Background: Inevitable recurrence after radiochemotherapy is the major problem in the treatment of glioblastoma, the most prevalent type of adult brain malignancy. Glioblastomas are notorious for a high degree of intratumor heterogeneity manifest through a diversity of cell types and molecular patterns. The current paradigm of understanding glioblastoma recurrence is that cytotoxic therapy fails to target effectively glioma stem cells. Recent advances indicate that therapy-driven molecular evolution is a fundamental trait associated with glioblastoma recurrence. There is a growing body of evidence indicating that intratumor heterogeneity, longitudinal changes in molecular biomarkers and specific impacts of glioma stem cells need to be taken into consideration in order to increase the accuracy of molecular diagnostics still relying on readouts obtained from a single tumor specimen. Methods: This study integrates a multisampling strategy, longitudinal approach and complementary transcriptomic investigations in order to identify transcriptomic traits of recurrent glioblastoma in whole-tissue specimens of glioblastoma or glioblastoma stem cells. In this study, 128 tissue samples of 44 tumors including 23 first diagnosed, 19 recurrent and 2 secondary recurrent glioblastomas were analyzed along with 27 primary cultures of glioblastoma stem cells by RNA sequencing. A novel algorithm was used to quantify longitudinal changes in pathway activities and model efficacy of anti-cancer drugs based on gene expression data. Results: Our study reveals that intratumor heterogeneity of gene expression patterns is a fundamental characteristic of not only newly diagnosed but also recurrent glioblastomas. Evidence is provided that glioblastoma stem cells recapitulate intratumor heterogeneity, longitudinal transcriptomic changes and drug sensitivity patterns associated with the state of recurrence. Conclusions: Our results provide a transcriptional rationale for the lack of significant therapeutic benefit from temozolomide in patients with recurrent glioblastoma. Our findings imply that the spectrum of potentially effective drugs is likely to differ between newly diagnosed and recurrent glioblastomas and underscore the merits of glioblastoma stem cells as prognostic models for identifying alternative drugs and predicting drug response in recurrent glioblastoma. With the majority of recurrent glioblastomas being inoperable, glioblastoma stem cell models provide the means of compensating for the limited availability of recurrent glioblastoma specimens.

The diagnosis of intracranial meningiomas as incidental findings is increasing by growing availability of MRI diagnostics. However, the psychological distress of patients with incidental meningiomas under a wait-and-watch strategy is unknown. Therefore, we aimed to compare the psychosocial situation of meningioma patients under wait-and-watch to patients after complete resection to bridge this gap. The inclusion criteria for the prospective monocenter study were either an incidental meningioma under a wait-and-watch strategy or no neurologic deficits after complete resection. Sociodemographic, clinical, and health-related quality of life and clinical data were assessed. Psychosocial factors were measured by the Distress Thermometer (DT), Hospital Anxiety and Depression Scale (HADS), Brief Fatigue Inventory (BFI), and the Short Form (SF-36). A total of 62 patients were included (n = 51 female, mean age 61 (SD 13) years). According to HADS, the prevalence of anxiety was 45% in the postoperative and 42% in the wait-and-watch group (p = 0.60), and depression was 61% and 87%, respectively (p = 0.005). In total, 43% of patients under wait-and-watch and 37% of patients in the postoperative group scored ≥6 on the DT scale. SF-36 scores were similar in all categories except general health (p = 0.005) and physical component aggregate score (43.7 (13.6) vs. 50.5 (9.5), (p = 0.03), both lower in the wait-and-watch group. Multivariate analysis revealed the wait-and-watch strategy was associated with a 4.26-fold higher risk of a pathological depression score based on HADS (p = 0.03). This study demonstrates a high prevalence of psychological distress in meningioma patients. Further evaluation is necessary to identify the patients in need of psychooncological support.

