Repeated blood-brain barrier opening with a nine-emitter implantable ultrasound device in combination with carboplatin in recurrent glioblastoma: a phase I/II clinical trial.

Here, the results of a phase 1/2 single-arm trial (NCT03744026) assessing the safety and efficacy of blood-brain barrier (BBB) disruption with an implantable ultrasound system in recurrent glioblastoma patients receiving carboplatin are reported. A nine-emitter ultrasound implant was placed at the end of tumor resection replacing the bone flap. After surgery, activation to disrupt the BBB was performed every four weeks either before or after carboplatin infusion. The primary objective of the Phase 1 was to evaluate the safety of escalating numbers of ultrasound emitters using a standard 3 + 3 dose escalation. The primary objective of the Phase 2 was to evaluate the efficacy of BBB opening using magnetic resonance imaging (MRI). The secondary objectives included safety and clinical efficacy. Thirty-three patients received a total of 90 monthly sonications with carboplatin administration and up to nine emitters activated without observed DLT. Grade 3 procedure-related adverse events consisted of pre syncope (n = 3), fatigue (n = 1), wound infection (n = 2), and pain at time of device connection (n = 7). BBB opening endpoint was met with 90% of emitters showing BBB disruption on MRI after sonication. In the 12 patients who received carboplatin just prior to sonication, the progression-free survival was 3.1 months, the 1-year overall survival rate was 58% and median overall survival was 14.0 months from surgery.

Social cognition in adult survivors of brain tumors: studying the relationship between theory of mind and quality of life.

OBJECTIVE: The present study is the first to examine theory of mind (ToM) sequelae in a sample of adult survivors of primary brain tumors, and to investigate the assumed relationship between ToM and health-related quality of life (HRQoL). METHOD: Participants were 40 long-term adult survivors of primary brain tumors and 40 matched healthy controls. They completed ToM tests (Faux-Pas test and Advanced ToM task) and two questionnaires assessing HRQoL (36-Item Short-Form Health Survey and EORTC QLQ-C30/QLQ-BN20). Their relatives also completed an observer-rated version of the SF-36 questionnaire. RESULTS: Survivors performed worse than controls only on the Advanced ToM task. Overall, patients and caregivers reported more problems than healthy controls and their relatives regarding both global HRQoL and its social/emotional aspects. No relationship was found between ToM and HRQoL scores. CONCLUSION: Adult survivors of primary brain tumors may exhibit ToM deficits several years after treatment and report more problems on social/emotional HRQoL components. Our findings highlight the need to consider these late effects in survivors' long-term follow-up, even if the clinical involvement of ToM deficits still needs to be elucidated. The assessment of ToM deficits and their potential impact on survivors' everyday life is thoroughly discussed.

Associations between Adult Primary Brain Tumor Survivors' Behavioral Executive Functions, Health Related Quality of Life and their Caregivers' Health Related Quality : A cross-sectional study.

The present study focused on adult primary brain tumor (PBT) survivors' caregivers. The main objective was to study associations between PBT survivors' health-related quality of life (HRQOL), their behavioral executive functions (EF) and their caregivers' HRQOL. Forty PBT survivors of PBT and 37 caregivers (mostly patient's spouses 81.08%; n = 30) participated in the study. PBT survivors completed a cancer related Quality of Life (QOL) questionnaire. Caregivers completed informant rated HRQOL and behavioral EF reports relating to PBT survivors and a self-rated HRQOL questionnaire relating to themselves. Correlational and multiple regression analyses were conducted. No associations were found between caregivers' physical HRQOL and PBT survivors' HRQOL nor behavioral EF. Analyses yielded several significant correlations between caregivers' mental HRQOL and variables pertaining to PBT survivors' HRQOL and behavioral EF. Multiple regression analyses showed that caregivers' mental HRQOL is predicted by PBT survivors' mental HRQOL, global cancer-related QOL scores and global behavioral EF scores. This study provides evidence suggesting that during the survivorship phase, at an average of 3.67 (SD = 2.31) years following treatment for a PBT, caregivers mental HRQOL is linked to PBT survivors' long-term effects. These findings shed some light regarding post-cancer care for both PBT survivors and their caregivers.

