Use of complementary therapies and supportive measures of patients with intracranial gliomas-a prospective evaluation in an outpatient clinic.

PURPOSE: Patients with intracranial gliomas frequently seek for complementary and alternative medicine (CAM), in addition to guideline-directed therapy. In this study, we therefore assessed patients' information needs regarding treatment and support, and evaluated their attitudes toward experimental trials and alternative therapies. METHODS: A prospective, cross-sectional, descriptive survey was conducted in our center. We developed an interview focusing on how patients obtain further information about therapy and the use of alternative/complementary therapies. RESULTS: A total of 102 patients participated in the survey. 50% (n = 51) of patients reported that they had not attempted any additional therapies. When patients attempted self-therapy, it was most commonly in the areas of nutrition (25%, n = 26) and dietary supplements (17%, n = 17). Alternative or complementary therapies were used by 14% (n = 14) of the patients. Younger age (Odds ratio (OR) 0.96 (95% Confidence interval (CI) 0.92-0.99, p = 0.012) and tumor entity (OR 5.01 (95% CI 1.66-15.11, p = 0.004) for grade 4 vs. 3 tumors and OR 7.22 (95% CI 1.99-26.28) for grade 4 vs. other tumors p = 0.003) were significantly associated with a greater interest in CAM. CONCLUSIONS: Interest in complementary and alternative medicine, as well as nutrition and dietary supplements is high (51%) among glioma patients, and significantly higher among younger patients and those with a worse diagnosis (WHO grade 4). A comprehensive approach to information, including paramedical topics, is needed to provide optimal patient counseling and care for glioma patients.

Insights from a multicenter study on adult H3 K27M-mutated glioma: Surgical resection's limited influence on overall survival, ATRX as molecular prognosticator.

BACKGROUND: H3 K27M-mutated gliomas were first described as a new grade 4 entity in the 2016 World Health Organization classification. Current studies have focused on its typical appearance in children and young adults, increasing the need to better understand the prognostic factors and impact of surgery on adults. Here, we report a multicentric study of this entity in adults. METHODS: We included molecularly confirmed H3 K27M-mutated glioma cases in patients ≥ 18 years diagnosed between 2016 and 2022. Clinical, radiological, and surgical features were analyzed. Univariate and multivariate analyses were performed to identify prognostic factors. RESULTS: Among 70 patients with a mean age of 36.1 years, the median overall survival (OS) was 13.6 ±â€…14 months. Gross-total resection was achieved in 14.3% of patients, whereas 30% had a subtotal resection and 54.3% a biopsy. Tumors located in telencephalon/diencephalon/myelencephalon were associated with a poorer OS, while a location in the mesencephalon/metencephalon showed a significantly longer OS (8.7 vs. 25.0 months, P = .007). Preoperative Karnofsky-Performance Score (KPS) ≤ 80 showed a reduced OS (4.2 vs. 18 months, P = .02). Furthermore, ATRX loss, found in 25.7%, was independently associated with an increased OS (31 vs. 8.3 months, P = .0029). Notably, patients undergoing resection showed no survival benefit over biopsy (12 vs. 11 months, P = .4006). CONCLUSIONS: The present study describes surgical features of H3 K27M-mutated glioma in adulthood in a large multicentric study. Our data reveal that ATRX status, location and KPS significantly impact OS in H3 K27M-mutated glioma. Importantly, our dataset indicates that resection does not offer a survival advantage over biopsy.

Treatment outcome of IDH1/2 wildtype CNS WHO grade 4 glioma histologically diagnosed as WHO grade II or III astrocytomas.

BACKGROUND: Isocitrate dehydrogenase (IDH)1/2 wildtype (wt) astrocytomas formerly classified as WHO grade II or III have significantly shorter PFS and OS than IDH mutated WHO grade 2 and 3 gliomas leading to a classification as CNS WHO grade 4. It is the aim of this study to evaluate differences in the treatment-related clinical course of these tumors as they are largely unknown. METHODS: Patients undergoing surgery (between 2016-2019 in six neurosurgical departments) for a histologically diagnosed WHO grade 2-3 IDH1/2-wt astrocytoma were retrospectively reviewed to assess progression free survival (PFS), overall survival (OS), and prognostic factors. RESULTS: This multi-center study included 157 patients (mean age 58 years (20-87 years); with 36.9% females). The predominant histology was anaplastic astrocytoma WHO grade 3 (78.3%), followed by diffuse astrocytoma WHO grade 2 (21.7%). Gross total resection (GTR) was achieved in 37.6%, subtotal resection (STR) in 28.7%, and biopsy was performed in 33.8%. The median PFS (12.5 months) and OS (27.0 months) did not differ between WHO grades. Both, GTR and STR significantly increased PFS (P < 0.01) and OS (P < 0.001) compared to biopsy. Treatment according to Stupp protocol was not associated with longer OS or PFS compared to chemotherapy or radiotherapy alone. EGFR amplification (P = 0.014) and TERT-promotor mutation (P = 0.042) were associated with shortened OS. MGMT-promoter methylation had no influence on treatment response. CONCLUSIONS: WHO grade 2 and 3 IDH1/2 wt astrocytomas, treated according to the same treatment protocols, have a similar OS. Age, extent of resection, and strong EGFR expression were the most important treatment related prognostic factors.

