Residual pattern of the hyperintense area on T2-weighted magnetic resonance imaging after initial treatment predicts the pattern and location of recurrence in patients with newly diagnosed glioblastoma.

OBJECTIVE: This study examined the clinical significance of residual hyperintense area on T2-weighted magnetic resonance imaging without gadolinium-enhanced lesions at the end of initial treatment (debulking surgery, concomitant radiotherapy, and temozolomide) in patients with glioblastoma (GB). METHODS: Among 150 GB cases, 77 cases without enhanced lesions at the end of initial treatment and without factors modifying the distribution of residual hyperintense area or pattern of recurrence were included. We retrospectively reviewed the relationship of residual hyperintense area after initial treatment with progression-free survival (PFS), overall survival (OS), and pattern of recurrence. RESULTS: In these 77 cases, the median PFS and OS were 12.4 and 27.4 months, respectively. At the end of initial treatment, 55 (71.4%) cases had residual hyperintense area (T2 residual group, T2R), whereas 22 (28.6%) showed no hyperintense area (T2 disappeared group, T2D). Based on univariate and multivariate analyses, the residual hyperintense area after initial treatment was not a prognostic factor for PFS or OS. Distant recurrences occurred more frequently in the T2D group than in the T2R group 50.0% vs. 9.5%). In the T2R group, the recurrence site coincided with the residual hyperintense area in 36 (85.7%) of 42 recurrences. CONCLUSION: The residual hyperintense area on T2WI at the end of initial treatment can predict local recurrence. However, the distant recurrence occurred frequently in T2D group. Thus, attention should be paid to local recurrences in T2R group and distant recurrences in T2D group.

AB004. Transsylvian approach for radical resection of insular gliomas: emphasizing the importance of the transsylvian approach for elderly patients with Zone II and III insular gliomas.

BACKGROUND: Insular gliomas present significant challenges due to their deep-seated location and proximity to critical structures, including sylvian veins, middle cerebral arteries (MCAs), lenticulostriate arteries, long insular arteries, and functional cortices and white matter tracts. The Berger-Sanai classification categorizes them into four zones (I-IV), providing a framework for understanding insular gliomas. The key factors for successful insular glioma removal are achieving the greatest insular exposure and surgical freedom. There are two main types of approach methods, such as transsylvian approach with meticulous wider dissection of the sylvian fissure and transcorticosubcortical approach with intraoperative functional brain mapping under awake surgery to remove the functionally silent cortices and white matter tracts. Because splitting the distal sylvian fissure is more challenging, a transcortical approach through the parietorolandic operculum in awake patients has been reported to be more effective access to the posterior insular gliomas (Zone II and III) in the dominant hemisphere. The object of this study emphasize the importance of the transsylvian approach for radical resection of insular gliomas. METHODS: We retrospectively analyzed our experiences with radically resected insulo-opercular gliomas. Basically, we pursue the transsylvian approach for resecting insular gliomas without removal of any normal brain. RESULTS: Motor pathways running beneath the parietorolandic operculum can be damaged by ischemia caused by sacrificing the medullary arteries (MAs) arising from the pial arteries of the M3 and M4 portions of the MCA. Motor deficit after resection of this area was significantly found in the elderly patients. This phenomenon might be described by the age-associated decreasing the vascular reserve capacity. Autopsy brains showed that the sclerotic rate of the MAs increased with age and hypertension. Even with the intraoperative functional brain mapping, we cannot avoid the ischemic complication caused by sacrificing the MAs during stepwise removal of the functionally silent cortices and white matter tracts. CONCLUSIONS: We make a suggestion not to remove the parietorolandic operculum in elderly patients with insular gliomas located at Zone II and III. Distal transsylvian approach should be applied.

AB012. A phase III randomized trial of gross total resection versus possible resection of fluid-attenuated inversion recovery (FLAIR) hyperintensity lesion on magnetic resonance image for newly diagnosed supratentorial glioblastoma (JCOG2209).

