Vestibular schwannoma extending into the tympanic cavity and jugular fossa by invasion of the petrous bone.

Vestibular schwannomas usually originate in the internal acoustic meatus, and gradually extends into the cerebellopontine cistern. Invasive growth into the petrous bone is extremely rare. We describe a case of a vestibular schwannoma that aggressively extended into the petrous bone and extracranial space. This may have arisen because of an unusually peripheral site of origin on the vestibular nerve.

Endoscopic endonasal transmaxillary-pterygoid approach for skull-base non-vestibular schwannomas in 10 consecutive patients.

PURPOSE: Non-vestibular schwannomas (NVSs) of the skull base occur in several sites, and few previous studies have evaluated the usefulness of the endoscopic endonasal transmaxillary-pterygoid approach (EETMPA) to resect these lesions. We aimed to evaluate the characteristics and clinical outcomes of patients who underwent EETMPA for skull-base NVSs and to investigate the efficacy, safety, and indications for the procedure. METHODS: We retrospectively reviewed the clinical data of 10 consecutive patients (mean age, 45 ± 17) who underwent EETMPA for skull-base NVSs at the University of Tsukuba hospital between 2013 and 2020. We also calculated the total tumor volume and the size of the corridor to the tumor for EEA (SCEEA) in nine patients who underwent EEA for NVSs adjacent to the Meckel's cave or cavernous sinus. RESULTS: Nine patients (9/10), including five women (5/10), underwent primary surgery. Gross total resection and subtotal resection were achieved in five patients each (5/10). Postoperatively, one patient showed a new and mild cranial nerve V sensory deficit and one patient showed slight worsening of abducens nerve palsy. The greater palatine nerve was amputated in two patients; however, permanent perception loss in the soft palate was observed in one patient. The Vidian nerve was sacrificed in four patients, and new dry eye occurred in one patient. None of the patients experienced postoperative tumor recurrence or regrowth during the follow-up period of 40 ± 28 months. CONCLUSION: EETMPA is safe and effective for excising skull-base NVSs which are not eligible for radiosurgery leading to a high rate of successful resection and a high rate of but mild neurological sequela. The EEA is appropriate when the tumor extends to the paranasal sinus with sufficient SCEEA.

Hemagglutinating virus of Japan-envelope containing programmed cell death-ligand 1 siRNA inhibits immunosuppressive activities and elicits antitumor immune responses in glioma.

The programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) pathway is involved in preventing immune system-mediated destruction of malignant tumors including glioblastoma. However, the therapeutic influence of PD-1/PD-L1 inhibition alone in glioblastoma is limited. To develop effective combination therapy involving PD-1/PD-L1 inhibition, we used a non-replicating virus-derived vector, hemagglutinating virus of Japan-envelope (HVJ-E), to inhibit tumor cell PD-L1 expression by delivering siRNA targeting PD-L1. HVJ-E is a promising vector for efficient delivery of enclosed substances to the target cells. Moreover, HVJ-E provokes robust antitumoral immunity by activating natural killer (NK) cells and cytotoxic T lymphocytes (CTLs), and by suppressing regulatory T lymphocytes (Treg). We hypothesized that we could efficiently deliver PD-L1-inhibiting siRNAs to tumor cells using HVJ-E, and that synergistic activation of antitumoral immunity would occur due to the immunostimulating effects of HVJ-E and PD-1/PD-L1 inhibition. We used artificially induced murine glioma stem-like cells, TS, to create mouse (C57BL/6N) glioblastoma models. Intratumoral injection of HVJ-E containing siRNA targeting PD-L1 (siPDL1/HVJ-E) suppressed the expression of tumor cell PD-L1 and significantly suppressed tumor growth in subcutaneous models and prolonged overall survival in brain tumor models. Flow cytometric analyses of brain tumor models showed that the proportions of brain-infiltrating CTL and NK cells were significantly increased after giving siPDL1/HVJ-E; in contrast, the rate of Treg/CD4+ cells was significantly decreased in HVJ-E-treated tumors. CD8 depletion abrogated the therapeutic effect of siPDL1/HVJ-E, indicating that CD8+ T lymphocytes mainly mediated this therapeutic effect. We believe that this non-replicating immunovirotherapy may be a novel therapeutic alternative to treat patients with glioblastoma.