Predictors of Neurological Worsening after Resection of Spinal Meningiomas.

BACKGROUND: Due to the slow-growing nature of spinal meningiomas, they are mostly asymptomatic for a long time, and become symptomatic after the compression of the spinal cord or nerve roots. The aim of this study was to identify predictors for a poor clinical outcome after the surgical resection of spinal meningiomas and thereby to allow a preoperative identification of high-risk spinal meningiomas. METHODS: Data acquisition was conducted as a single-center retrospective analysis. From 1 January 2004 to 31 December 2019, 121 patients who underwent surgical resection of a spinal meningioma were reviewed. Clinical and radiological data (such as tumor size, location, occupation ratio of the spinal canal, and the degree of spinal cord compression) were assessed. The functional clinical findings of the patients were recorded using the Karnofsky Performance Score, modified McCormick scale, and Frankel scale preoperatively, at discharge, and 3-6 months after surgery. RESULTS: The mean patient age was 66 ± 13 years. A total of 104 (86%) patients were female and 17 (14%) were male. The thoracic spine (68%) was the most common location, followed by the cervical (29%) and lumbar (3%) spine. Preoperatively, 11.7% of patients were categorized as McCormick 1, 35.8% as 2, 39.2% as 3, 11.7% as 4, and 1.7% as 5. The neurological function of the patients with a functional deficit prior to surgery improved in 46% of the patients, remained unchanged in 52%, and worsened in 2% at discharge. At early follow-up, the proportions were 54%, 28%, and 5%, respectively. Preoperative Frankel scale was a significant predictor of a postoperative deterioration. Patients with Frankel score A to C preoperatively had a 9.2 times higher chance of clinical deterioration postoperatively (OR = 9.16). We found that the Frankel scale weakly correlated with the degree of spinal cord compression. In this study, other radiological parameters, such as the degree of cord compression and spinal canal occupation ratio, did not show a significant effect on the outcome. CONCLUSIONS: Surgery of intraspinal meningiomas can be considered safe. Neurological function improves in a large proportion of patients after surgery. However, a relevant preoperative deficit according to the Frankel scale (grade A-C) was a significant predictor of a postoperative neurological deterioration.

Pituitary Surgery in Germany - Findings from the European Pituitary Adenoma Surgery Survey.

BACKGROUND: Surgery is, next to medical and radiation therapy, the mainstay therapy for pituitary adenomas. While scientific consensus regarding the key aspects of pituitary surgery exists among neurosurgeons, procedures are not standardized and might vary significantly between hospitals and surgeons. OBJECTIVE: To provide an overview of how neurosurgical departments in Germany manage pituitary surgery. METHODS: Responses from the European Pituitary Adenoma Surgery Survey were analyzed. The survey contained 60 questions regarding demographics, training, surgical and endocrinological aspects, and patient management. RESULTS: Sixty neurosurgical centers from Germany responded to the survey. Among the centers, 35.3% (n=18) exclusively use the microscopic and 31.1% (n=14) the endoscopic technique; all other centers (n=28) use both approaches. Of responding centers, 20% (n=12) perform less than 10 transsphenoidal pituitary surgeries per year, and 1.7% (n=1), more than 100 operations. The number of transcranial pituitary operations is significantly smaller, with 53.3% of centers performing only 0-2 per year, 35% performing 3-5, and only one center (1.7%) performing more than 15 transcranial operations per year. In 8 centers (13.3%), surgeries are always performed together with an ENT surgeon; in 29 centers (48.4%) ENT surgeons are never involved. In most centers (n=54, 90%) intraoperative MRI is not available. Image guidance (with preoperative CT and/or MRI data) is used by 91.7% of respondents (n=55). Forty-two centers (72.4%) routinely prescribe hydrocortisone after pituitary surgery, and 75% (n=45) have pituitary board meetings with endocrinologists, radiologists, and radiosurgeons. Fifty-two (86.7%) respondents perform the first follow-up scan by MRI 3-4 months after surgery. CONCLUSIONS: The data showed differences as well as similarities between centers and could help to discuss the standardization of methods and the formation of networks and certification to improve patient care.