BACKGROUND: Complete resection of contrast-enhanced lesions [gross total resection (GTR)] without severe neurological deficits has been generally accepted as the goal of surgery. However, it remains unclear if additional resection of surrounding fluid-attenuated inversion recovery (FLAIR) hyper-intense lesions combined with GTR (FLAIRectomy) has survival advantage of primary glioblastoma patients. Multicenter, open-label, randomized phase III trial was commenced to confirm the superiority of FLAIRectomy to GTR alone followed by radiotherapy with concomitant and adjuvant temozolomide in terms of overall survival (OS) for primary glioblastoma IDH-wildtype patients. This trial investigates not only survival but also postoperative neurological and neurocognitive deficits in detail. METHODS: We assumed a 2-year OS of 50% in the GTR arm and expected a 15% improvement in the FLAIRectomy arm. A total of 130 patients is required with a one-sided alpha of 5%, power of 70%, and will be accrued from 49 Japanese institutions in 4 years and follow-up will last 2.5 years. Patients aged 18-75 years will be registered and randomly assigned to each arm with 1:1 allocation. The primary endpoint is OS, and the secondary endpoints are progression-free survival, frequency of adverse events, proportion of Karnofsky performance status preservation, proportion of National Institutes of Health stroke scale preservation, proportion of mini-mental state examination preservation and proportion of health-related quality of life preservation. The Japan Clinical Oncology Group Protocol Review Committee approved this study protocol in May 2023. Ethics approval was granted by the National Cancer Center Hospital Certified Review Board. Patient enrollment began in July 2023. RESULTS: If FLAIRectomy is superior to GTR alone, aggressive surgery will become a standard surgical treatment for glioblastoma with resectable contrast-enhanced lesion. CONCLUSIONS: Registry number: jRCT1031230245. Date of registration: 19/July/2023. Date of first participant enrollment: 28/July/2023.

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.

Protocol digest of a phase III randomized trial of gross total resection versus possible resection of fluid-attenuated inversion recovery-hyperintense lesion on MRI for newly diagnosed supratentorial glioblastoma: JCOG2209 (FLAMINGO).

The goal of surgery for patients with newly diagnosed glioblastoma (GBM) is maximum safe resection of the contrast-enhancing (CE) lesion on magnetic resonance imaging. However, there is no consensus on the efficacy of FLAIRectomy, which is defined as the possible resection of fluid-attenuated inversion recovery (FLAIR)-hyperintense lesions surrounding the CE lesion. Although retrospective analyses suggested the potential benefits of FLAIRectomy, such outcomes have not been confirmed by prospective studies. Therefore, we planned a multicenter, open-label, randomized controlled phase III trial to evaluate the efficacy of FLAIRectomy compared with gross total resection of CE lesions in patients with newly diagnosed GBM. The primary endpoint is overall survival. In total, 130 patients will be enrolled from 47 institutions over 5 years. This trial has been registered at the Japan Registry of Clinical Trials (study number jRCT1031230245).

Complete removal of a cavernous malformation in the dorsal pons, in contact with the expanded transpontine vein: illustrative case.

BACKGROUND: Craniotomy is required for the removal of brainstem cavernous malformations (CMs) with repeated hemorrhage, and this condition is often complicated by an accompanying developmental venous anomaly (DVA). However, a DVA of the brainstem or cerebellum with drainage penetrating the pons is an exceptional finding. OBSERVATIONS: A 57-year-old man presented with double vision. Computed tomography revealed progressive enlargement of the hemorrhage in the dorsal pons. Contrast-enhanced magnetic resonance angiography revealed an expanded transverse vessel penetrating the center of the pons in contact with the CM. Digital subtraction angiography revealed that the DVA, comprising the expanded transpontine vein and some cerebellar medullary veins acting as normal venous drainage, coexisted with the CM. By utilizing the angioarchitecture and intraoperative neuronavigation system data, electrophysiological mapping, and indocyanine green videoangiography, complete removal of the CM was accomplished while preserving the DVA and brain function. LESSONS: This study presents the intraoperative images of an expanded transpontine vein as a DVA, which has never been depicted in a live patient before, accompanied by a CM in the dorsal portion of the pons. https://thejns.org/doi/10.3171/CASE24314.

Clinical significance of cerebral microbleeds in patients with germinoma who underwent long-term follow-up.

