A 43-year-old woman presented with bilateral lower extremity weakness due to an intradural extramedullary spinal cord tumor. Surgery revealed Ewing sarcoma, a rare presentation known as primary intradural extramedullary Ewing sarcoma (PIEES). Despite initial treatment with radiation and chemotherapy, tumor recurrence occurred after 17 months. Further interventions included additional surgery, radiation, and chemotherapy. The disease progressed to leptomeningeal metastases along the spinal cord, prompting various treatments including targeted spinal radiation and systemic therapies. Brain metastases subsequently developed, necessitating whole-brain radiation and intrathecal chemotherapy. This case highlights the aggressive nature of PIEES, its potential for widespread leptomeningeal metastasis, and the challenges in its management, underscoring the need for multidisciplinary approaches in treating this rare and aggressive malignancy.

Background: Stereotactic radiotherapy (SRT) is a less invasive, widely accepted treatment for brainmetastases, particularly in patients with poor general condition. However, large cystic metastases can complicate radiotherapy because of their morphology. This study evaluated the efficacy and safety of continuous cyst drainage under natural pressure combined with fractionated SRT (f-SRT) for these lesions. Methods: We retrospectively reviewed patients treated at Yokohama Rosai Hospital betweenAugust 2022 and February 2024. Eligible patients had cystic brain metastases ≥10 cm³ and underwent cyst drainage under local or general anesthesia, followed by f-SRT (35 Gy in 5 fractions). Outcomes included Karnofsky Performance Status (KPS), tumor and cyst volumes, local control, and neurological symptoms. Results: Four patients (one male, three females; median age, 52 years) were analyzed. Primarycancers were lung (n=1), breast (n=1), breast and lung (n=1), and esophageal (n=1). After drainage, median KPS increased from 65 to 70, and neurological symptoms improved in three cases. Tumor volume decreased from 35.6 cm 3 to 12.4 cm 3 (65.5% reduction). No treatment-related complications or radiation-induced adverse events were observed. Conclusion Continuous cyst drainage under natural pressure combined with f-SRT appears safeand effective for large cystic metastases, enabling continuation of f-SRT in patients who are not suitable candidates for resection and providing a minimally invasive treatment option.

Tumor treating fields (TTFields) therapy at 200 kHz is FDA-approved for supratentorial glioblastoma.However, reports of TTFields in patients with infratentorial high-grade glioma (HGG) are rare. Two patients with infratentorial HGG received off-label 200 kHz TTFields. To reduce impaired neck range of motion, the electrode transducer arrays were “skeletonized” by cutting a portion of the adhesive material. The electrode arrays were applied with the neck in flexion to further promote range of neck motion. Patient 1, a 22-year-old man with high-grade diffuse pontine glioma with recurrences and prior treatments, tolerated TTFields combined with systemic treatment (initially with a bifunctional DNA alkylating agent; subsequently with temozolomide and bevacizumab) for 5 months with stable disease for 4 months. He experienced grade 1 rash (neck). Patient 2, a 58-year-old woman with diffuse glioma of the brainstem (H3K27M-mutated) with multiple recurrences and prior treatments, tolerated TTFields combined with systemic treatment (lomustine and bevacizumab). With the TTFields + systemic combination therapy, the patient was stable for 8 months with no TTFields-related side effects. We provide two initial post-marketing cases demonstrating that off-label use of 200 kHz TTFields in infratentorial HGG is safe and feasible. Prospective studies are necessary to validate the efficacy of this approach.

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.

