José Juan González Sánchez

Background: Preservation of language function is a critical objective during awake craniotomy for gliomas involving language-eloquent regions. However, intraoperative language mapping relies predominantly on spoken output, which can be transiently disrupted by cortical stimulation during functional testing. Under these conditions, the behaviour of alternative communication systems remains largely unexplored. Objective: To investigate whether recently acquired, task-specific signed responses remain executable during stimulation-induced speech arrest in patients undergoing awake craniotomy. Methods: We conducted a prospective single-centre pilot study including seven adult patients with gliomas in language-eloquent regions of the dominant hemisphere undergoing awake craniotomy. Participants completed a structured 15-day preoperative Catalan Sign Language (LSC, Llengua de Signes Catalana) training programme. Acquisition was assessed through predefined comprehension and production assessments. Patients performed both spoken and signed language tasks under direct electrical stimulation during intraoperative cortical mapping. The primary outcome was the ability to perform task-specific signed responses during stimulation-induced speech arrest. Results: The seven analysed patients completed the training programme and achieved predefined performance thresholds. Cortical stimulation induced speech arrest in all cases. During these episodes, patients maintained accurate and clinically interpretable signed responses across all tasks. No intraoperative seizures or protocol-related adverse events were observed. Conclusion: In this pilot study, patients were able to perform task-specific signed responses despite stimulation-induced speech arrest. These findings indicate that transient disruption of spoken output did not prevent the execution of recently acquired signed responses under the tested intraoperative conditions. Given the exploratory design and task-specific nature of the training, these findings should not be interpreted as evidence of postoperative communicative efficacy or as support for changes in surgical decision-making. Further studies are required to determine whether this observation has any broader clinical relevance.

Background: Extracranial metastasis (EM) from glioblastoma (GB), IDH-wildtype (WHO CNS 2021 grade 4) is rare and often under-recognized, yet it has immediate implications for staging and management. We report a case series integrating advanced neuroimaging, whole-body imaging, and pathology/biomarkers to characterize imaging–pathology correlates of EM and highlight practical clinical triggers that should prompt systemic evaluation. Case presentation: We report three patients with adult-type, IDH-wildtype GB who developed EM confirmed by cytology/histology and/or concordant multimodality imaging. Brain MRI (1.5T/3T) demonstrated aggressive primary tumors with qualitative elevation of DSC-perfusion and frequent tumor–surface contact (dural, ependymal/leptomeningeal contact). Intratumoral susceptibility signal reached grade 3 where assessed. All patients underwent surgical resection followed by temozolomide-based chemoradiation; two received fotemustine and bevacizumab, and one underwent re-irradiation. EM presented with clinical triggers including severe axial/back pain, palpable cervical masses, and/or cytopenias. Initial EM sites were bone marrow/vertebrae (n = 1) and cervical lymph nodes (n = 2); staging revealed additional osseous disease in both nodal cases and a small pulmonary nodule in one. Nodal and osseous lesions were FDG-avid on 18F-FDG PET/CT. OLIG2-positive cytology confirmed cervical nodal metastases, and bone marrow aspiration with GFAP/OLIG2 positivity confirmed medullary infiltration. All tumors shared a molecular profile of TERT-promoter mutation, ATRX wild-type, TP53 mutation, and MGMT-promoter methylation. Despite attempts at second- and third-line therapies, disease progression was rapid, and all patients succumbed within 8–16 months of diagnosis. Discussion: This series underscores that EM can occur despite MGMT-promoter methylation and supports the concept of heterogeneous metastatic phenotypes in GB. Our cases reinforce that new axial/back pain or hematologic abnormalities may signal osseous or marrow involvement, and necrotic cervical lymphadenopathy in GB patients warrants dedicated imaging and tissue confirmation with glial markers. Integrating brain MRI features (high perfusion, surface contact, susceptibility burden) with FDG-PET/CT and targeted cytology/pathology can expedite diagnosis and inform multidisciplinary care. Conclusions: EM can arise despite MGMT-promoter methylation in IDH-wildtype GBM. Imaging red flags (high perfusion, surface contact, necrotic/FDG-avid cervical nodes) and clinical cues (axial pain, cytopenias, neck masses) should prompt early systemic staging (CT/PET-CT) and targeted tissue confirmation to advance management.

Glioblastoma (GB) is one of the most aggressive brain tumors, characterized by high infiltrative capacity that enables tumor cells to invade healthy brain tissue and evade complete surgical resection. This invasiveness contributes to resistance against conventional therapies and a high recurrence rate. Strategies capable of eliminating residual tumor cells are urgently needed. Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA), an FDA- and EMA-approved compound, induces selective accumulation of the photosensitizer protoporphyrin IX (PpIX) in metabolically active tumor cells, enabling targeted cytotoxicity through light activation. A major limitation to its clinical application is the unclear variation in the cytotoxic effect of PDT according to individual tumoral differences. In this study, we propose and validate an in vivo model of patient-derived GB initiating cells (GICs) and brain organoids to test the effects of PDT. First, patient-derived GICs were molecularly characterized by flow cytometry and copy number variation profiling using OncoScan CNV Assays, then co-cultured with human brain organoids to generate a hybrid model recapitulating key aspects of the tumor microenvironment. 5-ALA photodynamic therapy (PDT) efficacy was assessed in vitro by GFP-based viability measurements, LDH release assays, and TUNEL staining. Then, a murine model was generated to study PDT in vivo, based on a heterotopic (renal subcapsular engraftment) xenograft of the GICs-human brain organoid co-culture. PDT was tested in the model; in each subject, one kidney tumoral engraftment was treated and the contralateral served as a control. Immunofluorescence analysis was used to study the cell composition of the brain organoid-tumoral engraftment after PDT, and the effects on non-GIC cells. The antitumoral effect was determined by the degree of cell death analysis with the TUNEL technique. The GICs-brain organoid co-culture resulted in tumoral growth and infiltration both in vitro and in vivo. The pattern of growth and infiltration varied according to the tumoral genetic profile. 5-ALA PDT resulted in a reduction in the number of GICs and an increase in apoptotic cells in all four lines tested in vitro. A correlation was found between the induced phototoxicity in vivo with the molecular typification of GICs cell lines in vitro. There were no changes in the number or distribution of neuronal cells after the application of PDT, while a reduction in active astrocytes was observed. 5-ALA PDT could be effective in eradicating GICs with a heterogeneous molecular profile. The hybrid human-murine model presented here could be useful in investigating adjuvant therapies in GB, under the concept of personalized medicine.

