Precision neuro-oncology: a pilot analysis of personalized treatment in recurrent glioma.

PURPOSE: When brain cancer relapses, treatment options are scarce. The use of molecularly matched targeted therapies may provide a feasible and efficacious way to treat individual patients based on the molecular tumor profile. Since little information is available on this strategy in neuro-oncology, we retrospectively analyzed the clinical course of 41 patients who underwent advanced molecular testing at disease relapse. METHODS: We performed Sanger sequencing, targeted next generation sequencing, and immunohistochemistry for analysis of potential targets, including programmed death ligand 1, cyclin D1, phosphorylated mechanistic target of rapamycin, telomerase reverse transcriptase promoter mutation, cyclin-dependent kinase inhibitor 2A/B deletion, or BRAF-V600E mutation. In selected patients, whole exome sequencing was conducted. RESULTS: The investigation included 41 patients, of whom 32 had isocitrate dehydrogenase (IDH) wildtype glioblastoma. Molecular analysis revealed actionable targets in 31 of 41 tested patients and 18 patients were treated accordingly (matched therapy group). Twenty-three patients received molecularly unmatched empiric treatment (unmatched therapy group). In both groups, 16 patients were diagnosed with recurrent IDH wildtype glioblastoma. The number of severe adverse events was comparable between the therapy groups. Regarding the IDH wildtype glioblastoma patients, median progression-free survival (mPFS) and median overall survival (mOS) were longer in the matched therapy group (mPFS: 3.8 versus 2.0 months, p = 0.0057; mOS: 13.0 versus 4.3 months, p = 0.0357). CONCLUSION: These encouraging data provide a rationale for molecularly matched targeted therapy in glioma patients. For further validation, future study designs need to additionally consider the prevalence and persistence of actionable molecular alterations in patient tissue.

Long-term outcome after management of pilocytic astrocytoma in the posterior fossa in a pediatric population.

Background and purpose: To assess the impact of posterior fossa pilocytic astrocytoma (PA) removal in pediatric patients, with special focus on postoperative neurological outcome after repeated surgery for tumor remnants. Methods: Our institutional database was screened for patients with PA treated between 2000 and 2019. Patients ≤ 18 years of age with complete clinical records, preoperative contrast enhanced magnetic resonance imaging (MRI) and postoperative follow-up time of ≥ 6 months were suitable for study inclusion. Functional outcome was quantified with the modified Ranking Scale (mRS) score and assessed at admission, at discharge and at every follow-up investigation. Predictors of hydrocephalus, cranial nerve deficits and tumor recurrence were evaluated. Results: A total of 57 pediatric patients with a mean age of 7.7 ± 4.8 years were included in the analysis. 27 (47.3%) children suffered from hydrocephalus at diagnosis, out of which 19 (33.3%) required a subsequent VP-Shunt. 22 (39.3%) patients had a partial resection, of which 9 (40.9%) went through second-look surgery. 2 patients with initially radiological confirmation of complete resection, had a tumor recurrence at FU and needed second-look surgery. Among the children requiring second-look surgery, 7 (63.6%) had a complete resection. Favorable outcome (mRS≤2) after initial and second-look surgery was observed in 52 patients (91.2%). Univariate analysis identified tumor location in the floor of the 4th ventricle (p = 0.030), and repeated surgery for tumor remnant removal (p = 0.043) as predictors for post-operative cranial nerve deficits. Multivariate analysis confirmed this independent association. The incidence of tumor recurrence occurred more often in patients with previous partial resection (p = 0.009) as well as in lesions located in the cerebellar peduncles (p = 0.043). Partial resection remained an independent predictor after multivariate logistic regression analysis (p = 0.045). Conclusions: Incomplete resection of posterior fossa PA is a risk factor for tumor recurrence and repeated surgery to remove tumor remnants increases the risk of new postoperative deficits. Thus, the risk of iatrogenic deterioration due to second look surgery should be implemented in the primary pre- and intraoperative decision-making.

Time interval between the diagnosis of breast cancer and brain metastases impacts prognosis after metastasis surgery.