Background: In the targeted therapy era, the indication for stereotactic radiosurgery (SRS) has ex-panded to include patients with multiple brain metastases (BMs). This study aimed to compare treatment outcomes in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients with 1–4 versus 5–10 BMs, all treated with tyrosine kinase inhibitors (TKIs) and upfront Gamma Knife radiosurgery. Methods: We retrospectively reviewed 74 consecutive EGFR-mutant NSCLC patients with 1–10synchronous BMs treated with first-line EGFR-TKIs and upfront Gamma Knife SRS at Vietnam National Cancer Hospital from 2021 to 2024. Patients were divided into 1–4 BMs (n=39) and 5–10 BMs (n=35) groups. Primary endpoints were intracranial progression-free survival (iPFS) and overall survival (OS). Results: Baseline characteristics were balanced between the two groups. Median iPFS wasnot reached in the 1–4 BMs group and 19 months in the 5–10 BMs group (hazard ratio [HR] 1.06, 95% confidence interval [CI] 0.95–1.17; p=0.31). Median OS was not reached in the 1–4 BMs group and was 23 months in the 5–10 BMs group (HR 1.03, 95% CI 0.91–1.16; p=0.41). Multivariate analysis revealed extracranial response (HR 4.30, p<0.01 for iPFS; HR 7.29, p<0.01 for OS) and presence of extracranial metastases (HR 3.20, p=0.01 for iPFS) as the only independent prognostic factors; number of BMs was not prognostic. Radionecrosis occurred in 6.8%, of which 2.7% were symptomatic. Conclusion In EGFR-mutant NSCLC patients receiving TKIs and upfront Gamma Knife radiosur-gery, the survival time in patients with 5–10 BMs was comparable to that with 1–4 BMs. The number of BMs should not be regarded as a contraindication for SRS in this subgroup.

Background: Posterior fossa group A (PFA) ependymoma is a lethal pediatric brain tumor drivenpredominantly by epigenetic dysregulation. Enhancer of Zeste Homologs Inhibitory Protein (EZHIP) is a defining oncogenic factor in PFA ependymoma that inhibits PRC2 activity, inducing a global loss of H3K27me3 and sustaining aberrant developmental transcriptional programs. Although the metabolic modulator, metformin, reduces EZHIP protein levels, the mechanisms governing EZHIP regulation remain undefined. Methods: We generated a stable HEK293T reporter cell expressing HA- and RFP-taggedEZHIP together with a GFP viability control, enabling quantitative and viability-normalized assessment of EZHIP abundance. In silico post-translational modification prediction was performed using PhosphoSitePlus and NetPhos 3.1 to identify candidate regulatory residues and upstream kinases. A focused panel of pathway targeting compounds was evaluated using fluorescence-based high-throughput screening, followed by secondary validation including cell counting, LC 50 (half-maximal lethal concentration) analysis, and Western blotting. Results: Computational analyses identified multiple high-confidence serine phosphorylationsites on EZHIP and implicated AMPK, MAPK, PKC, AKT, and CK2 signaling pathways. High-throughput screening revealed that activation of the AMPK axis robustly suppressed EZHIP protein levels.Secondary validation demonstrated that biguanides activating AMPK reduced EZHIP abundance independently of cytotoxicity and restored global H3K27me3 levels. In contrast, PKC activation increased EZHIP protein abundance. Conclusion Our study identifies EZHIP as a dynamically regulated oncoprotein controlled by post-translational signaling pathways. AMPK and PKC exert opposing effects on EZHIP stability, defining actionable regulatory mechanisms for therapeutic targeting in EZHIP-driven cancers.

Background: Access to advanced histomolecular diagnostic testing for central nervous system(CNS) tumors is limited in low and middle-income countries (LMICs), hindering adequate characterization and failure to reach a WHO CNS 2021 diagnosis. LMICs also lack access to targeted therapies, and even conventional chemotherapy and radiation therapies vary between LMICs and high-income countries. Consequently, whether histomolecular subclassification is clinically beneficial and if it provides prognostic information in an LMIC setting is not clear. Here, we address this question by presenting the first systematic prospective study of CNS glioma patients from Pakistan, examining differences in overall survival (OS) by histomolecular subtype. Methods: A total of 194 patients with CNS tumors were enrolled at a single tertiary-care centerin Karachi, Pakistan. Routine histochemical processing, immunohistochemistry, and molecular testing using fluorescence in situ hybridization analysis, limited targeted-panel next-generation sequencing, and polymerase chain reaction were performed to test for isocitrate dehydrogenase (IDH) 1 and 2, P53, ATRX, Ki-67, 1p/19q co-deletion, and MGMT promoter methylation. Results: The results revealed that IDH status was a significant independent prognostic factor,regardless of age (p=0.016), with a 1-year survival rate of 76% and median OS of 16.15 months in IDH-wildtype high-grade gliomas. Conversely, the 1-year survival rate was 95% for IDH-mutant gliomas. Significant survival differences were observed for ATRX status (retained vs. loss) in IDH-mutant gliomas (p=0.046), P53 mutations in IDH-wildtype high-grade gliomas (p=0.05), and 1p/19q co-deletion in grade 3 gliomas (log-rank p=0.023). Conclusion We provide empirical evidence supporting a role for histo-morphological and limitedmolecular testing in neuro-oncology practice in LMICs.

