CNS Oncology最新文献

This case report characterizes the molecular pathology of two synchronous IDH mutant gliomas in a 28-year-old female patient. The patient exhibited symptoms of dizziness, retro-orbital pain, headache, and numbness with paresthesia in her right arm. MRI imaging revealed two distinct non-enhancing T2/FLAIR hyperintense lesions in the left frontal and parietal lobes. Histopathologic and molecular analyses, including whole exome sequencing, were performed on the resected specimens from each location. The left parietal tumor was diagnosed as a grade 4 astrocytoma with an IDH1 R132H mutation, while the left frontal tumor was classified as a grade 2 oligodendroglioma with an IDH1 R132S mutation. Given the distinct molecular profiles of both synchronous tumors, treatment consideration was given to each individual primary tumor.

Diffuse pediatric-type high-grade glioma (pHGG), RTK1 subtype, is an uncommon aggressive tumor affecting both children and adults. We describe the case of a 66-year-old woman who presented with a left frontal lobe mass. Following surgical resection, the patient developed herpes simplex virus 2 meningoencephalitis, resulting in death. Histological examination revealed a high-grade glioma demonstrating nuclear pleomorphism, high mitotic activity, vascular proliferation and necrosis. The tumor also exhibited oligodendroglial-like features, nuclear clusters and small true rosette-like structures. Genetic analysis identified partial arm 1p loss and 19q loss, PDGFRA, MYCN and MDM4 amplification, an ATRX mutation and a novel SYN2::PPARG fusion. Homozygous CDKN2A/B deletion was also present. Genomic DNA methylation profiling matched diffuse pediatric-type high-grade glioma, RTK1 subtype, subclass C. This case underscores the importance of utilizing advanced molecular and genomic techniques for accurately diagnosing glial tumors. Further study of the SYN2::PPARG fusion in gliomas could potentially offer insights into its role in glioma biology and possibly help elucidate therapeutic strategies for tumors with PPARG fusions.

Glioblastoma (GBM) is the most common malignant primary brain tumor, characterized by a high recurrence rate despite aggressive therapy. We present a case of a 32-year-old male with a recurrent WHO Grade IV IDH1-mutant astrocytoma after undergoing standard Stupp protocol chemoradiation and tumor-treating field therapy. Repeat surgery was performed where in vitro analysis of recurrent GBM cells revealed atypical behavior, rapid adhesion within minutes of plating, and the formation of radial glial-like cells (RGCs) with 3D aggregated cells, phenotypes absent in the primary tumor. These brain lipid-binding protein positive RGCs exhibited elongated processes that facilitated cancer cell migration, potentially contributing to tumor invasiveness. Extensive treatment between the primary and recurrent tumors may have induced this phenotypic shift, highlighting therapy-induced plasticity as a key factor in recurrence. The emergence of RGCs in recurrent GBM underscores the need for targeted therapies addressing tumor adaptability to improve treatment outcomes.

Aims: We aimed to investigate a potential association between hypofractionated radiotherapy (HFRT) vs. conventional radiotherapy (CRT) and development of pseudoprogression in patients over the age of 65 treated for glioblastoma (GBM).

Materials & methods: Seventy-nine patients with glioblastoma (29 who received HFRT and 50 who received CRT) were included in this retrospective cohort study from a single institution. Demographic, clinical, and radiation information, including development of pseudoprogression and standard prognostic factors like Karnofsky Performance Status (KPS) and extent of surgical resection, were collected.

Results: Radiation regimen alone was not associated with development of pseudoprogression. Patients who had lower KPS at the time of diagnosis and received HFRT had lower rates of pseudoprogression. There was no association between radiation regimen, pseudoprogression, and any other clinical factors.

Conclusion: Older patients with glioblastoma who receive HFRT are not more likely to develop pseudoprogression than those who receive CRT. Patients with lower functional status receiving HFRT may be less likely to mount an inflammatory response leading to pseudoprogression. Prospective investigation is warranted to validate these results and evaluate other factors leading to treatment complications in older patients with glioblastoma in order to optimize outcomes and minimize toxicity.

Whether to surgically resect a margin of grossly normal appearing brain around anatomically amenable diffuse gliomas (i.e., perform a supratotal, supramarginal, or supramaximal resection) has been controversial. Over the past 5-10 years, however, evidence published by multiple independent groups has established a substantial survival benefit to this approach, moving the field towards a consensus that supramarginal resections should be offered when possible. However, many practitioners remain hesitant to offer supratotal resections due to concerns for variable neuropsychological outcomes and a mindset of "first, do no harm." Unfortunately, and perhaps counterintuitively, available data also suggest that opting for more conservative surgical approaches when more aggressive resections are possible may result in both suboptimal long-term functional and survival outcomes. To explore this complex and actively evolving issue, here I review evidence surrounding the multidimensional clinical impacts of supramarginal resections across all diffuse glioma subtypes. I then evaluate what is known about anatomical-functional relationships subserving cognition, behavior, and mood regulation, and I examine ethical considerations that arise when counseling patients at the difficult time of diagnosis. I then conclude with a set of case examples that demonstrate how the principles explored in this review can be applied in real-world situations to optimize, individualize, and humanize oncological and functional outcomes.