PURPOSE: Breast cancer (BC) is the most frequently diagnosed tumor entity in women. Occurring at different time intervals (TI) after BC diagnosis, brain metastases (BM) are associated with poor prognosis. We aimed to identify the risk factors related to and the clinical impact of timing on overall survival (OS) after BM surgery. METHODS: We included 93 female patients who underwent BC BM surgery in our institution (2008-2019). Various clinical, radiographic, and histopathologic markers were analyzed with respect to TI and OS. RESULTS: The median TI was 45.0 months (range: 9-334.0 months). Fifteen individuals (16.1%) showed late occurrence of BM (TI ≥ 10 years), which was independently related to invasive lobular BC [adjusted odds ratio (aOR) 9.49, 95% confidence interval (CI) 1.47-61.39, p = 0.018] and adjuvant breast radiation (aOR 0.12, 95% CI 0.02-0.67, p = 0.016). Shorter TI (< 5 years, aOR 4.28, 95% CI 1.46-12.53, p = 0.008) was independently associated with postoperative survival and independently associated with the Union for International Cancer Control stage (UICC) III-IV of BC (aOR 4.82, 95% CI 1.10-21.17, p = 0.037), midline brain shift in preoperative imaging (aOR10.35, 95% CI 1.09-98.33, p = 0.042) and identic estrogen receptor status in BM (aOR 4.56, 95% CI 1.35-15.40, p = 0.015). CONCLUSIONS: Several factors seem to influence the period between BC and BM. Occurrence of BM within five years is independently associated with poorer prognosis after BM surgery. Patients with invasive lobular BC and without adjuvant breast radiation are more likely to develop BM after a long progression-free survival necessitating more prolonged cancer aftercare of these individuals.

Prediction of Short and Long Survival after Surgery for Breast Cancer Brain Metastases.

Background: Brain metastases requiring surgical treatment determine the prognosis of patients with breast cancer. We aimed to develop the scores for the prediction of short (<6 months) and long (≥3 years) survival after BCBM surgery. Methods: Female patients with BCBM surgery between 2008 and 2019 were included. The new scores were constructed upon independent predictors for short and long postoperative survival. Results: In the final cohort (n = 95), 18 (18.9%) and 22 (23.2%) patients experienced short and long postoperative survival, respectively. Breast-preserving surgery, presence of multiple brain metastases and age ≥ 65 years at breast cancer diagnosis were identified as independent predictors of short postoperative survival. In turn, positive HER2 receptor status in brain metastases, time interval ≥ 3 years between breast cancer and brain metastases diagnosis and KPS ≥ 90% independently predicted long survival. The appropriate short and long survival scores showed higher diagnostic accuracy for the prediction of short (AUC = 0.773) and long (AUC = 0.775) survival than the breast Graded Prognostic Assessment score (AUC = 0.498/0.615). A cumulative survival score (total score) showed significant association with overall survival (p = 0.001). Conclusion: We identified predictors independently impacting the prognosis after BCBM surgery. After external validation, the presented scores might become useful tools for the selection of proper candidates for BCBM surgery.

A New Subform? Fast-Progressing, Severe Neurological Deterioration Caused by Spinal Epidural Lipomatosis.

Spinal epidural lipomatosis (SEL) is a rare condition caused by hypertrophic growth of epidural fat. The prevalence of SEL in the Western world is approximately 1 in 40 patients and is likely to increase due to current medical and socio-economic developments. Rarely, SEL can lead to rapid severe neurological deterioration. The pathophysiology, optimal treatment, and outcome of these patients remain unclear. This study aims to widen current knowledge about this "SEL subform" and to improve its clinical management. A systematic literature review according to the PRISMA guidelines using PubMed, Scopus, Web of Science, and Cochrane Library was used to identify publications before 7 November 2021 reporting on acute/rapidly progressing, severe SEL. The final analysis comprised 12 patients with acute, severe SEL. The majority of the patients were male (9/12) and multimorbid (10/12). SEL mainly affected the thoracic part of the spinal cord (11/12), extending a median number of 7 spinal levels (range: 4-19). Surgery was the only chosen therapy (11/12), except for one critically ill patient. Regarding the outcome, half of the patients regained independence (6/11; = modified McCormick Scale ≤ II). Acute, severe SEL is a rare condition, mainly affecting multimorbid patients. The prognosis is poor in nearly 50% of the patients, even with maximum therapy. Further research is needed to stratify patients for conservative or surgical treatment.

