Thirty-day surgical morbidity and risk factors in pediatric brain tumor surgery: a 10-year nationwide retrospective study.

OBJECTIVE: Pediatric neuro-oncological surgery is often associated with significant risk; however, comprehensive data on surgical morbidity remain limited. The purpose of this study was therefore to provide national population-based data on both the incidence and characteristics of poor postoperative outcomes following pediatric intracranial neuro-oncological surgery. Additionally, the authors aimed to evaluate key risk factors for poor postoperative outcomes including overall morbidity, significant morbidity, and the most frequent types of morbidity. METHODS: The authors conducted a registry-based, nationwide, retrospective study including all children receiving surgical treatment for a CNS tumor over a 10-year period. Patients were identified using the Danish Childhood Cancer Registry, and 30-day morbidity was assessed through manual review of electronic health records. Significant morbidity was defined as complications in need of treatment under general anesthesia, ICU admission, or persistent neurological deficits at 30 days following surgery or death. Risk factors including sex, age, tumor location, tumor malignancy grade, and preoperative hydrocephalus were investigated using multivariate logistic regression analysis. RESULTS: A total of 349 children undergoing 473 tumor procedures were included, with an overall morbidity rate of 66.0% and a significant morbidity rate of 34.2%. The most frequent complications included neurological deficits (41.4%) and CSF-related morbidity consisting of CSF leaks, pseudomeningoceles, and postoperative hydrocephalus. Highly significant associations between infratentorial tumor location and both significant morbidity (OR 1.26, 95% CI 1.11-1.43; p < 0.001) and neurological deficits (OR 1.38, 95% CI 1.21-1.57; p < 0.001) were identified. In addition, younger age was revealed as a major risk factor of both postoperative CSF leakage and CSF-related morbidity in general. CONCLUSIONS: In this large, population-based cohort, the authors show that postoperative morbidity is frequent, occurring in about two-thirds of all patients, largely driven by neurological deficits and CSF-related complications. In addition, infratentorial tumor location and younger age emerged as key risk factors for poor postoperative outcomes.

Focused ultrasound for the treatment of brain tumors.

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 carried out for better penetration of chemotherapy. Numerous studies on neuro-oncological treatments are ongoing, signaling increasing popularity for the technique in the near future.

Allocating operating room capacity to non-elective neurosurgical patients improves access and safety for elective patients at Aarhus University Hospital.

INTRODUCTION: This study addresses surgical scheduling within the Department of Neurosurgery at Aarhus University Hospital (AUH). The department provides neurosurgical care to a population of 1.3 million in central Denmark, and has treatment obligations for specific neurosurgical diseases for the entire country, which has a population of 5.8 million. Efficient utilisation of the department's four operating suites is crucial to ensure that patients have timely access to both non-elective and elective neurosurgical procedures. Historically, the elective operating room (OR) schedule was made without consideration of the possible arrival of non-elective patients; consequently, elective surgeries were often cancelled to accommodate those with more urgent indications. The challenge was thus to introduce a structured way of planning for these non-elective surgical procedures that would minimise the need for cancelling elective surgeries without decreasing overall productivity. METHODS: Using a mathematical model developed in a previous study at Leiden University Medical Center, the effect of allocating OR time during regular working hours for non-elective neurosurgical procedures at AUH was analysed, so that a weighted trade-off could be made between cancellations of elective patients due to an overflow of non-elective patients and unused OR time due to excessive reservation of time for non-elective patients. This allocation was tested in a six-week pilot study during weeks 24 & 25 and weeks 34-37 of 2020 before being implemented in 2021. RESULTS: In the 35 weeks following the implementation, the new allocation strategy resulted in a significant 77% decrease in the cancellation of elective neurosurgical procedures when compared with the same time period in 2019, with a significant 16% increase in surgical productivity. CONCLUSIONS: This study shows that with mathematical modelling complex problems in the distribution of neurosurgical OR capacity can be solved, improving both patient safety and the working environment of neurosurgeons and OR staff.

Assessment of the Milan Complexity Scale for prediction of postoperative morbidity in pediatric neuro-oncological surgery.

