Impact of Treatment Modality and Route of Administration on Cytokine Release Syndrome in Relapsed or Refractory Multiple Myeloma: A Meta-Analysis.

B-cell maturation antigen (BCMA)-targeting immunotherapies (e.g., chimeric antigen receptor T cells (CAR-T) and bispecific antibodies (BsAbs)) have achieved remarkable clinical responses in patients with relapsed and/or refractory multiple myeloma (RRMM). Their use is accompanied by exaggerated immune responses related to T-cell activation and cytokine elevations leading to cytokine release syndrome (CRS) in some patients, which can be potentially life-threatening. However, systematic evaluation of the risk of CRS with BCMA-targeting BsAb and CAR-T therapies, and comparisons across different routes of BsAb administration (intravenous (i.v.) vs. subcutaneous (s.c.)) have not previously been conducted. This study utilized a meta-analysis approach to compare the CRS profile in BCMA-targeting CAR-T vs. BsAb immunotherapies administered either i.v. or s.c. in patients with RRMM. A total of 36 studies including 1,560 patients with RRMM treated with BCMA-targeting CAR-T and BsAb therapies were included in the analysis. The current analysis suggests that compared with BsAbs, CAR-T therapies were associated with higher CRS incidences (88% vs. 59%), higher rates of grade ≥ 3 CRS (7% vs. 2%), longer CRS duration (5 vs. 2 days), and more prevalent tocilizumab use (44% vs. 25%). The proportion of CRS grade ≥ 3 may also be lower (0% vs. 4%) for BsAb therapies administered via the s.c. (3 studies, n = 311) vs. i.v. (5 studies, n = 338) route. This meta-analysis suggests that different types of BCMA-targeting immunotherapies and administration routes could result in a range of CRS incidence and severity that should be considered while evaluating the benefit-risk profiles of these therapies.

Comparative Complications Associated With BMP Use In Patients Undergoing ACDF for Degenerative Spinal Conditions: Systematic Review and Meta-Analysis.

STUDY DESIGN: Systematic Review and Meta-Analysis. OBJECTIVES: To compare complication incidence in patients with or without the use of recombinant human Bone Morphogenic Protein-2 (BMP2) undergoing anterior cervical discectomy and fusion (ACDF) for degenerative conditions. METHODS: A systematic search of eight online databases was conducted using PRISMA guidelines. Inclusion criteria included English language studies with a minimum of 10 adult patients undergoing instrumented ACDF surgery for a degenerative spinal condition in which BMP2 was used in all patients or one of the treatment arms. Studies with patients undergoing circumferential fusions, with non-degenerative indications, or which did not report post-operative complication data were excluded. Patients with and without BMP2 were compared in terms of the incidence of dysphagia/dysphonia, anterior soft tissue complications (hematoma, seroma, infection, dysphagia/dysphonia), nonunion, medical complications, and new neurologic deficits. RESULTS: Of 1832 preliminary search results, 27 manuscripts were included. Meta-analysis revealed the relative risk of dysphagia or dysphonia (RR = 1.39, CI 95% 1.18 - 1.64, P = <.001), anterior soft tissue complications (RR = 1.43, CI 95% 1.25-1.64, P = <.001), and medical complications (RR = 1.32, CI 95% 1.06-1.66, P = .013) were statistically significant in the BMP2 group while the relative risk of non-union (RR = .5, CI 95% .23 - 1.13, P = .09) trended lower in the BMP2 group. Neurological deficit (RR = 1.06, CI 95% .82-1.37, P = .66), and additional medical complications (RR = 1.53, CI 95% .98-2.38, P = .06) were not found to be statistically different between the groups. CONCLUSIONS: This meta-analysis identified a high rate of arthrodesis when BMP2 was used in ACDF, but confirmed increased rates of dysphagia and anterior soft tissue complications. Surgeons may consider reserving BMP2 implementation for cases with a high risk of non-union, and should be aware of the risk of airway compromise.

Neurosurgery resident training using blended learning concepts: course development and participant evaluation.