Radiographic markers of breast cancer brain metastases: relation to clinical characteristics and postoperative outcome.

OBJECTIVE: Occurrence of brain metastases BM is associated with poor prognosis in patients with breast cancer (BC). Magnetic resonance imaging (MRI) is the standard of care in the diagnosis of BM and determines further treatment strategy. The aim of the present study was to evaluate the association between the radiographic markers of BCBM on MRI with other patients' characteristics and overall survival (OS). METHODS: We included 88 female patients who underwent BCBM surgery in our institution from 2008 to 2019. Data on demographic, clinical, and histopathological characteristics of the patients and postoperative survival were collected from the electronic health records. Radiographic features of BM were assessed upon the preoperative MRI. Univariable and multivariable analyses were performed. RESULTS: The median OS was 17 months. Of all evaluated radiographic markers of BCBM, only the presence of necrosis was independently associated with OS (14.5 vs 22.5 months, p = 0.027). In turn, intra-tumoral necrosis was more often in individuals with shorter time interval between BC and BM diagnosis (< 3 years, p = 0.035) and preoperative leukocytosis (p = 0.022). Moreover, dural affection of BM was more common in individuals with positive human epidermal growth factor receptor 2 status (p = 0.015) and supratentorial BM location (p = 0.024). CONCLUSION: Intra-tumoral necrosis demonstrated significant association with OS after BM surgery in patients with BC. The radiographic pattern of BM on the preoperative MRI depends on certain tumor and clinical characteristics of patients.

Fully Automated MR Based Virtual Biopsy of Cerebral Gliomas.

OBJECTIVE: The aim of this study was to investigate the diagnostic accuracy of a radiomics analysis based on a fully automated segmentation and a simplified and robust MR imaging protocol to provide a comprehensive analysis of the genetic profile and grading of cerebral gliomas for everyday clinical use. METHODS: MRI examinations of 217 therapy-naïve patients with cerebral gliomas, each comprising a non-contrast T1-weighted, FLAIR and contrast-enhanced T1-weighted sequence, were included in the study. In addition, clinical and laboratory parameters were incorporated into the analysis. The BraTS 2019 pretrained DeepMedic network was used for automated segmentation. The segmentations generated by DeepMedic were evaluated with 200 manual segmentations with a DICE score of 0.8082 ± 0.1321. Subsequently, the radiomics signatures were utilized to predict the genetic profile of ATRX, IDH1/2, MGMT and 1p19q co-deletion, as well as differentiating low-grade glioma from high-grade glioma. RESULTS: The network provided an AUC (validation/test) for the differentiation between low-grade gliomas vs. high-grade gliomas of 0.981 ± 0.015/0.885 ± 0.02. The best results were achieved for the prediction of the ATRX expression loss with AUCs of 0.979 ± 0.028/0.923 ± 0.045, followed by 0.929 ± 0.042/0.861 ± 0.023 for the prediction of IDH1/2. The prediction of 1p19q and MGMT achieved moderate results, with AUCs of 0.999 ± 0.005/0.711 ± 0.128 for 1p19q and 0.854 ± 0.046/0.742 ± 0.050 for MGMT. CONCLUSION: This fully automated approach utilizing simplified MR protocols to predict the genetic profile and grading of cerebral gliomas provides an easy and efficient method for non-invasive tumor decoding.

Electrolyte and renal disorders in patients with newly diagnosed glioblastoma.

Purpose: Disturbances of electrolytes and renal function have been linked to the prognosis of critically ill patients and recently also of cancer patients. This study aimed to assess electrolyte and renal disorders in glioblastoma patients and evaluate their prognostic effect. Methods: Medical records of patients with newly diagnosed glioblastoma between 2005 and 2018 were retrospectively reviewed for electrolyte and renal function parameters and for demographic, clinical and outcome parameters. Results: Electrolyte and renal function disorders were associated with poorer survival in univariate and Kaplan-Meier analysis. Multivariate analysis revealed hypochloremia as an independent prognostic factor for overall and 1-year survival. Conclusion: Only hypochloremia showed an association with glioblastoma prognosis, independent of other known prognostic factors, as age or molecular status.

Risk score for outcome prediction after microsurgical resection of spinal ependymoma (SOURSE score).