Virtual Reality-Assisted Awake Craniotomy: A Retrospective Study.

BACKGROUND: Awake craniotomy (AC) with brain mapping for language and motor functions is often performed for tumors within or adjacent to eloquent brain regions. However, other important functions, such as vision and visuospatial and social cognition, are less frequently mapped, at least partly due to the difficulty of defining tasks suitable for the constrained AC environment. OBJECTIVE: The aim of this retrospective study was to demonstrate, through illustrative cases, how a virtual reality headset (VRH) equipped with eye tracking can open up new possibilities for the mapping of language, the visual field and complex cognitive functions in the operating room. METHODS: Virtual reality (VR) tasks performed during 69 ACs were evaluated retrospectively. Three types of VR tasks were used: VR-DO80 for language evaluation, VR-Esterman for visual field assessment and VR-TANGO for the evaluation of visuospatial and social functions. RESULTS: Surgery was performed on the right hemisphere for 29 of the 69 ACs performed (42.0%). One AC (1.5%) was performed with all three VR tasks, 14 ACs (20.3%) were performed with two VR tasks and 54 ACs (78.3%) were performed with one VR task. The median duration of VRH use per patient was 15.5 min. None of the patients had "VR sickness". Only transitory focal seizures of no consequence and unrelated to VRH use were observed during AC. Patients were able to perform all VR tasks. Eye tracking was functional, enabling the medical team to analyze the patients' attention and exploration of the visual field of the VRH directly. CONCLUSIONS: This preliminary experiment shows that VR approaches can provide neurosurgeons with a way of investigating various functions, including social cognition during AC. Given the rapid advances in VR technology and the unbelievable sense of immersion provided by the most recent devices, there is a need for ongoing reflection and discussions of the ethical and methodological considerations associated with the use of these advanced technologies in AC and brain mapping procedures.

Challenges in glioblastoma research: focus on the tumor microenvironment.

Glioblastoma (GBM) is the most deadly type of malignant brain tumor, despite extensive molecular analyses of GBM cells. In recent years, the tumor microenvironment (TME) has been recognized as an important player and therapeutic target in GBM. However, there is a need for a full and integrated understanding of the different cellular and molecular components involved in the GBM TME and their interactions for the development of more efficient therapies. In this review, we provide a comprehensive report of the GBM TME, which assembles the contributions of physicians and translational researchers working on brain tumor pathology and therapy in France. We propose a holistic view of the subject by delineating the specific features of the GBM TME at the cellular, molecular, and therapeutic levels.

Surgery for glioblastomas in the elderly: an Association des Neuro-oncologues d'Expression Française (ANOCEF) trial.