OBJECTIVE: Restrictions on working time and healthcare expenditures, as well as increasing subspecialization with caseload requirements per surgeon and increased quality-of-care expectations, provide limited opportunities for surgical residents to be trained in the operating room. Yet, surgical training requires goal-oriented and focused practice. As a result, training simulators are increasingly utilized. The authors designed a two-step blended course consisting of a personalized adaptive electronic learning (e-learning) module followed by simulator training. This paper reports on course development and the evaluation by the first participants. METHODS: Adaptive e-learning was curated by learning engineers based on theoretical information provided by clinicians (subject matter experts). A lumbar spine model for image-guided spinal injections was used for the simulator training. Residents were assigned to the e-learning module first; after its completion, they participated in the simulator training. Performance data were recorded for each participant's e-learning module, which was necessary to personalize the learning experience to each individual's knowledge and needs. Simulator training was organized in small groups with a 1-to-4 instructor-to-participant ratio. Structured assessments were undertaken, adapted from the Student Evaluation of Educational Quality. RESULTS: The adaptive e-learning module was curated, reviewed, and approved within 10 weeks. Eight participants have taken the course to date. The overall rating of the course is very good (4.8/5). Adaptive e-learning is well received compared with other e-learning types (8/10), but scores lower regarding usefulness, efficiency, and fun compared with the simulator training, despite improved conscious competency (32.6% ± 15.1%) and decreased subconscious incompetency (22.8% ± 10.2%). The subjective skill level improved by 20%. Asked about the estimated impact of the course, participants indicated that they had either learned something new that they plan to use in their practice (71.4%) or felt reassured in their practice (28.6%). CONCLUSIONS: The development of a blended training course combining adaptive e-learning and simulator training in a rapid manner is feasible and leads to improved skills. Simulator training is rated more valuable by surgical trainees than theoretical e-learning; the impact of this type of training on patient care needs to be further investigated.

Management and outcome of spinal implant-associated surgical site infections in patients with posterior instrumentation: analysis of 176 cases.

PURPOSE: The management of implant-associated surgical site infections (SSI) in patients with posterior instrumentation is challenging. Evidence regarding the most appropriate treatment and the need for removal of implants is equivocal. We sought to evaluate the management and outcome of such patients at our institution. METHODS: We searched our prospectively documented databases for eligible patients with posterior spinal instrumentation, excluding the cervical spine (January 2008-June 2018). Patient files were reviewed, demographic data and treatment details were recorded. Patient-reported outcome (PRO) was assessed with the Core Outcome Measures Index (COMI) preoperatively and postoperatively at 3 and 12 months. RESULTS: A total of 170 patients underwent 210 revisions for 176 SSIs. Two-thirds presented within four weeks (105/176, 59.7%, median 22.5d, 7d-11.1y). The most common pathogens were Staphylococcus aureus (n = 79/210, 37.6%) and Staphylococcus epidermidis (n = 56/210, 26.7%). Debridement and implant retention was performed in 135/210 (64.3%) revisions and partial replacement in 62/210 (29.5%). In 28/176 SSI (15.9%), persistent infection required multiple revisions (≤ 4). Surgery was followed by intravenous and oral antimicrobial treatment (10-12w). In 139/176 SSIs (79%) with ≥ 1y follow-up, infection was cured in 115/139 (82.7%); relapse occurred in 9 (relapse rate: 5.1%). Two patients (1.4%) died. COMI decreased significantly (8.2 ± 1.5 vs. 4.8 ± 2.9, p < 0.0001) over 12 months. 72.7% of patients were (very) satisfied with their care. CONCLUSION: Patients with SSI after posterior (thoraco-)lumbo(-sacral) instrumentation can be successfully treated in most cases with surgical and specific antibiotic treatment. An interdisciplinary approach is recommended. Loose implants should be replaced. In some cases, multiple revisions may be necessary. Patient outcomes were satisfactory.

Neuro-oncological patients' and caregivers' psychosocial burden during the COVID-19 pandemic-A prospective study with qualitative content analysis.

