Development of a scoring system to predict local recurrence in brain metastases following complete resection and observation.

PURPOSE: Postoperative stereotactic radiosurgery to the resection cavity in patients with brain metastases is guideline-recommended therapy. However, Japanese Clinical Oncology Group 0504 study showed that postoperative observation could be a therapeutic option in patients with completed resected brain metastases. We hereby investigated the incidence and risk factors for local recurrence after complete resection without immediate radiotherapy and developed a scoring system for its prediction. METHODS: We included 53 patients with 54 brain metastases, who underwent complete resection between January 2016 and December 2021. We identified risk factors for local recurrence and developed a scoring system to predict it using the extracted risk factors, by assigning one point to each risk factor and calculating the total scores for each patient. We evaluated the correlation between the prognostic score and time to local recurrence. RESULTS: Local recurrence occurred in 37 of 54 tumors (68.5%), with a median follow-up duration of 21.0 months. The median time to local recurrence was 5.1 months. Univariate and multivariate analyses revealed that non-lung adenocarcinoma, infratentorial tumors, and no postoperative systemic therapy were identified as risk factors for local recurrence (non-lung adenocarcinoma, p = 0.035; infratentorial tumors, p = 0.044; and no postoperative systemic therapy, p = 0.0069). A score ≥ 2 showed a median time to local recurrence of 2.1 months, starkly contrasting with 30.8 months for a score ≤ 1 (p = 0.0002). CONCLUSIONS: Non-lung adenocarcinoma, infratentorial tumors, and no postoperative systemic therapy were risk factors for local recurrence. Our scoring system can predict local recurrence, thus potentially aiding treatment decisions.

Clinical characteristics and prognosis of Glioblastoma patients with infratentorial recurrence.

BACKGROUND: Glioblastoma (GBM) infrequently recurs in the infratentorial region. Such Infratentorial recurrence (ITR) has some clinically unique characteristics, such as presenting unspecific symptoms and providing patients a chance to receive additional radiotherapy. However, the clinical significances of ITR are not well studied. METHODS: We reviewed newly diagnosed isocitrate dehydrogenase (IDH)-wildtype GBM patients treated at our institution between October 2008 and December 2018. ITR was defined as any type of recurrence in GBM, including dissemination or distant recurrence, which primarily developed in the supratentorial region and recurred in the infratentorial region. RESULTS: Of 134 patients with newly diagnosed IDH-wildtype GBM, six (4.5%) were classified as having ITR. There was no significant difference in median duration from the first surgery to ITR development between patients with and without ITR (12.2 vs. 10.2 months, P = 0.65). The primary symptoms of ITR were gait disturbance (100%, n = 6), dizziness (50.0%, n = 3), nausea (33.3%, n = 2), and cerebellar mutism (16.7%, n = 1). In four cases (66.7%), symptoms were presented before ITR development. All patients received additional treatments for ITR. The median post-recurrence survival (PRS) of ITR patients was significantly shorter than that of general GBM patients (5.5 vs. 9.1 months, P = 0.023). However, chemoradiotherapy contributed to palliating symptoms such as nausea. CONCLUSIONS: ITR is a severe recurrence type in GBM patients. Its symptoms are neurologically unspecific and can be overlooked or misdiagnosed as side effects of treatments. Carefully checking the infratentorial region, especially around the fourth ventricle, is essential during the GBM patient follow-up.

Consulting a neurosurgeon upon initial medical assessment reduces the time to the first surgery and potentially contributes to improved prognosis for glioblastoma patients.

BACKGROUND: The neurological status of glioblastoma patients rapidly deteriorates. We recently demonstrated that early diagnosis and surgery within 3 weeks from the initial symptoms are associated with improved survival. While glioblastoma is a semi-urgent disease, the prehospital behaviors and clinical outcomes of glioblastoma patients are poorly understood. We aimed to disclose how prehospital patient behavior influences the clinical outcomes of glioblastoma patients. METHODS: Isocitrate dehydrogenase-wildtype glioblastoma patients treated at our institution between January 2010 and December 2019 were reviewed. Patients were divided into two groups, neurosurgeon and non-neurosurgeon groups, based on the primary doctor whom patients sought for an initial evaluation. Patient demographics and prognoses were examined. RESULTS: Of 170 patients, 109 and 61 were classified into the neurosurgeon and non-neurosurgeon groups, respectively. The median age of neurosurgeon group was significantly younger than the non-neurosurgeon group (61 vs. 69 years old, P = 0.019) and in better performance status (preoperative Karnofsky performance status scores $\ge$80: 72.5 vs. 55.7%, P = 0.027). The neurosurgeon group exhibited a significantly shorter duration from the first hospital visit to the first surgery than the non-neurosurgeon group (18 vs. 29 days, P < 0.0001). Furthermore, the overall survival of the neurosurgeon group was significantly more prolonged than that of the non-neurosurgeon group (22.9 vs. 14.0 months, P = 0.038). CONCLUSION: Seeking an initial evaluation by a neurosurgeon was potentially associated with prolonged survival in glioblastoma patients. A short duration from the first hospital visit to the first surgery is essential in enhancing glioblastoma patient prognosis.