Safety and efficacy of depatuxizumab mafodotin in Japanese patients with malignant glioma: A nonrandomized, phase 1/2 trial.

INTELLANCE-J was a phase 1/2 study of a potent antibody-drug conjugate targeting epidermal growth factor receptor (EGFR), depatuxizumab mafodotin (Depatux-M), as a second- or first-line therapy, alone or combined with chemotherapy or chemoradiotherapy in 53 Japanese patients with World Health Organization (WHO) grade III/IV glioma. In second-line arms, patients with EGFR-amplified recurrent WHO grade III/IV glioma received Depatux-M plus chemotherapy (temozolomide) or Depatux-M alone regardless of EGFR status. In first-line arms, patients with newly diagnosed WHO grade III/IV glioma received Depatux-M plus chemoradiotherapy. The study was halted following lack of survival benefit with first-line Depatux-M in the global trial INTELLANCE-1. The primary endpoint was 6-month progression-free survival (PFS) in patients with EGFR-amplified tumors receiving second-line Depatux-M plus chemotherapy. Common nonocular treatment-emergent adverse events (TEAEs) with both second-line and first-line Depatux-M included lymphopenia (42%, 33%, respectively), thrombocytopenia (39%, 47%), alanine aminotransferase increase (29%, 47%), and aspartate aminotransferase increase (24%, 60%); incidence of grade ≥3 TEAEs was 66% and 53%, respectively. Ocular side effects (OSEs) occurred in 93% of patients receiving second-line Depatux-M plus chemotherapy and all patients receiving second-line Depatux-M alone or first-line Depatux-M plus chemoradiotherapy. Most OSEs were manageable with dose modifications and concomitant medications. The 6-month PFS estimate was 25.6% (95% confidence interval [CI] 11.4-42.6), and median PFS was 2.1 months (95% CI 1.9-3.9) with second-line Depatux-M plus chemotherapy in the EGFR-amplified subgroup. This study showed acceptable safety profile of Depatux-M alone or plus chemotherapy/chemoradiotherapy in Japanese patients with WHO grade III/IV glioma. The study was registered at ClinicalTrials.gov (NCT02590263).

Maximum resection and immunotherapy improve glioblastoma patient survival: a retrospective single-institution prognostic analysis.

Glioblastoma (GBM) is a refractory disease with a poor prognosis and various methods, including maximum resection and immunotherapy, have been tested to improve outcomes. In this retrospective study we analyzed the prognostic factors of 277 newly diagnosed GBM patients over 11 years of consecutive cases at our institution to evaluate the effect of these methods on prognosis. Various data, including the extent of removal (EOR) and type of adjuvant therapy, were examined and prognostic relationships were analyzed. The median overall survival (OS) of the entire 277-case cohort, 200 non-biopsy cases, and 77 biopsy cases was 16.6 months, 19.7 months, and 9.7 months, respectively. Gross total removal (GTR; 100% of EOR) was achieved in 32.9% of the cases. Univariate analysis revealed younger age, right side, higher Karnofsky performance status, GTR, intraoperative magnetic resonance imaging (MRI) use for removal, proton therapy, combination immunotherapy, and discharge to home as good prognostic factors. Intraoperative MRI use and EOR were closely related. In the multivariate analysis, GTR, proton therapy, and a combination of immunotherapies, including autologous formalin-fixed tumor vaccine, were the significant prognostic factors. A multivariate analysis of 91 GTR cases showed that immunotherapy contributed to prognostic improvements. The median OS and 5-year OS % values were 36.9 months and 43.3% in GTR cases receiving immunotherapy. In conclusion, GTR, proton therapy, and immunotherapy were good prognostic factors in single-center GBM cases. Tumor vaccine therapy for GTR cases achieved a notably high median survival time and long-term survival ratio, indicating its usefulness in GTR cases.

Involvement of the optic pathway and outcome of visual function in patients with neurohypophyseal germ cell tumor.

