OPHG)who experienced treatment failure after initial treatment with standard chemotherapy. However, there have been no reports on vinblastine monotherapy against OPHG in Japan. Since vinblastine is an unauthorized drug under the Ministry of Health and Welfare, we used it after completing an in-hospital institutional review board application for each case. In the first case, a 6-year-old boy with recurrent OPHG with hydrocephalus was referred to our hospital. Weekly vinblastine was started at a dose of 6mg/m2 and was then reduced to 5mg/m2 and 4mg/m2 sequentially due to hematotoxicity. After 11 cycles of vinblastine, improvement in hydrocephalus was observed. After 22 cycles of vinblastine, the best response was observed, and we continued treatment up to 35 cycles. Progression of the disease was observed after 47 cycles and then we changed treatment to another regimen after 48 cycles of vinblastine. In the second case, a 6-year-old boy with chemotherapy-naïve recurrent OPHG underwent chemotherapy with vincristine and carboplatin. After 9 treatment cycles with carboplatin, hypersensitivity was observed. Subsequently, he was treated using weekly vinblastine as per the same protocol as that in our first case. A moderate response was observed after 18 cycles of vinblastine. After 48 cycles of vinblastine, the best response was observed, and we completed treatment. In both cases, severe adverse events were not observed and the treatment was well-tolerated. Vinblastine administered once per week is well-tolerated and maintains quality of life in children with OPHG.

Ruptured dissecting aneurysms of the A1 segment of the anterior cerebral artery: three case reports and a review of the literature.

Dissecting aneurysms in the anterior cerebral artery (ACA), although rare, can cause ischemic and/or hemorrhagic stroke. Hemorrhagic dissecting aneurysms in the A1 portion of the ACA are often associated with a poor prognosis. We retrospectively investigated three rare cases of hemorrhagic dissecting aneurysms in the A1 portion. Dissecting aneurysms were diagnosed by carotid angiography or computed tomography angiography to visualize morphological changes in the vessel. All patients presented with diffuse subarachnoid hemorrhage. In one case, computed tomography angiography performed at the onset of the subarachnoid hemorrhage revealed fusiform dilatation at the right ACA (A1), which did not appear on a magnetic resonance angiogram obtained 1 year prior to the onset of the subarachnoid hemorrhage. In the other two cases, A1 dissecting aneurysms were diagnosed from a growing aneurysmal bulge revealed at a non-bifurcated site via repeated carotid angiography. Two patients underwent surgical intervention (trapping or clipping), and their outcome was favorable, whereas the third patient died of delayed rebleeding before receiving surgical treatment. Hemorrhagic dissecting aneurysms in the A1 portion cause severe subarachnoid hemorrhage. Surgical treatments that include revascularization are necessary to prevent rebleeding, and direct surgery is recommended, particularly at the A1 portion.

[A Case of Cervical Spinal Dural Arteriovenous Fistula with Extradural Drainage Presenting with Subarachnoid Hemorrhage due to a Ruptured Anterior Spinal Artery Aneurysm].

We report a rare case of a cervical spinal dural arteriovenous fistula(AVF)at the C2 level presenting with subarachnoid hemorrhage(SAH)due to a ruptured anterior spinal artery aneurysm. A 61-year-old man presented with sudden onset headache. Initial computed tomography revealed SAH around the brainstem. Digital subtraction angiography(DSA)demonstrated a cervical dural AVF that was fed by the left C1 radicular, left C2 radicular, and anterior spinal arteries, and drained into the epidural plexus. An aneurysm in the branch of the cervical anterior spinal artery was considered the bleeding point. A left lateral suboccipital craniotomy and C1 hemilaminectomy were performed on day 43. The feeding arteries were clipped, followed by coagulation of the draining veins. However, the aneurysm was not clipped because we deemed that obliteration of the aneurysm would be difficult without disrupting the blood flow of the parent artery. The patient showed no neurological deterioration after the operation. Postoperative DSA revealed residual dural AVF. Therefore, a second surgery was performed. After the second open surgery, DSA showed that the dural AVF and aneurysm disappeared. The patient also showed no neurological deterioration after the second surgery.