Objective: This retrospective study aimed to assess the efficacy, safety, and feasibility of the DTRAX system for posterior cervical facet fusion in cervical degenerative pathology.Methods: A retrospective analysis of 50 cases involving DTRAX for posterior cervical facet fusion between January 2017 and January 2022. Patient selection criteria, surgical techniques, outcome measures, and data analysis methods were defined.Results: Among the 50 patients included in this study, 21 were women (42%) and 29 were men (58%). Fusion levels varied, with 36 patients undergoing fusion at a single level (72%), 12 at 2 levels (24%), and 2 at 3 levels (4%), totalling 132 implants. The average age was 44.26 years; most patients presented with neck pain, and 23 also reported arm pain (46%). Discharge within 24 hours was common. Pseudoarthrosis was the leading indication (32%), followed by foraminal stenosis (28%) and failed prosthetic implants (24%). Postoperatively, significant reductions in neck and radicular pain were observed, with visual analogue scale scores decreasing steadily over 12 months (p<0.001). Functional improvements, measured by Neck Disability Index scores, were sustained, with a slight increase at 6 and 12 months (p<0.001). The fusion rates at 6 and 12 months were 88% and 96%, respectively. Complications were infrequent, including transient paraesthesia (2%), anterior revision surgery for foraminal stenosis (2%), and suboptimal implant positioning (4%).Conclusion: Favourable clinical and functional outcomes, high fusion rates, and relatively low complication rates were observed with the DTRAX system. Further studies are needed for validation and long-term assessment of efficacy and safety.

Purpose: Glioblastoma often recurs after treatment. Bevacizumab increases progression-free survival in some patients with recurrent glioblastoma. Identifying pretreatment predictors of survival can help clinical decision making. Magnetic resonance texture analysis (MRTA) quantifies macroscopic tissue heterogeneity indirectly linked to microscopic tissue properties. We investigated the usefulness of MRTA in predicting survival in patients with recurrent glioblastoma treated with bevacizumab. Methods: We evaluated retrospective longitudinal data from 33 patients (20 men; mean age 56 ± 13 years) who received bevacizumab on the first recurrence of glioblastoma. Volumes of contrast-enhancing lesions segmented on postcontrast T1-weighted sequences were co-registered on apparent diffusion coefficient maps to extract 107 radiomic features. To assess the performance of textural parameters in predicting progression-free survival and overall survival, we used receiver operating characteristic curves, univariate and multivariate regression analysis, and Kaplan–Meier plots. Results: Longer progression-free survival (>6 months) and overall survival (>1 year) were associated with lower values of major axis length (MAL), a lower maximum 2D diameter row (m2Ddr), and higher skewness values. Longer progression-free survival was also associated with higher kurtosis, and longer overall survival with higher elongation values. The model combining MAL, m2Ddr, and skewness best predicted progression-free survival at 6 months (AUC 0.886, 100% sensitivity, 77.8% specificity, 50% PPV, 100% NPV), and the model combining m2Ddr, elongation, and skewness best predicted overall survival (AUC 0.895, 83.3% sensitivity, 85.2% specificity, 55.6% PPV, 95.8% NPV). Conclusions: Our preliminary analyses suggest that in patients with recurrent glioblastoma pretreatment, MRTA helps to predict survival after bevacizumab treatment.

Background: The high recurrence of glioblastoma (GB) that occurs adjacent to the resection cavity within two years of diagnosis urges an improvement of therapies oriented to GB local control. Photodynamic therapy (PDT) has been proposed to cleanse infiltrating tumor cells from parenchyma to ameliorate short long-term progression-free survival. We examined 5-aminolevulinic acid (5-ALA)-mediated PDT effects as therapeutical treatment and determined optimal conditions for PDT efficacy without causing phototoxic injury to the normal brain tissue. Methods: We used a platform of Glioma Initiation Cells (GICs) infiltrating cerebral organoids with two different glioblastoma cells, GIC7 and PG88. We measured GICs-5-ALA uptake and PDT/5-ALA activity in dose-response curves and the efficacy of the treatment by measuring proliferative activity and apoptosis. Results: 5-ALA (50 and 100 µg/mL) was applied, and the release of protoporphyrin IX (PpIX) fluorescence measures demonstrated that the emission of PpIX increases progressively until its stabilization at 24 h. Moreover, decreased proliferation and increased apoptosis corroborated the effect of 5-ALA/PDT on cancer cells without altering normal cells. Conclusions: We provide evidence about the effectiveness of PDT to treat high proliferative GB cells in a complex in vitro system, which combines normal and cancer cells and is a useful tool to standardize new strategic therapies.

Supplementary Figure from A Novel EGFRvIII T-Cell Bispecific Antibody for the Treatment of Glioblastoma

Supplementary Figure from A Novel EGFRvIII T-Cell Bispecific Antibody for the Treatment of Glioblastoma