PURPOSE: To assess the performance of the risk-predicting Milan Complexity Scale (MCS) on postoperative morbidity in pediatric neuro-oncological surgery. METHODS: A retrospective dual-center review of children undergoing primary brain tumor resection in Denmark over a 10-year period. MCS scoring was performed based on preoperative imaging, blinded to individual outcomes. Surgical morbidity was registered according to existing complication scales and dichotomized as significant or nonsignificant morbidity. The MCS was evaluated using logistic regression modeling. RESULTS: 208 children (50% female, mean age 7.9 y, and SD 5.2) were included. Of the original "Big Five" predictors included in the MCS, only posterior fossa (OR: 2.31, 95% CI: 1.25-4.34, p-value = 0.008) and eloquent area (OR: 3.32, 95% CI: 1.50-7.68, p-value = 0.004) locations were significantly associated with increased risk of significant morbidity in our pediatric cohort. The absolute MCS score correctly classified 63.0% of cases. Its accuracy increased to 69.2% when mutually adjusting for each of the "Big Five" predictors with corresponding positive and negative predictive values of 66.2% and 71.0%, using a predicted probability cutoff of 0.5. CONCLUSION: The MCS is predictive of postoperative morbidity also in pediatric neuro-oncological surgery, although only two of its original five variables were significantly associated with poor outcome in children. The clinical value of the MCS is likely limited for the experienced pediatric neurosurgeon. Future clinically impactful risk-prediction tools should include a larger number of relevant variables and be tailored to the pediatric population.

Cerebral Macro- and Microcirculation during Ephedrine versus Phenylephrine Treatment in Anesthetized Brain Tumor Patients: A Randomized Clinical Trial Using Magnetic Resonance Imaging.

BACKGROUND: This study compared ephedrine versus phenylephrine treatment on cerebral macro- and microcirculation, measured by cerebral blood flow, and capillary transit time heterogeneity, in anesthetized brain tumor patients. The hypothesis was that capillary transit time heterogeneity in selected brain regions is greater during phenylephrine than during ephedrine, thus reducing cerebral oxygen tension. METHODS: In this single-center, double-blinded, randomized clinical trial, 24 anesthetized brain tumor patients were randomly assigned to ephedrine or phenylephrine. Magnetic resonance imaging of peritumoral and contralateral hemispheres was performed before and during vasopressor infusion. The primary endpoint was between-group difference in capillary transit time heterogeneity. Secondary endpoints included changes in cerebral blood flow, estimated oxygen extraction fraction, and brain tissue oxygen tension. RESULTS: Data from 20 patients showed that mean (± SD) capillary transit time heterogeneity in the contralateral hemisphere increased during phenylephrine from 3.0 ± 0.5 to 3.2 ± 0.7 s and decreased during ephedrine from 3.1 ± 0.8 to 2.7 ± 0.7 s (difference phenylephrine versus difference ephedrine [95% CI], -0.6 [-0.9 to -0.2] s; P = 0.004). In the peritumoral region, the mean capillary transit time heterogeneity increased during phenylephrine from 4.1 ± 0.7 to 4.3 ± 0.8 s and decreased during ephedrine from 3.5 ± 0.9 to 3.3 ± 0.9 s (difference phenylephrine versus difference ephedrine [95%CI], -0.4[-0.9 to 0.1] s; P = 0.130). Cerebral blood flow (contralateral hemisphere ratio difference [95% CI], 0.3 [0.06 to 0.54]; P = 0.018; and peritumoral ratio difference [95% CI], 0.3 [0.06 to 0.54; P = 0.018) and estimated brain tissue oxygen tension (contralateral hemisphere ratio difference [95% CI], 0.34 [0.09 to 0.59]; P = 0.001; and peritumoral ratio difference [95% CI], 0.33 [0.09 to 0.57]; P = 0.010) were greater during ephedrine than phenylephrine in both regions. CONCLUSIONS: Phenylephrine caused microcirculation in contralateral tissue, measured by the change in capillary transit time heterogeneity, to deteriorate compared with ephedrine, despite reaching similar mean arterial pressure endpoints. Ephedrine improved cerebral blood flow and tissue oxygenation in both brain regions and may be superior to phenylephrine in improving cerebral macro- and microscopic hemodynamics and oxygenation.