Multiple myeloma presenting as a cervical intraforaminal tumor: A case report and review of literature.

Multiple myeloma (MM) is a hematological malignancy with characteristic clonal plasma cell proliferation and production of monoclonal immunoglobulins. Although it can often metastasize to the bony spine, completely extravertebral and extra-/intradural manifestations are exceedingly rare. In this case report, we describe a 51-year-old male patient with cervical extradural and intraforaminal MM who was surgically treated in our department. Clinical findings and radiological images were retrieved from medical records and an imaging system. This unusual localization of MM and similar cases in the literature are reviewed in detail. The patient underwent tumor resection via a ventral approach, and postoperative MRI demonstrated a sufficient decompression of neural structures. No new neurological deficits were observed at subsequent follow-ups. Although 7 cases of extramedullary extradural manifestations of multiple myeloma have been described in the literature so far, this is the first case of intraforaminal extramedullary multiple myeloma located in the cervical spine and treated by surgery.

Qualitative Assessment of Titanium versus Carbon Fiber/Polyetheretherketone Pedicle Screw-Related Artifacts: A Cadaveric Study.

BACKGROUND: Dorsal instrumentation and decompression are the mainstays of spinal tumor treatment. Replacing titanium screws with carbon fiber-reinforced polyetheretherketone (CFRP) screws can reduce imaging artifacts on neural structures and perturbations of radiation dose. Further reduction of metal content in such screws might enhance the benefit. The aim of this study was to assess the artifacts produced by all-titanium screws (Ti-Ti), CFRP thread-titanium screw heads (C-Ti), and all-CFRP screws (C-C). METHODS: A cadaveric spine was used to place Ti-Ti, C-Ti, and C-C consecutively from T2 to S1. Computed tomography and 1.5T and 3T magnetic resonance imaging were performed for each screw system. Axial T1- and T2-weighted sequences of representative thoracic and lumbar regions were assessed for artifacts. The artifacts were classified as not relevant, considerable, or severe. RESULTS: We evaluated 92 screws and made 178 artifact assessments. The artifacts were clearly visible in computed tomography scans but did not influence the visualization of intraspinal structures. Severe magnetic resonance imaging artifacts were found in 28% (17/60, mostly in the thoracic spine) of Ti-Ti, 2% (1/60, all T1 sequences) of C-Ti, and 0% of C-C, and considerable artifacts were found in 47% (28/60) of Ti-Ti, 10% (6/60, only 1 T2 sequence) of C-Ti, and 0% of C-C screws (P < 0.001). CONCLUSIONS: CFRP pedicle screws reduced the artifact intensity in spinal structures compared with titanium screws, and may be beneficial for planning radiotherapy and for follow-up imaging. C-C demonstrated an enhanced effect on dorsal structures.

Beyond Glioma: The Utility of Radiomic Analysis for Non-Glial Intracranial Tumors.

The field of radiomics is rapidly expanding and gaining a valuable role in neuro-oncology. The possibilities related to the use of radiomic analysis, such as distinguishing types of malignancies, predicting tumor grade, determining the presence of particular molecular markers, consistency, therapy response, and prognosis, can considerably influence decision-making in medicine in the near future. Even though the main focus of radiomic analyses has been on glial CNS tumors, studies on other intracranial tumors have shown encouraging results. Therefore, as the main focus of this review, we performed an analysis of publications on PubMed and Web of Science databases, focusing on radiomics in CNS metastases, lymphoma, meningioma, medulloblastoma, and pituitary tumors.

Frailty in Glioblastoma Is Independent From Chronological Age.