[A case of cavernous angioma at the convexity in the dura mater: characteristics of images in the literature].

We describe a rare case of cavernous angioma in the dura mater and discuss published MRI findings on similar cases. The patient was a 78-year-old woman who was referred to Shimane Prefectural Central Hospital with complaints of headaches. We were subsequently able to identify a tumor at the convexity in the dura mater. The tumor showed a high intensity on T2-weighted images and was heterogeneously enhanced on contrast-enhanced T1-weighted images. The maximum size of the tumor was 35 mm. Moreover, preoperative angiography showed a slight vascularity in the tumor. We performed surgery with the expectation of finding a meningioma, metastatic brain tumor, or another mesenchymal tumor. The tumor was dark and red, attached to the dura mater, and adhered to the arachnoid. However, we were able to peel the tumor away from the meninges and achieved a total removal of the mass, successfully cutting a fine feeding cortical artery. The patient was discharged without neurological defects 9 days after surgery;the pathological diagnosis was cavernous angioma. In conclusion, it is difficult to discern between meningioma and cavernous angioma in the dura mater. However, the specificity of high intensity on T2-weighted images is relatively high, and preoperative diagnosis can be determined by MRI and angiography findings.

Preventing Post-incisional Dural Shrink in Craniotomy: Introducing the "Roll-up Technique".

Dural dryness makes suturing difficult during dural closure after craniotomy. In this case, dural plasty is often performed using a membrane taken from the surrounding tissue (e.g., fascia or periosteum) or an artificial replacement membrane. Herein, we introduce our novel "roll-up technique" to reduce the utilization of substitute membranes and explore its effectiveness in dural closure. We retrospectively examined the medical records of 50 patients who underwent craniotomy for the first time for supratentorial intracranial lesions between 2015 and 2022. Furthermore, we divided them into two groups: (1) the conventional technique group, which consisted of patients in whom the dura mater was flipped after incision and protected with a moistened gauze (n = 23), and (2) the roll-up technique group, which consisted of patients in whom the dura mater was incised in a U shape, rolled up, and protected with a moist gauze (n = 27). After surgery, we compared the success rates of primary closure, operating time, craniotomy area, and percentage of complications (e.g., cerebrospinal fluid [CSF] leakage or infection) between the groups. Dural closure without dural substitutes using the roll-up technique had a higher success rate than that using the conventional technique (26/27 [96.3%] cases vs. 14/23 [60.9%] cases; P = 0.003). Postoperative CSF leakage or infection did not occur, and no statistically significant difference was observed in the operating time between the groups (P = 0.247). The roll-up technique for dural closure may effectively prevent post-incisional dural shrink after craniotomy.

Characteristics of radiation-induced brain tumors: case series and systematic review.

OBJECTIVE: Radiation therapy (RT) improves the outcome of patients with cancer but introduces the risk of radiation-induced neoplasms in cancer survivors. The most common radiation-induced brain tumors (RIBTs) are gliomas (RIGs), meningiomas (RIMs), and sarcomas (RISs). To investigate the characteristics of these RIBTs, the authors conducted a comprehensive review and analysis of their case series and relevant cases from the literature. METHODS: Sixteen patients in the case series and 941 patients from the literature who previously underwent cranial irradiation were included in this study. The age at irradiation for primary disease was recorded, and the latency period from irradiation to the development of RIBT and the median overall survival (OS) of patients with RIBTs were analyzed using the Kaplan-Meier method. Patients were stratified by age at the time of irradiation (pediatric vs nonpediatric) and the irradiation dose (higher vs lower dose), and latency and OS were compared using the log-rank test. RESULTS: Among patients with RIBTs, 23.4% underwent radiation at < 5 years of age, and 46.6% underwent RT in the 1st decade of life. The median ages at cranial irradiation were 8.4 (IQR 4.1-16) years in patients with RIMs, 9 (IQR 5-23) years in patients with RIGs, and 27.7 (IQR 13.8-40) years in patients with RISs. The median latency period from irradiation to the development of RIM was significantly longer than that to the development of RIG and RIS (RIM: 20 years, RIG: 9 years, RIS: 10 years; p < 0.0001). The latency period was shorter in the nonpediatric patient group with RIMs (p = 0.047). The OS was significantly longer in patients with RIMs than in those with RIGs and RISs (RIM: not reached, RIG: 11 months, RIS: 11 months; p < 0.0001). The OS of patients with RIMs and RIGs was significantly shorter in patients who received higher radiation doses (p = 0.0095 and p = 0.0026, respectively). CONCLUSIONS: The prognosis was poor and worse for patients with RIGs and RISs than for those with RIMs, and patients with RIBTs who underwent higher-dose irradiation for primary disease had poor prognoses. Because RIBTs develop more than a decade after cranial irradiation, long-term follow-up is crucial.