[MR-guided laser interstitial thermal therapy in the treatment of brain tumours and epilepsy].

MR-guided laser interstitial thermal therapy (LITT) is a minimally invasive neurosurgical procedure, which in the last decade has gained significant momentum of the treatment of intracranial tumours and epileptic foci. In brief, LITT utilises the heat from a stereotactically placed laser catheter to selectively ablate a lesion or a structure under real-time MRI guidance, which is summarised and discussed in this review. The first LITT system gained FDA approval in 2007 and was CE-marked in 2018. In December 2020, the first patient with recurrent glioblastoma was treated at the Department of Neurosurgery at Rigshospitalet, Copenhagen.

OptimalTTF-1: Enhancing tumor treating fields therapy with skull remodeling surgery. A clinical phase I trial in adult recurrent glioblastoma.

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 toward the tumor and increase the treatment dose. This study aimed to test the safety and feasibility of this concept in a phase I setting. METHODS: Fifteen adult patients with the first recurrence of GBM were treated with personalized SR-surgery, TTFields, and physician's choice oncological therapy. The primary endpoint was toxicity and secondary endpoints included standard efficacy outcomes. RESULTS: SR-surgery resulted in a mean skull defect area of 10.6 cm2 producing a median TTFields enhancement of 32% (range 25-59%). The median TTFields treatment duration was 6.8 months and the median compliance rate 90%. Patients received either bevacizumab, bevacizumab/irinotecan, or temozolomide rechallenge. We observed 71 adverse events (AEs) of grades 1 (52%), 2 (35%), and 3 (13%). There were no grade 4 or 5 AEs or intervention-related serious AEs. Six patients experienced minor TTFields-induced skin rash. The median progression-free survival (PFS) was 4.6 months and the PFS rate at 6 months was 36%. The median overall survival (OS) was 15.5 months and the OS rate at 12 months was 55%. CONCLUSIONS: TTFields therapy combined with SR-surgery and medical oncological treatment is safe and nontoxic and holds the potential to improve the outcome for GBM patients through focal dose enhancement in the tumor.

Ephedrine versus Phenylephrine Effect on Cerebral Blood Flow and Oxygen Consumption in Anesthetized Brain Tumor Patients: A Randomized Clinical Trial.

BACKGROUND: Studies in anesthetized patients suggest that phenylephrine reduces regional cerebral oxygen saturation compared with ephedrine. The present study aimed to quantify the effects of phenylephrine and ephedrine on cerebral blood flow and cerebral metabolic rate of oxygen in brain tumor patients. The authors hypothesized that phenylephrine reduces cerebral metabolic rate of oxygen in selected brain regions compared with ephedrine. METHODS: In this double-blinded, randomized clinical trial, 24 anesthetized patients with brain tumors were randomly assigned to ephedrine or phenylephrine treatment. Positron emission tomography measurements of cerebral blood flow and cerebral metabolic rate of oxygen in peritumoral and normal contralateral regions were performed before and during vasopressor infusion. The primary endpoint was between-group difference in cerebral metabolic rate of oxygen. Secondary endpoints included changes in cerebral blood flow, oxygen extraction fraction, and regional cerebral oxygen saturation. RESULTS: Peritumoral mean ± SD cerebral metabolic rate of oxygen values before and after vasopressor (ephedrine, 67.0 ± 11.3 and 67.8 ± 25.7 µmol · 100 g · min; phenylephrine, 68.2 ± 15.2 and 67.6 ± 18.0 µmol · 100 g · min) showed no intergroup difference (difference [95% CI], 1.5 [-13.3 to 16.3] µmol · 100 g · min [P = 0.839]). Corresponding contralateral hemisphere cerebral metabolic rate of oxygen values (ephedrine, 90.8 ± 15.9 and 94.6 ± 16.9 µmol · 100 g · min; phenylephrine, 100.8 ± 20.7 and 96.4 ± 17.7 µmol · 100 g · min) showed no intergroup difference (difference [95% CI], 8.2 [-2.0 to 18.5] µmol · 100 g · min [P = 0.118]). Ephedrine significantly increased cerebral blood flow (difference [95% CI], 3.9 [0.7 to 7.0] ml · 100 g · min [P = 0.019]) and regional cerebral oxygen saturation (difference [95% CI], 4 [1 to 8]% [P = 0.024]) in the contralateral hemisphere compared to phenylephrine. The change in oxygen extraction fraction in both regions (peritumoral difference [95% CI], -0.6 [-14.7 to 13.6]% [P = 0.934]; contralateral hemisphere difference [95% CI], -0.1 [- 12.1 to 12.0]% [P = 0.989]) were comparable between groups. CONCLUSIONS: The cerebral metabolic rate of oxygen changes in peritumoral and normal contralateral regions were similar between ephedrine- and phenylephrine-treated patients. In the normal contralateral region, ephedrine was associated with an increase in cerebral blood flow and regional cerebral oxygen saturation compared with phenylephrine.