Objective: Treatment of glioblastoma in elderly patients is particularly challenging due to their general condition and comorbidities. Treatment decisions are often based on chronological age. Frailty screening tests promise an assessment tool to stratify geriatric patients and identify those at risk for an unfavorable outcome. This study aims to evaluate the impact of age and frailty on the surgical outcome and overall survival in geriatric patients with glioblastoma. Methods: Data acquisition was conducted as a single-center retrospective analysis. From January 1st 2015, and December 31st 2019, 104 glioblastoma patients over 70 years of age were included in our study. Demographic data, tumor size, Karnofsky Performance Score (KPS), and Eastern Cooperative Oncology Group Performance Status (ECOG), as well as treatment modalities, were assessed. The Geriatric 8 health status screening tool (G8) and Groningen Frailty Index (GFI) were compiled pre-and postoperatively. Results: The mean patient age was 76.86 ± 4.11 years. Forty-nine (47%) patients were female, 55 (53%) male. Sixty-seven patients underwent microsurgical tumor resection, 37 received tumor biopsy alone. Mean G8 on admission was 12.4 ± 2.0, mean GFI 5.0 ± 2.5. In our cohort, frailty was independent of patient age, tumor size, or localization. Frailty, defined by G8 and GFI, is associated with shorter overall survival (G8: p = 0.0035; GFI: p = 0.0136) and higher numbers of surgical complications (G8: p = 0.0326; GFI: p = 0.0388). Frailer patients are more likely to receive best supportive care (p = 0.004). Nevertheless, frailty did not affect adjuvant treatment decision-making toward either single-use of chemo- or radiation therapy, stratified treatment, or concomitant therapy. The surgical decision on the extent of resection was not based on pre-operative frailty. Conclusion: In our study, frailty is a predictor of poorer surgical outcomes, post-operative complications, and impaired overall survival independent of chronological age. Frailty screening tests offer an additional assessment tool to stratify geriatric patients with glioblastoma and identify those at risk for a detrimental outcome and thus should be implemented in therapeutic decision making.

Distress and quality of life do not change over time in patients with operated and conservatively managed intracranial meningioma.

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.

An age-dependent outcome analysis of microvascular decompression and percutaneous thermocoagulation in trigeminal neuralgia.

BACKGROUND: Trigeminal neuralgia (TN) is a severe pain condition and the most common facial neuralgia. While microvascular decompression (MVD) presents an excellent treatment in neurovascular compression cases, percutaneous thermocoagulation (PT) of the ganglion Gasseri is an alternative option. This study aimed to evaluate post-operative complication rate and outcome of both treatment strategies related to the patient's age. METHODS: The medical records of all patients with the diagnosis of trigeminal neuralgia undergoing an MVD or PT of the ganglion Gasseri (between January 2007 and September 2017) were reviewed to determine the efficacy and the complication rate of both methods in regard to the patient's age. RESULTS: Seventy-nine patients underwent MVD surgery and 39 a PT. The mean age of patients in the MVD group was 61 years and 73 years in the PT group. There were 59 (50%) female patients. Nerve-vessel conflict could be identified in 78 (98.7%) MVD and 17 (43.6%) PT patients on preoperative MRI. Charlson comorbidity index was significantly higher in PT group (2.4 (1.8) versus 3.8 (1.8) p < 0.001). The Barrow pain score (BPS) at the last follow-up demonstrated higher scores after PT (p = 0.007). The complication rate was markedly higher in PT group, mostly due to the facial hypesthesia (84.6% versus 27.8%; p < 0.001). Mean symptom-free survival was significantly shorter in the PT group (9 vs. 26 months, p < 0.001). It remained statistically significant when stratified into age groups: (65 years and older: 9 vs. 18 months, p = 0.001). Duration of symptoms (OR 1.005, 95% CI 1.000-1.010), primary procedure (OR 6.198, 95% CI 2.650-14.496), patient age (OR 1.033, 95% CI 1.002-1.066), and postoperative complication rate (OR 2.777, 95% CI 1.309-5.890) were associated with treatment failure. CONCLUSION: In this patient series, the MVD is confirmed to be an excellent treatment option independent of patient's age. However, while PT is an effective procedure, time to pain recurrence is shorter, and the favorable outcome (BPS 1 and 2) rate is lower compared to MVD. Hence MVD should be the preferred treatment and PT should remain an alternative in very selected cases when latter is not possible but not in the elderly patient per se.

Evaluation of Resection Margin after Image-Guided Dural Tail Resection in Convexity Meningiomas.