OBJECTIVE: The COVID-19 pandemic may reinforce psychosocial distress of neuro-oncological patients. We aimed to (1) differentiate the burden caused by the pandemic versus the tumor and (2) establish topics relevant for brain tumor patients (BTPs) and caregivers. METHODS: Patients and caregivers were prospectively assessed from April 2020-July 2020 by a 10-item comprising interview over the phone, including qualitative and quantitative questions. They were quantitatively evaluated i.a. by the distress thermometer (DT, score 1-10). The qualitative questions were analyzed using structured content analysis: The interview questions defined the main categories. Subcategories were derived by an inductive approach assessing the frequency of patients' and caregivers' answers. RESULTS: A total of 69 patients and 20 caregivers were interviewed; n = 36 were female (49%), mean age was 53 years (range 32-81). Patients' disease-related DT scores were higher than the COVID-19-related DT scores: the median of the disease-related DT score was 7 (range 2-10) versus median of COVID-19-related distress: 5.0 (range 2-7). Caregivers perceived a higher burden due to the disease (DT median disease: 8; range 2-10 vs. DT pandemic: 3, range 0-10). A total of five main and 21 subcategories were elaborated, most frequently mentioned were "restrictions in public and private affairs" (28%), "changes in the psychological well-being" (23%), "limited social interaction by contact restriction" (25%). Subcategories relevant for caregivers were similar to those of BTPs. CONCLUSION: A considerable proportion of patients and caregivers still perceived the brain tumor disease as more burdensome than the pandemic. We established main and subcategories of interview items possibly of great relevance to patients during these difficult times, which could be implemented in the content-related adaption of the psychosocial assessment.

Health-related quality of life and distress in elderly vs. younger patients with high-grade glioma-results of a multicenter study.

OBJECTIVE: Half of all newly diagnosed patients with glioblastoma are > 65 years still with a poor prognosis. Preserving quality of life is of high importance. However, patient reported outcome (PRO) data in this patient group is rare. The aim was to compare health-related quality of life (HRQoL) and distress between elderly and younger patients with high-grade glioma (HGG). METHODS: We used baseline data of a prospective study where HGG patients were enrolled from 4 hospitals. Distress was measured using the distress thermometer (DT), HRQoL using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (QLQ-C30) plus brain module (BN20). We compared distress and HRQoL by age (≥ 65 vs. < 65 years), gender, performance score, and time since diagnosis using multivariate linear and logistic regressions. RESULTS: A total of n = 93 (30%) out of n = 309 patients were ≥ 65 years (mean 70 years, range 65-86 years). Mean DT score of elderly patients (5.2, SD 2.6) was comparable with younger patients (4.9, SD 2.6). Elderly patients reported significantly lower global health (GHS, mean elderly vs. younger; 50.8 vs. 60.5, p = 0.003), worse physical (56.8 vs. 73.3, p < 0.001) and lower cognitive functioning (51.1 vs. 63.2, p = 0.002), worse fatigue (52.5 vs. 43.5, p = 0.042), and worse motor dysfunction (34.9 vs. 23.6, p = 0.030). KPS and not age was consistently associated with HRQoL. CONCLUSION: Physical functioning was significantly reduced in the elderly compared with younger HGG patients, and at the same time, emotional functioning and DT scores were comparable. KPS shows a greater association with HRQoL than with calendric age in HGG patients reflecting the particular importance for adequate assessment of HRQoL and general condition in elderly patients.

Molecular tumor analysis and liquid biopsy: a feasibility investigation analyzing circulating tumor DNA in patients with central nervous system lymphomas.

BACKGROUND: Central nervous system lymphomas (CNSL) is a devastating disease. Currently, a confirmatory biopsy is required prior to treatment. OBJECTIVE: Our investigation aims to prove the feasibility of a minimally-invasive diagnostic approach for the molecular characterization of CNSL. METHODS: Tissue biopsies from 6 patients with suspected CNSL were analyzed using a 649gene next-generation sequencing (NGS) tumor panel (tumor vs. reference tissue (EDTA-blood)). The individual somatic mutation pattern was used as a basis for the digital PCR analyzing circulating tumor DNA (ctDNA) from plasma and cerebrospinal fluid (CSF) samples, identifying one selected tumor mutation during this first step of the feasibility investigation. RESULTS: NGS-analysis of biopsy tissue revealed a specific somatic mutation pattern in all confirmed lymphoma samples (n = 5, NGS-sensitivity 100%) and none in the sample identified as normal brain tissue (NGS-specificity 100%). cfDNA-extraction was dependent on the extraction-kit used and feasible in 3 samples, in all of which somatic mutations were detectable (100%). Analysis of CSF-derived cfDNA was superior to plasma-derived cfDNA and routine microscopic analysis (lymphoma cells: n = 2, 40%). One patient showed a divergent molecular pattern, typical of Burkitt-Lymphoma (HIV+, serologic evidence of EBV-infection). Lumbar puncture was tolerated without complications, whereas biopsy caused 3 hemorrhages. CONCLUSIONS: Our investigation provides evidence that analysis of cfDNA in central nervous system tumors is feasible using the described protocol. Molecular characterization of CNSL could be achieved by analysis of CSF-derived cfDNA. Knowledge of a tumor's specific mutation pattern may allow initiation of targeted therapies, treatment surveillance and could lead to minimally-invasive diagnostics in the future.