Background: Health-related quality of life (HR-QoL) is a critical consideration in glioma surgery,alongside improving patient survival. Current evidence highlights maximal surgical resection as a key independent prognostic factor for enhancing HR-QoL and survivability. This study aimed to compare the impact on HR-QoL and survival rates in glioma patients before and after surgery with varying degrees of tumor resection (<10%, 10%–90%, >90%) and residual tumor volumes (≤2 cm 3 , >2 cm 3 ). Methods: This single-institution prospective study analyzed 117 patients with newly diagnosedgliomas (2009–2015). HR-QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) (global quality of life status [GQLS], physical, emotional, role, cognitive, and social function, as well as insomnia and fatigue).We compared survival rates and HR-QoL outcomes based on extent of resection and residual tumor volume. Clinically meaningful thresholds and statistical significance were used to evaluate HR-QoL changes. Results: In grade 4 gliomas, resections >90% and residual tumor volumes ≤2 cm 3 significantlyimproved median survival compared to lesser resections. For HR-QoL, resections >90% led to clinically and statistically significant improvements in GQLS, emotional, role, and cognitive function, as well as insomnia. Residual volumes ≤2 cm 3 significantly enhanced emotional and role function, with statistical improvements in GQLS, cognitive function, social function, insomnia, and fatigue. Lower resection rates and higher residual volumes resulted in significant HR-QoL declines. When stratified by tumor grade, high- and low-grade gliomas showed clinically significant improvements in different HR-QoL domains. Conclusion Resections greater than 90% and residual volumes ≤2 cm 3 significantly improve HR-QoL and overall survival. Conversely, partial resections and larger residual tumor volumes are associated with worse HR-QoL outcomes.

Cerebral sparganosis is a rare parasitic infection caused by plerocercoid larvae of Spirometra species.Intracranial involvement is uncommon and may mimic other parasitic or neoplastic diseases. We report the case of a 64-year-old man who presented with dysarthria and dizziness, later diagnosed with cerebellar sparganosis. Retrosigmoid craniotomy was performed, and two intact spargana were removed with the surrounding capsule. Histopathology demonstrated granulomatous inflammation with eosinophilic infiltration and characteristic calcareous corpuscles within degenerated parasitic tissue fragments. Postoperatively, dysarthria and dizziness improved, and the patient was able to ambulate independently. Sparganosis has been continuously reported in Korea for nearly a century, though incidence has declined in recent decades. Parasite invasion into the central nervous system is thought to occur through the foramen magnum, with the brain parenchyma particularly vulnerable due to its soft tissue composition. In our case, prior cerebellar infarction may have provided a structural weakness that facilitated parasite invasion. Differentiation from neurocysticercosis is essential, as imaging findings and clinical implications differ. Surgical excision remains the standard treatment, although recent evidence indicates that long-term, high-dose praziquantel may be effective in selected cases. Cerebral sparganosis should be considered in patients with compatible clinical and radiologic features in endemic regions. Complete surgical removal offers definitive therapy, while high-dose praziquantel may serve as a noninvasive alternative for inoperable cases.

The National Comprehensive Cancer Network (NCCN) recommends a regimen of rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHOP) with methotrexate (MTX) given at ≥3 g/m² for stage IV diffuse large B-cell lymphoma with parenchymal involvement. Tumor lysis syndrome (TLS) may occur after initiation of treatment. MTX, though beneficial, may induce toxicity, especially in elderly patients with comorbidities. This paper discusses a case of 74-year-old female with secondary central nervous system lymphoma with multiple comorbidities and high risk for TLS given a modified schedule of R-CHOP and a lower dose of MTX at 2–2.5 g/m² with a good treatment response. This paper aims to contribute additional information on optimal treatment for this disease.