Brain tumor research and treatment最新文献

Mutations in tumor protein p53 (TP53) and ataxia telangiectasia mutated (ATM) genes are frequently observed across various solid and hematologic malignancies and are associated with genomic instability, treatment resistance, and poor clinical outcomes. These alterations compromise the G1/S cell cycle checkpoint and increase cellular dependence on compensatory DNA damage response (DDR) pathways, including the ataxia telangiectasia and Rad3-related protein kinase (ATR)-checkpoint kinase 1 (CHK1)-WEE1 G2 checkpoint kinase (WEE1) axis. This has led to the development of DDR-targeted therapies that exploit synthetic lethality in tumors with TP53 or ATM dysfunction. Inhibitors targeting ATM, ATR, CHK1, and WEE1 have all shown encouraging activity in early-phase clinical trials, particularly in biomarker-enriched subgroups. Poly(ADP-ribose) polymerase (PARP) inhibitors-originally approved for BRCA1/2-mutated breast cancers-are now being evaluated in TP53- or ATM-deficient tumors, often in combination with other DDR-targeting agents to enhance efficacy. Clinical trials increasingly support the efficacy of DDR inhibitors in biomarker-defined DDR-deficient tumors, specifically beyond BRCA mutations. This review summarizes current understanding of DDR-targeted strategies in TP53- and ATM-mutant cancers, with an emphasis on relevant clinical data and ongoing trials. Expanding the clinical use of DDR inhibitors based on molecular profiles may provide new therapeutic options for genomically unstable tumors across adult and pediatric populations.

Tentorial meningiomas are rare skull base tumors that may cause pulsatile tinnitus when they compress adjacent dural venous sinuses, particularly the transverse sinus. Gamma Knife radiosurgery (GKRS) is an established modality for tumor control, but its role in relieving tinnitus has been infrequently reported. We report a 61-year-old woman with right-sided pulsatile tinnitus caused by a 2-cm tentorial meningioma compressing the right transverse sinus. She underwent GKRS with 13 Gy prescribed to the 50% isodose line, concentrating the 80% isodose volume along the sinus-abutting tumor margin. Her tinnitus resolved completely within one week and remained absent during follow-up. At seven months post-treatment, MRI showed a slight volume decrease (2.81 cm³ to 2.66 cm³), most notable along the sinus interface. The rapid symptom relief despite minimal volumetric change suggests that focused irradiation of sinus-adjacent tumor may alleviate tinnitus by modulating local venous hemodynamics. This case underscores the potential of GKRS to offer early symptomatic improvement in select patients with sinus-involving tentorial meningiomas.

Glioblastoma (GBM) remains one of the most lethal and treatment-resistant malignancies, characterized by high recurrence rates following standard-of-care therapy. While previous longitudinal studies employing whole-exome and RNA sequencing have revealed patient-specific clonal evolution, they have not identified conserved biological programs that drive recurrence or therapeutic resistance. A recent study published in Cancer Cell presents the first integrated proteogenomic analysis of matched primary and recurrent GBMs. This integrative approach reveals a striking phenotypic transition in recurrent tumors, characterized by neuronal reprogramming supported by coordinated transcriptional, proteomic, and phosphoproteomic evidence. In this review, we contextualize these findings within the broader landscape of GBM evolution, emphasizing the mechanistic contributions of WNT/planar cell polarity (PCP) signaling and BRAF kinase activation in facilitating a neuronal-like state that enhances tumor plasticity, invasion, and treatment resistance. We further discuss how these profound insights align with preclinical models of tumor-neuron synaptic crosstalk, and propose that proteogenomics offers a powerful lens through which to uncover clinically actionable vulnerabilities. By redefining the functional landscape of recurrent GBM, the current study establishes a new framework for biomarker discovery and the rational design of targeted therapies informed by tumor evolution and neuronal niche adaptation.

Background: The discovery of histone alterations has changed fundamental understanding of pediatric-type diffuse high-grade gliomas (HGG). The glycine-to-arginine (or valine) substitution at position 34 of histone H3.3 (H3 G34) is found exclusively in diffuse hemispheric glioma (DHG). This report summarizes clinical outcomes of a contemporary mono-institutional cohort of H3 G34-mutant DHG treated in low- and middle-income country setting.

Methods: Patients with biopsy-proven, molecularly-confirmed H3 G34-mutant DHG registered at a tertiary-care comprehensive cancer center between 2015 and 2023 were identified from a neuro-oncology database. Clinico-demographic characteristics, histo-molecular features, treatment details, and outcomes were retrospectively extracted from electronic medical records. Progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan-Meier methods and expressed as point estimates with 95% confidence intervals (CI).

Results: Twenty-five patients with H3 G34-mutant DHG, with a median age of 19 years (interquartile range [IQR] of 14-24 years), constituted the study cohort. Sixteen patients received postoperative radiotherapy (RT) while 13 patients also received temozolomide chemotherapy. At a median follow-up of 14 months, the 1-year Kaplan-Meier estimates of PFS and OS were 47% (95% CI: 30%-75%) and 63% (95% CI: 45%-87%) yielding median PFS and OS of 12 months (IQR: 6-22 months) and 15 months (IQR: 9-31 months), respectively. Older age at diagnosis (≥18 years) and administration of RT emerged as significant prognostic factors for survival.

