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Purpose Psychosocial screening for glioma patients is challenging because many patients suffer from neurocognitive deficits, which may impair assessment. This study’s aim was to exploratively develop three screening questions for unmet needs to prospectively be applicable in patient–doctor consultation. Methods Patient interviews, a survey for health-care professionals and a weighted scoring procedure were developed for this study. Six main areas were defined according to main areas of validated questionnaires (psyche, cognition, body, role functioning, social support, unmet needs). Patients and health-care professionals rated the importance of these areas and corresponding items, patients additionally stated whether the issues addressed affected them. Results A total of 50 patients were included, and 36 health-care professionals participated in the online survey. The three areas (psyche, body and cognition) considered to be most relevant by both, health-care professionals and patients, generated three screening questions. If the patient was affected by the issue addressed with a screening question, a subordinate question from that area that our patient sample considered most important could additionally be asked. The elaborated screening questions are the following: (1) main area psyche: “Has your mood worsened?”, (2) main area body: “Do physical changes put a strain on you?”, and (3) main area cognition: “Has your memory capacity worsened?” Conclusion These questions represent a basis for further research regarding their application in neuro-oncological clinical routine.

PurposeMeeting the information needs of patients adequately is of high importance in informed consent consultations in surgery. However, information needs often remain unmet in the informed consent consultation. The aim of this study was to assess anxiety and pain in relation to the patients’ information needs fulfillment perioperatively.MethodsWe applied a question prompt list (QPL) for patients undergoing spine surgery (SN-QPL) before (t1) and a question answering list (SN-QAL) after (t2) the informed consent consultation. The patients additionally completed the “State-Trait Anxiety Operation Inventory” (STOA, cognitive and affective scale) at t1, as well as a pain numerical rating scale (NRS) at t2 and postoperative (t3). We analyzed (1) the association between anxiety, information needs and pain and (2) anxiety and pain scores regarding information needs fulfillment after the consent consultation.ResultsA total of n = 118 patients was included. Affective and cognitive state anxiety was only reduced postoperatively (affective p < .001, cognitive p < .05). The higher trait anxiety was, the more patients longed for information at t1–t3 (t1: r = .58/r = .74, each p < .001), (t2: r = .38/r = .49, each p < .001) and (t3: r = .29, p < .01/r = 34, p < .001). Higher grades of trait anxiety resulted in lower information needs fulfilment. Higher state anxiety levels were associated with higher pain levels. Information needs more often remained unfulfilled in high trait and state anxiety patients.ConclusionPatients’ anxiety was associated with (un)fulfilled information needs. Meeting information needs should be optimized in the process of surgeon–patient communication. Adapting the information to the patients’ anxiety levels seem to be an effective way to reduce anxiety.

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.

Rapid vascular recovery is a key feature preceding glioblastoma (GBM) recurrence after radiotherapy (RT). We performed spatial expression analyses, providing a rationale for dual inhibition of two non-redundant, spatially distinct acting factors, CXCL12 and VEGF. Subsequently, we expanded a multicentric phase 1/2 trial (NCT04121455), which initially combined RT and the CXCL12-neutralizing L-RNA-aptamer olaptesed pegol (NOX-A12) in patients with incompletely resected, newly-diagnosed GBM lacking MGMT promoter methylation. The primary endpoint was safety, secondary endpoints included maximum tolerable dose, recommended phase 2 dose, NOX-A12 plasma levels, topography of recurrence, tumor vascularization, neurologic assessment in neuro-oncology (NANO), quality of life, median progression-free survival (PFS), 6-months PFS and overall survival (OS). For the expansion arm, six patients were included that additionally received the VEGF-targeting antibody bevacizumab (BEV) to RT and NOX-A12. Combinatory treatment was well-tolerated and safe with no treatment-related deaths, resulting in abrogated tumor perfusion (rCBV, FTB high ) and delayed tumor regrowth as per mRANO. Median progression-free (PFS) and overall survival (OS) after RT + BEV + NOX-A12 were 9.1 and 19.9 months, respectively, significantly outperforming RT + NOX-A12 ( p  = 0.009; p  = 0.021) in a post-hoc comparative analysis, with two patients exceeding 2-year OS. These findings establish proof-of-principle for dual inhibition of CXCL12 and VEGF in patients with newly-diagnosed GBM following RT. Recently, the dose escalation stage of the GLORIA trial investigating NOX-A12 (L-RNA aptamer-based CXCL12 inhibitor) in combination with radiotherapy in patients with glioblastoma was reported. Here, the authors report the preclinical rationale and an expansion arm of the GLORIA trial combining NOX-A12, radiotherapy and bevacizumab (anti-VEGF) in patients with newly diagnosed glioblastoma.