OBJECTIVE: The role of surgery in the treatment of malignant gliomas in the elderly is not settled. The authors conducted a randomized trial that compared tumor resection with biopsy only-both followed by standard therapy-in such patients. METHODS: Patients ≥ 70 years of age with a Karnofsky Performance Scale (KPS) score ≥ 50 and presenting with a radiological suspicion of operable glioblastoma (GBM) were randomly assigned between tumor resection and biopsy groups. Subsequently, they underwent standard radiotherapy during the first years of the trial (2008-2017), with the addition of adjunct therapy with temozolomide when this regimen became standard (2017-2019). The primary endpoint was survival, and secondary endpoints were progression-free survival (PFS), cognitive status (Mini-Mental State Examination), autonomy (KPS), quality of life (European Organisation for Research and Treatment of Cancer [EORTC] QLQ-C30 and QLQ-BN20), and perioperative morbidity and mortality. RESULTS: Between 2008 and 2019, 107 patients from 9 centers were enrolled in the study; 101 were evaluable for analysis because a GBM was histologically confirmed (50 in the surgery arm and 51 in the biopsy arm). There was no statistically significant difference in median survival between the surgery (9.37 months) and the biopsy (8.96 months, p = 0.36) arms (adjusted HR 0.79, 95% CI 0.52-1.21, p = 0.28). However, the surgery group had an increased PFS (5.06 vs 4.02 months; p = 0.034) (adjusted HR 0.50, 95% CI 0.32-0.78, p = 0.002). Less deterioration of quality of life and KPS score evolution than in the biopsy group was observed. Surgery was not associated with increased mortality or morbidity. CONCLUSIONS: This study suggests that debulking surgery is safe, and-compared to biopsy-is associated with a less severe deterioration of quality of life and autonomy, as well as a significant although modest improvement of PFS in elderly patients suffering from newly diagnosed malignant glioma. Although resection does not provide a significant survival benefit in the elderly, the authors believe that the risk/benefit analysis favors an attempt at optimal tumor resection in this population, provided there is careful preoperative geriatric evaluation. Clinical trial registration no.: NCT02892708 (ClinicalTrials.gov).

Frontal aslant tract in the non-dominant hemisphere: A systematic review of anatomy, functions, and surgical applications.

Knowledge of both the spatial organization and functions of white-matter fiber tracts is steadily increasing. We report here the anatomy and functions of the frontal aslant tract (FAT) in the non-dominant hemisphere (usually the right hemisphere). Despite the structural symmetry between the right and left FAT, these two tracts seem to display functional asymmetry, with several brain functions in common, but others, such as visuospatial and social cognition, music processing, shifting attention or working memory, more exclusively associated with the right FAT. Further studies are required to determine whether damage to the right FAT causes permanent cognitive impairment. Such studies will constitute the best means of testing whether this tract is a critical pathway that must be taken into account during neurosurgical procedures and the essential tasks to be incorporated into intraoperative monitoring during awake craniotomy.

Management of Recurrent Glioblastomas: What Can We Learn from the French Glioblastoma Biobank?

Safe maximal resection followed by radiotherapy plus concomitant and adjuvant temozolomide (TMZ) is universally accepted as the first-line treatment for glioblastoma (GB), but no standard of care has yet been defined for managing recurrent GB (rGB). We used the French GB biobank (FGB) to evaluate the second-line options currently used, with a view to defining the optimal approach and future directions in GB research. We retrospectively analyzed data for 338 patients with de novo isocitrate dehydrogenase (IDH)-wildtype GB recurring after TMZ chemoradiotherapy. Cox proportional hazards models and Kaplan-Meier analyses were used to investigate survival outcomes. Median overall survival after first surgery (OS1) was 19.8 months (95% CI: 18.5-22.0) and median OS after first progression (OS2) was 9.9 months (95% CI: 8.8-10.8). Two second-line options were noted for rGB patients in the FGB: supportive care and treatments, with systemic treatment being the treatment most frequently used. The supportive care option was independently associated with a shorter OS2 (p < 0.001). None of the systemic treatment regimens was unequivocally better than the others for rGB patients. An analysis of survival outcomes based on time to first recurrence (TFR) after chemoradiotherapy indicated that survival was best for patients with a long TFR (≥18 months; median OS1: 44.3 months (95% CI: 41.7-56.4) and median OS2: 13.0 months (95% CI: 11.2-17.7), but that such patients constituted only a small proportion of the total patient population (13.0%). This better survival appeared to be more strongly associated with response to first-line treatment than with response to second-line treatment, indicating that the recurring tumors were more aggressive and/or resistant than the initial tumors in these patients. In the face of high rates of treatment failure for GB, the establishment of well-designed large cohorts of primary and rGB samples, with the help of biobanks, such as the FGB, taking into account the TFR and survival outcomes of GB patients, is urgently required for solid comparative biological analyses to drive the discovery of novel prognostic and/or therapeutic clinical markers for GB.