Evaluation of the psychological burden during the early disease trajectory in patients with intracranial tumors by the ultra-brief Patient Health Questionnaire for Depression and Anxiety (PHQ-4).

PURPOSE: Depressive symptoms of patients with intracranial tumors need to be assessed adequately. The Patient Health Questionnaire for Depression and Anxiety (PHQ-4) is an ultra-short screening tool consisting of four items, a cutoff of six indicates depressive symptoms. The aim was to assess patients' psychological burden by the PHQ-4 compared with the results of well-established screening instruments. METHODS: Patients were screened three times after primary diagnosis postoperatively (t1), after 3 (t2) and 6 (t3) months using the PHQ-4, the Hornheide Screening Instrument (HSI), the NCCN Distress Thermometer (DT), and the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire with its brain module (EORTC QLQ-C30 + BN20). Demographic, tumor-related data, and Karnofsky Performance Scale (KPS) were analyzed. A cutoff value for PHQ-4 indicating a need for support or increased distress was determined by applying receiver operating characteristic (ROC). RESULTS: The proportion of patients reaching a total score ≥ 6 was n = 32 out of 139 (23%) at t1; at t2, n = 12 out of 117 (10%) scored ≥ 6. At t3, n = 8 out of 96 (8%) scored ≥ 6. At t1, PHQ-4 scores did not differ significantly between gender, age groups, and tumor laterality. A cutoff value of 2.5 was identified to moderately discriminate between patients in or not in distress (sensitivity 76.8%) and between patients wishing further, specific support or not (sensitivity 82.5%). CONCLUSION: The PHQ4 can be applied in this patient cohort to detect those with relevant psychological comorbidities. The cutoff value should be re-evaluated in a larger cohort as we observed that a cutoff of 6, as recommended previously, may be too high in order to detect affected patients adequately.

Feasibility and accuracy of a voxel-based neuronavigation system with 3D image rendering in preoperative planning and as a learning tool for young neurosurgeons, exemplified by the anatomical localization of the superior sagittal sinus.

It is essential for a neurosurgeon to know individual anatomy and the corresponding anatomical landmarks before starting a surgery. Continuous training, especially of young neurosurgeons, is crucial for understanding complex neuroanatomy. In this study, we used a neuronavigation system with 3D volumetric image rendering to determine the anatomical relationship between the sagittal suture and the superior sagittal sinus (SSS) in patients with intracranial lesions. Furthermore, we discussed the applicability of such system in preoperative planning, residency training, and research. The study included 30 adult patients (18 female/12 male) who underwent a cranial computed tomography (CT) scan combined with venous angiography, for preoperative planning. The position of the sagittal suture in relation to the SSS was assessed in 3D CT images using an image guidance system (IGS) with 3D volumetric image rendering. Measurements were performed along the course of the sagittal sinus at the bregma, lambda, and in the middle between these two points. The SSS deviated to the right side of the sagittal suture in 50% of cases at the bregma, and in 46.7% at the midpoint and lambda. The SSS was displaced to the left of the sagittal suture in 10% of cases at the bregma and lambda and in 13% at the midpoint. IGSs with 3D volumetric image rendering enable simultaneous visualization of bony surfaces, soft tissue and vascular structures and interactive modulation of tissue transparency. They can be used in preoperative planning and intraoperative guidance to validate external landmarks and to determine anatomical relationships. In addition, 3D IGSs can be utilized for training of surgical residents and for research in anatomy.

Screening for distress in patients with intracranial tumors during the first 6 months after diagnosis using self-reporting instruments and an expert rating scale (the basic documentation for psycho-oncology short form - PO-Bado SF).