Infiltration of adjacent dura with meningioma cells is a common phenomenon. Wide resection of the dural tail (DT) to achieve a gross total resection is a general recommendation. We aimed to investigate a tumor cell infiltration of the DT after image-guided resection of convexity meningiomas. The study's inclusion criteria were the diagnosis of convexity meningioma, planned Simpson I° resection, and an identifiable DT. Intraoperative image-guidance was applied to identify the outer edge of the DT and to guide resection. After resection, en-bloc specimen or four samples of outermost pieces of DT in case of piecemeal resection were sent for histological analysis. In addition to resection margin infiltration, the radiological extent of DT, radiomic characteristics (109 in total), histology, and demographic data were assessed. Hierarchical clustering was used to generate patient clusters for radiomic analysis. Twenty-two patients were included in the study, while 20 (91%) were female. The mean age was 54.2 (Standard deviation (SD) 13.9, range 30-85) years. En-bloc resection could be achieved in 4 patients. The remaining patients received piecemeal resection. 2 DT samples were omitted due to tumor infiltration of the superior sagittal sinus. None of the en-bloc resection samples demonstrated dural infiltration on the resection margin. Tumor cells were detected in 4 of 70 (5.7%) dural tail samples and could not be excluded in another 5 of 70 (7.1%). No tumor recurrences were detected at follow-up MRI examinations after a mean follow-up of 27.5 (SD 13.2, range 0 to 50.0) months. There was no significant association between DT infiltration and histological subtype or patient characteristics and between DT extent and tumor infiltration. Clustering according to radiomic characteristics was not associated with tumor infiltration (p = 0.89). The radiological dural tail does not reliably outline the extent of tumor cell infiltration in convexity meningiomas. Hence, the extent of dural tail resection should not exclusively be guided by preoperative radiological appearance.

The association of patient age with postoperative morbidity and mortality following resection of intracranial tumors.

Introduction: The postoperative functional status of patients with intracranial tumors is influenced by patient-specific factors, including age. Research question: This study aimed to elucidate the association between age and postoperative morbidity or mortality following the resection of brain tumors. Material and methods: A multicenter database was retrospectively reviewed. Functional status was assessed before and 3-6 months after tumor resection by the Karnofsky Performance Scale (KPS). Uni- and multivariable linear regression were used to estimate the association of age with postoperative change in KPS. Logistic regression models for a ≥10-point decline in KPS or mortality were built for patients ≥75 years. Results: The total sample of 4864 patients had a mean age of 56.4 â€‹± â€‹14.4 years. The mean change in pre-to postoperative KPS was -1.43. For each 1-year increase in patient age, the adjusted change in postoperative KPS was -0.11 (95% CI -0.14 - - 0.07). In multivariable analysis, patients ≥75 years had an odds ratio of 1.51 to experience postoperative functional decline (95%CI 1.21-1.88) and an odds ratio of 2.04 to die (95%CI 1.33-3.13), compared to younger patients. Discussion: Patients with intracranial tumors treated surgically showed a minor decline in their postoperative functional status. Age was associated with this decline in function, but only to a small extent. Conclusion: Patients ≥75 years were more likely to experience a clinically meaningful decline in function and about two times as likely to die within the first 6 months after surgery, compared to younger patients.

Evaluation of 3D Robotic-Guided Exoscopic Visualization in Microneurosurgery.

Objective: The three-dimensional (3D) exoscope is a novel apparatus introduced in recent years. Although an operating microscope (OM) is customarily used, this novel application offers several advantages. Therefore, this study aimed to determine the feasibility of deploying a robotic-guided 3D-exoscope for microneurosurgery and gauge its subsequent performance. Methods: The use of a 3D exoscope was compared with that of OM during 16 surgical procedures. Postoperatively, surgeons completed an eight-item Likert-scale satisfaction survey. As a second step, a predefined surgical task was then undertaken by surgeons with varying levels of experience, assessing the time entailed. Two questionnaires, the satisfaction survey and NASA task load index (NASA-TLX), were administered. Results: During routine procedures, the exoscope proved superior in magnification and ergonomic maintenance, showing inferior image contrast, quality, and illumination. It again ranked higher in magnification and ergonomic maintenance during the suturing task, and the OM excelled in treatment satisfaction and stereoscopic orientation. Workload assessment using the NASA-TLX revealed no difference by modality in the pairwise analysis of all components. At varying levels of experience, beginners bear a significantly higher burden in all principle components than mid-level and expert participants (p = 0.0018). Completion times for the suturing task did not differ (p = 0.22). Conclusion: The quality of visualization by 3D exoscope seems adequate for treatment and its ergonomic benefit is superior to that of OM. Although experienced surgeons performed a surgical simulation faster under the OM, no difference was evident in NASA-TLX surveys. The 3D exoscope is an excellent alternative to the OM.

