1.Prognostic Value of EGFR Mutation Subtypes After Linac-Based Stereotactic Radiosurgery or Fractionated Stereotactic Radiotherapy for Brain Metastasis From EGFR-Mutated Non-Small Cell Lung Cancer
Ryosuke MATSUDA ; Shigeto HONTSU ; Tetsuro TAMAMOTO ; Nobuyoshi INOOKA ; Akihiro DOI ; Kaori YAMAKI ; Sachiko MIURA ; Ryosuke MAEOKA ; Tsutomu NAKAZAWA ; Tomoko OCHI ; Toshiteru MIYASAKA ; Yasuhiro TAKESHIMA ; Shuichi YAMADA ; Fumihiko NISHIMURA ; Young-Soo PARK ; Fumiaki ISOHASHI ; Ichiro NAKAGAWA
Brain Tumor Research and Treatment 2026;14(2):66-73
Background:
This study aimed to evaluate the differences in common types of epidermal growthfactor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) with brain metastasis (BM) treated using linear accelerator-based stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT).
Methods:
Between January 2011–December 2023, among 294 consecutive patients with BMfrom NSCLC, 84 patients with EGFR-mutated NSCLC were enrolled in this study.
Results:
The median follow-up time after SRS/fSRT was 20.1 months (range: 0.6–109.7months), while the median overall survival (mOS) after SRS/fSRT was 25.1 months (95% confidence interval [CI]: 18.4–33.5 months). The mOS after initial treatment for NSCLC was 56.2 months (95% CI:41.7–77.0 months). The mOS after SRS/fSRT in 34 patients with exon 19 deletions and 45 patients with exon 21 mutations with L858R was 20.4 months (95% CI: 13.6–55.9 months) and 28.5 months (95% CI: 16.2–33.5). The two groups showed no difference in the mOS. In univariate analyses using the Cox proportional hazards model, no prognostic factors associated with prolonged survival were identified except for good pretreatment Karnofsky Performance Status score and no prior tyrosine kinase inhibitor use before SRS/fSRT in EGFR-mutated NSCLC. There was no difference in both distant failure and local control in the two groups.
Conclusion
The difference in survival between EGFR subtypes (exon 21 L858R mutations vs.exon 19 deletion) was not observed after SRS/fSRT in NSCLC.
2.Effect of Intraoperative Ventricular Opening on Recurrence Patterns Following Bis-Chloroethyl-Nitrosourea Wafer Implantation for Newly Diagnosed Glioblastoma
Ryosuke MATSUDA ; Ryosuke MAEOKA ; Takayuki MORIMOTO ; Tsutomu NAKAZAWA ; Noriaki TOKUDA ; Masashi KOTSUGI ; Yasuhiro TAKESHIMA ; Kentaro TAMURA ; Shuichi YAMADA ; Fumihiko NISHIMURA ; Young-Soo PARK ; Ichiro NAKAGAWA
Journal of Korean Neurosurgical Society 2025;68(1):60-66
Objective:
: To evaluate the effect of ventricular opening (VO) on recurrence patterns in patients with newly diagnosed glioblastoma (GBM) treated with bis-chloroethyl-nitrosourea (BCNU) wafer implantation.
Methods:
: This single-center retrospective study included 40 patients with newly diagnosed GBM who received BCNU wafer implantation after tumor resection between March 2013 and February 2022. The patients were categorized into two groups based on whether VO occurred during the GBM resection. While 18 patients had VO, 22 did not have VO. In cases with VO, the ventricular wall defect is closed with gelatin or oxidized regenerated cellulose and fibrin glue before BCNU wafer implantation. Recurrence patterns—classified as local, diffuse, distant, or multifocal—and time to recurrence were compared between patients with and without VO.
Results:
: The median follow-up period for the entire cohort was 32.2 months (interquartile range, 16.7–38 months). Median survival time was comparable between patients with VO and patients without VO (38 vs. 26 months, p=0.53). Recurrence occurred in 31/40 patients (77.5%) in entire cohort. The incidence of recurrence was comparable between patients with VO and patients without VO (14 [77.8%] vs. 17 [77.3%], p=1.0). No significant differences were seen between the two groups in time to recurrence (p=0.59) or recurrence patterns (p=0.35).
