Array Placement Research Articles

Compatibility of topical agents with tumor treating fields (TTFields) for treatment of associated skin events in glioblastoma (GBM).

e24126 Background: TTFields are low intensity, intermediate frequency, alternating electric fields applied continuously using 2 pairs of skin-affixed transducer arrays. TTFields are FDA-approved in GBM and mesothelioma. The most common TTFields-related adverse event (AE) is mild-to-moderate dermatitis (beneath arrays), via long-term irritant exposure and local hyperhidrosis and occlusion exacerbation. Skin reaction mitigation strategies may improve quality-of-life (QoL) and ensure usage, as maximal survival benefits have been correlated with duration of use. Not all skin care products are TTFields compatible and may increase electrical impedance and lead to beneath array temperature increases. The aim of this in vivo study was to investigate the effects of 62 commercially available skin care products on electrical impedance during TTFields treatment. Methods: TTFields (200 kHz; optimal GBM frequency) were applied to rats using transducer arrays made of the same ceramic disks and hydrogels used in patients with GBM. To test electrical impedance effects, skin care products were applied to the skin immediately before array placement. The change in impedance relative to naïve skin was measured using the Optune device. Sixty-two commercially available products from 8 groups (adhesive removers, antibiotics, antiperspirants, antiseptics, cleansers, moisturizers, skin barriers, and topical corticosteroids) were evaluated. Results: Most lotions, soaps, foams, and solutions had minimal effect on electrical impedance, while petrolatum-based ointments significantly increased electrical impedance. Conclusions: TTFields compatible skin care products that did not affect electrical impedance were identified from each of the 8 groups and could be considered for further evaluation. All petrolatum-based ointments that were tested led to an increase in electrical impedance and are thus not recommended. Local application of TTFields compatible skin care products should be prospectively investigated in the clinical setting for their potential role in minimizing TTFields–related skin AEs. The randomized, double-blind PROTECT (PROphylactic skin Toxicity thErapy with Clindamycin and triamcinolone in GBM patients Treated with TTFields) study, should help establish which products best reduce skin AEs in patients with GBM and assess impact on QoL.

PRIMA subretinal wireless photovoltaic microchip implantation in non-human primate and feline models.

PurposeTo evaluate the surgical technique for subretinal implantation of two sizes of PRIMA photovoltaic wireless microchip in two animal models, and refine these surgical procedures for human trials.MethodsCats and Macaca fascicularis primates with healthy retina underwent vitrectomy surgery and were implanted with subretinal wireless photovoltaic microchip at the macula/central retina. The 1.5mm PRIMA chip was initially studied in feline eyes. PRIMA implant (2mm,1.5mm sizes) arrays were studied in primates. Feasibility of subretinal chip implantation was evaluated with a newly-developed surgical technique, with surgical complications and adverse events recorded.ResultsThe 1.5mm implant was placed in the central retina of 11 feline eyes, with implantation duration 43–106 days. The 1.5mm implant was correctly positioned into central macula of 11 primate eyes, with follow-up periods of minimum 6 weeks (n = 11), 2 years (n = 2), and one eye for 3 years. One primate eye underwent multi-chip 1.5mm implantation using two 1.5mm chips. The 2mm implant was delivered to 4 primate eyes. Optical coherence tomography confirmed correct surgical placement of photovoltaic arrays in the subretinal space in all 26 eyes. Intraoperative complications in primate eyes included retinal tear, macular hole, retinal detachment, and vitreous hemorrhage that resolved spontaneously. Postoperatively, there was no case of significant ocular inflammation in the 1.5mm implant group.ConclusionsWe report subretinal implantation of 1.5mm and 2mm photovoltaic arrays in the central retina of feline and central macula of primate eyes with a low rate of device-related complications. The in vivo PRIMA implantation technique has been developed and refined for use for a 2mm PRIMA implant in ongoing human trials.

