Extended stereotactic brain biopsy in suspected primary central nervous system angiitis: good diagnostic accuracy and high safety.

Objective: To evaluate the diagnostic accuracy and safety of extended stereotactic brain biopsy (ESBB) in a single center cohort with suspected primary angiitis of the central nervous system (PACNS).

Methods: A standardized stereotactic biopsy targeting MRI-positive lesions and collecting samples from the meninges and the cortex as well as from the white matter was performed in 23 patients with clinically suspected PACNS between 2010 and 2017. The relationship between biopsy yield and clinical characteristics, cerebrospinal fluid parameters, MR-imaging, time point of biopsy and exact localization of biopsy as well as number of tissue samples were examined.

The IL-1 Antagonist Anakinra Attenuates Glioblastoma Aggressiveness by Dampening Tumor-Associated Inflammation.

Background: The recombinant IL-1 receptor antagonist anakinra-currently approved for the treatment of autoinflammatory diseases-blocks IL-1β-mediated inflammatory signaling. As inflammation is a major driver of cancer, we hypothesized that anakinra might be able to mitigate glioblastoma (GBM) aggressiveness.

Methods: Primary GBM or T98G cells were incubated alone or with peripheral blood mononuclear cells (PBMCs) and were subsequently treated with IL-1β and/or anakinra.

Non-invasive prediction of IDH-wildtype genotype in gliomas using dynamic F-FET PET.

Purpose: According to the updated WHO classification of gliomas with its emphasis on molecular parameters, tumours with an IDH-wildtype status have a dismal prognosis. To ensure timely adjustment of treatment, demand for non-invasive prediction methods is high. F-FET PET has been shown to be an important diagnostic tool for glioma management.

Bevacizumab reduces toxicity of reirradiation in recurrent high-grade glioma.

Purpose: The role of bevacizumab (BEV) in the setting of reirradiation (reRT) of malignant glioma recurrences is poorly defined. At our institution, reRT plus BEV was routinely used until its disapproval for glioma treatment by the European Medical Agency. Accordingly, reRT was applied without the addition of BEV since 2017.

The surgical perspective in precision treatment of diffuse gliomas.

Over the last decade, advances in molecular and imaging-based biomarkers have induced a more versatile diagnostic classification and prognostic evaluation of glioma patients. This, in combination with a growing therapeutic armamentarium, enables increasingly individualized, risk-benefit-optimized treatment strategies. This path to precision medicine in glioma patients requires surgical procedures to be reassessed within multidimensional management considerations.

Outcome after individualized stereoelectroencephalography (sEEG) implantation and navigated resection in patients with lesional and non-lesional focal epilepsy.

Background: Refined localization of the epileptogenic zone (EZ) in patients with pharmacoresistant focal epilepsy proceeding to resective surgery might improve postoperative outcome. We here report seizure outcome after stereo EEG (sEEG) evaluation with individually planned stereotactically implanted depth electrodes and subsequent tailored resection.

Methods: A cohort of consecutive patients with pharmacoresistant focal epilepsy, evaluated with a non-invasive evaluation protocol and invasive monitoring with personalized, stereotactically implanted depth electrodes for sEEG was analyzed.

Radiation dose and image quality in intraoperative CT (iCT) angiography of the brain with stereotactic head frames.

Objectives: Intraoperative CT (iCT) angiography of the brain with stereotactic frames is an integral part of navigated neurosurgery. Validated data regarding radiation dose and image quality in these special examinations are not available. We therefore investigated two iCT protocols in this IRB-approved study.

Stereotactic Internal Shunt Placement in Congenital Intracranial Cysts.

Introduction: Treatment of symptomatic intracranial cysts remains a controversial issue. We present a risk/benefit profile of a minimally invasive, not yet described, stereotactic internal shunt implantation technique. The provided data might serve as a reference against which other treatment modalities could be compared.

Contrast enhancement is a prognostic factor in IDH1/2 mutant, but not in wild-type WHO grade II/III glioma as confirmed by machine learning.