OBJECTIVE: Microsurgical resection of spinal ependymomas is associated with a considerable risk of postoperative neurological deterioration. We aimed to develop a risk score for outcome prediction after surgery for spinal ependymoma. MATERIALS AND METHODS: All patients who underwent microsurgical resection of spinal ependymoma between 1980 and 2015 were included. Different perioperative parameters were collected for the score construction. Poor outcome was defined as the modified McCormick Scale (MMCS) >2 at 6 months after surgery. RESULTS: Of 131 patients (mean age: 45.6 ± 16.7 years; 63 females), 38 cases (29%) showed poor outcome. Based on the univariate analysis, preoperative MMCS, subtotal tumor resection, proximal tumor level on the spinal cord, tumor extension, intramedullary location, and WHO grading were included in the multivariate analysis. The final risk score consisted of the following independent predictors: preoperative MMCS > 1 (1 point), proximal tumor level at Th 10 and higher (1 point), and tumor extension ≥ 3 vertebrae (1 point). The constructed score (0-3 points; Score for OUtcome after Resection of Spinal Ependymoma [SOURSE]) showed high diagnostic accuracy (area under the curve [AUC] = 0.883), which was superior to preoperative MMCS (AUC = 0.798) and Karnofsky Performance Status (AUC = 0.794). Patients scoring 0, 1, 2, and 3 points showed poor outcome in 0%, 12.9%, 54.6%, and 76.2% of the cases respectively. CONCLUSION: The presented SOURSE score based on preoperative neurologic condition, tumor location, and tumor extension could accurately predict the postoperative outcome in patients undergoing microsurgery of spinal ependymoma. Our data should be validated in a prospective trial.

Role of Brain Natriuretic Peptide in the Prediction of Early Postoperative Seizures Following Surgery for Traumatic Acute Subdural Hematoma: A Prospective Study.

INTRODUCTION: Brain natriuretic peptide (BNP) is a reliable biomarker in the acute phase of traumatic brain injury. However, the relationship between BNP and traumatic acute subdural hematoma (aSDH) has not yet been addressed. This study aimed to analyze BNP levels on admission in surgically treated patients and assess their relationship with early postoperative seizures (EPS) and functional outcomes. METHODS: Patients with unilateral traumatic aSDH who were surgically treated in our department between July 2017 and May 2020 were included in the study. BNP was preoperatively measured. Patients' neurologic condition, radiographic variables on initial cranial computed tomography, sodium serum levels on admission, and occurrence of EPS were prospectively assessed. Functional outcome was assessed using the modified Rankin Scale (mRS) at discharge and follow-up (at 2-3 months). A poor outcome was defined by a mRS score > 3. RESULTS: EPS occurred in 20 (19.6%) of 102 surgically treated patients in the final cohort on the median day 3. A significant association between EPS and a poor Glasgow Coma Scale score at the 7th postoperative day was found, which in turn independently predicted a poor functional outcome at discharge and follow-up. Nonetheless, EPS were not associated with poor functional outcomes. The multivariate analysis revealed BNP > 95.4 pg/ml (aOR = 5.7, p = 0.003), sodium < 137.5 mmol/l (aOR = 4.6, p = 0.009), and left-sided aSDH (aOR = 4.4, p = 0.020) as independent predictors of EPS. CONCLUSION: In the early postoperative phase of traumatic aSDH, EPS were associated with worse neurologic conditions, which in turn independently predicted poor outcomes at discharge and follow-up. Although several EPS risk factors have already been elucidated, this study presents BNP as a novel reliable predictor of EPS. Further larger studies are needed to determine whether a more precise estimate of EPS risk using BNP levels can be reached.

How about Levetiracetam in Glioblastoma? An Institutional Experience and Meta-Analysis.

