Anders Korshøj

Aarhus University Hospital | AUH · Department of Neurosurgery

Background Subarachnoid haemorrhage (SAH) and intraventricular haemorrhage (IVH) are associated with poor patient outcomes. Intraventricular fibrinolysis is effective in clearing IVH and improving patient survival and neurological outcome. By similar rationale, cisternal irrigation has been proposed as a potential method to accelerate haematoma cle...

The presence of heterogeneity in responses to oncolytic virotherapy poses a barrier to clinical effectiveness, as resistance to this treatment can occur through the inhibition of viral spread within the tumor, potentially leading to treatment failures. Here we show that 4-octyl itaconate (4-OI), a chemical derivative of the Krebs cycle-derived meta...

Background Intraventricular hemorrhage (IVH) is a severe condition with poor outcomes and high mortality. IRRA flow ® (IRRAS AB) is a new technology introduced to accelerate IVH clearance by minimally invasive wash-out. The IRRA flow ® system performs active and controlled intracranial irrigation and aspiration with physiological saline, while simu...

Background This Danish cohort study aims to (1) compare patterns of care (POC) and survival of patients with multifocal glioblastoma (mGBM) to those with unifocal glioblastoma (uGBM), and (2) explore the association of patient-related factors with treatment assignment and prognosis, respectively, in the subgroup of mGBM patients. Methods Data on a...

Tumor Treating Fields (TTFields) is currently a Category 1A treatment recommendation by the U.S. National Comprehensive Cancer Center for patients with newly diagnosed glioblastoma. Although the mechanism of action of TTFields has been partly elucidated, tangible and standardized metrics are lacking to assess anti-tumor dose and effects of the trea...

Introduction Intraventricular haemorrhage (IVH) is associated with high morbidity and mortality. External ventricular drainage (EVD) has been shown to decrease mortality. Although EVD is widely used, outcome and complication rates in EVD-treated patients with IVH are not fully elucidated. This study aims to describe EVD complication rates and outco...

Glioblastomas (GBM) are renowned for their pronounced intratumoral heterogeneity, characterized by a diverse array of plastic cell types, which poses a significant challenge to effective targeting and treatment. Recent research has documented the presence of neuronal-progenitor-like transcriptomic cell states of GBM, notably in the leading edge of...

Objective This is a secondary analysis of data from a previous study of anesthetized brain tumor patients receiving ephedrine or phenylephrine infusions. 18 patients with magnetic imaging verified tumor contrast enhancement were included. We hypothesized that vasopressors induce microcirculatory flow changes, characterized by increased capillary tr...

Glioblastoma (GBM) is a highly lethal cancer due to its inter- and intra-patient molecular and physiological heterogeneity, and its complex interaction with brain tissue. Recent findings demonstrate that Neuron-to-brain tumor-synaptic-communications (NBTSCs) engage in a vicious cycle of enhanced neuronal activity, driving glioma progression and inv...

Human cortex transcriptomic studies have revealed a hierarchical organization of γ-aminobutyric acid–producing (GABAergic) neurons from subclasses to a high diversity of more granular types. Rapid GABAergic neuron viral genetic labeling plus Patch-seq (patch-clamp electrophysiology plus single-cell RNA sequencing) sampling in human brain slices was...

Importance Intraventricular lavage has been proposed as a minimally invasive method to evacuate intraventricular hemorrhage. There is little evidence to support its use. Objective To evaluate the safety and potential efficacy of intraventricular lavage treatment of intraventricular hemorrhage. Design, Setting, and Participants This single-blinded...

This review investigates focused ultrasound for treating neuro-oncological diseases as an emerging treatment modality. The technique is based on focused ultrasound waves guided by MRI. By using high or low-frequency waves, thermoablation of smaller tissue volumes centrally in the brain or a safe, temporary opening of the blood-brain barrier can be...

BACKGROUND Glioblastoma (GBM) is a highly lethal cancer with a low treatment success rate due to its inter- and intra-patient molecular and physiological heterogeneity, and its complex interaction with brain tissue. Neuron-to-brain tumor-synaptic-communications (NBTSCs) are believed to contribute to glioma progression and tumor-induced epilepsy. Ho...

Background: The aim of this retrospective registry-based Danish patterns of care study was (1) to evaluate the real-world utilisation of short-course hypofractionated radiotherapy (HFRT) in glioblastoma (GBM) patients over time, and (2) to evaluate the impact of short-course HFRT by assessing trends in multimodality treatment utilisation, complian...