SPARC: Minimally Invasive Recording of Neural Activity During Natural Voiding in Anaesthetized Rats

BackgroundControlling urination with bioelectric neuromodulation devices is an emerging treatment strategy for bladder incontinence/retention as it can be rapidly adjusted to respond to changing patient needs, known as closed‐looped control. However, true closed‐loop bioelectric neuromodulation requires sensing of neural activity to allow accurate and timely delivery of the stimulation to maximally affect the end‐organ. As such, developing a neural recording feedback system that is highly specific for different neural fibre types is a crucial first step towards closed‐loop control.ObjectiveTo develop and validate a minimally invasive recording technology that differentiates between afferent and efferent neural activity, as well as distinguishing between fast and slow fibre types.MethodsA custom‐designed, two pair platinum electrode array was implanted onto the pelvic nerve of urethane‐anaesthetised Sprague Dawley rats (male; 8–10 weeks; n=6) with catheterised bladders. Evoked compound action potentials (ECAPs) were generated to confirm placement of the electrode array and cystometry and neural activity recorded during bladder filling and voiding.ResultsECAPs show recruitment of slow and fast conduction neural populations. Our recording technology distinguished between afferent and efferent activity during the micturition reflex. Within these neural types, distinctive patterns of fast and slow conducting fibres were identified and their firing patterns were consistent with results reported using invasive single‐ and multi‐unit recording techniques.ConclusionClosed‐loop bioelectric neuromodulation requires the ability to stimulate or inhibit neural activity, as well as precisely sense ongoing neural activity. We have completed the first step in developing closed loop technology by validating technology that precisely records multiple distinct populations of neural activity using a minimally invasive technique. Future studies will investigate the effectiveness of this recording technique in awake, freely moving rats.Support or Funding InformationResearch reported in this publication was supported by the Office Of The Director, National Institutes Of Health of the National Institutes of Health under Award Number OT2OD023872.

Sculpting the temporal bone: an easy reversible cochlear implant electro-array stabilization technique

Since the beginning of cochlear implant (CI) surgery, several techniques to fixate the electrode array at the cochleostomy and stabilize it have been described; however, most techniques use autologous tissues such as fascia, muscle, fat or fibrin glue. We describe a new surgical technique aimed to stabilize the electrode array of a CI without using autologous tissues or artificial materials. The surgical technique described consists in creating three stabilizing channels in the temporal bone for the electrode array. The first one in a partially opened aditus, the second one in a partially preserved Koerner's septum (KS) and the last one in the sinodural angle. The procedure was performed in five human temporal bones using a straight array; a radiography was made to confirm the correct placement of the electrode array and afterwards all temporal bones were shaken using a Titramax 1000 platform. The correct placement of the array post-shaking was then confirmed using the microscope and another radiography. No migration of the electrodes outside the cochlea was observed. The CI cable remained in the same position at the aditus and the KS in all the temporal bones. In three cases (60%), the electrode array moved away from the groove carved in the sinodural angle. The new surgical technique described stabilizes the electrode array using the temporal bone's normal anatomy, preserving the middle ear spaces, facilitating the ulterior explantation and reimplantation if necessary, and may reduce cost and surgery time.

Optimisation for large-scale photovoltaic arrays’ placement based on Light Detection And Ranging data

The availability of high-resolution LiDAR (Light Detection And Ranging) geospatial data has increased immensely, providing new opportunities to solve challenges in the field of spatial energy planning. This paper presents a new method for large-scale placement of photovoltaic arrays over buildings’ rooftops in an optimal manner by using the global optimisation approach. The position, aspect and slope are the ey geometrical parameters being optimised for each photovoltaic array. The predicted energy generation (i.e. photovoltaic potential) is simulated by using state-of-the-art hourly shadowing estimation from the surroundings, anisotropic diffuse, reflected, and direct irradiances that are based on a Typical Meteorological Year, and non-linear efficiency characteristics of a considered photovoltaic system configuration. The optimisation performs multiple simulation scenarios throughout an entire year for each photovoltaic array, in order to maximise its photovoltaic potential. The method was tested over three LiDAR datasets with different landscape topographies and urban densities. In comparison to the methods for photovoltaic arrays’ fixed optimal slope estimation, the proposed method is substantially more suitable for application in urban environments.