Despite multimodal treatment, the prognosis of patients with glioblastoma (GBM) remains poor. Previous studies showed conflicting results on the effect of antiepileptic drugs (AED) on GBM survival. We investigated the associations of different AED with overall survival (OS) and progression-free survival (PFS) in a large institutional GBM cohort (n = 872) treated January 2006 and December 2018. In addition, we performed a meta-analysis of previously published studies, including this study, to summarize the evidence on the value of AED for GBM prognosis. Of all perioperatively administered AED, only the use of levetiracetam (LEV) was associated with longer OS (median: 12.8 vs. 8.77 months, p < 0.0001) and PFS (7 vs. 4.5 months, p = 0.001). In the multivariable analysis, LEV was independently associated with longer OS (aHR = 0.74, p = 0.017) and PFS (aHR = 0.68, p = 0.008). In the meta-analysis with 5614 patients from the present and seven previously published studies, outcome benefit for OS (HR = 0.83, p = 0.02) and PFS (HR = 0.77, p = 0.02) in GBM individuals with LEV was confirmed. Perioperative treatment with LEV might improve the prognosis of GBM patients. We recommend a prospective randomized controlled trial addressing the efficacy of LEV in GBM treatment.

HER2 Receptor Conversion Is a strong Survival Predictor in Patients with Breast Cancer Brain Metastases.

BACKGROUND: Hormone and human epidermal growth factor receptor 2 (HER2/neu) receptor status is prognostic and predictive in breast cancer (BC) and guides the choice of therapy. However, owing to receptor conversion, the receptor status can differ in metastases compared with that of the primary tumor. The aim of the present study was to analyze the prognostic value of receptor status, receptor conversion, and clinical parameters in patients with resected BC brain metastases (BMs). METHODS: Patients with BCBMs treated at our institution from July 2007 to December 2019 were eligible for the present study. The receptor status of the BC and corresponding BMs and the occurrence of receptor conversion were separately recorded for 3 common receptors: HER2/neu, estrogen receptor, and progesterone receptor. The association between the receptor status or receptor conversion and clinical parameters was adjusted for outcome-relevant patient and tumor characteristics. RESULTS: The final analysis included 78 patients. HER2/neu receptor status in BMs was associated with overall survival (P = 0.033). Receptor conversion was identified in 39 patients (50.0%): HER2/neu, n = 9 (11.5%); estrogen receptor, n = 22 (28.2%); and progesterone receptor, n = 25 (32.1%). In the final multivariate Cox regression analysis, HER2/neu receptor conversion (adjusted hazard ratio [aHR], 3.58; P = 0.006), Karnofsky performance status score <70% (aHR, 3.11; P = 0.048), infratentorial BM location (aHR, 2.49; P = 0.007), and age ≥55 years at BM diagnosis (aHR, 2.20; P = 0.046) were independently associated with poorer survival. CONCLUSIONS: Of the 3 common BC receptors, only HER2/neu receptor conversion was strongly associated with the prognosis of patients with surgically treated BCBMs. The clinical relevance of the reevaluation of receptor status in BMs favors surgical treatment of patients with noneloquent BCBMs.

Case Report: Pseudomeningeosis and Demyelinating Metastasis-Like Lesions From Checkpoint Inhibitor Therapy in Malignant Melanoma.

Immune checkpoint inhibitors (ICIs) have considerably expanded the effective treatment options for malignant melanoma. ICIs revert tumor-associated immunosuppression and potentiate T-cell mediated tumor clearance. Immune-related neurologic adverse events (irNAEs) manifest in the central (CNS) or peripheral nervous system (PNS) and most frequently present as encephalitis or myasthenia gravis respectively. We report on a 47-year old male patient with metastatic melanoma who developed signs of cerebellar disease five weeks after the start of ICI treatment (ipilimumab and nivolumab). Magnetic resonance imaging (MRI) of the brain and spine revealed multiple new contrast enhancements suggestive of parenchymal and leptomeningeal metastasis. Cerebral spinal fluid (CSF) evaluation showed a lymphomononuclear pleocytosis in the absence of tumor cells. Subsequent stereotactic brain biopsy confirmed demyelinating disease. High-dose corticosteroid treatment resulted in immediate improvement of the clinical symptoms. MRI scans and CSF re-evaluation were conducted six weeks later and showed a near-complete remission. The strong resemblance to neoplastic CNS dissemination and irNAEs is a particularly difficult diagnostic challenge. Treating physicians should be aware of irNAEs as those can be effectively treated with high-dose steroids.

The 2016 Edition of the WHO Classification of Primary Brain Tumors: Applicable to Assess Individual Risk of Recurrence in Atypical Meningioma? A Single-Center Experience.