Conclusion
: Ventricular opening during surgery with BCNU wafer implantation does not seem to influence the recurrence patterns. Ventricular opening does not induce distant recurrence if appropriate ventricular closure is performed.
3.Clinical and Genetic Overview of Neurofibromatosis Type 2 (NF2)
Tae-Kyun KIM ; Young-Soo PARK ; Ichiro NAKAGAWA
Journal of Korean Neurosurgical Society 2025;68(3):272-277
Neurofibromatosis type 2 (NF2) is an autosomal dominant disease characterized by bilateral vestibular schwannomas and other central nervous tumors such as meningiomas and spinal ependymomas. Symptoms vary according to the age at diagnosis and the location of these tumors. The diagnostic criteria of NF2 have been regularly revised and recently updated in 2022 with a new nomenclature “NF2-related schwannomatosis” to differentiate NF2 from other schwannoma predisposing disorders, such as SMARCB1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily b, member 1)-, LZTR1 (leucine zipper-like transcription regulator 1)-, and 22q-related schwannomatosis. Addition to the clinical features, genetic testing for pathogenic variants in these genes became an important essence to support diagnosis of NF2 and other schwannomatosis, including mosaic conditions.
4.Effect of Intraoperative Ventricular Opening on Recurrence Patterns Following Bis-Chloroethyl-Nitrosourea Wafer Implantation for Newly Diagnosed Glioblastoma
Ryosuke MATSUDA ; Ryosuke MAEOKA ; Takayuki MORIMOTO ; Tsutomu NAKAZAWA ; Noriaki TOKUDA ; Masashi KOTSUGI ; Yasuhiro TAKESHIMA ; Kentaro TAMURA ; Shuichi YAMADA ; Fumihiko NISHIMURA ; Young-Soo PARK ; Ichiro NAKAGAWA
Journal of Korean Neurosurgical Society 2025;68(1):60-66
Objective:
: To evaluate the effect of ventricular opening (VO) on recurrence patterns in patients with newly diagnosed glioblastoma (GBM) treated with bis-chloroethyl-nitrosourea (BCNU) wafer implantation.
Methods:
: This single-center retrospective study included 40 patients with newly diagnosed GBM who received BCNU wafer implantation after tumor resection between March 2013 and February 2022. The patients were categorized into two groups based on whether VO occurred during the GBM resection. While 18 patients had VO, 22 did not have VO. In cases with VO, the ventricular wall defect is closed with gelatin or oxidized regenerated cellulose and fibrin glue before BCNU wafer implantation. Recurrence patterns—classified as local, diffuse, distant, or multifocal—and time to recurrence were compared between patients with and without VO.
Results:
: The median follow-up period for the entire cohort was 32.2 months (interquartile range, 16.7–38 months). Median survival time was comparable between patients with VO and patients without VO (38 vs. 26 months, p=0.53). Recurrence occurred in 31/40 patients (77.5%) in entire cohort. The incidence of recurrence was comparable between patients with VO and patients without VO (14 [77.8%] vs. 17 [77.3%], p=1.0). No significant differences were seen between the two groups in time to recurrence (p=0.59) or recurrence patterns (p=0.35).
Conclusion
: Ventricular opening during surgery with BCNU wafer implantation does not seem to influence the recurrence patterns. Ventricular opening does not induce distant recurrence if appropriate ventricular closure is performed.
5.Clinical and Genetic Overview of Neurofibromatosis Type 2 (NF2)
Tae-Kyun KIM ; Young-Soo PARK ; Ichiro NAKAGAWA
Journal of Korean Neurosurgical Society 2025;68(3):272-277
Neurofibromatosis type 2 (NF2) is an autosomal dominant disease characterized by bilateral vestibular schwannomas and other central nervous tumors such as meningiomas and spinal ependymomas. Symptoms vary according to the age at diagnosis and the location of these tumors. The diagnostic criteria of NF2 have been regularly revised and recently updated in 2022 with a new nomenclature “NF2-related schwannomatosis” to differentiate NF2 from other schwannoma predisposing disorders, such as SMARCB1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily b, member 1)-, LZTR1 (leucine zipper-like transcription regulator 1)-, and 22q-related schwannomatosis. Addition to the clinical features, genetic testing for pathogenic variants in these genes became an important essence to support diagnosis of NF2 and other schwannomatosis, including mosaic conditions.