PURPOSE: This study identified the factors affecting cerebral microbleed (CMBs) development. Moreover, their effects on intelligence and memory and association with stroke in patients with germinoma who had long-term follow-up were evaluated. METHODS: This study included 64 patients with germinoma who were histologically and clinically diagnosed with and treated for germinoma. These patients were evaluated cross-sectionally, with a focus on CMBs on susceptibility-weighted magnetic resonance imaging (SWI), brain atrophy assessed through volumetric analysis, and intelligence and memory. RESULTS: The follow-up period was from 32 to 412 (median: 175.5) months. In total, 43 (67%) patients had 509 CMBs and 21 did not have CMBs. Moderate correlations were observed between the number of CMBs and time from initial treatments and recurrence was found to be a risk factor for CMB development. Increased temporal CMBs had a marginal effect on the processing speed and visual memory, whereas brain atrophy had a statistically significant effect on verbal, visual, and general memory and a marginal effect on processing speed. Before SWI acquisition and during the follow-up periods, eight strokes occurred in four patients. All of these patients had ≥ 15 CMBs on SWI before stroke onset. Meanwhile, 33 patients with < 14 CMBs or 21 patients without CMBs did not experience stroke. CONCLUSION: Patients with a longer time from treatment initiation had a higher number of CMBs, and recurrence was a significant risk factor for CMB development. Furthermore, brain atrophy had a stronger effect on memory than CMBs. Increased CMBs predict the stroke onset.

Clinical and molecular features of patients with IDH1 wild-type primary glioblastoma presenting unexpected short-term survival after gross total resection.

BACKGROUND: This study investigated the factors influencing short-term survivors (STS) after gross total resection (GTR) in patients with IDH1 wild-type primary glioblastoma. METHODS: We analyzed five independent cohorts who underwent GTR, including 83 patients from Kitasato University (K-cohort), and four validation cohorts of 148 patients from co-investigators (V-cohort), 66 patients from the Kansai Molecular Diagnosis Network for the Central Nervous System tumors, 109 patients from the Cancer Genome Atlas, and 40 patients from the Glioma Longitudinal AnalySiS. The study defined STS as those who had an overall survival ≤ 12 months after GTR with subsequent radiation therapy, and concurrent and adjuvant temozolomide (TMZ). RESULTS: The study included 446 patients with glioblastoma. All cohorts experienced unexpected STS after GTR, with a range of 15.0-23.9% of the cases. Molecular profiling revealed no significant difference in major genetic alterations between the STS and non-STS groups, including MGMT, TERT, EGFR, PTEN, and CDKN2A. Clinically, the STS group had a higher incidence of non-local recurrence early in their treatment course, with 60.0% of non-local recurrence in the K-cohort and 43.5% in the V-cohort. CONCLUSIONS: The study revealed that unexpected STS after GTR in patients with glioblastoma is not uncommon and such tumors tend to present early non-local recurrence. Interestingly, we did not find any significant genetic alterations in the STS group, indicating that such major alterations are characteristics of GB rather than being reliable predictors for recurrence patterns or development of unexpected STS.

Excessive Heat Generation by Power-Driven Craniotomy Tools: A Possible Cause of Autologous Bone Flap Resorption Observed in an Ex Vivo Simulation.

BACKGROUND: Bone flap resorption is an issue after autologous cranioplasty. Critical temperatures above 50°C generated by power-driven craniotomy tools may lead to thermal osteonecrosis, a possible factor in resorption. This ex vivo study examined whether the tools produced excessive heat resulting in bone flap resorption. METHODS: Using swine scapulae maintained at body temperature, burr holes, straight and curved cuts, and wire-pass holes were made with power-driven craniotomy tools. Drilling was at the conventional feed rate (FR) plus irrigation (FR-I+), at a high FR plus irrigation (hFR-I+), and at high FR without irrigation (hFR-I-). The temperature in each trial was recorded by an infrared thermographic camera. RESULTS: With FR-I+, the maximum temperature at the burr holes, the cuts, and the wire-pass holes was 69.0°C, 56.7°C, and 46.2°C, respectively. With hFR-I+, these temperatures were 53.1°C, 52.1°C, and 46.0°C, with hFR-I- they were 56.0°C, 66.5°C, and 50.0°C; hFR-I- burr hole- and cutting procedures resulted in the highest incidence of bone temperatures above 50°C followed by FR-I+, and hFR-I+. At the site of wire-pass holes, only hFR-I- drilling produced this temperature. CONCLUSIONS: Except during prolonged procedures in thick bones, most drilling with irrigation did not reach the critical temperature. Drilling without irrigation risked generating the critical temperature. Knowing those characteristics may be a help to perform craniotomy with less thermal bone damage.