The clinical characteristics and outcomes of incidentally discovered glioblastoma.

OBJECTIVE: With an increase in the number of imaging examinations and the development of imaging technology, a small number of glioblastomas (GBMs) are identified by incidental radiological images. These incidentally discovered glioblastomas (iGBMs) are rare, and their clinical features are not well understood. Here, we investigated the clinical characteristics and outcomes of iGBM. METHODS: Data of newly diagnosed iGBM patients who were treated at our institution between August 2005 and October 2019 were reviewed. An iGBM was defined as a GBM without a focal sign, discovered on radiological images obtained for reasons unrelated to the tumor. Kaplan-Meier analysis was performed to calculate progression-free survival (PFS) and overall survival (OS). RESULTS: Of 315 patients with newly diagnosed GBM, four (1.3%) were classified as having iGBM. Health screening was the most common reason for tumor discovery (75.0%). The preoperative Karnofsky performance status score was 100 in three patients. Tumors were found on the right side in three cases. The mean volume of preoperative enhanced tumor lesion was 16.8 cm3. The median duration from confirmation of an enhanced lesion to surgery was 13.5 days. In all cases, either total (100%) or subtotal (95-99%) resections were achieved. The median PFS and OS were 10.5 and 20.0 months, respectively. CONCLUSIONS: The iGBMs were often small and in the right non-eloquent area, and the patients had good performance status. We found that timely therapeutic intervention provided iGBM patients with favorable outcomes. This report suggests that early detection of GBM may lead to a better prognosis.

Assessment of radiographic and prognostic characteristics of programmed death-ligand 1 expression in high-grade gliomas.

PURPOSE: Gliomas are characterized by immunosuppressive features. Programmed death-ligand 1 (PD-L1) is overexpressed and plays an important role in the immunosuppressive tumor microenvironments of gliomas. However, the radiographical and prognostic significance of PD-L1 expression remains unclear. METHODS: Using tissue microarrays, we evaluated PD-L1 expression and the presence of tumor-infiltrating CD4+ and CD8+T cells and CD204+macrophages using immunohistochemical analysis. Contrast enhancement area and fluid-attenuated inversion recovery (FLAIR) hyperintensity area were evaluated by two-dimensional analysis. Kaplan-Meier analysis was performed to evaluate the overall survival time in 44 patients with isocitrate dehydrogenase (IDH)-wildtype glioblastoma. RESULTS: We evaluated 71 patients with newly diagnosed high-grade gliomas who were treated between October 1998 and April 2012. PD-L1 expression was observed in 15 patients (21.1%). A significant association of PD-L1 expression with the CD4+ and CD8+ T cell densities, but not with CD204+ macrophage densities, was observed (p = 0.025, p = 0.0098, and p = 0.19, respectively). The FLAIR-to-enhancement ratio was significantly higher in PD-L1+ tumors than in PD-L1- tumors (p = 0.0037). PD-L1 expression did not show a significant association with the median survival time (PD-L1 + vs. PD-L1-: 19.2 vs 14.9 months; p = 0.39). CONCLUSION: PD-L1 expression was associated with CD4+ and CD8+ T cell infiltration, indicating a significant interplay between PD-L1 and immune cells. The positive correlation of PD-L1 expression with an increased FLAIR-to-enhancement ratio suggested that radiographical characteristics could reflect the immunological status. Our results did not support the prognostic impact of PD-L1 in patients with IDH-wildtype glioblastomas.

MGMT gene promoter methylation by pyrosequencing method correlates volumetric response and neurological status in IDH wild-type glioblastomas.