BACKGROUND AND STUDY AIMS/OBJECT: Despite the relevance of molecular criteria for brain tumor diagnosis and prognosis, meningioma grading is still solely based on histologic features. Atypical meningiomas (AMs; WHO grade II) display a great histologic heterogeneity and individual courses of disease can differ significantly. This study aimed to identify clinically aggressive AMs that are prone to early recurrence after gross total resection (GTR) by assessing a specific histologic score. PATIENTS AND METHODS: A retrospective analysis of 28 consecutive patients (17 females and 11 males; mean age of 62 years [range: 35-88 years]) treated in our institution between January 2006 and December 2015 was performed. Basic demographic and clinical characteristics were assessed. A scoring scale was designed to address the histologic diversity by summing up the individual histologic features in every tumor sample. According to that, points were awarded as follows: major AM defining criterion (3 points) and minor criterion (1 point). RESULTS: The subclassification based on our specific histologic score revealed no significant difference in frequency of one (46.4%) or two (42.9%) AM defining features; three criteria were less frequently seen (10.7%). Mean follow-up was 61.89 ± 9.03 months. Local recurrence occurred in 35.7% after a mean time of 37.4 ± 22.6 months after primary surgery. Age > 60 years was significantly associated with a shorter progression-free survival (PFS). There was a trend toward shorter PFS with increasing scores, tantamount with the presence of several AM defining histologic criteria in one sample. No tumor relapse was seen when diagnosis was based only on minor criteria. CONCLUSION: AMs display a histologic diversity. There is a trend toward shorter PFS with increasing numbers of AM defining histologic features. The inclusion of this score in the decision algorithm regarding further treatment for patients >60 years after GTR might be helpful and should be evaluated in further studies.

Lipomas as an Extremely Rare Cause for Brachial Plexus Compression: A Case Series and Systematic Review.

Introduction Brachial plexus lipomas are extremely rare benign tumors that may cause slow progression of neurological deficits leading to thoracic outlet syndrome. Up to now, surgery remains challenging. The aim of this study is to present our surgical treatment regime and long-term neurological outcome in three cases of giant brachial plexus lipomas and to show results of systematic review. Patients and Methods Retrospective analysis of our database "peripheral nerve lesion" to identify patients suffering from brachial plexus lipomas between January 1, 2012, and December 31, 2019. Systematic review was performed for literature published until March 31, 2020, analyzing PubMed, Google Scholar, Scopus, and the Cochrane Collaboration Library independently by two authors. Results Over the past years, three patients suffering from giant brachial plexus lipomas attended to our neurosurgical department. All patients underwent preoperative magnetic resonance imaging (MRI), ultrasound examinations, and electrophysiological testing. Tumors were removed microsurgically via anterior/posterior, supraclavicular/infraclavicular, and combined approaches. The patients were accessed postoperatively by MRI and clinical follow-up. Systematic review of the literature revealed 22 cases, which were analyzed in regard to demographics, surgical treatment, and neurological outcome. Conclusion Brachial plexus lipomas are an extremely rare cause for brachial plexus compression. Total microsurgical removal with intraoperative electrophysiological monitoring is the treatment of choice with excellent long-term MRI and clinical outcome.

Size does matter: The role of decompressive craniectomy extent for outcome after aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: In previous studies in patients with traumatic brain injury and ischemic stroke, the size of decompressive craniectomy (DC) was reported to be paramount with regard to patient outcomes. We aimed to identify the impact of DC size on treatment results in individuals with aneurysmal subarachnoid hemorrhage (SAH). METHODS: The extent of DC in 232 patients with SAH who underwent bifrontal or hemicraniectomy between January 2003 and December 2015 was analyzed using semi-automated surface measurements. The study endpoints were course of intracranial pressure (ICP) treatment after DC, occurrence of cerebral infarcts, in-hospital mortality, and unfavorable outcome at 6 months (defined as modified Rankin scale score >3). The associations of DC size with the study endpoints were adjusted for DC timing, patient age, clinical and radiographic severity of SAH, aneurysm location, and treatment modality. RESULTS: The mean DC surface area was 100.9 (±45.8) cm2 . In multivariate analysis, a large DC (>105 cm2 ) was independently associated with a lower risk of cerebral infarcts (adjusted odds ratio [aOR] 0.30, 95% confidence interval [CI] 0.16-0.56), in-hospital mortality (aOR 0.28, 95% CI 0.14-0.56) and unfavorable outcome (aOR 0.51, 95% CI 0.27-0.98). Moreover, SAH patients with a small DC size (<75 cm2 ) were more likely to require prolonged (>3 days, aOR 3.60, 95% CI 1.37-9.42) and enhanced (aOR 2.31, 95% CI 1.12-4.74) postoperative ICP treatment. CONCLUSION: This is the first study showing the impact of DC size on postoperative ICP control and patient outcome in the context of SAH; specifically, a large craniectomy flap (>105 cm2 ) might lead to better outcomes in SAH patients requiring decompressive surgery.