BACKGROUND: Patients with neurohypophyseal germ cell tumors (GCTs) typically present with visual problems. Hence, this study aimed to assess optic pathway involvement based on clinical and radiological findings and to validate the outcome of visual function. METHODS: A total of 16 patients with newly diagnosed neurohypophyseal GCTs who were treated at the University of Tsukuba Hospital between 2000 and 2020 were included in this study. RESULTS: The median interval from symptom onset to diagnosis was 173.5 days (range, 33-1588 days). Patients with visual disturbance at diagnosis had a longer time to diagnosis compared with those without. Ophthalmologic abnormalities were frequently observed, with an incidence rate of 69%. Fifty percent of patients exhibited optic pathway involvement detected via magnetic resonance imaging (MRI). Visual impairment was more severe in the patients with optic pathway involvement (p = 0.002). Post-treatment visual impairment was improved but was still significantly severe in patients with optic pathway involvement than in those without involvement (p = 0.010). Visual field deficit more likely remained with an improvement rate of 50%, whereas the improvement rate of visual acuity was 78%. Further, none developed late-onset visual deterioration during the follow-up period. CONCLUSIONS: Visual disturbance and optic pathway involvement are common in neurohypophyseal GCTs. Visual impairment particularly in patients with optic pathway involvement on MRI is more likely to remain at follow-up, although the outcome of visual function is acceptable in most cases.

Malignant transformation of pleomorphic xanthoastrocytoma and differential diagnosis: case report.

BACKGROUND: Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytic glioma, characterized by large pleomorphic and frequently multinucleated cells, spindle and lipidized cells, a dense pericellular reticulin network, and numerous eosinophilic granular bodies according to the grade II glial tumor standards of the World Health Organization's (WHO) 2016 guidelines. PXA rarely transforms into anaplastic PXA or glioblastoma (GBM) and anaplastic PXA, classified as WHO grade III, has a more aggressive clinical behavior with poorer prognosis than PXA. CASE PRESENTATION: Here we describe an unusual case of PXA in a 19-year-old woman, first admitted with headache and a mass in the left temporal lobe in 2005 that was removed. Twelve years later, she returned with left temporal headache, diplopia and tinnitus. A local tumor recurrence was found, and a second resection was performed. The specimen showed highly malignant findings, such as necrosis, microvascular proliferation, and multiple mitoses. The integrated diagnosis was made as high grade glioma, probably derived from PXA. Immunohistochemical (IHC) stains were positive for oligo2, and approximately 21% positive for Ki-67, while negative for CD34, IDH1 R132H. INI1 and ATRX were retained. As the histological classification was glioblastoma, the patient received GBM-appropriate chemotherapy and radiation therapy and outpatient follow-ups have demonstrated no obvious symptoms for 1 year after surgery. Additional molecular analyses found BRAF V600E mutations in both resections, supporting the idea that the recurrent tumor had derived from PXA. CONCLUSIONS: This case highlights the complexities of differential diagnosis based on the World Health Organization's 2016 guidelines. More integrated criteria to differentiate anaplastic PXA from GBM and epithelioid GBM, combined with genetic screening results, might be needed.

Potential use of prostate specific membrane antigen (PSMA) for detecting the tumor neovasculature of brain tumors by PET imaging with 89Zr-Df-IAB2M anti-PSMA minibody.

Tumor angiogenesis has attracted increasing attention because of its potential as a valuable marker in the differential diagnosis of brain tumors as well as a novel therapeutic target. Prostate-specific membrane antigen (PSMA) is expressed by the neovasculature endothelium of some tumors, with little to no expression by the tumor cells or normal vasculature endothelium. The aim of this study was to investigate the potential of PSMA for the evaluation of the tumor neovasculature of various brain tumors and the possibility of detecting PSMA expression in brain tumors using PET imaging with 89Zr-Df-IAB2M (anti-PSMA minibody). Eighty-three tissue specimens including gliomas, metastatic brain tumors, primary central nervous system lymphomas (PCNSL), or radiation necroses were analyzed by immunohistochemical staining with PSMA antibody. 89Zr-Df-IAB2M PET scans were performed in three patients with recurrent high-grade gliomas or metastatic brain tumor. PSMA was highly expressed in the vascular endothelium of high-grade glioma and metastatic brain tumor, whereas PSMA was poorly expressed in the vascular endothelium of PCNSL and radiation necrosis. PSMA expression in high-grade gliomas and a metastatic brain tumor was clearly visualized by PET imaging with 89Zr-Df-IAB2M. Furthermore, a trend toward a positive correlation between the degree of 89Zr-Df-IAB2M uptake and PSMA expression levels in tumor specimens was observed. PET imaging of PSMA using 89Zr-Df-IAB2M may have potential value in the differential diagnosis of high-grade glioma from PCNSL or radiation necrosis as well as in the prediction of treatment efficacy and assessment of treatment response to bevacizumab therapy for high-grade glioma.