What surgical approach for left-sided eloquent glioblastoma: biopsy, resection under general anesthesia or awake craniotomy?

PURPOSE: Neurosurgeons use three main surgical approaches for left-sided glioblastoma (GB) in eloquent areas: biopsy, tumor resection under general anesthesia (GA), and awake craniotomy (AC) with brain mapping for maximal safe resection. We performed a retrospective study of functional and survival outcomes for left-sided eloquent GB, comparing these surgical approaches. METHODS: We included 87 patients with primary left-sided eloquent GB from two centers, one performing AC and the other biopsy or resection under GA. We assessed Karnofsky performance score (KPS), language and motor deficits one month after surgery, progression-free survival (PFS) and overall survival (OS). RESULTS: The 87 patients had a median PFS of 8.6 months [95% CI: 7.3-11.6] and a median OS of 20.2 months [17-3-24.4], with no significant differences between the three surgical approaches. One month after surgery, functional outcomes for language were similar for all approaches, but motor function was poorer in the biopsy group than in other patients. The proportion of patients with a KPS score > 80 was higher in the resection with AC group than in the other patients at this timepoint. CONCLUSION: We detected no real benefit of a resection with AC over resection under GA for left-sided eloquent GB in terms of survival or functional outcomes for language. However, given the poorer motor function of biopsy patients, resection with AC should be proposed, when possible, to patients ineligible for surgical resection under GA, to improve functional outcomes and patient autonomy.

Characteristics of Anaplastic Oligodendrogliomas Short-Term Survivors: A POLA Network Study.

BACKGROUND: Anaplastic oligodendrogliomas IDH-mutant and 1p/19q codeleted (AO) occasionally have a poor outcome. Herein we aimed at analyzing their characteristics. METHODS: We retrospectively analyzed the characteristics of 44 AO patients with a cancer-specific survival <5 years (short-term survivors, STS) and compared them with those of 146 AO patients with a survival ≥5 years (classical survivors, CS) included in the POLA network. RESULTS: Compared to CS, STS were older (P = .0001), less frequently presented with isolated seizures (P < .0001), more frequently presented with cognitive dysfunction (P < .0001), had larger tumors (P = .= .003), a higher proliferative index (P = .= .0003), and a higher number of chromosomal arm abnormalities (P = .= .02). Regarding treatment, STS less frequently underwent a surgical resection than CS (P = .= .0001) and were more frequently treated with chemotherapy alone (P = .= .009) or with radiotherapy plus temozolomide (P = .= .05). Characteristics independently associated with STS in multivariate analysis were cognitive dysfunction, a number of mitosis > 8, and the absence of tumor resection. Based on cognitive dysfunction, type of surgery, and number of mitosis, patients could be classified into groups of standard (18%) and high (62%) risk of <5 year survival. CONCLUSION: The present study suggests that although STS poor outcome appears to largely result from a more advanced disease at diagnosis, surgical resection may be particularly important in this population.

Overt speech critically changes lateralization index and did not allow determination of hemispheric dominance for language: an fMRI study.

