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P01.048 A novel transducer array layout for delivering Tumor Treating Fields to the infratentorial brain at therapeutic levels

ABSTRACT: Abstract Background Tumor Treating Fields (TTFields) is an antimitotic cancer treatment that utilizes low intensity (1–3 V/cm) alternating electric fields in the intermediate frequency (100–300 kHz), approvedfor the treatment of Glioblastoma Multiforme (GBM) located in the supratentorial regions of the brain. A clinical trial testing the efficacy of TTFields for treating brain metastases is currently underway (METIS, NCT02831959). TTFields are delivered via two pairs of transducer arrays placed on the patient’s skin in proximity to the tumor. The standard array layouts used to deliver TTFields involve placement of the arrays on the supratentorial regions of the head. Using these layouts, therapeutic field intensities above 1 V/cm are achieved within the surpatentorial brain. However, field intensities in the infratenorium fall to sub-therapeutic levels. . Brain metastases commonly occur in the infratentorium. In addition, infratentorial tumors are common in the pediatric population. Hence, there is a need to for array layouts that can be used to deliver TTFields effectively to the infratentorial brain. Here we present a new array layout designed to deliver high field intensities to the infratentorial brain. Materials and methods To simulate delivery of TTFields to the brain, realistic computerized head models of an adult human female and an adult human male were used. Virtual transducer arrays were placed on the models, and boundary conditions were set to simulate delivery of TTFields at 200 kHz. Various array layouts were tested, and field distributions resulting from the layouts were evaluated. Results In both models, TTfields was delivered to the infratentorium most effectively with a layout, in which each array of one pair was laterally placed superficially to the lower region of the occipital lobe, and the two arrays of the second pair were placed on the calvarium and the superior aspect of the neck. In both models, the pair of arrays in which one array was placed on the calvarium and one array on the superior aspect of the neck delivered field intensities above 1.1 V/cm to over 95% of the volume of the infratentorial brain, and the pair of arrays placed on the lateral aspects of the occipital lobe delivered field intensities above 1 V/cm to over 95% of the infratentorial brain. Both pairs of arrays delivered field intensities above 1 V/cm to significant portions of the supratentorial brain. Conclusions This work suggests a practical approach for delivering TTFields to the cerebellum, brain-stem and surrounding regions which are located inferior to the tentorium.

SUBMITTER: Bomzon Z

PROVIDER: S-EPMC6144458 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Project description: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.

Project description:Abstract BACKGROUND High-grade meningioma are aggressive intracranial tumors and currently only limited treatment options exist. Therefore, there is a need for further studies in search of new therapies. Tumor Treating TTFields (TTFields) therapy serves as an effective treatment against glioblastoma (GBM). Phase 3 clinical trials investigate the use of TTFields in other intracranial tumors, i.e. brain metastases of the non-small cell lung cancer. We here provide an overview of the currently available data regarding the use of TTFields in meningioma. MATERIALS AND METHODS We performed a literature search using the term “Tumor treating fields” “NovoTTF”, “TTFields” and “Optune” in combination with “Meningioma”. A brief overview of TTFields in meningioma is provided here. RESULTS In vitro studies using patient-derived anaplastic grade III meningioma cell lines showed that TTFields treatment at a frequency of 200 kHz causes a significant reduction of cell proliferation and clonogenicity as well as altering cell morphology. In a case report of a 44-year-old woman suffering from a right anterior temporal tumor as well as a distant right parietal extra-axial convexity meningioma TTFields and Temozolomide treatment was initiated. Brain MRI scans 8, 16 and 20 weeks later showed a reduction in the meningioma tumor size of 42%, 58% & 60%, respectively. Currently, two ongoing trials test the efficacy and safety of the use of TTFields in meningioma patients: a phase II single arm trial (n=27), investigating the combination of TTFields and Bevacizumab in recurrent or progressive meningioma (NCT02847559); and a pilot trial, investigating the effects of TTFields as monotherapy on recurrent atypical and anaplastic meningioma (NCT01892397). CONCLUSIONS First data indicate that TTFields might be an option in future high-grade meningioma treatment. Clinical trials need to show safety and efficacy for the TTFields treatment in meningioma patients.

Project description:Background and objective200 kHz tumor treating fields (TTFields) is clinically approved for newly-diagnosed glioblastoma (nGBM). Because its effects on conventional surveillance MRI brain scans are equivocal, we investigated its effects on perfusion MRI (pMRI) brain scans.MethodsEach patient underwent institutional standard pMRI: dynamic contrast-enhanced (DCE) and dynamic susceptibility contrast (DSC) pMRI at three time points: baseline, 2-, and 6-months on-adjuvant therapy. At each timepoint, the difference between T1 pre- versus post-contrast tumor volume (ΔT1) and these pMRI metrics were evaluated: normalized and standardized relative cerebral blood volume (nRCBV, sRCBV); fractional plasma volume (Vp), volume of extravascular extracellular space (EES) per volume of tissue (Ve), blood-brain barrier (BBB) permeability (Ktrans), and time constant for gadolinium reflux from EES back into the vascular system (Kep). Between-group comparisons were performed using rank-sum analysis, and bootstrapping evaluated likely reproducibility of the results.ResultsAmong 13 pMRI datasets (11 nGBM, 2 recurrent GBM), therapies included temozolomide-only (n = 9) and temozolomide + TTFields (n = 4). No significant differences were found in patient or tumor characteristics. Compared to temozolomide-only, temozolomide + TTFields did not significantly affect the percent-change in pMRI metrics from baseline to 2 months. But during the 2- to 6-month period, temozolomide + TTFields significantly increased the percent-change in nRCBV (+26.9% [interquartile range 55.1%] vs -39.1% [37.0%], p = 0.049), sRCBV (+9.5% [39.7%] vs -30.5% [39.4%], p = 0.049), Ktrans (+54.6% [1768.4%] vs -26.9% [61.2%], p = 0.024), Ve (+111.0% [518.1%] vs -13.0% [22.5%], p = 0.048), and Vp (+98.8% [2172.4%] vs -24.6% [53.3%], p = 0.024) compared to temozolomide-only.ConclusionUsing pMRI, we provide initial in-human validation of pre-clinical studies regarding the effects of TTFields on tumor blood volume and BBB permeability in GBM.

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P01.048 A novel transducer array layout for delivering Tumor Treating Fields to the infratentorial brain at therapeutic levels

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