Primary meningeal myxoid liposarcoma with aggressive behavior after recurrence: case report.

Although liposarcomas are the most common soft tissue sarcomas, their intracranial variants are extremely rare. Here, we present a case of a primary intracranial myxoid liposarcoma in a 23-year-old Japanese man who presented with generalized seizures and a mass in the left frontal lobe. The tumor was totally removed, and histological analyses pointed to liposarcoma. Thirteen years after his initial treatment, the patient presented with right-side weakness and local recurrence of tumor was discovered. Histology from the second resection confirmed the diagnosis of myxoid liposarcoma. Shortly after the second resection, progressive, new intracranial lesions were observed and despite a third resection, extensive intracerebral invasion by the tumor proved fatal. The histological features of myxoid liposarcoma were essentially similar with each recurrence, but the aggressive tumor behavior after the second operation did not align with expectations based on histological classification.

Genome-wide methylation profiles in primary intracranial germ cell tumors indicate a primordial germ cell origin for germinomas.

Intracranial germ cell tumors (iGCTs) are the second most common brain tumors among children under 14 in Japan. The World Health Organization classification recognizes several subtypes of iGCTs, which are conventionally subclassified into pure germinoma or non-germinomatous GCTs. Recent exhaustive genomic studies showed that mutations of the genes involved in the MAPK and/or PI3K pathways are common in iGCTs; however, the mechanisms of how different subtypes develop, often as a mixed-GCT, are unknown. To elucidate the pathogenesis of iGCTs, we investigated 61 GCTs of various subtypes by genome-wide DNA methylation profiling. We showed that pure germinomas are characterized by global low DNA methylation, a unique epigenetic feature making them distinct from all other iGCTs subtypes. The patterns of methylation strongly resemble that of primordial germ cells (PGC) at the migration phase, possibly indicating the cell of origin for these tumors. Unlike PGC, however, hypomethylation extends to long interspersed nuclear element retrotransposons. Histologically and epigenetically distinct microdissected components of mixed-GCTs shared identical somatic mutations in the MAPK or PI3K pathways, indicating that they developed from a common ancestral cell.

Assessment of PD-1 positive cells on initial and secondary resected tumor specimens of newly diagnosed glioblastoma and its implications on patient outcome.

Glioblastoma (GBM) is the most common type of malignant brain tumor and has a very poor prognosis. Most patients relapse within 12 months despite aggressive treatment and patient outcome after recurrent is extremely worse. This study was designed to clarify the change of the molecular expression, including programmed cell death 1 (PD-1) and PD-ligand 1 (PD-L1), on the initial and secondary resected tumor specimens and to address the influence of these expressions for patient outcome after second surgery of glioblastoma. We investigated 16 patients, ranging in age from 14 to 65 years, with histologically verified WHO grade IV GBM, whose original tumor was resected between 2008 and 2014, and treated with fractionated radiotherapy and temozolomide. Four patients who were treated with immunotherapy using autologous formalin-fixed tumor vaccine were enrolled. All of the patients underwent secondary resection after tumor recurrence within 24 months. We carried out an immunohistochemical examination of the initial and secondary resected tumors from patients using a panel of immune system molecular markers, and assessed whether marker expression correlated with clinical outcomes. CD3, CD8 and PD-1 on tumor-infiltrating lymphocytes was significantly increased in secondary resected specimens compared with initially resected specimens (p ≤ 0.05). All patients expressed PD-L1 on tumor cells in initial and secondary resection specimens. Patients were divided into high or low expression group by median IHC score of PD-1 on initial or secondary resected specimens. No significant differences in patient outcomes were observed between high and low PD-1 or PD-L1 groups of initially resected specimens. In high expression group of secondary resected specimens, most patients score had increased which compared with initial resected tumor specimens. The PD-1 high expression score group of secondary resected specimens was associated with long progression-free survival and short survival after recurrence. PD-L1 expression was detected in almost all initial and secondary specimens. Patients with high PD-1 expression of secondary specimen had bad prognosis after secondary resection. PD-1/PD-L1 pathway may be associated with patient outcome after second surgery of glioblastoma.