Importance Intraventricular hemorrhage (IVH) is associated with high morbidity and mortality. A strong need exists for treatment advances. IRRAflow ® was recently introduced as a method for minimally invasive, controlled, and accelerated IVH wash-out. However, no current evidence supports this technology. Here, we present the first pivotal safety/e...

Background Intraventricular hemorrhage (IVH) is a severe condition with poor outcomes and high mortality. IRRAflow (IRRAS AB) is a new technology introduced to accelerate IVH clearance by minimally invasive wash-out. The IRRAflow system performs active and controlled intracranial irrigation and aspiration with physiological saline, while simultaneo...

Objective Intraventricular hemorrhage (IVH) is a severe condition with poor outcome and high mortality. New treatments are warranted to facilitate clot removal and accelerate recovery of IVH patients. We examined the effect to intraventricular lavage on IVH resolution, clearance and kinectics. The study is a post-hoc study on a recently performed r...

Altered metabolism and defective innate immune responses are hallmarks of tumor cells, creating a niche that can be exploited by viruses with oncolytic properties. However, heterogeneity in responses to oncolytic virotherapy is a barrier to clinical effectiveness. Resistance to oncolytic virotherapy exists and occurs via inhibition of viral spread...

Background: External ventricular drainage (EVD) is a key factor in the treatment of intraventricular hemorrhage (IVH) but associated with risks and complications. Intraventricular fibrinolysis (IVF) has been proposed to improve clinical outcome and reduce complications of EVD treatment. The following review and metaanalysis provides a comprehensiv...

Background Primary intraventricular hemorrhage (IVH) or IVH secondary to intracerebral (ICH) and subarachnoid hemorrhage (SAH) are known to have a very poor prognosis, with an expected mortality between 50 and 80% (Hinson et al. Current Neurology and Neuroscience Reports 10:73–82, 2010). Clearance of IVH might improve patient outcome. Methods The...

Skullremodeling surgery (SR-surgery) includes removing bone from the skull to enhance TTFields. In our phase 1 trial (NCT02893137) we tested multiple SR-configurations (craniectomy, burrholes, and skull thinning) with TTFields concluding it to be safe. To examine the efficacy, we recently initiated an investigator-initiated, randomized, comparative...

Background: Neurological injury is the primary cause of death after out-of-hospital cardiac arrest. There is a lack of studies investigating cerebral injury beyond the immediate post-resuscitation phase in a controlled cardiac arrest experimental setting. Methods: The aim of this study was to investigate temporal changes in measures of cerebral...

Background Primary intraventricular hemorrhage (IVH) or IVH secondary to intracerebral- (ICH) and subarachnoid hemorrhage (SAH) are known to have a very poor prognosis, with an expected mortality between 50% and 80%(1). Clearance of IVH might improve patient outcome. Methods The study is designed as an investigator-initiated, comparative, prospecti...

After severe traumatic brain injury (sTBI) proteins, neurotrophic factors and inflammatory markers are released into the biofluids. This review and meta-analysis searched the literature for prognostic candidate cerebrospinal fluid markers and their relation to sTBI patient outcome. A systematic search of the literature was carried out across PubMed...

Tumor treating fields (TTFields) is an anti-cancer technology increasingly used for the treatment of glioblastoma. Recently, cranial burr holes have been used experimentally to enhance the intensity (dose) of TTFields in the underlying tumor region. In the present study, we used computational finite element methods to systematically characterize th...

Background Primary intraventricular hemorrhage (IVH) or IVH secondary to intracerebral- (ICH) and subarachnoid hemorrhage (SAH) are known to have a very poor prognosis, with an expected mortality between 50% and 80%(1). Clearance of IVH might improve patient outcome. Methods The study is designed as an investigator-initiated, comparative, prospecti...

Simple Summary Complete surgical removal of high-grade gliomas (HGG) is known to increase the overall survival and progression-free survival. Several studies have shown that fluorescence-guided surgery with 5-aminolevulinic acid (5-ALA) increases gross total resection considerably compared to white light surgery (65% vs. 36%). Recently, an off-labe...

Background OptimalTTF-2 is a randomized, comparative, multi-center, investigator-initiated, interventional study aiming to test skull remodeling surgery in combination with Tumor Treating Fields therapy (TTFields) and best physicians choice medical oncological therapy for first recurrence in glioblastoma patients. OptimalTTF-2 is a phase 2 trial in...

Intraoperative neuromonitoring is a perioperative method, supplementary to stealth navigation and fluorescence microscopic imaging in brain surgery. It allows cortical and subcortical mapping, hence real time identification of eloquent brain areas through electrical stimulation of the cerebral cortex and subcortical areas. The method allows for fun...