Cognitive impairment following radiation to hippocampus and other brain structures in adults with primary brain tumours.

BACKGROUND: Radiation therapy (RT) to the brain may result in cognitive impairment. The primary objective of the present study was to examine the relationship between RT dose to the hippocampus and learning and memory functions. Secondary objective was to examine relationships between doses to other brain structures and specific cognitive functions. METHODS: A cross-sectional analysis was undertaken in 78 primary brain tumour patients after RT. Cognitive function was assessed by neuropsychological tests. Test scores were standardized using normative data adjusted for age and level of education. Test-specific cognitive impairment was determined as a z-score ≤-1.5. Radiation dose to brain structures and test-specific cognitive impairment outcomes were fitted to a logistic regression model. RESULTS: High RT dose to the left hippocampus was associated with impaired verbal learning and memory (p = 0.04). RT dose to the left hippocampus, left temporal lobe, left frontal lobe and total frontal lobe were associated with verbal fluency impairment (p < 0.05) and doses to the thalamus and the left frontal lobe with impaired executive functioning (p ≤ 0.03). Finally, RT dose to the brain and thalamus were associated with impaired processing speed (p ≤ 0.05). CONCLUSION: The present study indicates that the hippocampus may be vulnerable to radiation and that high radiation doses to the left hippocampus may lead to significant verbal learning and memory impairment. High RT doses to the left hippocampus and other left side structures may result in impairments in verbal fluency, executive function, and processing speed. Validation of these findings are being undertaken in a prospective study.

The supplementary motor area syndrome and the cerebellar mutism syndrome: a pathoanatomical relationship?

PURPOSE: The supplementary motor area (SMA) syndrome affects adults after tumour resection in SMA neighbouring motor cortex. Cerebellar mutism syndrome (CMS) affects children after tumour resection in the posterior fossa. Both syndromes include disturbances in speech and motor function. The causes of the syndromes are unknown; however, surgical damage to the dentato-thalamo-cortical pathway (DTCP) has been associated with CMS. Thus, an anatomical link between the areas associated with the syndromes is possible. We discuss the syndromes and their possible relationship through the DTCP. METHODS: We identified 61 articles (cohort studies, case reports and reviews) in MEDLINE and Embase searching for CMS, SMA syndrome or DTCP or synonyms and reviewed for evidence linking CMS and SMA. RESULTS: We found that SMA syndrome and CMS are similar regarding (1) surgical causation; (2) symptoms including speech impairment, disturbance in motor function and facial dysfunction; (3) delayed onset; (4) the courses of the syndromes are transient; and (5) long-term sequelae are seen in both. Relevant differences include age predominance of adults in SMA syndrome versus children in CMS. CONCLUSIONS: The similarities of the two syndromes could be traced back to their mutual connection through the DTCP and their membership to a cerebro-cerebellar circuit. The connectivity network could explain the emotional changes and speech reduction in CMS. The difference in time of post-surgical onset may be related to the anatomical distance between the surgical damage to the cerebellum and the SMA, respectively, and the effector neural loop underpinning symptoms.

Latency-shift of intra-operative visual evoked potential predicts reversible homonymous hemianopia after intra-ventricular meningioma surgery.