Background: Mutation of the isocitrate dehydrogenase (IDH) gene and co-deletion on chromosome 1p/19q is becoming increasingly relevant for the evaluation of clinical outcome in glioma. Among the imaging parameters, contrast enhancement (CE) in WHO II/III glioma has been reported to indicate poor outcome in the past. We aimed at reassessing the prognostic value of CE in these tumours within the framework of molecular markers using a machine learning approach (random survival forests [RSF]) as well as conventional Cox regression modelling.

Intronic miR-744 Inhibits Glioblastoma Migration by Functionally Antagonizing Its Host Gene MAP2K4.

Background: The second intron of Mitogen-Activated Protein Kinase Kinase 4 (MAP2K4), an important hub in the pro-invasive MAPK pathway, harbors miR-744. There is accumulating evidence that intronic micro-RNAs (miRNAs) are capable of either supporting or restraining functional pathways of their host genes, thereby creating intricate regulative networks. We thus hypothesized that miR-744 regulates glioma migration by interacting with its host's pathways.

Voxel-wise analysis of dynamic F-FET PET: a novel approach for non-invasive glioma characterisation.

Background: Glioma grading with dynamic F-FET PET (0-40 min p.i.) is typically performed by analysing the mean time-activity curve of the entire tumour or a suspicious area within a heterogeneous tumour.

F-FET-PET as a biomarker for therapy response in non-contrast enhancing glioma following chemotherapy.

Background: Monitoring treatment response after chemotherapy of gadolinium-(Gd)-negative gliomas is challenging as conventional MRI often indicates no radiological changes. We hypothesize that F-FET-PET can be used as a biomarker for response assessment in Gd-negative gliomas undergoing chemotherapy.

Methods: Sixty-one patients harboring Gd-negative WHO grade II or III glioma receiving alkylating agents (temozolomide or CCNU/procarbacine) were included.

Dual-room CT with a sliding gantry for intraoperative imaging: feasibility and workflow analysis of an interdisciplinary concept.

Purpose: Currently, intraoperative computed tomography (iCT) is a scarcely used technique in neurosurgery. It remains unclear whether this phenomenon is explained by unfavorable iCT-related workflows and/or a limited number of indications. We here analyzed workflows of an installed dual-room iCT (DR-iCT) as compared to surgical procedures lacking iCT.

Dynamic 18F-FET PET is a powerful imaging biomarker in gadolinium-negative gliomas.

Background: We aimed to elucidate the place of dynamic O-(2-[18F]-fluoroethyl)-L-tyrosine (18F-FET) PET in prognostic models of gadolinium (Gd)-negative gliomas.

Methods: In 98 patients with Gd-negative gliomas undergoing 18F-FET PET guided biopsy, time activity curves (TACs) of each tumor were qualitatively categorized as either increasing or decreasing. Additionally, post-hoc quantitative analyses were done using minimal time-to-peak (TTPmin) measurements.

Brachytherapy of Intracranial Gliomas.

Interstitial implantation of radioactive materials (brachytherapy [BT]) has been designed to protractedly deliver a high radiation dose to a well-defined target volume, while minimizing irradiation of the adjacent normal tissues. Even though promising results have been reported over time, the role of this treatment modality in the management of brain tumors is still poorly defined, and only a few centers worldwide apply it in clinical practice. Nevertheless, temporary or permanent interstitial implantation of low activity (<20 mCi) and low dose rate (≤10 cGy/h) iodine-125 (125I) seeds as possible therapy of intracranial gliomas is currently undergoing a definite revival, and several indications for its use have been identified.

The role of surgery for brain metastases from solid tumors.

Surgery, stereotactic radiosurgery, radiotherapy, and chemotherapy including novel targeted therapy strategies and any combination thereof as well as supportive care are the key elements for treatment of brain metastases. Goals of microsurgery are to obtain tissue samples for histologic diagnosis (particularly in case of uncertainty about the unknown primary tumor but also in the context of future targeted therapies), to relieve burden from space-occupying effects, to improve local tumor control, and to prolong overall survival. Complete surgical resection improves local tumor control and may even affect overall survival.