OBJECTIVE: Psychosocial screening in brain tumor patients is of high importance. We applied The Basic Documentation for Psycho-Oncology Short Form (PO-Bado SF) in primary brain tumor patients and patients with metastasis. The aim was to evaluating consistency between physicians' perception and the results of the patients' self-assessment. MATERIALS AND METHODS: 140 patients with first diagnosis of a brain tumor were screened during their hospital stay (t1) using Distress Thermometer (DT) and Hornheide Screening Instrument (HSI), health-related quality of life was assessed by EORTC QLQ-C30 + BN20. After 3 (t2) and 6 months (t3), patients were re-evaluated. Attending neuro-oncologists completed the PO-Bado SF at all three time points (cut-off for being in need for support >8). RESULTS: At t1, the mean of the PO-Bado SF total score was 7.71 (SD = 4.08), at t2 8.22 (SD = 5.40) and at t3 7.62 (SD = 5.72).The proportion of patients reaching a total score >8 was at t1: 43%, at t2: 41% and at t3: 47% (t1-3). Discrimination of PO-Bado SF total score, between patients in (DT ≥6) and those not in distress was more sensitive (cut-off 8.5, AUC 0.772, sens. 71.3%, spec. 67.6%) than discrimination compared to the HIS (cut-off 9.5, AUC 0.779, sens. 65.1%, spec. 77.7%). Higher PO-Bado-SF total score correlated with higher DT scores (r = 0.6, p < 0.0001) and lower EORTC GHS scores (r = -0.55, p < 0.0001). CONCLUSION: Physicians' perception according to PO-Bado SF provides a different measure for psychosocial burden in patients with brain tumors, however does not completely reflect patients' wishes.

Compliance with patient-reported outcome assessment in glioma patients: predictors for drop out.

BACKGROUND: Patient-reported outcomes are of high importance in clinical neuro-oncology. However, assessment is still suboptimal. We aimed at exploring factors associated with the probability for a) drop out of study and b) death during follow-up. METHODS: Patients were assessed twice during follow-up visits scheduled within 3 to 5 months of each other by using 3 validated patient-reported outcome measures (t1: first assessment, t2: second assessment). As "death" was seen as a competing risk for drop out, univariate competing risk Cox regression models were applied to explore factors associated with dropping out (age, gender, WHO grade, living situation, recurrent surgery, Karnofsky Performance Status, time since diagnosis, and patient-reported outcomes assessed by Distress Thermometer, EORTC-QLQ-C30, EORTC-QLQ-BN20, and SCNS-SF-34G). RESULTS: Two hundred forty-six patients were eligible, 173 (70%) participated. Patients declining participation were diagnosed with glioblastomas more often than with other gliomas (56% vs 39%). At t2, 32 (18%) patients dropped out, n = 14 death-related, n = 18 for other reasons. Motor dysfunction (EORTC-QLQ-BN20) was associated with higher risk for non-death-related drop out (HR: 1.02; 95% CI, 1.00-1.03; P = .03). Death-related drop out was associated with age (HR: 1.09; 95% CI, 1.03-1.14; P = .002), Karnofsky Performance Status (HR: 0.92; 95% CI, 0.88-0.96; P < .001), lower physical functioning (EORTC-QLQ-C30; HR: 0.98; 95% CI, 0.96-1.00; P = .04) and lower motor functioning (EORTC-QLQ-BN20; HR: 1.020; 95% CI, 1.00-1.04; P = .02). CONCLUSION: Patients with motor dysfunction and poorer clinical condition seem to be more likely to drop out of studies applying patient-reported outcome measures. This should be taken into account when planning studies assessing glioma patients and for interpretation of results of patient-reported outcome assessments in clinical routine.

The patients' view: impact of the extent of resection, intraoperative imaging, and awake surgery on health-related quality of life in high-grade glioma patients-results of a multicenter cross-sectional study.