6.Effect of Intraoperative Ventricular Opening on Recurrence Patterns Following Bis-Chloroethyl-Nitrosourea Wafer Implantation for Newly Diagnosed Glioblastoma
Ryosuke MATSUDA ; Ryosuke MAEOKA ; Takayuki MORIMOTO ; Tsutomu NAKAZAWA ; Noriaki TOKUDA ; Masashi KOTSUGI ; Yasuhiro TAKESHIMA ; Kentaro TAMURA ; Shuichi YAMADA ; Fumihiko NISHIMURA ; Young-Soo PARK ; Ichiro NAKAGAWA
Journal of Korean Neurosurgical Society 2025;68(1):60-66
Objective:
: To evaluate the effect of ventricular opening (VO) on recurrence patterns in patients with newly diagnosed glioblastoma (GBM) treated with bis-chloroethyl-nitrosourea (BCNU) wafer implantation.
Methods:
: This single-center retrospective study included 40 patients with newly diagnosed GBM who received BCNU wafer implantation after tumor resection between March 2013 and February 2022. The patients were categorized into two groups based on whether VO occurred during the GBM resection. While 18 patients had VO, 22 did not have VO. In cases with VO, the ventricular wall defect is closed with gelatin or oxidized regenerated cellulose and fibrin glue before BCNU wafer implantation. Recurrence patterns—classified as local, diffuse, distant, or multifocal—and time to recurrence were compared between patients with and without VO.
Results:
: The median follow-up period for the entire cohort was 32.2 months (interquartile range, 16.7–38 months). Median survival time was comparable between patients with VO and patients without VO (38 vs. 26 months, p=0.53). Recurrence occurred in 31/40 patients (77.5%) in entire cohort. The incidence of recurrence was comparable between patients with VO and patients without VO (14 [77.8%] vs. 17 [77.3%], p=1.0). No significant differences were seen between the two groups in time to recurrence (p=0.59) or recurrence patterns (p=0.35).
Conclusion
: Ventricular opening during surgery with BCNU wafer implantation does not seem to influence the recurrence patterns. Ventricular opening does not induce distant recurrence if appropriate ventricular closure is performed.
7.Clinical and Genetic Overview of Neurofibromatosis Type 2 (NF2)
Tae-Kyun KIM ; Young-Soo PARK ; Ichiro NAKAGAWA
Journal of Korean Neurosurgical Society 2025;68(3):272-277
Neurofibromatosis type 2 (NF2) is an autosomal dominant disease characterized by bilateral vestibular schwannomas and other central nervous tumors such as meningiomas and spinal ependymomas. Symptoms vary according to the age at diagnosis and the location of these tumors. The diagnostic criteria of NF2 have been regularly revised and recently updated in 2022 with a new nomenclature “NF2-related schwannomatosis” to differentiate NF2 from other schwannoma predisposing disorders, such as SMARCB1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily b, member 1)-, LZTR1 (leucine zipper-like transcription regulator 1)-, and 22q-related schwannomatosis. Addition to the clinical features, genetic testing for pathogenic variants in these genes became an important essence to support diagnosis of NF2 and other schwannomatosis, including mosaic conditions.
8.Effect of Intraoperative Ventricular Opening on Recurrence Patterns Following Bis-Chloroethyl-Nitrosourea Wafer Implantation for Newly Diagnosed Glioblastoma
Ryosuke MATSUDA ; Ryosuke MAEOKA ; Takayuki MORIMOTO ; Tsutomu NAKAZAWA ; Noriaki TOKUDA ; Masashi KOTSUGI ; Yasuhiro TAKESHIMA ; Kentaro TAMURA ; Shuichi YAMADA ; Fumihiko NISHIMURA ; Young-Soo PARK ; Ichiro NAKAGAWA
Journal of Korean Neurosurgical Society 2025;68(1):60-66
Objective:
: To evaluate the effect of ventricular opening (VO) on recurrence patterns in patients with newly diagnosed glioblastoma (GBM) treated with bis-chloroethyl-nitrosourea (BCNU) wafer implantation.