PURPOSE: Although the usefulness of O6-methylguanine DNA methyltransferase (MGMT) promoter methylation analysis for predicting response to chemoradiotherapy and the prognosis of patients with glioblastoma has been widely reported, there is still no consensus regarding how to define MGMT promoter methylation percentage (MGMTpm%) cutoffs by pyrosequencing method. The aim of this study was to determine the optimal cutoff value of MGMT promoter methylation status using volumetric analysis focused on the tumor volume ratio (TVR) measured by MRI. METHODS: This retrospective study included newly diagnosed IDH wild-type glioblastoma patients with residual tumor after surgery, followed by local radiotherapy with temozolomide. TVR was defined as the tumor volume at 6 months after the initial chemoradiotherapy administration divided by the tumor volume before the start of therapy. The mean MGMTpm% of 16 CpG islands (74-89) was analyzed using pyrosequencing. We statistically analyzed the correlation between MGMTpm%, TVR, and change in Karnofsky performance status. RESULTS: The study included 44 patients with residual tumors. Thirteen (92.9%) of 14 patients with MGMTpm% ≥ 23.9% showed 50% or more volumetric response, leading to prolonged survival, and 17 (70.8%) of 24 patients with MGMTpm% < 8.2% had progressive disease after initial chemoradiotherapy administration. Three (50.0%) of six patients with MGMTpm% 8.2% to < 23.9% had stable disease or partial response. CONCLUSION: Evaluation of MGMTpm% by pyrosequencing is important in predicting the volumetric response and prognosis of glioblastoma patients with residual tumors.

Continuing maintenance temozolomide therapy beyond 12 cycles confers no clinical benefit over discontinuation at 12 cycles in patients with IDH1/2-wildtype glioblastoma.

OBJECTIVE: The optimal duration of maintenance temozolomide therapy is controversial. We aimed to examine the clinical benefits of continuing temozolomide therapy beyond 12 cycles in patients with glioblastoma. METHODS: We included 41 patients with isocitrate dehydrogenase 1/2-wildtype glioblastoma, who received 12 or more cycles of temozolomide therapy between June 2006 and December 2019. We evaluated the outcome between 16 patients who continued temozolomide therapy beyond 12 cycles up to 24 cycles (≥13 cycles group) and 25 patients wherein temozolomide therapy was discontinued at 12 cycles (12 cycles group). RESULTS: The median progression-free survival and survival time after completing 12 cycles (residual progression-free survival and residual overall survival) did not differ between the 12 cycles group and ≥13 cycles group (residual progression-free survival: 11.3 vs. 9.2 months, P = 0.61, residual overall survival: 25.7 vs. 30.2 months, P = 0.76). Multivariate analysis including temozolomide therapy beyond 12 cycles, age at 12 cycles, Karnofsky performance status at 12 cycles, residual tumor at 12 cycles, maintenance therapy regimen and O-6-methylguanine deoxyribonucleic acid methyltransferase promoter methylation status revealed that extended temozolomide therapy beyond 12 cycles was not correlated with residual progression-free survival and residual overall survival (P = 0.80 and P = 0.41, respectively) but Karnofsky performance status at 12 cycles ≥80 was significantly associated with increased residual overall survival (P = 0.0012). CONCLUSIONS: Continuing temozolomide beyond 12 cycles confers no clinical benefit over the discontinuation of temozolomide at 12 cycles. Karnofsky performance status at 12 cycles ≥80 may serve as a novel predictive factor for long-term survival.

Disseminated Streptococcus anginosus invasive infection with intracranial subdural abscess formation.

We report the case of a 67-year-old woman with disseminated Streptococcus anginosus invasive infection. Even under a maximal dose of susceptible antibiotics, her condition was complicated by pulmonary septic emboli and intracranial subdural abscess. Effective antibiotics and emergent surgical drainage were performed, but the sequelae of aphasia and hemiplegia remained. Underlying immunocompromised conditions of diabetes mellitus and monoclonal gammopathy of unknown significance might partially affect the clinical course of invasive S. anginosus infection. Once the infection becomes invasive, it can be refractory and difficult to treat. Clinicians should acknowledge the characteristics of invasive S. anginosus infection.

Intracranial growing teratoma syndrome observed at 44 months after initial treatment; a case presentation and literature review.