Background Diffuse gliomas are the most common malignant tumors of the central nervous system with poor treatment efficacy. Infiltration of immune cells into tumors during immunosurveillance is observed in multiple tumor entities and often associated with a favorable outcome. The aim of this study was to evaluate the infiltration of immune cells in gliomas and their association with cerebrospinal fluid (CSF) cytokine concentrations. Methods We applied immunohistochemistry in tumor tissue sections of 18 high-grade glioma (HGG) patients (4 anaplastic astrocytoma, IDH-wildtype WHO-III; 14 glioblastomas (GBM), IDH-wildtype WHO-IV) in order to assess and quantify leucocytes (CD45) and macrophages (CD68, CD163) within the tumor core, infiltration zone and perivascular spaces. In addition, we quantified the concentrations of 30 cytokines in the same patients’ CSF and in 14 non-inflammatory controls. Results We observed a significantly higher percentage of CD68 + macrophages (21–27%) in all examined tumor areas when compared to CD45 + leucocytes (ca. 3–7%); CD163 + cell infiltration was between 5 and 15%. Compared to the tumor core, significantly more macrophages and leucocytes were detectable within the perivascular area. The brain parenchyma showing a lower tumor cell density seems to be less infiltrated by macrophages. Interleukin (IL)-7 was significantly downregulated in CSF of GBM patients compared to controls. Additionally, CD68 + macrophage infiltrates showed significant correlations with the expression of eotaxin, interferon-γ, IL-1β, IL-2, IL-10, IL-13, IL-16 and vascular endothelial growth factor. Conclusions Our findings suggest that the infiltration of lymphocytes is generally low in HGG, and does not correlate with cytokine concentrations in the CSF. In contrast, macrophage infiltrates in HGG are associated with CSF cytokine changes that possibly shape the tumor microenvironment. Although results point towards an escape from immunosurveillance or even exploitation of immune cells by HGG, further studies are necessary to decipher the exact role of the immune system in these tumors.

A transmembrane protein CD133 has been implicated as a marker of stem-like glioma cells and predictor for therapeutic response in malignant brain tumours. CD133 expression is commonly evaluated by using antibodies specific for the AC133 epitope located in one of the extracellular domains of membrane-bound CD133. There is conflicting evidence regarding the significance of the AC133 epitope as a marker for identifying stem-like glioma cells and predicting the degree of malignancy in glioma cells. The reasons for discrepant results between different studies addressing the role of CD133/AC133 in gliomas are unclear. A possible source for controversies about CD133/AC133 is the widespread assumption that expression patterns of the AC133 epitope reflect linearly those of the CD133 protein. Consequently, the readouts from AC133 assessments are often interpreted in terms of the CD133 protein. The purpose of this study is to determine whether and to what extent do the readouts obtained with anti-AC133 antibody correspond to the level of CD133 protein expressed in stem-like glioma cells. Our study reveals for the first time that CD133 expressed on the surface of glioma cells is poorly immunoreactive for AC133. Furthermore, we provide evidence that the level of CD133 occupancy on the surface of glioma cells fluctuates during the cell cycle. Our results offer a new explanation for numerous inconsistencies regarding the biological and clinical significance of CD133/AC133 in human gliomas and call for caution in interpreting the lack or presence of AC133 epitope in glioma cells.