[Combination Therapy with Radiation, Temozolomide, and Bevacizumab after Partial Tumor Removal in Glioblastoma Patients with Low Performance Status].

INTRODUCTION: It is unclear whether or not bevacizumab(Bev)has a curative ability in newly diagnosed glioblastoma(GBM) patients with low Karnofsky performance status(KPS). MATERIALS AND METHODS: Four of 14 patients with newly diagnosed GBM received combination therapy with extended local radiation, temozolomide(TMZ), and Bev after partialremovalor biopsy of the tumor. RESULTS: The average patient age was 77.2 years(range 67-85)and the male-to-female ratio was 1:3. In all cases, magnetic resonance imaging showed that combination therapy decreased tumor volume and peritumoral edema volume. The therapy was successfully administered to 3 patients without decreasing their KPS. However, 1 patient with seeding lesions dropped out of therapy because of deteriorating consciousness and decreasing KPS. DISCUSSION: Subgroup analysis in a randomized control study(AVAglio)showed that patients with a PS score of 1-2(corresponding to a KPS score of 60-80)tended to have prolonged survival after Bev treatment compared with those with a PS score of 0(corresponding to a KPS score of 90-100). In the present study, radiochemotherapy with Bev decreased lesion and edema volumes in all patients, and led to maintained or improved KPS in 3 patients. These results suggest that the treatment is potentially effective for patients with newly diagnosed GBM and lower KPS.

Proton beam therapy with concurrent chemotherapy for glioblastoma multiforme: comparison of nimustine hydrochloride and temozolomide.

To evaluate the safety and efficacy of postoperative proton beam therapy (PBT) combined with nimustine hydrochloride (ACNU) or temozolomide (TMZ) for glioblastoma multiforme (GBM). The subjects were 46 patients with GBM who were treated with high dose (96.6 GyE) PBT. There were 24 males and 22 females, and the median age was 58 years old (range 24-76). The Karnofsky performance status was 60, 70, 80, 90 and 100 in 5, 10, 12, 11 and 8 patients, respectively. Total resection, partial resection, and biopsy were performed for 31, 14 and 1 patients, respectively. Photon beams were delivered to high intensity areas on T2-weighted magnetic resonance imaging (MRI) in the morning (50.4 Gy in 28 fractions). More than 6 h later, PBT was delivered to the enhanced area plus a 10 mm margin in the first half of the protocol (23.1 GyE in 14 fractions) and to the enhanced volume in the second half (23.1 GyE in 14 fraction). Concurrent chemotherapy with ACNU during weeks 1 and 4 or daily TMZ was administered in 23 and 23 patients, respectively. The overall 1 and 2 year survival rates were 82.6 and 47.6 %, respectively. Median survival was 21.1 months (95 % CI 13.1-29.2), with no significant difference in survival between the ACNU and TMZ groups. The patient characteristics were similar in the two groups. Late radiation necrosis occurred in 11 patients (six ACNU, five TMZ), but was controlled by necrotomy and therapy including bevacizumab. PBT concurrent with ACNU or TMZ was tolerable and beneficial for carefully selected patients with GBM.

[Endoscopic Endonasal Transethmoidal Biopsy for IgG4-Related Intraorbital Pseudotumor:A Case Report].