Intracranial growing teratoma syndrome (iGTS) is rare phenomenon which is observed in non-germinomatous germ cell tumor (NGGCT) after chemotherapy. The clinical features of iGTS are rapidly increasing in size compared with relapse, no elevation of tumor marker in spite of tumor regrowth, multiple cystic lesions in cranial imaging, and histopathologically diagnosed as mature teratoma. Here we present a 14-year-old man with iGTS which was revealed at 44 months after initial chemotherapy. He was diagnosed as pineal immature teratoma by histopathological specimen, and we performed chemotherapy and radiation therapy. After this treatment, we found growing cystic lesion in tumor removal cavity at 26 months after surgery. The histopathological findings showed dermoid cyst in first salvage surgery. Following this result, we observed him without adjuvant chemotherapy. However he had continuous headache, abnormal eye movement at 44 months after initial treatment. Cranial MRI showed regrowing cyst. In second salvage surgery, mature teratoma was demonstrated on histopathological specimen, and we diagnosed as iGTS. Although most reported iGTSs show rapid increasing after initial chemotherapy, few reported cases show regrowth at chronic phase as our case. In long-term follow-up of germ cell tumor, iGTS is important as differential diagnosis.

Specific Factors to Predict Large-Vessel Occlusion in Acute Stroke Patients.

BACKGROUND: The effectiveness of thrombectomy for acute ischemic stroke has been established, and earlier treatment produces better outcomes. If possible to identify large-vessel occlusion (LVO) at the prehospital phase, eligible patients can be shipped directly to a hospital that can perform thrombectomy. The purpose of this study was to determine factors that are specific to LVO and can be known before hospital arrival. METHODS: The subjects were stroke patients during the period between July 2014 and June 2016, who had a National Institutes of Health Stroke Scale (NIHSS) score of 8 or higher and came to our hospital within 6 hours of onset. These patients were divided into an LVO group and a non-LVO group, and background factors, mode of onset, individual NIHSS item scores, and blood pressure at the time of the visit were retrospectively investigated. The selected factors were compared with LVO prediction scales reported in the past. RESULTS: There were 196 stroke patients who had NIHSS scores of 8 or higher and arrived at the hospital within 6 hours. Of these 196 patients, 56 had LVO. This LVO group included a significantly higher number of patients with the 2 items of atrial fibrillation (odds ratio [OR], 11.5: 95% confidence interval [CI], 4.04-32.9; P < .0001) and systolic blood pressure of 170 mm Hg or lower (OR, 2.99: 95% CI, 1.33-6.71, P = .008). These 2 items predicted LVO equally to existing LVO prediction scales. CONCLUSIONS: The 2 items of atrial fibrillation and systolic blood pressure of 170 mm Hg or lower were significantly correlated with LVO.

The Safety and Usefulness of Awake Surgery as a Treatment Modality for Glioblastoma: A Retrospective Cohort Study and Literature Review.

Awake surgery contributes to the maximal safe removal of gliomas by localizing brain function. However, the efficacy and safety thereof as a treatment modality for glioblastomas (GBMs) have not yet been established. In this study, we analyzed the outcomes of awake surgery as a treatment modality for GBMs, response to awake mapping, and the factors correlated with mapping failure. Patients with GBMs who had undergone awake surgery at our hospital between March 2010 and February 2023 were included in this study. Those with recurrence were excluded from this study. The clinical characteristics, response to awake mapping, extent of resection (EOR), postoperative complications, progression-free survival (PFS), overall survival (OS), and factors correlated with mapping failure were retrospectively analyzed. Of the 32 participants included in this study, the median age was 57 years old; 17 (53%) were male. Awake mapping was successfully completed in 28 participants (88%). A positive response to mapping and limited resection were observed in 17 (53%) and 13 participants (41%), respectively. The EOR included gross total, subtotal, and partial resections and biopsies in 19 (59%), 8 (25%), 3 (9%), and 2 cases (6%), respectively. Eight (25%) and three participants (9%) presented with neurological deterioration in the acute postoperative period and at 3 months postoperatively, respectively. The median PFS and OS were 15.7 and 36.9 months, respectively. The time from anesthetic induction to extubation was statistically significantly longer in the mapping failure cohort than that in the mapping success cohort. Functional areas could be detected during awake surgery in participants with GBMs. Thus, awake mapping influences intraoperative discernment, contributes to the preservation of brain function, and improves treatment outcomes.

Resection and postoperative pazopanib for intraspinal recurrent solitary fibrous tumor: illustrative case.