Synapses in the cerebral cortex constantly change and this dynamic property regulated by the action of neuromodulators such as dopamine (DA), is essential for reward learning and memory. DA modulates spike-timing-dependent plasticity (STDP), a cellular model of learning and memory, in juvenile rodent cortical neurons. However, it is unknown whether...

Tumor-treating fields (TTFields) are alternating fields (200 kHz) used to treat glioblastoma (GBM), which is one of the deadliest cancer diseases of all. Glioblastoma is a type of malignant brain cancer, which causes significant neurological deterioration and reduced quality of life, and for which there is currently no curative treatment. TTFields...

A lobular capillary hemangioma, previously known as a pyogenic granuloma, is a benign vascular lesion of the skin or mucous membrane. We report a case of capillary hemangioma of lobular subtype in the calvarium of a 28-year-old pregnant woman which presented as a sore and rapidly growing bulge over the left fronto-parietal region. Magnetic resonanc...

BACKGROUND We present an upcoming(Sep. 2020) randomized, comparative, multi-center, investigator-initiated, interventional, phase 2 trial testing the efficacy of a novel therapeutic concept for recurrent glioblastoma(GBM). The intervention combines personalized targeted skull remodeling surgery(SR-surgery) with Tumor Treating Fields(TTFields) and b...

Background Preclinical studies suggest that skull remodeling surgery (SR-surgery) increases the dose of tumor treating fields (TTFields) in glioblastoma (GBM) and prevents wasteful current shunting through the skin. SR-surgery introduces minor skull defects to focus the cancer-inhibiting currents towards the tumor and increase the treatment dose. T...

In this case report, a 71-year-old female developed headache and nausea and signs of brain stem involvement following lumbar surgery with intraoperative dural tear. A CT scan showed cerebellar haemorrhage and hydrocephalus, and the patient was transferred to a neurosurgical department and treated with an external ventricular drainage, haematoma eva...

Background: We present a clinical open label, phase-1 trial (OptimalTTF-1, NCT02893137), which aims to test a novel treatment for first recurrence glioblastoma (rGBM). The aim of the treatment is to optimize the electric field generated by Tumor Treating Fields (TTFields) with targeted and individualized skull-remodeling surgery (SR-surgery). Selec...

Background: We will initiate (March 2020) a randomized, comparative, multi-center, investigator-initiated, interventional, phase 2 trial (NCT04223999) testing the efficacy of a potentially new treatment modality for recurrent glioblastoma (GBM). The new treatment modality combines individualized targeted skull remodeling surgery (SR-surgery) with T...

Synapses in the cerebral cortex constantly change and this dynamic property, together with the action of neuromodulators such as dopamine (DA), is essential for reward learning and memory. DA modulates spike-timing-dependent plasticity (STDP), a cellular model of learning and memory, in juvenile rodent cortical neurons. However, it is unknown wheth...

The efficacy of Tumor-Treating Fields (TTFields) rests on the result of a large-scale clinical trial that demonstrated an increase in the survival of newly diagnosed glioblastoma patients when combined with temozolomide chemotherapy. Overall survival now extends to over 60 months in some of our patients when dexamethasone, which we suspected of int...

BACKGROUND OptimalTTF-1(open-label phase-1) combines Tumor Treating Fields(TTFields) treatment with targeted skull-remodeling surgery(SR-surgery) aiming to enhance the electric field strength in the tumor(NCT02893137). SR-surgery aims to reduce the electrical impedance of the skull. Pre-clinical modeling indicates that SR-surgery increases the elec...

Objectives: Intraoperative visual evoked potentials (VEPs) are used to monitor the function of optic radiation during neurosurgery with the P100 amplitude decrement as a predictor of post-operative visual deficit. However, there is currently no evidence of early VEP changes indicating reversible visual field affection. Methods: In this case repo...

Tumor treating fields (TTFields) is a new non-invasive approach to cancer treatment. TTFields is low-intensity (1-5 V/m), intermediate frequency (150-200 kHz) alternating electric fields delivered locally to the tumour to selectively kill dividing cells and disrupt cancer growth. TTFields has proven safe and effective for newly diagnosed glioblasto...

Objective: Maximal safe resection is an important surgical goal in the treatment for high-grade gliomas. Fluorescent dyes help the surgeon to distinguish malignant tissue from healthy. The aims of this study were 1) to compare the 2 fluorescent dyes 5-aminolevulinic acid (5-ALA) and sodium fluorescein (fluorescein) regarding extent of resection, p...