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 report, we used VEPs during surgery for a benign meningioma located in the atrium of the right lateral ventricle. The tumor was accessed through a transcortical approach via a two-centimeter corticotomy in the lateral aspect of the superior parietal lobule. We performed flash VEPs and simultaneous recordings of electroretinography alongside with multimodal intraoperative monitoring. RESULTS: We observed a significant and sustained unilateral latency shift of the P100 component of VEPs, while amplitudes temporarily dropped to 80% of baseline but recovered entirely at the end of surgery. After the operation, the patient had a left-sided lower-quadrant anopia, which recovered completely during the following three months. Diagnostic VEP with pattern reversal monocular full field stimulation at one month postoperatively showed normal latencies bilaterally. CONCLUSION: Our case indicates that the VEP (P100) latency may be a new and valuable indicator (in addition to VEP amplitude) of the visual pathways. SIGNIFICANCE: Monitoring VEPs may be useful to detect an imminent injury and a potentially reversible functional deficit.

[Tumor treating fields in cancer treatment in Denmark].

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 glioblastoma and is currently being tried for multiple other tumours. This review presents an introduction to TTFields, covering the main indications, the application method, the mechanism of action, the clinical results and the perspectives for implementation in Danish cancer treatment.

Reduced perioperative blood loss in children undergoing craniosynostosis surgery using prolonged tranexamic acid infusion: a randomised trial.

BACKGROUND: Tranexamic acid (TXA) reduces intraoperative blood loss and transfusion during paediatric craniosynostosis surgery. Additional reduction of postoperative blood loss may further reduce exposure to allogeneic blood products. We studied the effect of combined intra- and postoperative TXA treatment on postoperative blood loss in children. METHODS: Thirty children admitted for craniosynostosis surgery were randomised to combined intra- and postoperative TXA treatment or placebo. The primary endpoint was postoperative blood loss. Secondary endpoints included total blood loss, transfusion requirements, and clot stability evaluated by tissue plasminogen activator-stimulated clot lysis assay. RESULTS: TXA reduced postoperative blood loss by 18 ml kg-1 (95% confidence interval 8.9) and total blood loss from a mean of 52 ml kg-1 (standard deviation [SD]; 20) ml kg-1 to 28 (14) ml kg-1 (P<0.001). Intraoperative red blood cell (RBC) and fresh frozen plasma (FFP) transfusions were reduced in the treatment group from RBC 14.0 (5.2) ml kg-1 to 8.2 (5.1) ml kg-1 (P=0.01) and from FFP 13.0 (6.3) ml kg-1 to 7.8 (5.9) ml kg-1 (P=0.03). Postoperative RBC transfusion median was 5 (inter-quartile range [IQR] 0-6) ml kg-1 in the placebo group and 0 (0-5.7) ml kg-1 in the TXA group. Resistance to lysis was higher in the treatment group (P<0.001). CONCLUSIONS: Combined intra- and postoperative tranexamic acid treatment reduced postoperative and overall blood loss and transfusion requirements. Improved clot stability represents a possible mechanism for blood loss reduction.

Intra- and Postoperative Blood Loss and Transfusion Requirements in Children Undergoing Craniofacial Surgery.

Pediatric craniosynostosis (CS) surgery is frequently associated with extensive blood loss and transfusion requirements. The aim of the study was to evaluate the authors' institutional procedure with 2-surgeon approach and early transfusion strategy on blood loss and blood product transfusions in children undergoing craniofacial surgery. A retrospective analysis of medical records was performed of pediatric CS corrections during a 15-year period. Primary endpoint was blood loss and transfusion requirement during and the following 24 hours postoperatively. Linear regression analyses were performed of associations between intra and- postoperative blood loss and blood loss and weight. A total of 276 children (median 9 months) were included. Intraoperative blood loss was 22 mL/kg (14-33 mL/kg) and postoperatively 27 mL/kg (18-37 mL/kg), with no change during the study period. Intraoperative transfusions of red blood cell and plasma were 16 mL/kg (10-24 mL/kg) and postoperative 14 mL/kg (9-21 mL/kg). Postoperative red blood cell and plasma transfusions were 2 mL/kg (0-6 mL/kg) and of 0 mL/kg, respectively. Craniosynostosis type was related to blood loss (P < 0.001). There was an association between intraoperative and postoperative blood loss (P = 0.012) and intra- and postoperative blood loss and weight (P = 0.002, P = < 0.001). Duration of surgery was 110 minutes (range 60-300 minutes).Pediatric CS surgery is associated with substantial intra- and postoperative blood loss and transfusion requirements, which did not change over a 15-year period. Blood loss was associated with type of CS. Intraoperative blood loss was correlated to postoperative blood loss and body weight.