Estimating on-Board Power Generation by Solar Photo-Voltaic Array Integrated Lighter-Than-Air Platform Under Variable Pitching Conditions

Abstract Sustainable power generation on solar photovoltaic (SPV) modules integrated lighter-than-air platforms (LTAPs) is a daunting task since they are exposed to variable environmental factors such as wind, ambient air pressure, and incident solar insolation. Among these factors, the wind plays a significant role in destabilizing the system from its equilibrium position and affects the power generation. In this paper, we proposed a methodology for estimating the dynamics of power generation due to the destabilized pitching under different wind vectors. An alternative to the conventional fluid–structure interaction, a semi-analytical methodology has been formulated, utilizing commercial ansys fluent software, to estimate the pitching characteristics of lighter-than-air platform (LTAP). This pitching characteristic has been mapped to the body inertial frame for investigating the incident solar insolation followed by determining the corresponding power generation. The consequences of the envelope contour function (ECF) are also incorporated while characterizing the power generation. Furthermore, this study also provides scope for the placement of the solar PV array on LTAP in order to minimize losses in generated onboard power under variable pitching conditions.

Human Cochlear Nucleus on 7 Tesla Diffusion Tensor Imaging: Insights Into Micro-anatomy and Function for Auditory Brainstem Implant Surgery.

The cochlear nucleus (CN) is the target of the auditory brainstem implant (ABI). Most ABI candidates have Neurofibromatosis Type 2 (NF2) and distorted brainstem anatomy from bilateral vestibular schwannomas. The CN is difficult to characterize as routine structural MRI does not resolve detailed anatomy. We hypothesize that diffusion tensor imaging (DTI) enables both in vivo localization and quantitative measurements of CN morphology. We analyzed 7 Tesla (T) DTI images of 100 subjects (200 CN) and relevant anatomic structures using an MRI brainstem atlas with submillimetric (50 μm) resolution. Tertiary referral center. Young healthy normal hearing adults. Diagnostic. Diffusion scalar measures such as fractional anisotropy (FA), mean diffusivity (MD), mode of anisotropy (Mode), principal eigenvectors of the CN, and the adjacent inferior cerebellar peduncle (ICP). The CN had a lamellar structure and ventral-dorsal fiber orientation and could be localized lateral to the inferior cerebellar peduncle (ICP). This fiber orientation was orthogonal to tracts of the adjacent ICP where the fibers run mainly caudal-rostrally. The CN had lower FA compared to the medial aspect of the ICP (0.44 ± 0.09 vs. 0.64 ± 0.08, p < 0.001). 7T DTI enables characterization of human CN morphology and neuronal substructure. An ABI array insertion vector directed more caudally would better correspond to the main fiber axis of CN. State-of-the-art DTI has implications for ABI preoperative planning and future image guidance-assisted placement of the electrode array.

Use of intraoperative CT scanning for quality control assessment of cochlear implant electrode array placement*

Background: Imaging of cochlear implant (CI) electrode arrays (EAs) consists of intraoperative fluoroscopy to rule out tip fold-over and/or post-operative computerized tomography (CT) if concern exists regarding extrusion or misplacement of the EA. Intraoperative CT (iCT) can satisfy these current needs and enables specification of final intracochlear position.Aims/objectives: To describe iCT scanning of CI recipients at an academic medical center.Materials and methods: iCT was used to scan CI recipients within the operating room before recovering from general anesthesia.Results: In fiscal year 2019, 301 CI were placed (83 children, 218 adult). One hundred, seventy-five iCTs were performed (58% of total CIs) of which 52 were children (63% of pediatric CIs) and 123 were adult (57% of adult CIs). Of 7 CI surgeons, use of iCT ranged from 14% to 100% (mean 60%). Four tip fold-overs were identified and corrected intraoperatively. Surgeons reported using the images to improve technique (i.e. pulling back precurved EAs to improve perimodiolar positioning).Conclusion and significance: The current standard of care for CI is to insert EAs without feedback as to final location. iCT provides surgeons with rapid post-insertion feedback which allows detection and correction of suboptimally placed EAs as well as refinement of surgical technique.

