The latest medical research on Neuro Oncology

The objective of this prospective, single-centre case series was to investigate feasibility, clinical outcomes, and neural correlates of non-invasive Neuromodulation-Induced Cortical Prehabilitation (NICP) before brain tumor surgery. Previous studies have shown that gross total resection is paramount to increase life expectancy but is counterbalanced by the need of preserving critical functional areas. NICP aims at expanding functional margins for extensive tumor resection without functional sequelae. Invasive NICP (intracranial neuromodulation) was effective but characterized by elevated costs and high rate of adverse events. Non-invasive NICP (transcranial neuromodulation) may represent a more feasible alternative. Nonetheless, up to this point, non-invasive NICP has been examined in only two case reports, yielding inconclusive findings.

Treatment sessions consisted of non-invasive neuromodulation, to transiently deactivate critical areas adjacent to the lesion, coupled with intensive functional training, to activate alternative nodes within the same functional network. Patients were evaluated pre-NICP, post-NICP, and at follow-up post-surgery.

Ten patients performed the intervention. Feasibility criteria were met (retention, adherence, safety, and patient's satisfaction). Clinical outcomes showed overall stability and improvements in motor and executive function from pre- to post-NICP, and at follow-up. Relevant plasticity changes (increase in the distance between tumor and critical area) were observed when the neuromodulation target was guided by functional neuroimaging data.

This is the first case series demonstrating feasibility of non-invasive NICP. Neural correlates indicate that neuroimaging-guided target selection may represent a valid strategy to leverage neuroplastic changes before neurosurgery. Further investigations are needed to confirm such preliminary findings.

AQP4-antibody seropositive (AQP4-Ab+) neuromyelitis optica spectrum disorder (NMOSD) may cause reduced work capability due to disability. Here, we evaluated the socioeconomic status of patients with AQP4-Ab+NMOSD in off-label therapy era compared with the general population.

A longitudinal nationwide population-based study including all Danish patients with AQP4-Ab+NMOSD and matched controls from the general population. The cohort was linked to other Danish nationwide population-based databases. The study period was from 1992 to 2021. The main outcomes were loss of income from salary, limited work capability, disability pension and civil status. The longitudinal risks of outcomes were presented in cumulative incidence curves. Fisher's exact test, χ2 test or Wilcoxon test were applied for comparison.

We included 65 patients with a median follow-up of 8.6 years. Annual income declined significantly after disease onset (index year) compared with the general population. One year after the index year, the median annual income in 2015-indexed Euro for patients averaged 13 285 (IQR: 139 to 36 336) versus controls 33 035 (IQR: 6870 to 45 978); p=0.04. Five years postindex year, the average income for patients further dropped to 276 (IQR: 0 to 23 691) versus controls 22 141 (IQR: 0 to 42 986); p=0.03. At the end of follow-up, significantly higher proportion of patients were either in 'flexjob' (36.9% patients vs 14% controls, p<0.00) or receiving disability pension (16.9% patients vs 4.3% controls, p<0.00).

The socioeconomic status of patients with AQP4-Ab+NMOSD deteriorates rapidly following disease onset. A substantial proportion of these patients lose their work capacity leading to increased financial burden on both their families and society.

PreOperative radiotherapy (RT) is commonly used in the treatment of brain metastasis and different cancer types but has never been used in primary glioblastoma (GBM). Here, we aim to establish, describe, and validate the use of PreOperative RT for the treatment of GBM in a preclinical model.

Rat brains were locally irradiated with 30-Gy, hypofractionated in five doses 2 weeks before or after the resection of intracranial GBM. Kaplan-Meier analysis determined survival. Hematoxylin-eosin staining was performed, and nuclei size and p21 senescence marker were measured in both resected and recurrent rodent tumors. Immunohistochemistry assessed microglia/macrophage markers, and RNAseq analyzed gene expression changes in recurrent tumors. Akoya Multiplex Staining on two human patients from our ongoing Phase I/IIa trial served as proof of principle.

PreOperative RT group median survival was significantly higher than PostOperative RT (p < 0.05). Radiation enlarged cytoplasm and nuclei in PreOperative RT resected tumors (p < 0.001) and induced senescence in PostOperative RT recurrent tumors (p < 0.05). Gene Set Enrichment Analysis (GSEA) suggested a more proliferative profile in PreOperative RT group. PreOperative RT showed lower macrophage/microglia recruitment in recurrent tumors (p < 0.01) compared to PostOperative RT. Akoya Multiplex results indicated TGF-ß accumulation in the cytoplasm of TAMs and CD4 + lymphocyte predominance in PostOperative group.

This is the first preclinical study showing feasibility and longer overall survival using neoadjuvant radiotherapy before GBM resection in a mammalian model. This suggests strong superiority for new clinical radiation strategies. Further studies and trials are required to confirm our results.