Multidrug chemotherapy, whole-brain radiation and cytarabine therapy for primary central nervous system lymphoma in elderly patients with dose modification based on geriatric assessment: study protocol for a phase II, multicentre, non-randomised study.

INTRODUCTION: Multidrug chemoimmunotherapy with rituximab, high-dose methotrexate, procarbazine and vincristine (R-MPV) is a standard therapy for younger patients with primary central nervous system lymphoma (PCNSL); however, prospective data regarding its use in elderly patients are lacking. This multi-institutional, non-randomised, phase II trial will assess the efficacy and safety of R-MPV and high-dose cytarabine (HD-AraC) for geriatric patients with newly diagnosed PCNSL. METHODS AND ANALYSIS: Forty-five elderly patients will be included. If R-MPV does not achieve complete response, the patients will undergo reduced-dose, whole-brain radiotherapy comprising 23.4 Gy/13 fractions, followed by local boost radiotherapy comprising 21.6 Gy/12 fractions. After achieving complete response using R-MPV with or without radiotherapy, the patients will undergo two courses of HD-AraC. All patients will undergo baseline geriatric 8 (G8) assessment before HD-AraC and after three, five and seven R-MPV courses. Patients with screening scores of ≥14 points that decrease to <14 points during subsequent treatment, or those with screening scores <14 points that decrease from the baseline during subsequent treatment are considered unfit for R-MPV/HD-AraC. The primary endpoint is overall survival, and the secondary endpoints are progression-free survival, treatment failure-free survival and frequency of adverse events. The results will guide a later phase III trial and provide information about the utility of a geriatric assessment for defining chemotherapy ineligibility. ETHICS AND DISSEMINATION: This study complies with the latest Declaration of Helsinki. Written informed consent will be obtained. All participants can quit the study without penalty or impact on treatment. The protocol for the study, statistical analysis plan and informed consent form have been approved by the Certified Review Board at Hiroshima University (CRB6180006) (approval number: CRB2018-0011). The study is ongoing within nine tertiary and two secondary hospitals in Japan. The findings of this trial will be disseminated through national and international presentations and peer-reviewed publications. TRIAL REGISTRATION: jRCTs061180093.

[Astroblastoma with Rapid Cyst Expansion and Hemorrhage in an Adult: A Case Report].

Astroblastoma is an extremely rare primary brain tumor accounting for 0.45 to 2.8% of all neuroglial tumors and usually occurs in pediatrics and young adults. The natural history of astroblastoma still remains unknown. In the World Health Organization (WHO) classification of tumors of the central nervous system, astroblastoma is classified as other neuroepithelial tumors and standard treatment other than surgery has not been established. As molecular and genetic diagnosis becomes more important in the latest WHO classification of brain tumors, the development of therapeutic options based on the information of molecular genetics are expected. Here we report a case of astroblastoma in a 49-year-old male. Small tumor was discovered by coincidence during his check-up following traffic accident, but three months later, tumor bleeding with cystic enlargement resulted in disturbance of consciousness. Initial diagnosis of low grade astroblastoma with BRAFV600E mutation was made. After 1 year, local tumor recurrence was observed. The histological diagnosis at recurrence was high grade astroblastoma. We here, discuss about diagnosis, treatment and the possibility of usefulness of molecular genetic analysis for astroblastoma with some literature review. (Received 10 August, 2021; Accepted 15 December, 2021; Published 1 April, 2022).