Economic and technical assessment of rooftop solar photovoltaic potential in Brownsville, Texas, U.S.A

Localized assessment of solar energy economic feasibility will benefit the structuring of residential solar energy deployment globally. In the U.S. growing interest in rooftop residential solar among city managers has spurred the development of photovoltaic (PV) feasibility maps of the technical and economic solar potential within cities. The City of Brownsville, Texas was interested in evaluating solar feasibility for their city but lacked information to make informed policy decisions on PV development. This paper presents novel and systems approaches for determining the technical and economic feasibility of solar development for homes in the Brownsville using LiDAR and local information. Residential technical and economic potential was assessed by optimizing the internal rate of return (IRR) and an average residential building demand profile to determine ideal size and placement of solar arrays. Results showed that residential structures in Brownsville have the technical potential to generate approximately 11% of the total energy provided by the local utility; however, average IRR was only 2.9% with a payback period of over 15 years. Five neighborhoods in the City of Brownsville were identified with spatially clustered homes that had relatively higher IRRs compared with other areas in the city. Despite the high technical potential, modeled results indicate that perspective home owners interested in solar development may require additional incentives to improve the economic feasibility of PV in Brownsville. This study provides a demonstration of an interdisciplinary systems approach and methodology that can be adopted internationally to evaluate the feasibility of solar development in other areas.

Iterative positioning of microphone arrays for acoustic imaging

For the characterization of acoustic sources, a common approach is to retro-propagate the sound pressure measured with a microphone array, which is often performed through the resolution of an inverse problem. The ill-posed nature of this problem, as well as the limited number of measurements, are known to reduce the quality of the source reconstruction. A practical solution to these limitations is to increase the number of measurements with new array placements. However, finding the best array positions is not a straightforward process. The present paper tackles this issue by introducing a sequential approach that selects at each iteration the optimal array placement. The proposed approach builds on two features rooted in a Bayesian framework: an inverse method called “Bayesian focusing” and a Bayesian search criterion based on the Kullback-Leibler divergence. Simulations results for the characterization of a directive source are used to illustrate the performance of the approach. It is shown that for a fixed number of iterations, the proposed approach performs better than ones where the successive placements are randomly selected around the source, or others where the placements follow a deterministic spherical grid pattern.

A robust sequential hypothesis testing method for brake squeal localisation.

This contribution deals with the in situ detection and localisation of brake squeal in an automobile. As brake squeal is emitted from regions known a priori, i.e., near the wheels, the localisation is treated as a hypothesis testing problem. Distributed microphone arrays, situated under the automobile, are used to capture the directional properties of the sound field generated by a squealing brake. The spatial characteristics of the sampled sound field is then used to formulate the hypothesis tests. However, in contrast to standard hypothesis testing approaches of this kind, the propagation environment is complex and time-varying. Coupled with inaccuracies in the knowledge of the sensor and source positions as well as sensor gain mismatches, modelling the sound field is difficult and standard approaches fail in this case. A previously proposed approach implicitly tried to account for such incomplete system knowledge and was based on ad hoc likelihood formulations. The current paper builds upon this approach and proposes a second approach, based on more solid theoretical foundations, that can systematically account for the model uncertainties. Results from tests in a real setting show that the proposed approach is more consistent than the prior state-of-the-art. In both approaches, the tasks of detection and localisation are decoupled for complexity reasons. The localisation (hypothesis testing) is subject to a prior detection of brake squeal and identification of the squeal frequencies. The approaches used for the detection and identification of squeal frequencies are also presented. The paper, further, briefly addresses some practical issues related to array design and placement.