BACKGROUND OptimalTTF-1 is an open-label phase-1 study on the combination of Tumor Treating Fields (TTFields) treatment together with targeted skull remodeling surgery aiming to enhance the electric field intensity in the brain (NCT02893137). Skull-remodeling surgery (SR-surgery) in this trial aims to reduce the electrical impedance of the skull. P...

Tumor-treating fields (TTFields) are a new cancer treatment that inhibits tumor growth with alternating electrical fields. Finite element (FE) methods are used to calculate the intensity of TTFields as a measure of therapeutic “dose.” However, the antitumor efficacy also depends on the direction and exposure time of the induced fields. We recently...

Skull-remodeling surgery has been proposed to enhance the dose of tumor treating fields in glioblastoma treatment. This abstract describes the finite element methods used to plan the surgery and evaluate the treatment efficacy.

Tumor treating fields (TTFields) are increasingly used to treat newly diagnosed and recurrent glioblastoma (GBM). Recently, the authors proposed a new and comprehensive method for efficacy estimation based on singular value decomposition of the sequential field distributions. The method accounts for all efficacy parameters known to affect anti-canc...

Tumor treating fields (TTFields) is a new non-invasive approach to cancer treatment. TTFields are low-intensity (1-5 V/m), intermediate frequency (150-200 kHz) alternating electric fields delivered locally to the tumour to selectively kill dividing cells and disrupt cancer growth. TTFields has proven safe and effective for newly diagnosed glioblast...

BACKGROUND We present a pre-specified interim analysis of an ongoing open-label, phase-1 IST (NCT02893137) testing safety/efficacy of a new rGBM treatment. The intervention combines personalized skull-remodeling (SR) surgery with TTFields and best-choice chemotherapy. SR-surgery involves minor craniectomy or burr-holes personalized to enhance TTFie...

INTRODUCTION Tumor treating fields (TTFields, Optune®) is an effective treatment for glioblastoma. The antimitotic effects of TTFields are induced by low-intensity, intermediate frequency (200 kHz) alternating electric fields, delivered through two pairs of transducer arrays placed on the patient’s scalp. The present study aimed to identify optimal...

INTRODUCTION The non-invasive glioblastoma treatment, tumor treating fields (TTFields, Optune®), uses alternating electrical fields (200 kHz) to inhibit cancer cell division. TTFields are induced by two sequentially active pairs of transducer arrays placed on the patient’s scalp. Finite element (FE) methods are used to estimate the field intensity...

Background Tumor treating fields (TTFields, Optune®) is an effective treatment for glioblastoma. The antimitotic effects of TTFields are induced by low-intensity, intermediate frequency (200 kHz) alternating electric fields, delivered through two pairs of transducer arrays placed on the patient’s scalp. The present study aimed to identify optimal a...

Background We present a pre-specified interim analysis of an ongoing open-label, investigator-sponsored phase 1 trial (NCT02893137) testing safety/efficacy of a new rGBM treatment. The intervention combines personalized skull-remodeling (SR) surgery with TTFields and best-choice chemotherapy. SR-surgery involves minor craniectomy, burr-holes, and/o...

Background The non-invasive glioblastoma treatment, tumor treating fields (TTFields, Optune®), uses alternating electrical fields (200 kHz) to inhibit cancer cell division. TTFields are induced by two sequentially active pairs of transducer arrays placed on the patient’s scalp. Finite element (FE) methods are used to estimate the field intensity of...

Tumor treating fields (TTFields) is a new modality used for the treatment of glioblastoma. It is based on antineoplastic low-intensity electric fields induced by two pairs of electrode arrays placed on the patient’s scalp. The layout of the arrays greatly impacts the intensity (dose) of TTFields in the pathology. The present study systematically ch...

Field distribution for rotation of a single array pair at the tumor position x = 50 mm. (MP4)

Field distribution for rotation of a single array pair at the tumor position y = -20 mm. (MP4)

Field distribution for orthogonal array pairs at various rotations and tumor position x = 30 mm. (MP4)

Field distribution for rotation of a single array pair at the tumor position y = 20 mm. (MP4)

Field distribution for orthogonal array pairs at various rotations and tumor position y = -20 mm. (MP4)

Field distribution for rotation of a single array pair at the tumor position x = 30 mm. (MP4)

Field distribution for rotation of a single array pair at the tumor position x = 42.5 mm. (MP4)

Field distribution of optimal array position for all tumors translated in the left-right direction. (MP4)

Field distribution for orthogonal array pairs at various rotations and tumor position x = 42.5 mm. (MP4)