Long-term cognitive dysfunction after radiation therapy for primary brain tumors.

Background: The extent of radiation therapy (RT)-induced changes in cognitive function is unknown. RT with protons instead of photons spares the healthy brain tissue more and is believed to reduce the risk of cognitive dysfunction. There is modest knowledge on which parts of the brain we need to spare, to prevent cognitive dysfunction. To uncover which cognitive domains is most affected, we compared cognitive functioning in brain tumor patients treated with neurosurgery and RT with brain tumor patients treated with neurosurgery alone. Methods: A cross-sectional study assessing cognitive function in 110 patients with a primary brain tumor grades I-III or medulloblastoma (grade IV) treated at Aarhus University Hospital (AUH), Denmark between 2006 and 2016. Two cohorts were established: a cohort of 81 brain tumor patients who had received neurosurgery followed by RT (RT+), and a cohort of 29 brain tumor patients who had only received neurosurgery (RT-). The patients underwent questionnaires and neuropsychological assessment with standardized tests. Results: Mean age was 53.5 years with an average time since diagnosis of 7.3 years. Compared with normative data, lower average scores were observed for the entire group on domains concerning of verbal learning and memory (p < .001), attention and working memory (p < .001), processing speed (p < .001), and executive functioning (p < .001). Compared to RT- patients, RT + patients scored lower on domains concerning processing speed (p = .04) and executive function (p = .05) and had higher impairment frequency on verbal fluency (p = .02) with 16% of patients exceeding 1.5 SD below normative data. Conclusions: Our results indicate that treatment, including RT, for a primary brain tumor may have negative long-term impact on cognitive function, especially on processing speed and executive function.

[Tumor treating fields in cancer treatment in Denmark].

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 glioblastoma and is currently being tried for multiple other tumours. This review presents an introduction to TTFields, covering the main indications, the application method, the mechanism of action, the clinical results and the perspectives for implementation in Danish cancer treatment.

Optimization of tumor treating fields using singular value decomposition and minimization of field anisotropy.

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-cancer efficacy of TTFields, i.e. intensity, exposure time, and spatial field correlation. In this paper, we describe a further development, which enables individual optimization of the TTFields activation cycle. The method calculates the optimal device settings to obtain a desired average field intensity in the tumor, while minimizing unwanted field correlation. Finite element (FE) methods were used to estimate the electrical field distribution in the head. The computational head model was based on MRI data from a GBM patient. Sequential field vectors were post-processed using singular value decomposition. A linear transformation was applied to the resulting field matrix to reduce fractional anisotropy (FA) of the principal field components in the tumor. Results were computed for four realistic transducer array layouts. The optimization method significantly reduced FA and maintained the average field intensity in the tumor. The algorithm produced linear gain factors to be applied to the transducer array pairs producing the sequential fields. FA minimization was associated with an increase in total current delivered through the head during a activation cycle. Minimized FA can be obtained for an unchanged total current level, albeit with a reduction in average field intensity. We present an algorithm for optimization of the TTFields activation cycle settings. The method can be used to minimize the spatial correlation between sequential TTFields, while adjusting the total current level and mean field intensity to a desired level. Future studies are needed to validate clinical impact and assess sensitivity towards model parameters.

Importance of electrode position for the distribution of tumor treating fields (TTFields) in a human brain. Identification of effective layouts through systematic analysis of array positions for multiple tumor locations.