The objective of the present study is to assess the influence of extent of resection (EoR), use of intraoperative imaging, and awake surgery on health-related quality of life (HRQoL) in high-grade glioma (HGG) patients in a prospective multicenter study. We analyzed 170 surgeries of patients suffering from a HGG. During the first year after resection, HRQoL was evaluated using the European Organization of Research and Treatment of Cancer Core Questionnaire C30 and Brain Neoplasm 20 questionnaires. We assessed the influence of EoR; awake surgery; and use of 5-aminolevulinic acid (5-ALA), intraoperative MRI (iMRI), and their combination on sum scores for function and symptoms as well as several neurological single items. In mixed-model analyses, adjustments for age, Karnofsky performance status (KPS), and eloquent location were performed. In the mixed model, EoR generally did not significantly influence HRQoL (p = 0.10). Yet, patients receiving subtotal resection (STR) vs. patients with biopsy showed significantly better QoL and role and cognitive functions (p = 0.04, p = 0.02, and p < 0.01, respectively). The combination of iMRI and 5-ALA reached the highest EoR (95%) followed by iMRI alone (94%), 5-ALA alone (74%), and no imaging (73%). Thereby, neurological symptoms were lowest and functioning score highest after combined use of iMRI and 5-ALA, without reaching significance (p = 0.59). Despite lower scores in emotional function (59 vs. 46, p = 0.24), no significant impact of awake surgery on HRQoL was found (p = 0.70). In HGG patients, STR compared to biopsy was significantly associated with better HRQoL and fewer neurological symptoms in this series. An escalated use of intraoperative imaging increased EoR with stable or slightly better HRQoL and fewer neurological symptoms. Based on HRQoL, awake surgery was a well-tolerated and safe method in our series.

Factors associated with supportive care needs in glioma patients in the neuro-oncological outpatient setting.

Objective of this study aimed at assessing glioma patients' supportive care needs in a neurosurgical outpatient setting and identifying factors that are associated with needs for support. In three neuro-oncological outpatient departments, glioma patients were assessed for their psychosocial needs using the Supportive Care Needs Survey short-form (SCNS-SF34-G). Associations between clinical, sociodemographic, treatment related factors as well as distress (measured with the distress thermometer) and supportive care needs were explored using multivariable general linear models. One-hundred and seventy three of 244 eligible glioma patients participated, most of them with primary diagnoses of a high-grade glioma (81%). Highest need for support was observed in 'psychological needs' (median 17.5, range 5-45) followed by 'physical and daily living needs' (median 12.5, range 0-25) and 'health system and information needs' (median 11.3, range 0-36). Needs in the psychological area were associated with distress (R2 = 0.36) but not with age, sex, Karnofsky performance status (KPS), extend of resection, currently undergoing chemotherapy and whether guidance during assessment was offered. Regarding 'health system and information needs', we observed associations with distress, age, currently undergoing chemotherapy and guidance (R2 = 0.31). In the domain 'physical and daily living needs' we found associations with KPS, residual tumor, as well as with distress (R2 = 0.37). Glioma patients in neuro-oncological departments report unmet supportive care needs, especially in the psychological domain. Distress is the factor most consistently associated with unmet needs requiring support and could serve as indicator for clinical neuro-oncologists to initiate support.

Therapy for Recurrent High-Grade Gliomas: Results of a Prospective Multicenter Study on Health-Related Quality of Life.

OBJECTIVE: To assess the impact of therapy on patients' health-related quality of life (HRQoL) in recurrent high-grade glioma (HGG) in an unselected cohort. METHODS: In this prospective multicenter study, we analyzed European Organization for Research and Treatment of Cancer Quality of Life core questionnaire and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Brain Neoplasm module questionnaires of 92 patients within 1 year after diagnosis of tumor recurrence of a HGG and respective treatment. We evaluated the influence of re-radiation, second- and third-line chemotherapies, and number of recurrent surgeries on summary scores for functioning, symptoms, and total score as well as on subscores for functioning and neurologic symptoms using multivariate mixed models and descriptive statistics. RESULTS: After we adjusted for Karnofsky Performance Score and age, different recurrent therapies did not significantly impact HRQoL. Neither re-radiation nor recurrent surgery significantly influenced HRQoL (total score, P = 0.66; P = 0.64). Patients receiving second-line chemotherapy showed moderately better physical and role functioning as well as less motor dysfunction than patients receiving third-line chemotherapy. When we compared HRQoL after second-line chemotherapies, patients receiving intensified temozolomide dosages demonstrated a moderately better outcome for cognitive functioning and less communication deficits (P = 0.055) than patients treated with bevacizumab. Regarding number of recurrent surgeries, we found stable HRQoL scores until second recurrent surgery, whereas after third recurrent surgery HRQoL decreased. CONCLUSIONS: Our results from an unselected cohort of recurrent HGGs show that the currently available treatment options have no negative impact on HRQoL. Thus, treatment decisions can be made individually, without fear of jeopardizing HRQoL for better survival. Only, the third recurrent surgery remains a very individual decision even in younger patients with high Karnofsky Performance Score.