NIMG-20. EVALUATION OF HEAD SEGMENTATION QUALITY FOR TREATMENT PLANNING OF TUMOR TREATING FIELDS IN BRAIN TUMORS

Abstract Tumor treating fields (TTFields) is an FDA approved therapy for the treatment of glioblastoma multiform (GBM), malignant pleural mesothelioma (MPM), and currently being investigated for additional tumor types. TTFields are delivered to the tumor through the placement of transducer arrays (TAs) placed on the patient’s shaved scalp. The positions of the TAs are associated with treatment outcomes via simulations of the electric fields. Therefore, we are currently developing a method for recommending optimal placement of TAs. A key step to achieve this goal is to correctly segment the head into tissues of similar electrical properties. Visual inspection of segmentation quality is invaluable but time-consuming. Automatic quality assessment can assist in automatic refinement of the segmentation parameters, suggest flaw points to the user and indicate if the segmented method is of sufficient accuracy for TTFields simulation. As a first step in this direction, we identified a set of features that are relevant to atlas-based segmentation and show that these are significantly correlated (p &lt; 0.05) with a similarity measure between gold-standard and automatically computed segmentations. Furthermore, we incorporated these features in a decision tree regressor to predict the similarity of the gold-standard and computed segmentations of 20 TTFields patients using a leave-one-out approach. The predicted similarity measures were highly correlated with the actual ones (average absolute difference 3% (SD = 3%); r = 0.92, p &lt; 0.001). We conclude that automatic quality estimation of segmentations is feasible by incorporating segmentation-relevant features with statistical and machine learning methods, such as decision tree regressor.

A Flattop Radiation Pattern Antenna with Special-Shaped Array Placement for Stadium Communications

A flattop radiation pattern antenna with special-shaped array placement for large-scale stadium communications is presented in this paper. The antenna array consists of only 16 electric dipoles, each of that is ± 45° linear polarizations, placed in three rings configuration above a ground plane. Under the ground plane two feeding networks with ± 45° linear polarizations, respectively are used to divide signals to the 16 electric dipoles to produce flattop radiation patterns. A prototype operated at 2300–2700 MHz for stadium wireless communications, such as 4G LTE, is manufactured and tested, and good agreements between simulation and measurement are demonstrated. The measured gain is above 12 dBi and the side-lobe levels are lower than − 20 dB. The measured isolations between the two polarization ports are less than − 30 dB within the operating band. A fast beam ramp of less than 20° from − 3 to − 20 dB is achieved.

490 High-Resolution Electrogastrogram Identifies Disturbed Gastric Slow Waves and Dysautonomia in Subjects With Dumping Syndrome

INTRODUCTION: Rapid gastric emptying is the sine qua non of Dumping Syndrome (DS), which can arise from multiple etiologies including gastric surgery and diabetes mellitus. The relationship between DS and gastric myoelectric activity is unknown, but dysautonomia may play a role. We sought to characterize features of gastric slow waves and autonomic indices among subjects with DS using the ambulatory high-resolution electrogastrogram (HR-EGG). METHODS: Eleven subjects completed 24-hour ambulatory HR-EGG. Fasting abdominal computed tomography scan was utilized for stomach localization and placement of the ambulatory HR-EGG array, consisting of 10 skin mounted electrodes. Subjects were divided into two groups: DS (4F, age 53.2 ± 9.3, BMI 31.7 ± 11, 79-93% gastric emptying at 1 hour on scintigraphy, two diabetics, one prior gastric surgery, one gastrointestinal amyloidosis) and healthy age-matched controls (4M/3F, age 47.6 ± 28, BMI 24.5 ± 3.7). All subjects completed the PAGI-SYM foregut symptom questionnaire and a diary capturing all meals and sleep/wake times. RESULTS: Subjects with DS had significantly higher mean PAGI-SYM foregut symptom severity scores (1.9 ± 1.0 vs 0.1 ± 0.1; P = 0.0007). HR-EGG showed that DS subjects had a significantly lower slow wave speed (4.6 vs 5.9 ± 0.4; P = 0.0003) and higher post-prandial power change (11 vs 3.5 ± 3.6; P = 0.002) compared to healthy controls. The global percent stomach activity throughout the 24-hour ambulatory recordings was not different between groups. DS subjects trended towards higher post-prandial area under the curve EGG activity at both the 1-hour (261.9 ± 360.7 vs 172.9 ± 137.5) and 4-hour marks (1108.8 ± 1589.4 vs 656.3 ± 442.2). In addition, subjects with DS had significantly lower heart rate variability than controls: RMSDD (39.9 ± 9.7 vs 58.1 ± 7.8) and SDNN (12.6 ± 4.2 vs 23.7 ± 3.2); no differences were noted in mean heart rate (Table 1). CONCLUSION: Ambulatory HR-EGG clearly identifies that there are spatial abnormalities of the gastric slow wave present among subjects with DS. Moreover, reduced heart rate variability - a marker of autonomic dysfunction - was observed among subjects with DS. These findings suggest that gastric dysrhythmias and autonomic disturbances should be given important consideration in the pathogenesis of Dumping Syndrome.