Methods:
: This single-center retrospective study included 40 patients with newly diagnosed GBM who received BCNU wafer implantation after tumor resection between March 2013 and February 2022. The patients were categorized into two groups based on whether VO occurred during the GBM resection. While 18 patients had VO, 22 did not have VO. In cases with VO, the ventricular wall defect is closed with gelatin or oxidized regenerated cellulose and fibrin glue before BCNU wafer implantation. Recurrence patterns—classified as local, diffuse, distant, or multifocal—and time to recurrence were compared between patients with and without VO.
Results:
: The median follow-up period for the entire cohort was 32.2 months (interquartile range, 16.7–38 months). Median survival time was comparable between patients with VO and patients without VO (38 vs. 26 months, p=0.53). Recurrence occurred in 31/40 patients (77.5%) in entire cohort. The incidence of recurrence was comparable between patients with VO and patients without VO (14 [77.8%] vs. 17 [77.3%], p=1.0). No significant differences were seen between the two groups in time to recurrence (p=0.59) or recurrence patterns (p=0.35).
Conclusion
: Ventricular opening during surgery with BCNU wafer implantation does not seem to influence the recurrence patterns. Ventricular opening does not induce distant recurrence if appropriate ventricular closure is performed.
9.Clinical and Genetic Overview of Neurofibromatosis Type 2 (NF2)
Tae-Kyun KIM ; Young-Soo PARK ; Ichiro NAKAGAWA
Journal of Korean Neurosurgical Society 2025;68(3):272-277
Neurofibromatosis type 2 (NF2) is an autosomal dominant disease characterized by bilateral vestibular schwannomas and other central nervous tumors such as meningiomas and spinal ependymomas. Symptoms vary according to the age at diagnosis and the location of these tumors. The diagnostic criteria of NF2 have been regularly revised and recently updated in 2022 with a new nomenclature “NF2-related schwannomatosis” to differentiate NF2 from other schwannoma predisposing disorders, such as SMARCB1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily b, member 1)-, LZTR1 (leucine zipper-like transcription regulator 1)-, and 22q-related schwannomatosis. Addition to the clinical features, genetic testing for pathogenic variants in these genes became an important essence to support diagnosis of NF2 and other schwannomatosis, including mosaic conditions.
10.Lynch Syndrome-Associated Glioblastoma Treated With Concomitant Chemoradiotherapy and Immune Checkpoint Inhibitors: Case Report and Review of Literature
Kenta NAKASE ; Ryosuke MATSUDA ; Shoh SASAKI ; Ichiro NAKAGAWA
Brain Tumor Research and Treatment 2024;12(1):70-74
Lynch syndrome (LS) is an autosomal dominant disorder caused by mutations in mismatch repair (MMR) genes and is also known to be associated with glioblastomas. The efficacy of immunotherapy for LS-associated glioblastomas remains unknown. Herein, we report a rare case of LS-associated glioblastoma, treated with chemotherapy using immune checkpoint inhibitors (ICI). A 41-year-old female patient presented with headaches and sensory disturbances in the right upper limb for 6 weeks. She had been treated for rectal cancer and had a family history of LS. MRI revealed two ring-enhancing lesions in the left precentral gyrus. She underwent subtotal resection, leading to a pathological diagnosis of isocitrate dehydrogenase wild-type glioblastoma. She received daily administration of (temozolomide, 75 mg/m 2 ) and concurrent radiotherapy (60 Gy) postoperatively. However, the tumor recurred 1 year after the initial treatment. A molecular genetic study showed high microsatellite instability (MSI), and she was treated with pembrolizumab therapy. Disease progression occurred despite six cycles of pembrolizumab therapy and radiotherapy at the dose of 40 Gy. She died due to glioblastoma progression 19 months after the initial treatment. The present case demonstrates that some LS-associated glioblastomas may be resistant to ICI despite high MSI, possibly because of intratumor heterogeneity related to MMR deficiency.

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