Distant recurrence in the cerebellar dentate nucleus through the dentato-rubro-thalamo-cortical pathway in supratentorial glioma cases.

BACKGROUND: Distant recurrence can occur by infiltration along white matter tracts or dissemination through the cerebrospinal fluid (CSF). This study aimed to clarify the clinical features and mechanisms of recurrence in the dentate nucleus (DN) in patients with supratentorial gliomas. Based on the review of our patients, we verified the hypothesis that distant DN recurrence from a supratentorial lesion occurs through the dentato-rubro-thalamo-cortical (DRTC) pathway. METHODS: A total of 380 patients with supratentorial astrocytoma, isocitrate dehydrogenase (IDH)-mutant (astrocytoma), oligodendroglioma, IDH mutant and 1p/19q-codeleted (oligodendroglioma), glioblastoma, IDH-wild type (GB), and thalamic diffuse midline glioma, H3 K27-altered (DMG), who underwent tumor resection at our department from 2009 to 2022 were included in this study. Recurrence patterns were reviewed. Additionally, clinical features and magnetic resonance imaging findings before treatment, at the appearance of an abnormal signal, and at further progression due to delayed diagnosis or after salvage treatment of cases with recurrence in the DN were reviewed. RESULTS: Of the 380 patients, 8 (2.1%) had first recurrence in the DN, 3 were asymptomatic when abnormal signals appeared, and 5 were diagnosed within one month after the onset of symptoms. Recurrence in the DN developed in 8 (7.4%) of 108 cases of astrocytoma, GB, or DMG at the frontal lobe or thalamus, whereas no other histological types or sites showed recurrence in the DN. At the time of the appearance of abnormal signals, a diffuse lesion developed at the hilus of the DN. The patterns of further progression showed that the lesions extended to the superior cerebellar peduncle, tectum, tegmentum, red nucleus, thalamus, and internal capsule along the DRTC pathway. CONCLUSION: Distant recurrence along the DRTC pathway is not rare in astrocytomas, GB, or DMG at the frontal lobe or thalamus. Recurrence in the DN developed as a result of the infiltration of tumor cells through the DRTC pathway, not dissemination through the CSF.

Angiographic evaluation of the distance from the top of the jugular bulb to the inferior petrosal sinus-internal jugular vein junction: simple classification and identification method for the orifice of the non-visualized inferior petrosal sinus during neuroendovascular surgery.

BACKGROUND: The inferior petrosal sinus (IPS) is the transvenous access route for neurointerventional surgery that is occasionally undetectable on digital subtraction angiography (DSA) because of blockage by a clot or collapse. This study was aimed at analyzing the distance from the jugular bulb (JB) to the IPS-internal jugular vein (IJV) junction and proposing a new anatomical classification system for the IPS-IJV junction to identify the non-visualized IPS orifice. METHODS: DSA of 708 IPSs of 375 consecutive patients were retrospectively investigated to calculate the distance from the top of the JB to the IPS-IJV junction, and a simple classification system based on this distance was proposed. RESULTS: The median distance from the top of the JB to the IPS-IJV junction was 20.8 ± 14.7 mm. Based on the lower (10.9 mm) and upper (31.1 mm) quartiles, IPS-IJV junction variants were: type I, 0-10 mm (22.3%); type II, 11-30 mm (45.8%); type III, > 31 mm (23.9%); and type IV, no connection to the IJV (8.0%). Bilateral distances showed a positive interrelationship, with a correlation coefficient of 0.86. The bilateral symmetry type (visualized IPSs bilaterally) according to our classification occurred in 267 of 300 (89.0%) patients. CONCLUSIONS: In this study, the IPS-IJV junction was located far from the JB (types II and III), with a higher probability (69.6%). This distance and the four-type classification demonstrated high degrees of homology with the contralateral side. These results would be useful for identifying the non-visualized IPS orifice.

Frontotemporal craniotomy with skin incision along the superior temporal line outside the hairline in bald male patients with temporal gliomas.

