Frequent Alzheimer's disease neuropathological change in patients with glioblastoma.

Background: The incidence of brain cancer and neurodegenerative diseases is increasing with a demographic shift towards aging populations. Biological parallels have been observed between glioblastoma and Alzheimer's disease (AD), which converge on accelerated brain aging. Here, we aimed to map the cooccurrence of AD neuropathological change (ADNC) in the tumor-adjacent cortex of patients with glioblastoma. Methods: Immunohistochemical screening of AD markers amyloid beta (Abeta), amyloid precursor protein (APP), and hyperphosphorylated tau (pTau) was conducted in 420 tumor samples of 205 patients. For each cortex area, we quantified ADNC, neurons, tumor cells, and microglia. Results: Fifty-two percent of patients (N = 106/205) showed ADNC (Abeta and pTau, Abeta or pTau) in the tumor-adjacent cortex, with histological patterns widely consistent with AD. ADNC was positively correlated with patient age and varied spatially according to Thal phases and Braak stages. It decreased with increasing tumor cell infiltration (P < .0001) and was independent of frequent expression of APP in neuronal cell bodies (N = 182/205) and in tumor necrosis-related axonal spheroids (N = 195/205; P = .46). Microglia response was most present in tumor cell infiltration plus ADNC, being further modulated by patient age and sex. ADNC did not impact patient survival in the present cohort. Conclusions: Our findings highlight the frequent presence of ADNC in the glioblastoma vicinity, which was linked to patient age and tumor location. The cooccurrence of AD and glioblastoma seemed stochastic without clear spatial relation. ADNC did not impact patient survival in our cohort.

Glioblastoma in the real-world setting: patterns of care and outcome in the Austrian population.

PURPOSE: We present results of a retrospective population-based investigation of patterns of care and outcome of glioblastoma patients in Austria. PATIENTS AND METHODS: In this nation-wide cooperative project, all Austrian glioblastoma patients newly diagnosed between 2014 and 2018 and registered in the ABTR-SANOnet database were included. Histological typing used criteria of the WHO classification of CNS tumors, 4th edition 2016. Patterns of care were assessed, and all patients were followed until the end of 2019. RESULTS: 1,420 adult glioblastoma cases were identified. 813 (57.3%) patients were male and 607 (42.7%) female. Median age at diagnosis was 64 years (range: 18-88). Median overall survival (OS) was 11.6 months in the total cohort and 10.9 months in patients with proven IDH-wildtype. Median OS in the patient group ≤ 65 years receiving postoperative standard of care therapy was 16.1 months. In the patient group > 65 years with postoperative therapy, median OS was 11.2 months. Follow-up ≥ 5 years identified 13/264 (4.9%) long-term survivors. Brain tumor surgery frequently was assisted by 5-aminolevulinic acid (5-ALA) fluorescence (up to 55%). Postoperative treatment was initiated around one month after surgery (median: 31 days) following standardized protocols in 1,041/1,420 (73.3%) cases. In 830 patients (58.5%), concomitant radiochemotherapy was started according to the established standard of care. Treatment in case of progressive disease was considerably variable. 170/1,420 patients (12.0%) underwent a second surgical procedure, 467 (33.0%) received systemic treatment after progression, and 173 (12.2%) were re-irradiated. CONCLUSION: Our data illustrate and confirm nation-wide translation of effective standard of care to Austrian glioblastoma patients in the recent past. In the case of progressive disease, highly variable therapeutic approaches were used, most frequently accompanied by anti-angiogenic therapy. Long-term survival was observed in a minor proportion of mostly younger patients who typically had gross total tumor resection, a favorable postoperative ECOG score, and standard of care therapy.

Longitudinal investigation of a xenograft tumor zebrafish model using polarization-sensitive optical coherence tomography.

Breast cancer is a leading cause of death in female patients worldwide. Further research is needed to get a deeper insight into the mechanisms involved in the development of this devastating disease and to find new therapy strategies. The zebrafish is an established animal model, especially in the field of oncology, which has shown to be a promising candidate for pre-clinical research and precision-based medicine. To investigate cancer growth in vivo in zebrafish, one approach is to explore xenograft tumor models. In this article, we present the investigation of a juvenile xenograft zebrafish model using a Jones matrix optical coherence tomography (JM-OCT) prototype. Immunosuppressed wild-type fish at 1-month post-fertilization were injected with human breast cancer cells and control animals with phosphate buffered saline in the tail musculature. In a longitudinal study, the scatter, polarization, and vasculature changes over time were investigated and quantified in control versus tumor injected animals. A significant decrease in birefringence and an increase in scattering signal was detected in tumor injected zebrafish in comparison to the control once. This work shows the potential of JM-OCT as a non-invasive, label-free, three-dimensional, high-resolution, and tissue-specific imaging tool in pre-clinical cancer research based on juvenile zebrafish models.