Dosimetric impact of the positioning variation of tumor treating field electrodes in the PriCoTTF-phase I/II trial.

PURPOSE: The aim of the present study based on the PriCoTTF-phase I/II trial is the quantification of skin-normal tissue complication probabilities of patients with newly diagnosed glioblastoma multiforme treated with Tumor Treating Field (TTField) electrodes, concurrent radiotherapy, and temozolomide. Furthermore, the skin-sparing effect by the clinically applied strategy of repetitive transducer array fixation around their center position shall be examined. MATERIAL AND METHODS: Low-dose cone-beam computed tomography (CBCT) scans of all fractions of the first seven patients of the PriCoTTF-phase I/II trial, used for image guidance, were applied for the dosimetric analysis, for precise TTField transducer array positioning and contour delineation. Within this trial, array positioning was varied from fixation-to-fixation period with a standard deviation of 1.1 cm in the direction of the largest variation of positioning and 0.7 cm in the perpendicular direction. Physical TTField electrode composition was examined and a respective Hounsfield Unit attributed to the TTField electrodes. Dose distributions in the planning CT with TTField electrodes in place, as derived from prefraction CBCTs, were calculated and accumulated with the algorithm Acuros XB. Dose-volume histograms were obtained for the first and second 2 mm scalp layer with and without migrating electrodes and compared with those with fixed electrodes in an average position. Skin toxicity was quantified according to Lyman's model. Minimum doses in hot-spots of 0.05 cm2 and 25 cm2 ( Δ D0.05cm 2 , Δ D25cm 2 ) size in the superficial skin layers were analyzed. RESULTS: Normal tissue complication probabilities (NTCPs) for skin necrosis ranged from 0.005% to 1.474% (median 0.111%) for the different patients without electrodes. NTCP logarithms were significantly dependent on patient (P < 0.0001) and scenario (P < 0.0001) as classification variables. Fixed positioning of TTField arrays increased skin-NTCP by a factor of 5.50 (95%, CI: 3.66-8.27). The variation of array positioning increased skin-NTCP by a factor of only 3.54 (95%, CI: 2.36-5.32) (P < 0.0001, comparison to irradiation without electrodes; P = 0.036, comparison to irradiation with fixed electrodes). NTCP showed a significant rank correlation with D25cm2 over all patients and scenarios (rs  = 0.76; P < 0.0001). CONCLUSION: Skin-NTCP calculation uncovers significant interpatient heterogeneity and may be used to stratify patients into high- and low-risk groups of skin toxicity. Array position variation may mitigate about one-third of the increase in surface dose and skin-NTCP by the TTField electrodes.

Preoperative and early postoperative seizures in patients with glioblastoma-two sides of the same coin?

BACKGROUND: Symptomatic epilepsy is a common symptom of glioblastoma, which may occur in different stages of disease. There are discrepant reports on association between early seizures and glioblastoma survival, even less is known about the background of these seizures. We aimed at analyzing the risk factors and clinical impact of perioperative seizures in glioblastoma. METHODS: All consecutive cases with de-novo glioblastoma treated at our institution between 01/2006 and 12/2018 were eligible for this study. Perioperative seizures were stratified into seizures at onset (SAO) and early postoperative seizures (EPS, ≤21days after surgery). Associations between patients characteristics and overall survival (OS) with SAO and EPS were addressed. RESULTS: In the final cohort (n = 867), SAO and EPS occurred in 236 (27.2%) and 67 (7.7%) patients, respectively. SAO were independently predicted by younger age (P = .009), higher KPS score (P = .002), tumor location (parietal lobe, P = .001), GFAP expression (≥35%, P = .045), and serum chloride at admission (>102 mmol/L, P = .004). In turn, EPS were independently associated with tumor location (frontal or temporal lobe, P = .013) and pathologic laboratory values at admission (hemoglobin < 12 g/dL, [P = .044], CRP > 1.0 mg/dL [P = 0.036], and GGT > 55 U/L [P = 0.025]). Finally, SAO were associated with gross-total resection (P = .006) and longer OS (P = .030), whereas EPS were related to incomplete resection (P = .005) and poorer OS (P = .009). CONCLUSIONS: In glioblastoma patients, SAO and EPS seem to have quite different triggers and contrary impact on treatment success and OS. The clinical characteristics of SAO and EPS patients might contribute to the observed survival differences.