EP1.18-18 Body Shape and Tissue Composition Influences Uniform Distribution of Tumor Treating Fields Intensity Delivered to the Lungs

Tumor Treating Fields (TTFields) are low intensity, alternating electric fields in the intermediate frequency range that disrupt mitosis. TTFields are approved for the treatment of glioblastoma. A Phase 3 study investigating the efficacy of TTFields in Non-Small Cell Lung Cancer is ongoing [LUNAR NCT02973789]. TTFields are delivered through two pairs of transducer arrays placed on the patient”s skin. Since the efficacy of TTFields increases with intensity, identifying factors that influence field intensity in the lungs is beneficial to understand how body shape and tissue composition influence the field intensity. We present a computer-simulation-based study investigating the effect of body size, shape, and composition on TTFields distribution in the lungs. This study was performed using the Sim4Life software package and realistic computational phantoms: female (ELLA), male (DUKE), and obese male (FATS). Various array layouts were placed on the models, and the distribution of TTFields within their lungs were calculated and compared. For all models, uniform field distributions within the lungs were obtained when the arrays were axially-aligned with the parenchyma as much as anatomically possible. The layouts that generated the highest average field intensities were those in which one pair of arrays delivered an electric field from the anterolateral to the posterior-contralateral aspect of the patient and the second pair inducing the field from the anterior-contralateral to the posterolateral aspect of the patient. In all models, these layouts led to average field intensities in the lungs above the therapeutic threshold (>1 V/cm). The highest field intensities were seen in DUKE”s lungs and the lowest field intensities in FATS”s lungs. Analysis suggests that field attenuation was caused primarily by layers of fat. Hence, the lower field intensities in the lungs of ELLA and FATS can be largely attributed to the thick layers of fat present in FATS and the fatty tissue in ELLA”s breasts. This study provides insights into how TTFields distribution in the lungs is influenced by body composition. These findings will help to optimize the placement and design of transducer array placement for the treatment of lung cancers.

Evaluation of the onshore wind energy potential in mainland China—Based on GIS modeling and EROI analysis

Due to the advantages of relatively mature technologies and low greenhouse gas pollution, wind energy represents a vital energy alternative for electricity generation. Using onshore wind power has become increasingly important in China. Currently, wind energy faces energy return on investment (EROI) and geographical constraints, which both have significant impacts on net wind energy potential. This study combines GIS modeling, wind turbine performance, and the wind speed distribution with a large daily dataset to estimate onshore technical and net wind energy potential in China and to visualize the available wind energy potential. In this study, more detailed local topographic effects (changing air density, surface roughness, air density, array placement efficiency) were considered despite the complexity of applying them at a country level. The results show that the technical potential of China’s onshore wind energy could reach 2560 TW h/yr in a 0% agriculture land scenario and 3501 TW h/yr in a 70% agriculture land scenario, and the net energy potential could reach 2335 TW h/yr and 3194 TW h/yr when EROI = 11.4:1 (when averaging performance of turbines across geographic areas) in these two different scenarios.