How I do it: The expanded trans/supraorbital approach for large space-occupying lesions of the anterior fossa.

BACKGROUND: The supraorbital rim often interferes with the required upward movement of the instruments for resection of large frontal-lobe tumours through a classic supraorbital craniotomy. Here, we present the expanded trans/supraorbital approach to overcome these limitations. METHODS: After an eyebrow skin incision, a one-piece bone flap was created incorporating the orbital rim and roof. Basal extension of the craniotomy allowed for a better intracranial visualisation with improved manoeuvrability and angulation of the instruments without using brain retraction. CONCLUSIONS: This approach poses a feasible alternative to large frontal craniotomies for frontal-lobe tumours, for which a regular supraorbital craniotomy is insufficient.

How I do it: the mononostril endonasal transethmoidal-paraseptal approach.

BACKGROUND: The use of endoscopes in transnasal surgery offers increased visualization. To minimize rhinological morbidity without restriction in manipulation, we introduced the mononostril transethmoidal-paraseptal approach. METHODS: The aim of the transethmoidal-paraseptal approach is to create sufficient space within the nasal cavity, without removal of nasal turbinates and septum. Therefore, as a first step, a partial ethmoidectomy is performed. The middle and superior turbinates are then lateralized into the ethmoidal space, allowing a wide sphenoidotomy with exposure of the central skull base. CONCLUSIONS: This minimally invasive transethmoidal-paraseptal approach is a feasible alternative to traumatic transnasal concepts with middle turbinate and extended septal resection.

Evaluating patients for psychosocial distress and supportive care needs based on health-related quality of life in primary brain tumors: a prospective multicenter analysis of patients with gliomas in an outpatient setting.

The association between health-related quality of life (HRQoL), psychosocial distress, and supportive care is in the focus of patient-centered neuro-oncology. We investigated the relationship between the aforementioned in glioma-patients to evaluate the association of these instruments and determine cut-off values for suitable HRQoL scales indicating a potential need for intervention. In an observational multi-center study, outpatients completed the Distress Thermometer (DT), EORTC Quality of Life Questionnaire (EORTC-QLQ-C30/BN20, HRQoL), and Supportive-Care-Needs-Survey-SF34-G (SCNS). Based on nine EORTC-function and selected -symptom scales items of the questionnaires were matched. Convergent validity of related single items and scores across the instruments was estimated. EORTC cut-off values were calculated. Data of 167 patients were analyzed. The strongest correlation of EORTC-QLQ-C30 and DT was found for cognitive function (cogf), global health status (GHS), emotional (emof), role function (rolef), future uncertainty (FU), fatigue, and between EORTC-QLQ-C30 and SCNS for FU, emof, rolef (r = |0.4-0.7|; p < 0.01). EORTC cut-off values of <54.2 (GHS/QoL) and <62.5 (emof) predicted a DT ≥ 6 (AUC 0.79, 0.85, p < 0.01). EORTC cut-off values of <70.8 (emof) and <52.8 (FU) predicted the need for supportive care (AUC 0.78, 0.85; p < 0.01). Worse EORTC-C30 scores correlate with higher DT and SCNS scores. With this exploratory assessment, cut-off values for EORTC-C30 subscores to predict distress and pathological SCNS-scores could be determined, which could influence patients' referral to further treatment. However, further prospective clinical trials are needed to confirm the clinical relevance of these cut-off values.

Suicidal ideation, depression, and health-related quality of life in patients with benign and malignant brain tumors: a prospective observational study in 83 patients.