Up to 60% of atypical meningiomas (World Health Organization (WHO) grade II) reoccur within 5 years after resection. However, no clear radiological criteria exist to identify tumors with higher risk of relapse. In this study, we aimed to assess the association of certain radiomic and semantic features of atypical meningiomas in MRI with tumor recurrence. We identified patients operated on primary atypical meningiomas in our department from 2007 to 2017. An analysis of 13 quantitatively defined radiomic and 11 qualitatively defined semantic criteria was performed based on preoperative MRI scans. Imaging characteristics were assessed along with clinical and survival data. The analysis included 76 patients (59% women, mean age 59 years). Complete tumor resection was achieved in 65 (86%) cases, and tumor relapse occurred in 17 (22%) cases. Mean follow-up time was 41.6 (range 3–168) months. Cystic component was significantly associated with tumor recurrence (odds ratio (OR) 21.7, 95% confidence interval (CI) 3.8–124.5) and shorter progression-free survival (33.2 vs. 80.7 months, p < 0.001), whereas radiomic characteristics had no predictive value in univariate analysis. However, multivariate analysis demonstrated significant predictive value of high cluster prominence (hazard ratio (HR) 5.89 (1.03–33.73) and cystic component (HR 20.21 (2.46–166.02)) for tumor recurrence. The combination of radiomic and semantic features might be an effective tool for identifying patients with high-risk atypical meningiomas. The presence of a cystic component in these tumors is associated with a high risk of tumor recurrence.

Hypofractionated radiotherapy is the mainstay of the current treatment for glioblastoma. However, the efficacy of radiotherapy is hindered by the high degree of radioresistance associated with glioma stem cells comprising a heterogeneous compartment of cell lineages differing in their phenotypic characteristics, molecular signatures, and biological responses to external signals. Reconstruction of radiation responses in glioma stem cells is necessary for understanding the biological and molecular determinants of glioblastoma radioresistance. To date, there is a paucity of information on the longitudinal outcomes of hypofractionated radiation in glioma stem cells. This study addresses long-term outcomes of hypofractionated radiation in human glioma stem cells by using a combinatorial approach integrating parallel assessments of the tumor-propagating capacity, stemness-associated properties, and array-based profiling of gene expression. The study reveals a broad spectrum of changes in the tumor-propagating capacity of glioma stem cells after radiation and finds association with proliferative changes at the onset of differentiation. Evidence is provided that parallel transcriptomic patterns and a cumulative impact of pathways involved in the regulation of apoptosis, neural differentiation, and cell proliferation underly similarities in tumorigenicity changes after radiation.

Purpose: The patients’ burden with asymptomatic meningiomas and patients with good clinical outcome after meningioma resection often remains neglected. In this study, we aimed to investigate the longitudinal changes of psychological distress and quality of life in these patient groups. Methods: Patients with conservatively managed (CM) or operated (OM) meningiomas and excellent neurological status, who were screened for psychological distress during the follow-up visit (t1), were included. We performed a follow-up mail/telephone-based survey 3–6 months (t2) after t1. Distress was measured using Hospital Anxiety and Depression Scale (HADS), Distress Thermometer (DT), 36-item Short Form (SF-36), and Brief Fatigue Inventory (BFI). Results: Sixty-two patients participated in t1 and 47 in t2. The number of patients reporting increased or borderline values remained high 3 months after initial presentation, with n = 25 (53%) of patients reporting increased anxiety symptom severity and n = 29 (62%) reporting increased depressive symptom severity values. The proportion of distressed patients according to a DT score remained similar after 3 months. Forty-four percent of patients reported significant distress in OM and 33% in CM group. The most common problems among distressed patients were fatigue (t2 75%) and worries (t2 50%), followed by pain, sleep disturbances, sadness, and nervousness. Tumor progress was associated with increased depression scores (OR 6.3 (1.1–36.7)). Conclusion: The level of psychological distress in asymptomatic meningiomas and postoperative meningiomas with excellent outcome is high. Further investigations are needed to identify and counsel the patients at risk.