P14.66 TTFields dose distribution and tumor growth patterns confirm clinical activity of TTFields: MRI analysis of the randomized phase 3 EF-14 trial

Abstract BACKGROUND The randomized phase 3 EF-14 trial showed that the addition of tumor treating fields (TTFields) to temozolomide (TMZ) treatment improved survival in newly diagnosed glioblastoma patients over TMZ alone. As TTFields delivery is designed to optimize dose at the tumor bed, we hypothesized that tumor recurrence is likely to occur in distant sites and we investigated the pattern of tumor growth at relapse in due consideration of TTFields dose intensity distribution. METHODS Patients on therapy for more than 2 months who exhibited radiological progression were included in the study (treatment: N=280/466, control: N=122/229) Contrast-enhanced T1-weighted scans at baseline and at relapse served for segmentation of enhancing tumor and necrosis. Lesions outside a proximal boundary zone of 20mm surrounding lesions identified at baseline were defined as distal. In addition, infratentorial progression was assessed. Moreover, we identified patients treated with TTFields with sufficient MRI data for dose calculations and radiographically confirmed tumor relapse (N=225/466). TTFields intensity distributions were computed in a finite element method applied in a realistic head model with virtual transducer arrays. TTFields dose density (mW/cm3) was defined as TTFields power loss density multiplied by average patient compliance during the first 6 months of therapy. At baseline, regions of residual tumor and regions of normal brain were identified to calculate TTFields dose within each of these regions and noted its relationship with subsequent recurrence. RESULTS Distal progressions were more common in the TTFields arm (18% vs. 8%). Infratentorial progression was seen in 4% of the treatment arm vs. 0 patients in the control. Lesions at progression were more distant from the original lesion in the TTFields arm (57.0 + 26.2 mm vs. 46.6 + 14.8 mm). Local tumors grew at a significantly lower pace in the TTFields arm as compared to the control arm (3.6 + 14.5 ml vs. 8.3 + 17.9 ml). The average dose density in areas of enhancing tumor that regressed to normal was higher than in the areas of normal brain that progressed to enhancing tumor (0.84 mW/cm3 vs. 0.75 mW/cm3). Regardless of the expansion margin used for analysis, TTFields dose density in areas of normal brain that remained normal at the time of progression was higher than in the areas that progressed to enhancing tumor. CONCLUSIONS TTFields appear to induce distant tumor growth pattern and are associated with a lower tumor growth rate. In addition, the importance of dose density at the tumor bed is stressed as higher dose densities were seen in areas of normal brain that remain normal at the time of progression providing further rationale for carefully planning array placement to maximize delivery to areas at higher risk of recurrence. Taken together, these findings confirm the clinical activity of TTFields.

Clinical Applicability of a Preoperative Angular Insertion Depth Prediction Method for Cochlear Implantation.

Evaluation of the accuracy and clinical applicability of a single measure cochlear implant angular insertion depth prediction method. Cochlear implantation outcomes still vary extensively between patients. One of the possible reasons could be variability in intracochlear electrode array placement. For this reason, single measure methods were suggested to preoperatively predict angular insertion depths. Based on a previously performed accuracy study in human temporal bones, we were interested in determining the extent to which the method could be applied in a clinical setting. A retrospective analysis was performed on pre- and postoperative radiographic images of 50 cochlear implant recipients. Preoperatively predicted angular insertion depths were compared with angular insertion depths measured on postoperative ground truth. The theoretical prediction error was computed under the assumption that all achieved insertions were matching the preoperatively assumed linear insertion depth. More importantly, the clinical prediction error was assessed using two different software tools performed by three experienced surgeons. Using the proposed method we found a theoretical prediction error of 5 degrees (SD = 41 degrees). The clinical prediction error including the cases with extracochlear electrodes was 70 degrees (SD = 96 degrees). The presented angular insertion depth prediction method is a first practical approach to support the preoperative selection of cochlear implant electrode arrays. However, the presented procedure is limited in that it is unable to predict the occurrence of insertion results with extracochlear electrodes and requires user training.