BACKGROUND: Pre-surgical mapping of language using functional MRI aimed principally to determine the dominant hemisphere. This mapping is currently performed using covert linguistic task in way to avoid motion artefacts potentially biasing the results. However, overt task is closer to natural speaking, allows a control on the performance of the task, and may be easier to perform for stressed patients and children. However, overt task, by activating phonological areas on both hemispheres and areas involved in pitch prosody control in the non-dominant hemisphere, is expected to modify the determination of the dominant hemisphere by the calculation of the lateralization index (LI). OBJECTIVE: Here, we analyzed the modifications in the LI and the interactions between cognitive networks during covert and overt speech task. METHODS: Thirty-three volunteers participated in this study, all but four were right-handed. They performed three functional sessions consisting of (1) covert and (2) overt generation of a short sentence semantically linked with an audibly presented word, from which we estimated the "Covert" and "Overt" contrasts, and a (3) resting-state session. The resting-state session was submitted to spatial independent component analysis to identify language network at rest (LANG), cingulo-opercular network (CO), and ventral attention network (VAN). The LI was calculated using the bootstrapping method. RESULTS: The LI of the LANG was the most left-lateralized (0.66 ± 0.38). The LI shifted from a moderate leftward lateralization for the Covert contrast (0.32 ± 0.38) to a right lateralization for the Overt contrast (- 0.13 ± 0.30). The LI significantly differed from each other. This rightward shift was due to the recruitment of right hemispheric temporal areas together with the nodes of the CO. CONCLUSION: Analyzing the overt speech by fMRI allowed improvement in the physiological knowledge regarding the coordinated activity of the intrinsic connectivity networks. However, the rightward shift of the LI in this condition did not provide the basic information on the hemispheric language dominance. Overt linguistic task cannot be recommended for clinical purpose when determining hemispheric dominance for language.

A Simple Preoperative Blood Count to Stratify Prognosis in Isocitrate Dehydrogenase-Wildtype Glioblastoma Patients Treated with Radiotherapy plus Concomitant and Adjuvant Temozolomide.

PURPOSE: The survival times of glioblastoma (GB) patients after the standard therapy including safe maximal resection followed by radiotherapy plus concomitant and adjuvant temozolomide are heterogeneous. In order to define a simple, reliable method for predicting whether patients with isocitrate dehydrogenase (IDH)-wildtype GB treated with the standard therapy will be short- or long-term survivors, we analyzed the correlation of preoperative blood counts and their combined forms with progression-free survival (PFS) and overall survival (OS) in these patients. METHODS: Eighty-five patients with primary IDH-wildtype GB treated with the standard therapy between 2012 and 2019 were analyzed retrospectively. Cox proportional hazards models and Kaplan-Meier analysis were used to investigate the survival function of preoperative hematological parameters. RESULTS: Preoperative high neutrophil-to-lymphocyte ratio (NLR, >2.42), high platelet count (>236 × 109/L), and low red blood cell (RBC) count (≤4.59 × 1012/L) were independent prognostic factors for poorer OS (p = 0.030, p = 0.030, and p = 0.004, respectively). Moreover, a high NLR was an independent prognostic factor for shorter PFS (p = 0.010). We also found that, like NLR, preoperative high derived NLR (dNLR, >1.89) was of poor prognostic value for both PFS (p = 0.002) and OS (p = 0.033). A significant correlation was observed between NLR and dNLR (r = 0.88, p < 0.001), which had a similar prognostic power for OS (NLR: AUC = 0.58; 95% CI: [0.48; 0.68]; dNLR: AUC = 0.62; 95% CI: [0.51; 0.72]). Two scores, one based on preoperative platelet and RBC counts plus NLR and the other on preoperative platelet and RBC counts plus dNLR, were found to be independent prognostic factors for PFS (p = 0.006 and p = 0.002, respectively) and OS (p < 0.001 for both scores). CONCLUSION: Cheap, routinely ordered, preoperative assessments of blood markers, such as NLR, dNLR, RBC, and platelet counts, can predict the survival outcomes of patients with IDH-wildtype GB treated with the standard therapy.

Immersive Virtual Reality and Ocular Tracking for Brain Mapping During Awake Surgery: Prospective Evaluation Study.