BACKGROUND: Intracranial solitary fibrous tumors (SFTs) rarely recur in the spinal space. Only 4 cases of spinal recurrence from intracranial SFT have been reported; therefore, the optimal treatment of recurrent spinal SFT remains unclear. OBSERVATIONS: A 53-year-old woman with a history of resection of a right occipital anaplastic SFT presented with progressive back and side pain. She was diagnosed with an intradural extramedullary tumor ventral to the spinal cord at the T5-7 level. She underwent tumor resection with T5-6 laminectomy and T4 and T7 partial laminectomy. The tumor was completely removed in a piecemeal fashion using an ultrasonic aspirator with careful control of bleeding. Her symptoms quickly improved after the surgery, and she returned to normal life. The tumor was diagnosed as SFT. Pazopanib was administered postoperatively. Despite the recurrence of the intracranial tumor, the patient was alive without recurrence of the spinal tumor 14 months after resection. LESSONS: Although rare, intracranial SFTs have a risk of spinal recurrence. Complete resection of a recurrent spinal SFT can be achieved even in the ventral location. Pazopanib could be a possible therapeutic option for preventing local tumor recurrence in the management of recurrent spinal SFT. https://thejns.org/doi/10.3171/CASE24217.

Successful treatment of pediatric patients with high-grade gliomas featuring leptomeningeal metastases by targeting BRAF V600E mutations with dabrafenib plus trametinib: two illustrative cases.

A combination of BRAF and MEK inhibitors is reported to be effective for gliomas with the BRAF V600E mutation; however, its efficacy in gliomas with leptomeningeal metastases (LMM) is still unknown. In this report, we describe two pediatric patients with high-grade glioma featuring the BRAF V600E mutation who were treated with dabrafenib and trametinib for LMM. Both 2 cases underwent craniotomy for primary intracranial lesions and were diagnosed as a high-grade glioma with BRAF V600E mutation; one case was consistent with anaplastic pleomorphic xanthoastorocytoma, the other was epithelioid glioblastoma. They received standard treatment for the lesions but subsequently were found to have new lesions including multiple spinal dissemination. We started administering dabrafenib and trametinib. Within a few days of starting treatment, the symptoms improved dramatically and MRI performed one month after the prescription of the two drugs demonstrated remission of both brain and spinal lesions. This report shows that dabrafenib and trametinib are effective not only for recurrent lesions but also for LMM in pediatric patients.

Pediatric atypical teratoid/rhabdoid tumor in the cauda equina with rapid tumor progression: illustrative case.

BACKGROUND: Atypical teratoid/rhabdoid tumor (AT/RT) is an uncommon malignant neoplasm and rarely occurs in the spinal space, especially in the cauda equina. Only 8 cases of pediatric AT/RT of the cauda equina have been reported. Therefore, its clinical behavior and optimal treatment remain unclear. OBSERVATIONS: The authors describe the case of a 9-year-old boy who presented with progressive back and left leg pain. Initial magnetic resonance imaging showed an intradural extramedullary lesion at the L3-4 level, which progressed rapidly to the L2-5 level within a month. He underwent partial resection of the tumor with an L2-5 laminectomy. The histopathological diagnosis was AT/RT. He received adjuvant chemotherapy and radiotherapy, and his gait disturbance improved postoperatively. At 6 months' follow-up, disease recurrence was not observed. LESSONS: Although extremely rare, AT/RT should be included in the differential diagnosis for prompt therapeutic intervention. Safe resection with minimal functional impairment, followed by postoperative chemoradiation, can lead to tumor control and improve neurological function. https://thejns.org/doi/10.3171/CASE24219.

Development of a rapid and comprehensive genomic profiling test supporting diagnosis and research for gliomas.

A prompt and reliable molecular diagnosis for brain tumors has become crucial in precision medicine. While Comprehensive Genomic Profiling (CGP) has become feasible, there remains room for enhancement in brain tumor diagnosis due to the partial lack of essential genes and limitations in broad copy number analysis. In addition, the long turnaround time of commercially available CGPs poses an additional obstacle to the timely implementation of results in clinics. To address these challenges, we developed a CGP encompassing 113 genes, genome-wide copy number changes, and MGMT promoter methylation. Our CGP incorporates not only diagnostic genes but also supplementary genes valuable for research. Our CGP enables us to simultaneous identification of mutations, gene fusions, focal and broad copy number alterations, and MGMT promoter methylation status, with results delivered within a minimum of 4 days. Validation of our CGP, through comparisons with whole-genome sequencing, RNA sequencing, and pyrosequencing, has certified its accuracy and reliability. We applied our CGP for 23 consecutive cases of intracranial mass lesions, which demonstrated its efficacy in aiding diagnosis and prognostication. Our CGP offers a comprehensive and rapid molecular profiling for gliomas, which could potentially apply to clinical practices and research primarily in the field of brain tumors.