Background The DNA repair protein O 6 -methylguanine-DNA methyltransferase (MGMT) causes resistance of cancer cells to alkylating agents and, therefore, is a well-established predictive marker for high-grade gliomas that are routinely treated with alkylating drugs. Since MGMT is highly epigenetically regulated, the MGMT promoter methylation status is taken as an indicator of MGMT silencing, predicting the outcome of glioma therapy. MGMT promoter methylation is usually determined by methylation specific PCR (MSP), which is a labor intensive and error-prone method often used semi-quantitatively. Searching for alternatives, we used closed-tube high resolution melt (HRM) analysis, which is a quantitative method, and compared it with MSP and pyrosequencing regarding its predictive value. Results We analyzed glioblastoma cell lines with known MGMT activity and formalin-fixed samples from IDH1 wild-type high-grade glioma patients (WHO grade III/IV) treated with radiation and temozolomide by HRM, MSP, and pyrosequencing. The data were compared as to progression-free survival (PFS) and overall survival (OS) of patients exhibiting the methylated and unmethylated MGMT status. A promoter methylation cut-off level relevant for PFS and OS was determined. In a multivariate Cox regression model, methylation of MGMT promoter of high-grade gliomas analyzed by HRM, but not MSP, was found to be an independent predictive marker for OS. Univariate Kaplan–Meier analyses revealed for PFS and OS a significant and better discrimination between methylated and unmethylated tumors when quantitative HRM was used instead of MSP. Conclusions Compared to MSP and pyrosequencing, the HRM method is simple, cost effective, highly accurate and fast. HRM is at least equivalent to pyrosequencing in quantifying the methylation level. It is superior in predicting PFS and OS of high-grade glioma patients compared to MSP and, therefore, can be recommended being used routinely for determination of the MGMT status of gliomas.

Background and Objectives: Immune checkpoint inhibitors (ICIs) have enriched tumor therapy, improving overall survival. Immunotherapy adverse events (irAEs) occur in up to 50% of patients and also affect the peripheral nervous system. The exact pathomechanism is unclear; however, an autoimmune process is implicated. Thus, the clinical evaluation of irAEs in the peripheral nervous system is still demanding. We retrospectively analyzed nerve ultrasound (NU) data of polyneuropathies (PNPs) secondary to checkpoint inhibitors. Materials and Methods: NU data of patients with PNP symptoms secondary to ICI therapy were retrospectively analyzed using the Ultrasound Pattern Sum Score (UPSS) as a quantitative marker. Our findings were compared with a propensity score match analysis (1:1 ratio) to NU findings in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and chemotherapy-associated PNP patients. Results: In total, 10 patients were included (4 female, mean age 66 ± 10.5, IQR 60–77), where NU was performed in 80%. The UPSS obtained ranged from 0 to 5 (mean 2 ± 1.6, IQR 1–2.5). The morphological changes seen in the NUs resembled sonographic changes seen in chemotherapy-associated PNP (n = 10, mean UPSS 1 ± 1, IQR 0–2) with little to no nerve swelling. In contrast, CIDP patients had a significantly higher UPSS (n = 10, mean UPSS 11 ± 4, IQR 8–13, p < 0.0001). Conclusions: Although an autoimmune process is hypothesized to cause peripheral neurological irAEs, NU showed no increased swelling as seen in CIDP. The nerve swelling observed was mild and comparable to ultrasound findings seen in chemotherapy-associated PNP.

Background Patients with high-grade gliomas (HGG) often suffer from high distress and require psychosocial support. However, due to neurological and neurocognitive deficits, adequate assessment of distress and support needs remains challenging in clinical practice. The objective of the present study is to investigate whether a systematic implementation of signaling questions into the routine outpatient consultation will be helpful to bridge this gap. Methods/design This is a multicenter cluster randomized study with two arms. Randomization is done on a cluster level with 13 hospitals providing regular neuro-oncological outpatient services conducted by neurologists and/or neurosurgeons. The intervention will include an assessment of psychosocial distress of patients in doctor–patient conversation compared to assessment of psychosocial distress via questionnaire (control, standard of care). In total, 616 HGG patients will be enrolled. The outcome will be the number of HGG patients with increased psychosocial distress who receive professional support from psychosocial services. Secondary endpoints are inter alia number of patients reporting psychosocial distress and unmet needs detected correctly by the respective method; quality of life; psychological well-being and burden of the patients before and after doctor–patient consultation; as well as the length of the doctor–patient consultation. Discussion Patients with HGG are confronted with an oncological diagnosis and at the same time with high symptom burden. This often leads to distress, which is not always adequately recognized and treated. So far, only a limited number of adequate instruments are available to assess HGG patient’s distress. Yet, an adequate care and support network might facilitate the course of the disease and tumor therapies for patients. Our hypothesis is that an assessment conducted directly by attending doctors and in which the doctors talk to patients with HGG will be more effective than an assessment via a questionnaire, leading to better identifying patients in need of support. This may lead to an improvement of health care in these patients. Further, this method might be implemented also in other brain tumor patients (e.g., patients with brain metastases). Trial registration German Clinical Trials Register, DRKS00018079 . Registered on 3rd September 2019.