Conclusion: H3 G34-mutant DHG is a rare, aggressive pediatric-type HGG with notable differences from adult counterparts. Recent biological insights implicating key signaling pathways provide unique opportunities to target therapeutic vulnerabilities in this enigmatic disease with universally poor prognosis.

We report a case of complete remission in anaplastic oligodendroglioma following adoptive cell therapy (ACT) with autologous Wilms tumor 1 (WT-1)-specific CD8+ T cells. A 40-year-old woman referred to our hospital for adjuvant chemotherapy after recurrent anaplastic oligodendroglioma initially presented with a left frontal tumor, diagnosed through seizure onset, and subtotal resection confirmed oligodendroglioma (WHO grade 2). Radiation therapy treated the residual tumor, achieving partial remission until recurrence 2.5 years later when malignant transformation to anaplastic oligodendroglioma (WHO grade 3) occurred following a second craniotomy. After three cycles of procarbazine, lomustine, and vincristine chemotherapy, the residual tumor stabilized for 3 years. However, follow-up MRI identified a new enhancing lesion, prompting a third craniotomy. Recurrent anaplastic oligodendroglioma was confirmed, and adjuvant proton beam therapy and temozolomide chemotherapy were initiated. Two years later, another enhancing lesion appeared on the adjacent medial frontal lobe. Following multidisciplinary review, we introduced WT-1-specific ACT. Although transient swelling was observed 1 month post-therapy, the tumor demonstrated a response within 3-9 months. Continued regression led to complete remission-confirmed via MRI at the 15-month follow-up and sustained for 4.7 years. The patient's peripheral blood monocyte profiles and immune-associated cytokine analysis indicated T-cell activation following WT-1 sensitization.

Background: This study analyzed the epidemiology and treatment outcomes of germ cell tumor patients at a single institution.

Methods: A retrospective analysis was conducted on intracranial germ cell tumor (iGCT) patients treated at a single tertiary hospital from 2004 to 2019. Patients were categorized based on treatment modality: Korean Society for Pediatric Neuro-Oncology (KSPNO) protocol or bleomycin, etoposide, and cisplatin with radiation therapy.

Results: Forty-nine iGCT patients treated with combined chemotherapy and radiotherapy were analyzed. The median age was 19 years (range: 6-40), with a median follow-up duration of 148.0 months (range: 10.5-265.5). Tumors were most common in the pineal gland (51.0%). Although no significant differences in outcomes were observed between treatment modalities, outcomes varied significantly by pathological type. The 10-year progression-free survival rates for germinoma and non-germinomatous germ cell tumors (NGGCTs) were 88.1% and 32.7%, respectively (p=0.003), while the 10-year overall survival rates were 92.9% and 67.5%, respectively (p<0.001). Fourteen patients experienced CTCAE (Common Terminology Criteria for Adverse Events) grade ≥3 adverse events, with one event-related death.

Conclusion: Pure germinoma demonstrated higher survival and lower recurrence rates compared to NGGCT. The KSPNO protocol appears to be an acceptable and safe treatment option for iGCT patients. Further multi-institutional studies with larger cohorts are warranted.

Radiation-induced cavernous malformations (RICMs) are rare but significant late complications of high-dose radiation therapy, particularly in young survivors of brain tumors. This report presents two cases of RICMs following aggressive multimodal treatment, including surgery, chemotherapy, and radiation therapy. Case 1 was a 22-year-old male patient with medulloblastoma treated with craniospinal irradiation, tumor bed boost, and tandem autologous peripheral blood stem cell transplantation. Approximately 8 years after treatment completion, routine follow-up imaging revealed a small focal hemorrhage in the right cerebellum, consistent with an RICM. The lesion was asymptomatic and managed conservatively with regular imaging, showing spontaneous resolution over time, with a significant size reduction noted 9 years post-treatment. Case 2 describes a 32-year-old male with an intracranial germinoma treated with whole-ventricular irradiation. Three years after treatment, the patient developed a symptomatic hemorrhagic RICM near a pre-existing developmental venous anomaly. Surgical resection and Gamma Knife Surgery stabilized the lesion; however, residual symptoms, including tremors and gait disturbances, persisted, affecting the patient's daily activities. These cases illustrate the diverse clinical courses of RICMs, ranging from spontaneous resolution to the necessity of surgical intervention, and emphasize the importance of long-term surveillance and tailored management strategies for late-onset complications.

Since the cortico-cortical evoked potential (CCEP) was first introduced in 2004, CCEP monitoring has been utilized in various types of brain surgery to achieve maximal safe resection (MSR). MSR is the primary goal in improving the prognosis of glioma; however, this is particularly challenging when the tumor is located around eloquent areas. Since the complexity of the language network system makes it more difficult to achieve MSR, language area mapping is essential when tumors are located around these areas. Awake surgery has been the gold standard for intraoperative language area mapping. However, awake craniotomy is not always feasible due to various clinical and patient-related factors. CCEP monitoring has emerged as a promising alternative for intraoperative language function assessment under general anesthesia to overcome the limitations of awake surgery. This review aims to summarize the current evidence on CCEP-guided surgery, focusing on its effectiveness in preserving language function.