BACKGROUND: We experienced a case of intraorbital pseudotumor associated with IgG4-related disease, for which we successfully performed an endoscopic endonasal transethmoidal biopsy for the intraorbital pseudotumor as well as endoscopic sinus surgery for a refractory pansinusitis at the same time. CASE REPORT: A 59-year-old man was referred to our hospital because of an intraorbital mass lesion. MRI showed 2 mass lesions:a large intraconal lesion encasing the left optic nerve on the orbital apex, and a small extraconal lesion medial to the left medial rectus muscle extending into the anterior ethmoid canal. In addition, CT showed severe pansinusitis. A blood test showed a marked elevation of IgG4. IgG4-related pseudotumor was suspected, but IgG4-related MALT lymphoma was an alternative diagnosis, and a biopsy of the mass lesion was required. We successfully performed both, an endoscopic endonasal transethmoidal biopsy for the mass lesion and endoscopic sinus surgery for the refractory pansinusitis at the same time. The pathological diagnosis was an IgG4-related pseudotumor. CONCLUSION: Endoscopic endonasal transethmoidal biopsy is an effective and minimally invasive method for making a definitive diagnosis of IgG4-related intraorbital pseudotumor. Using this method, refractory pansinusitis frequently associated with this disease can be treated. For successful treatment, interdisciplinary decision making and collaborative team surgery are crucial.

Abducent nerve palsy treated by microvascular decompression: a case report and review of the literature.

Too few cases of isolated abducent nerve palsy caused by neurovascular compression syndrome have been reported. We here report on a case of abducent nerve palsy caused by neurovascular compression syndrome that was successfully treated by microvascular decompression (MVD). A 46-year-old male presented with a 6-month history of right-sided persistent abducent nerve palsy. High-resolution magnetic resonance imaging revealed a neurovascular contact of the vertebral artery with the right abducent nerve. MVD was performed via a retrosigmoid craniotomy, with remarkable improvement of the palsy. Our report suggests that MVD might be considered as an optional treatment if the symptoms progress or persist.

CXCL12 secreted from glioma stem cells regulates their proliferation.

Emerging evidence suggests that the chemokine CXCL12 and its receptor CXCR4, which are expressed by glioma stem cells (GSCs), play an important role in tumorigenesis. To provide evidence for establishing a new therapy targeting the CXCL12/CXCR4 pathway, we investigated whether CXCL12 secreted from GSCs contributed to their proliferation and promoted angiogenesis in murine GSCs. Angiogenetic functions and proliferation of GSCs with or without CXCL12 inhibitors were evaluated in an in vitro model using tube formation assays, RT-PCR, and proliferation, as well as in an in vivo syngenic model. In endothelial culture, the morphology and gene expression of GSCs changed from stem cell-like characteristics to endothelial cell-like features. CXCL12 expression increased in endothelial cell-like GSCs. CXCL12 blockage with siRNA or shRNA markedly inhibited cell proliferation in vitro. CXCL12 knockdown with shRNA also inhibited tumor growth in vivo. On the other hand, CXCL12/CXCR4 blockage affected neither tube formation in vitro nor angiogenesis in vivo. The CXCL12 secreted from GSCs (autocrine/paracrine CXCL12) regulates their proliferation, but probably not angiogenesis.

Methyl-11C-L-methionine positron emission tomography for radiotherapy planning for recurrent malignant glioma.

OBJECTIVE: To investigate differences in uptake regions between methyl-11C-L-methionine positron emission tomography (11C-MET PET) and gadolinium (Gd)-enhanced magnetic resonance imaging (MRI), and their impact on dose distribution, including changing of the threshold for tumor boundaries. METHODS: Twenty consecutive patients with grade 3 or 4 glioma who had recurrence after postoperative radiotherapy (RT) between April 2016 and October 2017 were examined. The study was performed using simulation with the assumption that all patients received RT. The clinical target volume (CTV) was contoured using the Gd-enhanced region (CTV(Gd)), the tumor/normal tissue (T/N) ratios of 11C-MET PET of 1.3 and 2.0 (CTV (T/N 1.3), CTV (T/N 2.0)), and the PET-edge method (CTV(P-E)) for stereotactic RT planning. Differences among CTVs were evaluated. The brain dose at each CTV and the dose at each CTV defined by 11C-MET PET using MRI as the reference were evaluated. RESULTS: The Jaccard index (JI) for concordance of CTV (Gd) with CTVs using 11C-MET PET was highest for CTV (T/N 2.0), with a value of 0.7. In a comparison of pixel values of MRI and PET, the correlation coefficient for cases with higher JI was significantly greater than that for lower JI cases (0.37 vs. 0.20, P = 0.007). D50% of the brain in RT planning using each CTV differed significantly (P = 0.03) and that using CTV (T/N 1.3) were higher than with use of CTV (Gd). V90% and V95% for each CTV differed in a simulation study for actual treatment using CTV (Gd) (P = 1.0 × 10-7 and 3.0 × 10-9, respectively) and those using CTV (T/N 1.3) and CTV (P-E) were lower than with CTV (Gd). CONCLUSIONS: The region of 11C-MET accumulation is not necessarily consistent with and larger than the Gd-enhanced region. A change of the tumor boundary using 11C-MET PET can cause significant changes in doses to the brain and the CTV.