Cystic Craniopharyngiomas: Microsurgical or Stereotactic Treatment?

Background: Prognosis and treatment of cystic craniopharyngiomas are poorly defined.

Objective: To analyze progression-free survival (PFS) and safety profile of cystic craniopharyngiomas undergoing resection or minimally invasive drainage procedures. We compared further outcome measurements for cystic and solid tumors undergoing resection to elucidate the impact of the initial tumor composition on both PFS and the toxicity profile.

Outcome in unresectable glioblastoma: MGMT promoter methylation makes the difference.

In 2011, we reported a predominant prognostic/predictive role of MGMT promoter methylation status on progression-free survival (PFS) in unresectable glioblastoma patients undergoing upfront radiotherapy plus concomitant and maintenance temozolomide (RTX/TMZ → TMZ). We, here, present the final results of this prospective study focussing on the prognostic/predictive value of MGMT promoter methylation status for death risk stratification. Overall, 56 adult patients with unresectable, biopsy proven glioblastoma were prospectively assigned to upfront RTX/TMZ → TMZ treatment between March 2006 and August 2008.

Iodine-125 brachytherapy as upfront and salvage treatment for brain metastases : A comparative analysis.

Background: Outcome and toxicity profiles of salvage stereotactic ablative radiation strategies for recurrent pre-irradiated brain metastases are poorly defined. This study compared risk-benefit profiles of upfront and salvage iodine-125 brachytherapy (SBT) for small brain metastases. As the applied SBT treatment algorithm required histologic proof of metastatic brain disease in all patients, we additionally aimed to elucidate the value of biopsy before SBT.

Suspected recurrence of brain metastases after focused high dose radiotherapy: can [F]FET- PET overcome diagnostic uncertainties?

Background: After focused high dose radiotherapy of brain metastases, differentiation between tumor recurrence and radiation-induced lesions by conventional MRI is challenging. This study investigates the usefulness of dynamic O-(2-F-Fluoroethyl)-L-Tyrosine positron emission tomography (F-FET PET) in patients with MRI-based suspicion of tumor recurrence after focused high dose radiotherapy of brain metastases.

Methods: Twenty-two patients with 34 brain metastases (median age 61.

Re-irradiation strategies in combination with bevacizumab for recurrent malignant glioma.

The place of bevacizumab (BEV) in salvage re-irradiation (Re-RT) settings of malignant glioma is poorly defined. In the current study risk/benefit profiles of two BEV-based Re-RT protocols were analyzed and compared with that of salvage BEV plus irinotecan (BEV/IRI). According to interdisciplinary tumor board recommendations, patients were assigned to one of three BEV-based treatment protocols: (1) BEV/IRI, (2) Re-RT (36 Gy/18 fx) with concomitant BEV (Re-RT/BEV), and (3) Re-RT with concomitant/maintenance BEV (Re-RT/BEV→BEV).

Early treatment of complex located pediatric low-grade gliomas using iodine-125 brachytherapy alone or in combination with microsurgery.

To analyze efficacy, functional outcome, and treatment toxicity of low-dose rate I-125 brachytherapy (SBT) alone or in combination with best safe resection (in case of larger tumor volumes) as first-line treatment for pediatric low-grade gliomas (PLGGs) not suitable for complete resection. Consecutively treated (2000-2014) complex located circumscribed WHO grade I/II PLGGs were included. For small tumors (≤4 cm in diameter) SBT alone was performed; for larger tumors best safe resection and subsequent SBT was chosen.

The role of surgery in grade II/III oligodendroglial tumors.

Supratentorial gliomas WHO grade II and III with an oligodendroglial phenotype are highly infiltrative lesions that preferentially originate in lobar location. Open tumor resection represents one of the mainstays of management as beneficial decompressive effects for large space-occupying lesions and oncologically relevant cytoreductive effects from complete resection can be expected. In patients not eligible for safe tumor resection meticulous histological and molecular-genetic evaluation can be obtained from advanced stereotactic biopsy techniques.