Utility of real-time polymerase chain reaction for the assessment of CDKN2A homozygous deletion in adult-type IDH-mutant astrocytoma.

The World Health Organization Classification of Tumors of the Central Nervous System 5th Edition (WHO CNS5) introduced a newly defined astrocytoma, IDH-mutant grade 4, for adult diffuse glioma classification. One of the diagnostic criteria is the presence of a CDKN2A/B homozygous deletion (HD). Here, we report a robust and cost-effective quantitative polymerase chain reaction (qPCR)-based test for assessing CDKN2A HD. A TaqMan copy number assay was performed using a probe located within CDKN2A. The linear correlation between the Ct values and relative CDKN2A copy number was confirmed using a serial mixture of DNA from normal blood and U87MG cells. The qPCR assay was performed in 109 IDH-mutant astrocytomas, including 14 tumors with CDKN2A HD, verified either by multiplex ligation-dependent probe amplification (MLPA) or CytoScan HD microarray platforms. Receiver operating characteristic curve analysis indicated that a cutoff value of 0.85 yielded optimal sensitivity (100%) and specificity (99.0%) for determining CDKN2A HD. The assay applies to DNA extracted from frozen or formalin-fixed paraffin-embedded tissue samples. Survival was significantly shorter in patients with than in those without CDKN2A HD, assessed by either MLPA/CytoScan or qPCR. Thus, our qPCR method is clinically applicable for astrocytoma grading and prognostication, compatible with the WHO CNS5.

Early Diagnosis and Surgical Intervention Within 3 Weeks From Symptom Onset Are Associated With Prolonged Survival of Patients With Glioblastoma.

BACKGROUND: Glioblastoma (GBM) is a rapidly growing and most life-threatening malignant brain tumor. The significance of early treatment to the clinical outcomes of patients with GBM is unclear. OBJECTIVE: To determine whether early diagnosis and surgery improve the preoperative and postoperative Karnofsky performance status (KPS) and prognosis of patients with GBM. METHODS: Data of isocitrate dehydrogenase-wildtype patients with GBM treated at our institution between January 2010 and December 2019 were reviewed. Patients were classified into early or late diagnosis groups with a threshold of 14 days from initial symptoms. In addition, patients were divided into early, intermediate, and late surgery groups with thresholds of 21 and 35 days. Representative symptoms and patient prognoses were examined. RESULTS: Of 153 patients, 72 and 81 were classified into the early and late diagnosis groups. The median tumor volume was significantly smaller in the former group. The proportion of patients with preoperative KPS scores 90 was 48.6% and 29.6% in the early and late diagnosis groups ( P = .016). The early, intermediate, and late surgery groups included 43, 24, and 86 patients. The median overall survival was significantly longer in the early surgery group than in the late surgery group (28.4 vs 18.7 months, P = .006). Multivariate analysis demonstrated that significant predictors of shorter survival included extent of tumor resection (partial or biopsy), preoperative and postoperative KPS 60, and O6-methylguanine-DNA-methyltransferase promoter status (unmethylated). CONCLUSION: Early diagnosis within 2 weeks and surgical interventions within 3 weeks from the symptom onset are associated with prolonged patient survival. Early GBM treatment will benefit patients with GBM.

Combination of asleep and awake craniotomy as a novel strategy for resection in patients with butterfly glioblastoma: Two case reports.

Background: Several studies have reported that gross total resection contributes to improved prognosis in patients with butterfly glioblastoma (bGBM). However, it sometimes damages the corpus callosum and cingulate gyrus, leading to severe neurological complications. Case Description: We report two cases of bGBM that was safely and maximally resected using brief and exact awake mapping after general anesthesia. Two patients had butterfly tumors in both the frontal lobes and the genu of the corpus callosum. Tumor resection was first performed on the nondominant side under general anesthesia to shorten the resection time and maintain patient concentration during awake surgery. After that, awake surgery was performed for the lesions in the dominant frontal lobe and genu of the corpus callosum. Tumor resection was performed through minimal cortical incisions in both frontal lobes. Postoperative magnetic resonance imaging showed gross total resection, and the patients had no chronic neurological sequelae, such as akinetic mutism and abulia. Conclusion: bGBM could be safely and maximally resected by a combination of asleep and brief awake resection, which enabled patients to maintain their attention to the task without fatigue, somnolence, or decreased attention. The bilateral approach from a small corticotomy can avoid extensive damage to the cingulate gyrus.