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 characterizes the impact of array position on the TTFields distribution calculated in a realistic human head model using finite element methods. We investigate systematic rotations of arrays around a central craniocaudal axis of the head and identify optimal layouts for a large range of (nineteen) different frontoparietal tumor positions. In addition, we present comprehensive graphical representations and animations to support the users' understanding of TTFields. For most tumors, we identified two optimal array positions. These positions varied with the translation of the tumor in the anterior-posterior direction but not in the left-right direction. The two optimal directions were oriented approximately orthogonally and when combining two pairs of orthogonal arrays, equivalent to clinical TTFields therapy, we correspondingly found a single optimum position. In most cases, an oblique layout with the fields oriented at forty-five degrees to the sagittal plane was superior to the commonly used anterior-posterior and left-right combinations of arrays. The oblique configuration may be used as an effective and viable configuration for most frontoparietal tumors. Our results may be applied to assist clinical decision-making in various challenging situations associated with TTFields. This includes situations in which circumstances, such as therapy-induced skin rash, scar tissue or shunt therapy, etc., require layouts alternative to the prescribed. More accurate distributions should, however, be based on patient-specific models. Future work is needed to assess the robustness of the presented results towards variations in conductivity.

The role of computed tomography in the screening of patients presenting with symptoms of an intracranial tumour.

BACKGROUND: To improve the quality of care for brain cancer patients, the Danish Ministry of Health has set standards for the diagnosis and treatment. When a patient is suspected of having a malignant tumour involving the brain, it is required that a magnetic resonance imaging of the cerebrum (MRI-C) be obtained within seven calendar days of referral from a primary care provider. This standard has the potential to consume MR imaging time that might otherwise be used for evaluation or treatment monitoring of other patients. This study primarily aims to assess the sensitivity of computed tomography of the brain (CT-C) for the detection of intracranial tumour as the initial diagnostic imaging. METHODS: This is a single-center retrospective study of patients referred to the IBCP with brain cancer suspicion. The average follow-up was 37 months. All included patients underwent a CT-C scan and subsequently a MRI-C if deemed necessary. The study population was divided into two groups based on the findings: tumour versus non-tumour. Sensitivity and specificity of the CT-C was calculated. RESULTS: Eight hundred seventeen patients were included. Median age was 55 years and 50% were male. CT-C had a sensitivity of 98.5% and a specificity of 98.4%. The overall mortality rate was 7% in the non-tumour group and 58% in the tumour group over the course of the study period. The tumour group was on average older compared to the non-tumour group (65 years [55-75 years] vs 52 years [38-65 years]) p < .001). The only symptom associated with brain tumour was the presence of a focal deficit (p = .002). CONCLUSION: This study shows that CT-C scans are highly sensitive and specific and can be used as the primary screening tool for patients referred with a suspicion for brain cancer.

Noninvasive assessment of isocitrate dehydrogenase mutation status in cerebral gliomas by magnetic resonance spectroscopy in a clinical setting.

OBJECTIVE Mutations in the isocitrate dehydrogenase (IDH) genes are of proven diagnostic and prognostic significance for cerebral gliomas. The objective of this study was to evaluate the clinical feasibility of using a recently described method for determining IDH mutation status by using magnetic resonance spectroscopy (MRS) to detect the presence of 2-hydroxyglutarate (2HG), the metabolic product of the mutant IDH enzyme. METHODS By extending imaging time by 6 minutes, the authors were able to include a point-resolved spectroscopy (PRESS) MRS sequence in their routine glioma imaging protocol. In 30 of 35 patients for whom this revised protocol was used the lesions were subsequently diagnosed histologically as gliomas. Of the remaining 5 patients, 1 had a gangliocytoma, 1 had a primary CNS lymphoma, and 3 had nonneoplastic lesions. Immunohistochemistry and/or polymerase chain reaction were used to detect the presence of IDH mutations in the glioma tissue resected. RESULTS In vivo MRS for 2HG correctly identified the IDH mutational status in 88.6% of patients. The sensitivity and specificity was 89.5% and 81.3%, respectively, when using 2 mM 2HG as threshold to discriminate IDH-mutated from wildtype tumors. Two glioblastomas that had elevated 2HG levels did not have detectable IDH mutations, and in 2 IDH-mutated gliomas 2HG was not reliably detectable. CONCLUSIONS The noninvasive determination of the IDH mutation status of a presumed glioma by means of MRS may be incorporated into a routine diagnostic imaging protocol and can be used to obtain additional information for patient care.