BACKGROUND: Language mapping during awake brain surgery is currently a standard procedure. However, mapping is rarely performed for other cognitive functions that are important for social interaction, such as visuospatial cognition and nonverbal language, including facial expressions and eye gaze. The main reason for this omission is the lack of tasks that are fully compatible with the restrictive environment of an operating room and awake brain surgery procedures. OBJECTIVE: This study aims to evaluate the feasibility and safety of a virtual reality headset equipped with an eye-tracking device that is able to promote an immersive visuospatial and social virtual reality (VR) experience for patients undergoing awake craniotomy. METHODS: We recruited 15 patients with brain tumors near language and/or motor areas. Language mapping was performed with a naming task, DO 80, presented on a computer tablet and then in 2D and 3D via the VRH. Patients were also immersed in a visuospatial and social VR experience. RESULTS: None of the patients experienced VR sickness, whereas 2 patients had an intraoperative focal seizure without consequence; there was no reason to attribute these seizures to virtual reality headset use. The patients were able to perform the VR tasks. Eye tracking was functional, enabling the medical team to analyze the patients' attention and exploration of the visual field of the virtual reality headset directly. CONCLUSIONS: We found that it is possible and safe to immerse the patient in an interactive virtual environment during awake brain surgery, paving the way for new VR-based brain mapping procedures. TRIAL REGISTRATION: ClinicalTrials.gov NCT03010943; https://clinicaltrials.gov/ct2/show/NCT03010943.

What effects does awake craniotomy have on functional and survival outcomes for glioblastoma patients?

PURPOSE: Neurosurgeons adopt several different surgical approaches to deal with glioblastomas (GB) located in or near eloquent areas. Some attempt maximal safe resection by awake craniotomy (AC), but doubts persist concerning the real benefits of this type of surgery in this situation. We performed a retrospective study to evaluate the extent of resection (EOR), functional and survival outcomes after AC of patients with GB in critical locations. METHODS: Forty-six patients with primary GB treated with the Stupp regimen between 2004 and 2019, for whom brain mapping was feasible, were included. We assessed EOR, postoperative language and/or motor deficits three months after AC, progression-free survival (PFS) and overall survival (OS). RESULTS: Complete resection was achieved in 61% of the 46 GB patients. The median PFS was 6.8 months (CI 6.1; 9.7) and the median OS was 17.6 months (CI 14.8; 34.1). Three months after AC, more than half the patients asymptomatic before surgery remained asymptomatic, and one third of patients with symptoms before surgery experienced improvements in language, but not motor functions. The risk of postoperative deficits was higher in patients with preoperative deficits or incomplete resection. Furthermore, the presence of postoperative deficits was an independent predictive factor for shorter PFS. CONCLUSION: AC is an option for the resection of GB in critical locations. The observed survival outcomes are typical for GB patients in the Stupp era. However, the success of AC in terms of the recovery or preservation of language and/or motor functions cannot be guaranteed, given the aggressiveness of the tumor.

Relationships between executive functioning and health-related quality of life in adult survivors of brain tumor and matched healthy controls.

INTRODUCTION: Few studies have considered health-related quality of life (HRQOL) as a primary outcome measure in adult survivors of primary brain tumor (PBT), and fewer still have studied the cognitive factors that may influence it. Research suggests that executive functions (EFs) are associated with HRQOL, but there is scant evidence to support this. The present study was conducted to (1) extend prior findings about HRQOL limitations in a sample of stable, long-term adult survivors of PBT, (2) investigate the associations between objective/reported EFs and HRQOL, and (3) identify the EFs that contribute most to HRQOL. METHOD: We recruited 40 survivors of PBT (> 2 years post-treatment) and 40 matched healthy controls. Participants completed an objective EF assessment (inhibition, working memory, shifting, and rule detection) and two self-report questionnaires probing EFs (Behavior Rating Inventory of Executive Function-Adult) and HRQOL (Medical Outcomes Study Short-Form 36). Participants' relatives completed observer-rated versions of these questionnaires. RESULTS: Patients' objective EF performances were relatively intact. However, patients and caregivers reported significantly more problems than healthy controls and their relatives, for both EFs and HRQOL. There were only negligible links between objective EFs and HRQOL, whereas numerous associations were found between reported EFs and HRQOL components. ANCOVA models revealed that specific reported EF processes contributed to both the physical and mental components of HRQOL, regardless of group. CONCLUSIONS: From a clinical point of view, this study demonstrates that even several years after end of treatment, adult PBT survivors experience substantial problems across different HRQOL domains. HRQOL assessment should therefore be part of the long-term follow-up of PBT survivors, and clinicians should consider EF limitations when designing appropriate survivorship care plans. These findings indicate that cognitive interventions targeting EFs could improve HRQOL.