Decrease in the apparent diffusion coefficient in peritumoral edema for the assessment of recurrent glioblastoma treated by bevacizumab.

PURPOSES: Anti-edema effect of bevacizumab was evaluated using the apparent diffusion coefficient (ADC) of peritumoral edema associated with regional cerebral blood flow (rCBV) of the tumor. MATERIALS AND METHODS: Nine patients with recurrent glioblastoma were treated using bevacizumab for 4 ∼ 36 months (average 12 months). MRI was performed every 2 months. For each MRI, ADC value, Gd-enhanced area on T1 imaging, area of peritumoral edema on T2 imaging, and rCBV on perfusion imaging were measured. ADC and rCBV values were determined by the use of regions of interest positioned in areas of high signal intensity, as seen on T2-weighted images and ADC maps. RESULTS: After 2 months of bevacizumab treatment, ADC values and rCBV decreased 49 and 32 % respectively, associated with marked diminishment of the Gd-enhanced area compared with pretreatment. After 6 months, in 5 of the 9 cases, the Gd-enhanced area appeared again with no change in the ADC value and rCBV. In the other four cases, the Gd-enhanced area as well as the ADC value and rCBV returned to the initial status. CONCLUSION: The anti-edema effect of bevacizumab for treatment of recurrent glioblastoma that was demonstrated by decreased ADC values and rCBV was dramatic and -prolonged at 6 months even with tumor progression.

Hemorrhagic Complications After Brain Tumor Biopsy: Risk-Reduction Strategies Based on Safer Biopsy Targets and Techniques.

OBJECTIVE: Brain tumor biopsies are essential for pathologic diagnosis. However, hemorrhagic complications after biopsies may occur, leading to suboptimal outcomes. This study aimed to evaluate the associated factors of hemorrhagic complications after brain tumor biopsies and propose countermeasures. METHODS: We retrospectively collected data on 208 consecutive patients with brain tumors (malignant lymphoma or glioma) who underwent a biopsy from 2011-2020. We evaluated factors and microbleeds (MBs) in the tumor plus relative cerebral/tumoral blood flow (rCBF) at the biopsy site on preoperative magnetic resonance imaging (MRI). RESULTS: Postoperative all and symptomatic hemorrhage occurred in 21.6% and 9.6% of patients. In univariate analysis, a needle biopsy was significantly associated with the risk of all and symptomatic hemorrhages compared to techniques that allow adequate hemostatic manipulation (i.e., open and endoscopic biopsies). Multivariate analyses revealed that a needle biopsy and gliomas of World Health Organization (WHO) grade III/IV were significantly associated with postoperative all and symptomatic hemorrhages. Multiple lesions were also an independent risk factor for symptomatic hemorrhages. On preoperative MRI, abundant MBs in the tumor and MBs at the biopsy sites, in addition to high rCBF, were significantly associated with postoperative all and symptomatic hemorrhages. CONCLUSIONS: We recommend the following measures to prevent hemorrhagic complications: consider biopsy techniques that allow adequate hemostatic manipulation preferentially; perform more careful hemostasis in cases of suspected gliomas of WHO grade III/IV, multiple lesions, and abundant MBs in the tumors; and, if there are multiple candidate biopsy sites, select areas with lower rCBF and no MBs as a biopsy target.