Psychological Burden in Meningioma Patients under a Wait-and-Watch Strategy and after Complete Resection Is High-Results of a Prospective Single Center Study.

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.

Identification of High-Risk Atypical Meningiomas According to Semantic and Radiomic Features.

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.

Development and external validation of a clinical prediction model for functional impairment after intracranial tumor surgery.

OBJECTIVE: Decision-making for intracranial tumor surgery requires balancing the oncological benefit against the risk for resection-related impairment. Risk estimates are commonly based on subjective experience and generalized numbers from the literature, but even experienced surgeons overestimate functional outcome after surgery. Today, there is no reliable and objective way to preoperatively predict an individual patient's risk of experiencing any functional impairment. METHODS: The authors developed a prediction model for functional impairment at 3 to 6 months after microsurgical resection, defined as a decrease in Karnofsky Performance Status of ≥ 10 points. Two prospective registries in Switzerland and Italy were used for development. External validation was performed in 7 cohorts from Sweden, Norway, Germany, Austria, and the Netherlands. Age, sex, prior surgery, tumor histology and maximum diameter, expected major brain vessel or cranial nerve manipulation, resection in eloquent areas and the posterior fossa, and surgical approach were recorded. Discrimination and calibration metrics were evaluated. RESULTS: In the development (2437 patients, 48.2% male; mean age ± SD: 55 ± 15 years) and external validation (2427 patients, 42.4% male; mean age ± SD: 58 ± 13 years) cohorts, functional impairment rates were 21.5% and 28.5%, respectively. In the development cohort, area under the curve (AUC) values of 0.72 (95% CI 0.69-0.74) were observed. In the pooled external validation cohort, the AUC was 0.72 (95% CI 0.69-0.74), confirming generalizability. Calibration plots indicated fair calibration in both cohorts. The tool has been incorporated into a web-based application available at https://neurosurgery.shinyapps.io/impairment/. CONCLUSIONS: Functional impairment after intracranial tumor surgery remains extraordinarily difficult to predict, although machine learning can help quantify risk. This externally validated prediction tool can serve as the basis for case-by-case discussions and risk-to-benefit estimation of surgical treatment in the individual patient.

Diversity of Clinically Relevant Outcomes Resulting from Hypofractionated Radiation in Human Glioma Stem Cells Mirrors Distinct Patterns of Transcriptomic Changes.

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.

Intratumoral Heterogeneity and Longitudinal Changes in Gene Expression Predict Differential Drug Sensitivity in Newly Diagnosed and Recurrent Glioblastoma.

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.

Impact of postoperative radiotherapy on recurrence of primary intracranial atypical meningiomas.

BACKGROUND: Atypical meningiomas (WHO grade II) have high recurrence rate. However, data on the effect of radiotherapy (RT) is still conflicting. The aim of this study was to evaluate the influence of postoperative RT on the recurrence of primary atypical intracranial meningiomas. METHODS: The medical records of all patients who underwent surgery (2007-2017 in 4 neurosurgical departments) for a histologically diagnosed primary atypical meningioma were reviewed to assess progression-free survival (PFS) and prognostic factors. RESULTS: This analysis included 258 patients with a median age of 60 years (54.7% female). The predominant tumor locations were convexity and falx (60.9%) followed by the skull base (37.2%). Simpson grade I-II resection was achieved in 194 (75.2%) patients, Simpson grade III-IV in 53 patients (20.5%). Tumor progressed in 54 cases (20.9%). Postoperative RT was performed in 46 cases (17.8%). RT was more often applied after incomplete resection (37.7% vs. 13.4% Simpson III-IV vs. I-II). A multivariate analysis showed a significantly shorter PFS associated with Simpson III-IV [HR 1.19, (95% CI) 1.09-1.29, p < 0.001] and age > 65 years [HR 2.89, (95% CI) 1.56-5.33, p = 0.001]. A subgroup analysis with a minimal follow-up of 36 months revealed that Simpson III-IV [HR 3.01, 95% CI 1.31-6.931.03-1.24, p = 0.009] and age > 65 years [HR 2.48, 95% CI 1.20-5.13, p = 0.014] reduced PFS. The impact of postoperative RT on PFS remained statistically insignificant, even in a propensity-score matched survival analysis [n = 46; p = 0.438; OR 0.710 (0.299-1.687)]. CONCLUSIONS: In the present study, postoperative RT did not improve PFS. The most important prognostic factors remain the extent of resection and age.