Machine learning-based differentiation between multiple sclerosis and glioma WHO II°-IV° using O-(2-[18F] fluoroethyl)-L-tyrosine positron emission tomography.

INTRODUCTION: This study aimed to test the diagnostic significance of FET-PET imaging combined with machine learning for the differentiation between multiple sclerosis (MS) and glioma II°-IV°. METHODS: Our database was screened for patients in whom FET-PET imaging was performed for the diagnostic workup of newly diagnosed lesions evident on MRI and suggestive of glioma. Among those, we identified patients with histologically confirmed glioma II°-IV°, and those who later turned out to have MS. For each group, tumor-to-brain ratio (TBR) derived features of FET were determined. A support vector machine (SVM) based machine learning algorithm was constructed to enhance classification ability, and Receiver Operating Characteristic (ROC) analysis with area under the curve (AUC) metric served to ascertain model performance. RESULTS: A total of 41 patients met selection criteria, including seven patients with MS and 34 patients with glioma. TBR values were significantly higher in the glioma group (TBRmax glioma vs. MS: p = 0.002; TBRmean glioma vs. MS: p = 0.014). In a subgroup analysis, TBR values significantly differentiated between MS and glioblastoma (TBRmax glioblastoma vs. MS: p = 0.0003, TBRmean glioblastoma vs. MS: p = 0.0003) and between MS and oligodendroglioma (ODG) (TBRmax ODG vs. MS: p = 0.003; TBRmean ODG vs. MS: p = 0.01). The ability to differentiate between MS and glioma II°-IV° increased from 0.79 using standard TBR analysis to 0.94 using a SVM based machine learning algorithm. CONCLUSIONS: FET-PET imaging may help differentiate MS from glioma II°-IV° and SVM based machine learning approaches can enhance classification performance.

Demographic, radiographic, molecular and clinical characteristics of primary gliosarcoma and differences to glioblastoma.

OBJECTIVE: Gliosarcoma (GSC) is a rare histological variant of glioblastoma (GBM). Due to limited evidence regarding clinical, genetic and radiographic characteristics of GSC, this study aimed to analyze independent outcome predictors of GSC, and to address the differences between GSC and GBM concerning the baseline characteristics and patients' survival. METHODS: Patients treated between 2001 and 2018 for the diagnosis of GBM and GSC were included in this study. Patients' records were reviewed for demographic, clinical, genetic and radiographic characteristics. Univariate, multivariate and propensity score matched analyses were performed. RESULTS: In the GSC sub-cohort (N = 56), patients' age, preoperative clinical status, midline tumor location and tumor size were found to be independently associated with overall survival. As compared to GBM individuals (N = 1249), a temporal location (p = 0.002), presence of eccentric tumor cysts (p < 0.001), a higher ratio of TP53 staining (p = 0.002) and a lower ratio of GFAP staining (p = 0.005) were characteristic for GSC. The diagnosis of GSC was associated with a poorer survival (p = 0.002) independently of the patients' age, sex, clinical status and extent of resection, However, this association was no more significant, when enhancing the multivariate analysis with molecular-genetic characteristics (IDH1 mutation and MGMT promotor methylation status). DISCUSSION: Certain radiographic and molecular-genetic patterns present the distinct characteristics of GSC. There is an association between the diagnosis of GSC and a poorer outcome. This difference might be linked to different genetic alterations in GBM and GSC. Prospective studies are needed to further elucidate the characteristics of GSC and develop targeted treatment approaches for this rare variant.