Cerebral lesions are rare in hairy cell leukemia (HCL), and its incidence remains to be determined. Identifying the cause can be challenging. In this report, we present a case of brain lesions occurring several years after diagnosis. A 76-year-old male patient presented to the Emergency Department with confusion. He had been diagnosed with HCL in 1999 and had received five lines of treatment. Cerebral imaging revealed multiple nodular lesions, with edema and a hemorrhagic appearance. Cerebrospinal fluid tests were negative. The tumor origin was retained due to concomitant relapse (blood, lymph nodes). Despite the partial efficacy of rituximab-cladribine treatment, the patient died of Candida pneumonia. A review of the literature (PubMed, CrossRef, Google Scholar) identified seventeen cases between 1966 and 2024, with a median age of 59 years (33-80). Cladribine, with or without rituximab, was the most widely prescribed treatment regimen with a complete response rate of 57%. Four (23.5%) patients died (two from infection, one from gastrointestinal bleeding and one from an unknown cause). These atypical presentations suggest that brain imaging and advanced biological investigations should be performed to guide management.

A 7-year-old female with recurrent midline pilocytic astrocytoma harboring a rare STRN3::NTRK2 fusion achieved sustained near-complete radiographic and clinical response to larotrectinib, a selective TRK inhibitor. Initial subtotal resection of the midbrain/thalamic tumor was followed by progression, prompting molecular profiling that identified the STRN3::NTRK2 fusion. Larotrectinib therapy initiated at recurrence resulted in a rapid reduction by 3 months, resolution of pontine extension by 6 months, and near-complete resolution by 15 months. This case highlights the potential of molecular diagnostics in pediatric neuro-oncology, particularly for BRAF-negative midline gliomas where NTRK fusions are rare but actionable. The durable response supports prioritizing larotrectinib over conventional chemotherapy in unresectable/progressive NTRK-driven gliomas. Routine fusion screening in BRAF-negative cases should be considered to identify candidates for targeted therapy. This report expands the known spectrum of NTRK2 partners in pilocytic astrocytoma and reinforces the use of TRK inhibitors as a treatment for molecularly defined subsets of pediatric glioma.

Aim: Atypical teratoid rhabdoid tumor (ATRT) is a rare and highly aggressive primary CNS neoplasm, predominantly observed in children. The use of autologous stem cell transplantation (ASCT) in pediatric ATRT has shown promise; however, its utility in adult ATRT remains unclear. Patients & methods: This study presents the case of an adult patient with ATRT who is in remission after ASCT and reviews the literature on ASCT in adults with ATRT. Four cases of ATRT in adults who underwent ASCT were identified, with pertinent data summarized. Results: All five patients survived longer than the historical average survival rate, four of whom had no clinical or radiographic evidence of disease at the final follow-up. Conclusion: Based on limited data, there may be a role for ASCT in the treatment of adults with ATRT.

Aim: Brain metastases (BM) are a common site of disease progression and treatment failure in non-small-cell lung cancer (NSCLC) and can be identified in up to 30-50% of patients. Although they are common, there is no standardized screening protocol for development of BM in NSCLC. Multiple clinical variables predict increased BM occurrence, and, when present, should be used to initiate screening MRI.Materials & methods: We performed a single center retrospective review of NSCLC patients, examining BM development and overall survival. Available clinical, radiographic and molecular data were reviewed for association with BM and overall survival. A predictive model for BM development was created for multivariate analysis.Results: Risk factors for new BM development in NSCLC included younger age, larger primary lung tumor, Karnofsky performance score (KPS) <70, pre-existing liver or bone metastases, large cell histology and family history of cancer. Factors associated with decreased OS were larger primary lung tumor, extracranial metastases at time of diagnosis, large cell histology and poorly-differentiated carcinoma histology.Conclusion: There are multiple high risk features for developing BM in NSCLC. Each of these factors should routinely be investigated, and presence should prompt brain MRI to allow earlier diagnosis and treatment of BM.

Aim: A radio-pathomic machine learning (ML) model has been developed to estimate tumor cell density, cytoplasm density (Cyt) and extracellular fluid density (ECF) from multimodal MR images and autopsy pathology. In this multicenter study, we implemented this model to test its ability to predict survival in patients with recurrent glioblastoma (rGBM) treated with chemotherapy.Methods: Pre- and post-contrast T₁-weighted, FLAIR and ADC images were used to generate radio-pathomic maps for 51 patients with longitudinal pre- and post-treatment scans. Univariate and multivariate Cox regression analyses were used to test the influence of contrast-enhancing tumor volume, total cellularity, mean Cyt and mean ECF at baseline, immediately post-treatment and the pre- and post-treatment rate of change in volume and cellularity on overall survival (OS).Results: Smaller Cyt and larger ECF after treatment were significant predictors of OS, independent of tumor volume and other clinical prognostic factors (HR = 3.23 × 10^-6, p < 0.001 and HR = 2.39 × 10⁵, p < 0.001, respectively). Both post-treatment volumetric growth rate and the rate of change in cellularity were significantly correlated with OS (HR = 1.17, p = 0.003 and HR = 1.14, p = 0.01, respectively).Conclusion: Changes in histological characteristics estimated from a radio-pathomic ML model are a promising tool for evaluating treatment response and predicting outcome in rGBM.