RNA-sequencing of IDH-wild-type glioblastoma with chromothripsis identifies novel gene fusions with potential oncogenic properties.

Glioblastoma (GBM) is the most frequent and most aggressive form of glioma. It is characterized by marked genomic instability, which suggests that chromothripsis (CT) might be involved in GBM initiation. Recently, CT has emerged as an alternative mechanism of cancer development, involving massive chromosome rearrangements in a one-step catastrophic event. The aim of the study was to detect CT in GBM and identify novel gene fusions in CT regions. One hundred and seventy IDH-wild-type GBM were screened for CT patterns using whole-genome single nucleotide polymorphism (SNP) arrays. RNA sequencing was performed in 52 GBM with CT features to identify gene fusions within CT regions. Forty tumors (40/52, 77%) harbored at least one gene fusion within CT regions. We identified 120 candidate gene fusions, 30 of which with potential oncogenic activities. We validated 11 gene fusions, which involved the most recurrent fusion partners (EGFR, SEPT14, VOPP1 and CPM), by RT-PCR and Sanger sequencing. The occurrence of CT points to underlying gene fusions in IDH-wild-type GBM. CT provides exciting new research avenues in this highly aggressive cancer.

Patient-reported functional executive challenges and caregiver confirmation in adult brain tumor survivors.

PURPOSE: The main objective of this study was to provide further information concerning the validity of patient-reported executive function (EF) in survivors of primary brain tumor (PBT) compared with a report provided by each patient's caregiver. METHODS: Forty survivors of PBT, 40 non-cancer controls and their proxies completed an assessment of functional executive disorders (e.g., planning, inhibition, shifting, action initiation). Comparisons of self and informant EF reports were examined, for both patients and non-cancer controls. The extent of the concordance between patients' reports and their caregivers' reports was also determined. RESULTS: PBT survivors and their caregivers reported more problems related to EF in contrast with the non-cancer comparison group (significant differences). There was a high level of agreement between patients' and caregivers' ratings within the patient group. CONCLUSIONS: This study provides evidence suggesting that at an average of 3.67 (SD = 2.31) years following treatment for a PBT, EF difficulties are reported by patients and their caregivers. This study establishes a consistency between what is reported by survivors and what is reported by those who frequently interact with them. Further research investigating the link between these ratings and quality of life as well as other functions is encouraged. IMPLICATIONS FOR CANCER SURVIVORS: This study's results demonstrate the importance of listening to PBT survivors' perception of EF difficulties. While not confirmed by neuropsychological evaluations, the functional executive challenges reported by these survivors' close relatives reflect what PBT survivors themselves report. Specialists should pay close attention to these difficulties to guarantee optimal post-cancer care.

Mesenchymal Stromal-Like Cells in the Glioma Microenvironment: What Are These Cells?

The glioma microenvironment is a critical regulator of tumor progression. It contains different cellular components such as blood vessels, immune cells, and neuroglial cells. It also contains non-cellular components, such as the extracellular matrix, extracellular vesicles, and cytokines, and has certain physicochemical properties, such as low pH, hypoxia, elevated interstitial pressure, and impaired perfusion. This review focuses on a particular type of cells recently identified in the glioma microenvironment: glioma-associated stromal cells (GASCs). This is just one of a number of names given to these mesenchymal stromal-like cells, which have phenotypic and functional properties similar to those of mesenchymal stem cells and cancer-associated fibroblasts. Their close proximity to blood vessels may provide a permissive environment, facilitating angiogenesis, invasion, and tumor growth. Additional studies are required to characterize these cells further and to analyze their role in tumor resistance and recurrence.