Field distribution for orthogonal array pairs at various rotations and tumor position x = 50 mm. (MP4)

Field distribution of optimal array position for all tumors in the anterior-posterior direction. (MP4)

Field distribution for rotation of a single array pair at the tumor position y = - 40 mm. (MP4)

Field distribution for rotation of a single array pair at the tumor position y = 30 mm. (MP4)

Field distribution for orthogonal array pairs at various rotations and tumor position y = 20 mm. (MP4)

Field distribution for orthogonal array pairs at various rotations and tumor position y = -40 mm. (MP4)

Field distribution for orthogonal array pairs at various rotations and tumor position y = 30 mm. (MP4)

Introduction Tumor Treating Fields (TTFields) is approved for the treatment of recurrent glioblastoma (rGBM). Skull remodeling surgery involves formation of strategically placed craniectomies, burr holes or skull thinning, in order to facilitate electric current flow into the tumor region. Preclinical studies have indicated that these procedures pr...

Introduction: Tumor treating fields (TTFields) is a new and effective treatment for glioblastoma. Two pairs of transducer arrays are placed on the scalp of the patient to deliver low intensity, alternating electric fields, which inhibit mitosis and cancer growth. In the present study, we investigated systematic variations in electrode array positio...

Tumor treating fields (TTFields) is an anticancer treatment that inhibits tumor growth with alternating electrical fields. Finite element (FE) methods have been used to estimate the TTFields intensity as a measure of treatment "dose". However, TTFields efficacy also depends on field direction and exposure time. Here we propose a new FE based approa...

Tumor treating fields (TTFields) are increasingly used as a fourth modality in glioblastoma therapy. TTFields are alternating electrical fields, which inhibit cancer growth by disrupting mitotic processes. Optimization of TTFields efficacy requires thorough understanding of distribution of TTFields “dose” in the brain. Here we provide simple guidin...

We present an ongoing open label phase 1 investigator-sponsored trial (NCT02893137) testing safety/efficacy of a novel therapeutic concept for recurrent glioblastoma (GBM). The intervention combines best choice chemotherapy with tumor treating fields (TTFields) and personalized targeted skull remodeling surgery. The objective of skull remodeling su...

Background: Tumor treating fields (TTFields) are increasingly used in the treatment of glioblastoma. TTFields inhibit cancer growth through induction of alternating electrical fields. To optimize TTFields efficacy, it is necessary to understand the factors determining the strength and distribution of TTFields. In this study, we provide simple guid...

Changes in L/R field topography with tumor displacement along the x-axis. Axial section showing changes in field topography with gradually increasing lateral displacement of the tumor. Depicts field induced by the L/R electrode pair. (MP4)

Changes in A/P field topography with tumor displacement along the z-axis. Sagittal section showing changes in field topography with gradually increasing superior displacement of the tumor. Depicts field induced by the A/P electrode pair. (MP4)

Changes in A/P field topography with tumor displacement along the x-axis. Axial section showing changes in field topography with gradually increasing lateral displacement of the tumor. Depicts field induced by the A/P electrode pair. (MP4)

Changes in L/R field topography with tumor displacement along the y-axis. Axial section showing changes in field topography with gradually increasing anterior displacement of the tumor. Depicts field induced by the L/R electrode pair. (MP4)

Changes in A/P field topography with tumor displacement along the y-axis. Axial section showing changes in field topography with gradually increasing anterior displacement of the tumor. Depicts field induced by the A/P electrode pair. (MP4)

Changes in L/R field topography with tumor displacement along the z-axis. Coronal section showing changes in field topography with gradually increasing superior displacement of the tumor. Depicts field induced by the L/R electrode pair. (MP4)

Objectives: The use of Deep Brain Stimulation (DBS) in treatment of various brain disorders is constantly growing; however, the number of studies of the reaction of the brain tissue toward implanted leads is still limited. Therefore, the aim of our study was to analyze the impact of DBS leads on brain tissue in a large animal model using minipigs....

Objective The present work proposes a new clinical approach to TTFields therapy of glioblastoma. The approach combines targeted surgical skull removal (craniectomy) with TTFields therapy to enhance the induced electrical field in the underlying tumor tissue. Using computer simulations, we explore the potential of the intervention to improve the cli...

This paper reviews the state-of-the-art in simulation-based studies of Tumor Treating Fields (TTFields) and highlights major aspects of TTFields in which simulation-based studies could affect clinical outcomes. A major challenge is how to simulate multiple scenarios rapidly for TTFields delivery. Overcoming this challenge will enable a better under...