A head skin incision is inevitable in neurosurgical procedures and is usually concealed within the hairline. Androgenetic alopecia (AGA) is a progressive hair loss disorder or baldness highly prevalent in men. Therefore, if bald male patients require neurosurgical procedures, skin incisions cannot be concealed, but this subject is yet to be discussed in the literature. This study presents a frontotemporal craniotomy using a skin incision along the superior temporal line, ignoring the hairline in bald male patients. Thirty-three patients with temporal gliomas underwent surgical removal between 2015 and 2022. They were divided into three groups: bald male patients with skin incisions not concealed in the hairline (minimum group, n = 13), bald and non-bald male patients with skin incisions concealed in the hairline (male group, n = 11), and female patients with skin incisions concealed in the hairline (female group, n = 9). In the minimum group, patients had no complaints regarding the incision scar. Cosmetic outcome was excellent, and no cases showed surgical site infection or peripheral facial nerve palsy. Compared with the male and female groups, the minimum group had the shortest skin incision length; however, the craniotomy size and extent of resection were similar. Skin incision for frontotemporal craniotomy cannot be hidden in bald male patients, and the preferred location for the incision is unknown. The skin incision along the superior temporal line is a cosmetically favorable, feasible, and safe procedure.

[Glioblastoma, IDH-Wildtype].

The 5th edition of the WHO Classification of Central Nervous System Tumours(WHO2021)emphasizes the importance of molecular classification. A significant update was that glioblastoma IDH-mutant from WHO2016 was renamed and classified as astrocytoma IDH-mutant WHO grade 4 in WHO2021. This review describes the current updates to the glioblastoma classification, and discusses the essential knowledge regarding daily practice, especially for young neurosurgeons.

Bilateral Trans-Sulcal and Interhemispheric Approaches for Butterfly Glioblastoma: 2-Dimensional Operative Video.

Butterfly glioblastoma (bGB) poses significant surgical challenges, yet recent findings have highlighted the potential of surgical decompression in extending patient survival.1-10 The selection of a surgical strategy for bGB varies across studies. Generally, the side with a larger tumor volume is a preferred approach route, and the nondominant hemisphere is preferred when both tumors are similar in size. The contralateral tumor is removed via the resection cavity of the ipsilateral side,11 with successful utilization of endoscopic-assisted techniques.8 In the case of deep-seated bGB covered with a thick intact brain, accessing the tumor requires creating an invasive corridor, therefore minimizing the damage to the intact brain is ideal. A man in his 70s presented the new-onset seizure. Preoperatively, the patient exhibited a Karnofsky performance status of 50% without any motor deficits, and magnetic resonance imaging demonstrated a deep-seated anterior bGB with a larger tumor volume on the left dominant side. Imaging showed the tumor located just beneath the bilateral superior frontal sulci. Therefore we used these sulci to access the tumor with the minimum cut of the intact brain while preserving the frontal aslant tracts and used bilateral interhemispheric approaches to protect the cingulate bundles. We conducted the same technique for another deep-seated anterior bGB case, both resulting in postoperative Karnofsky performance status improvements (Video 1). Tailoring the surgical approach to the unique characteristics of each bGB case is important. The patients consented to the procedure and the publication of their images.

Randomized phase III study of high-dose methotrexate and whole-brain radiotherapy with/without temozolomide for newly diagnosed primary CNS lymphoma: JCOG1114C.

BACKGROUND: The goal was to determine whether the addition of temozolomide (TMZ) to the standard treatment of high-dose methotrexate (HD-MTX) and whole-brain radiotherapy (WBRT) for primary central nervous system lymphoma (PCNSL) improves survival. METHODS: An open-label, randomized, phase III trial was conducted in Japan, enrolling immunocompetent patients aged 20-70 years with histologically confirmed, newly diagnosed PCNSL. After administration of HD-MTX, patients were randomly assigned to receive WBRT (30 Gy) ±â€…10 Gy boost (arm A) or WBRT ±â€…boost with concomitant and maintenance TMZ for 2 years (arm B). The primary endpoint was overall survival (OS). RESULTS: Between September 29, 2014 and October 15, 2018, 134 patients were enrolled, of whom 122 were randomly assigned and analyzed. At the planned interim analysis, 2-year OS was 86.8% (95% confidence interval [CI]: 72.5-94.0%) in arm A and 71.4% (56.0-82.2%) in arm B. The hazard ratio was 2.18 (95% CI: 0.95-4.98), with the predicted probability of showing the superiority of arm B at the final analysis estimated to be 1.3%. The study was terminated early due to futility. O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status was measured in 115 tumors, and it was neither prognostic nor predictive of TMZ response. CONCLUSIONS: This study failed to demonstrate the benefit of concomitant and maintenance TMZ in newly diagnosed PCNSL.