OBJECTIVE: Health-related quality of life (HRQoL) and psychosocial burden are of relevance in patients with intracranial tumors. We investigated the prevalence of suicidal ideation (SI), depression, and their association with HRQoL in patients with intra- (IA) and extraaxial (EA) tumors during the first 9 months after diagnosis. METHODS: Patients were recruited immediately following surgery, and re-evaluated after 3, 6, and 9 months (EORTC QLQ-C30/BN20, Beck Depression Inventory (BDI) and Appendix). Patients with a personal history of psychological comorbidity were excluded. Sociodemographic and clinical data were evaluated. RESULTS: IA patients had lower functioning scores and experienced more symptoms. Global Health Status was significantly lower at baseline (p = 0.038), but improved over time (p < 0.001). Seventeen patients (21.5 %) admitted to having had SI at least once during the study period (IA: n = 10/EA: n = 7). The highest rates were observed after 6 (IA: 18.8 %) and 9 months (EA: 10.0 %). Patients reporting SI had significantly higher BDI scores [p = 0.22 (baseline), p = 0.031 (3 months), p < 0.001 (6 months)]. After 6 months, HRQoL differed greatest between patients with and without SI. Most patients experienced good familial support (76 %). CONCLUSIONS: Patients with intracranial tumors suffer from decreased HRQoL and SI regardless of histopathology. SI is associated with higher BDI scores, but not evident depression (BDI ≥ 18). Thus, patients should be screened specifically and regularly. Lower HRQoL and greatest prevalence of SI at 6 months may help clinicians to find the right time for careful monitoring of patients at risk.

Supraorbital Keyhole Approach to the Skull Base: Evaluation of Complications Related to CSF Fistulas and Opened Frontal Sinus.

AIM: Cerebrospinal fluid (CSF) rhinorrhea due to a breach in the frontal sinus (FS) presents one of the main postoperative complications of the supraorbital keyhole approach. The goal of this study was to further analyze the actual surgical morbidity and potential risk for patients due to an opened FS after a surgery via a supraorbital craniotomy and compare the results with data published in the current literature. METHODS AND PATIENTS: A total of 350 consecutive patients who underwent surgeries via the supraorbital keyhole approach for various lesions were included in this retrospective study. Information on clinical history, neurologic symptoms, surgical approach, and postoperative complications was obtained retrospectively by a review of the patients' charts, the radiologic reports, and a thorough review of pre- and postoperative cranial computed tomography (CCT) imaging. RESULTS: The frequency of CSF rhinorrhea after this type of craniotomy in the literature is reported to range between 0% and 9.1%. In this study, analysis of postoperative CCT scans revealed that 88 patients (25.1%) showed a radiographic breach of the FS. Only 8 of these patients (2.3%) developed a CSF leak with rhinorrhea postoperatively. In all cases conservative treatment with lumbar drainage failed, and therefore a surgical revision for permanent closure was required. Only one patient (0.3%) with a CSF leak also developed meningitis. CONCLUSION: Inadvertent opening of the FS during the supraorbital craniotomy is a common surgery-related morbidity; however, the risk for the patient to develop a potentially dangerous meningitis was found to be minimal.

Feasibility of fluorescence-guided resection of recurrent gliomas using five-aminolevulinic acid: retrospective analysis of surgical and neurological outcome in 58 patients.

Five-aminolevulinic-acid (5-ALA) is known for its benefits in surgery of primary gliomas, but has only been cautiously used in recurrent gliomas dreading over-resection, insufficient or false-positive fluorescence in adjuvantly treated tumors. We evaluated intraoperative fluorescence based on tumor pathology, pretreatment as well as surgical and neurological outcome in patients with recurrent gliomas. Patients who underwent fluorescence-guided surgery for recurrent gliomas between 6/2010 and 2/2014 at our institution were retrospectively selected. Degree of surgical resection, neurological status, pathology results, intraoperative fluorescence and follow up status were analyzed. Patients who underwent repeat surgery without 5-ALA were selected as controls. 58 patients with high grade gliomas (°III and °IV) were included. 10 of 63 tumors (15.9 %) failed to fluoresce intraoperatively of which nine (90 %) had been adjuvantly treated prior to recurrence, as were 46 of the 53 fluorescing tumors (86.8 %). Non-fluorescing tumors were IDH mutated significantly more often (p = 0.005). 30 tumors (47.6 %) were located eloquently. 51 (80.9 %) patients showed no new neurologic deficits postoperatively. 13 patients (20.6 %) showed no signs of recurrence at their latest follow up. Eight patients were lost to follow up. Overall survival was significantly longer in the 5-ALA group (p = 0.025). Fluorescence-guided surgery in recurrent gliomas is safe and allows for a good surgical and neurological outcome in a difficult surgical environment, especially when used in combination with neuronavigation and intraoperative ultrasound to prevent over-resection. Adjuvant therapy did not significantly influence fluorescing properties.