Tumor Treating Fields Therapy Influences Patterns of Failure in Glioblastoma Patients in a Dose-Dependent Manner: A Multidisciplinary Analysis of the Randomized Phase III EF-14 Clinical Trial

The phase 3 EF-14 trial showed that when combined with chemoradiation Tumor Treating Fields (TTFields) improve Overall Survival (OS) and Progression Free Survival (PFS) in newly diagnosed GBM. We correlated TTFields dose distributions and patient specific patterns of failure, hypothesizing that the antimitotic effects of TTFields therapy would result in measurable changes in the location of recurrence. Two hundred and twenty five patients treated on the TTFields arm of EF-14 had both MR imaging sufficient for dose calculations and radiographically measureable progression of disease. Realistic head models of patients were created with virtual transducer arrays placed on the models in a patient-specific manner. TTFields intensity distributions were calculated using a Finite Elements Method. TTFields dose (expressed as mW/cm3) was defined as the product of TTFields intensity, tissue conductivity and the average patient compliance during first 6 months of therapy. For each case, the resection cavity +/- any residual gross tumor and an expansion margin of 3, 5, 10, 15, or 20 mm was defined as the primary areas of interest. At baseline, regions of residual tumor and regions of normal brain were identified for calculation of the TTFields dose within each these regions and its relationship with subsequent recurrence. The average dose in areas of enhancing tumor that regressed to normal was higher than in the areas of normal brain that progressed to enhancing tumor (0.84 mW/cm3 vs 0.75 mW/cm3, p<0.001). Regardless of the expansion margin used for analysis, TTFields dose in areas of normal brain that remained normal (norm to norm) at the time of progression were consistently higher than in the areas of normal brain that progressed to enhancing tumor (norm to tumor). These results confirm the clinical activity of TTFields and the importance of dose intensity at the tumor bed. Higher dose was seen in areas of normal brain that remain normal at the time of progression, providing further rationale for optimizing the array placement to maximize delivery to areas at highest risk of recurrence. Efforts to improve patient-specific TTFields dose planning and optimization, similar to radiotherapy planning, are underway.Abstract 3845; Table 1Expansion margin (mm)avg Dose in norm to norm (mW/cm3)avg Dose in norm to tumor (mW/cm3)Difference (mW/cm3)p-value30.7940.7340.06<0.00150.7850.7340.051<0.001100.7690.7340.0350.011150.7600.7310.0290.026200.7560.7310.0250.048 Open table in a new tab

Tumor-Treating Field Arrays Do Not Reduce Target Volume Coverage for Glioblastoma Radiation Therapy

PurposeTo inform development of procedures for using tumor-treating field arrays (TTFields) during glioblastoma radiation therapy by determining whether the placement and repositioning of arrays affects target volume coverage and cranial skin dose. Methods and MaterialsRadiation plans from 10 consecutive patients treated for glioblastoma were copied to a cranial phantom and reoptimized for phantom anatomy. Dose distributions were then recalculated on 3 additional computed tomographic scans of the phantom with the TTFields electrode arrays placed over distinct locations on the phantom scalp to compare planning target volume (PTV) coverage and skin dose with and without TTFields in place in varying positions. Percent depth dose curves were also measured for radiation beams passing through the electrodes and compared with commonly used bolus material. ResultsThe presence of TTFields arrays decreased PTV V97% and D97% by as much as 1.7% and 2.7%, respectively, for a single array position, but this decrease was mitigated by array repositioning. On averaging the 3 array positions, there was no statistically significant difference in any dosimetric parameter of PTV coverage (V95-97%, D95-97%) across all cases compared with no array. Mean increases in skin D1cc and D20cc of 3.1% were calculated for the cohort. Surface dose for TTFields electrodes was less than that with a 5-mm superflab bolus. ConclusionsOur work demonstrates that placement of TTFields arrays does not significantly affect target volume coverage. We show that repositioning of TTFields arrays, as is required in clinical use, further minimizes any dosimetric changes and eliminates the need for replanning when arrays are moved. A slight, expected bolus effect is observed, but the calculated increases in skin dose are not clinically significant. These data support the development of clinical trials to assess the safety and efficacy of combining concurrent chemoradiotherapy with TTFields therapy for glioblastoma.