1,720,989 research outputs found
Abstract 4536: Using diffusion weighted imaging (DWI) data to accurately predict electric field delivery to the tumor during TTFields treatment
No full textAbstract
Tumor Treating Fields (TTFields) are low intensity (1-3 V/cm) alternating electric fields in the intermediate frequency range, delivered through two pairs of transducer arrays placed on the patient's scalp. TTFields are an anti-mitotic modality approved for the treatment of glioblastoma multiforme (GBM).
Simulation-based studies show that TTFields distribution within the brain depends on the location of the arrays on the scalp as well as the anatomy of the patient. Therefore, to study how field distribution influences disease progression requires the creation of patient-specific computational models. To date the creation of such models is based on accurate segmentation of MRI images into various tissues, and further of volume mesh assembly. These tasks are performed using semi-automatic, labor-intensive algorithms, making this approach impractical for studies which require the creation of a large number of patient models. We recently outlined that diffusion tensor imaging (DTI) could be used to construct realistic head models for simulating TTFields distribution without the need for complex segmentation of the brain. This is possible because the diffusion tensors evaluated from DTI can be scaled into anisotropic conductivity tensors using simple relationships. However, the approach is limited because the acquisition of high-quality DTI data is not widely practiced for GBM patients. Yet, shorter diffusion weighted imaging (DWI) sequences, such as an apparent diffusion coefficient (ADC) map or trace image, are common diagnostic techniques. The aim of this study was to test whether DWI data could potentially be used to create realistic head models.
We used a previously developed head model created from structural and DTI data of a healthy individual. To test pathological scenarios, virtual lesions were placed. To simulate data acquired with DWI, we substituted the diffusion tensor at each point within the model with the mean diffusion (MD), which is the value that can be measured using DWI. The computational model was then completed by scaling the MD into a voxel-wise isotropic conductivity map using the same relationship as applied to convert anisotropic diffusion into conductivity tensors. TTFields distributions within the model were then evaluated for various array layouts and tumor locations.
The field distribution within the DWI-derived models did not vary significantly from those found in the DTI-derived models. The highest deviation between models was a difference of 5% in the average electric field intensity in the tumor. The study shows that DWI data can be used to develop realistic head models for simulating TTFields, opening a new avenue for creating patient-specific computational models on a large scale. These models could be beneficial for retrospective studies investigating possible connections between field distribution and disease outcome.
Citation Format: Cornelia Wenger, Ze'ev Bomzon, Pedro Cavaleiro Miranda. Using diffusion weighted imaging (DWI) data to accurately predict electric field delivery to the tumor during TTFields treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4536. doi:10.1158/1538-7445.AM2017-4536</jats:p
Abstract CT071: LUNAR - A phase 3 trial of TTFields in combination with PD-1 inhibitors or docetaxel for second line treatment of non-small cell lung cancer (NSCLC)
No full textAbstract
BACKGROUND
Tumor Treating Fields (TTFields) is a novel, non-invasive, anti-mitotic treatment modality, based on low intensity alternating electric fields. TTFields predominantly affect two phases of mitosis: metaphase – by disrupting the formation of the mitotic spindle, and cytokinesis – by dielectrophoretic dislocation of intracellular constituents. TTFields were shown to significantly extend the survival of newly diagnosed glioblastoma patients when combined with temozolomide. Efficacy of TTFields in non-small cell lung cancer (NSCLC) of all histologies has been demonstrated in multiple in vitro and in vivo models as well as in a phase I/II pilot study in combination with pemetrexed, where overall survival was extended by more than five months compared to historical controls.
LUNAR TRIAL DESIGN
The hypothesis of the study is that the addition of TTFields to standard of care second line therapies in advanced NSCLC will increase OS compared to treatment with standard second line alone. 512 patients with either squamous or non-squamous NSCLC will be enrolled in this prospective, randomized study. Patients will be stratified based on: 1) second line therapy (either PD-1 inhibitor or docetaxel), histology (squamous Vs. non-squamous) and geographical region. The main eligibility criteria are first disease progression (per RECIST Criteria 1.1), ECOG score of 0-1, no prior surgery or radiation therapy, no electronic medical devices in the upper torso and absence of brain metastasis.
Docetaxel or PD-1 inhibitors (either nivolumab or pembrolizumab) will be administered at the standard dose. TTFields will be applied to the upper torso using a small, portable medical device for at least 18 hours/day at home, allowing patients to maintain daily activities. TTFields will be continued until progression in the thorax and/or liver according to the immune-related response criteria (irRC). Follow up will be performed once q6 weeks, including a CT scan of the chest and abdomen. Following progression in the upper torso, patients will be followed monthly for survival.
The primary endpoint will be superiority in overall survival (OS) between patients treated with TTFields in combination with either docetaxel or PD-1 inhibitors, compared to docetaxel or PD-1 inhibitors alone. A co-primary endpoint will compare the OS in patients treated with TTFields and docetaxel to those treated with PD-1 inhibitors alone in a non-inferiority analysis. Secondary endpoints include progression-free survival, radiological response rate based on the irRC, quality of life based on the EORTC QLQ C30 questionnaire and severity & frequency of adverse events. The sample size is powered to detect a Hazard Ratio of 0.75 of TTFields-treated patients compare to the control group.
Citation Format: Uri Weinberg, Ori Farber, Moshe Giladi, Ze'ev Bomzon, Eilon Kirson. LUNAR - A phase 3 trial of TTFields in combination with PD-1 inhibitors or docetaxel for second line treatment of non-small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT071. doi:10.1158/1538-7445.AM2017-CT071</jats:p
Of Fields and Phantoms : The Importance of Virtual Humans in Optimizing Cancer Treatment with Tumor Treating Fields
No full text
Abstract 691: Simulating TTFields-induced temperature changes within a patient’s brain - a proof of concept study
No full textAbstract 1569: Optimizing transducer array configuration for treatment of pancreatic cancer using Tumor Treating Fields (TTFields)
No full textAbstract
Introduction
TTFields is an antimitotic cancer treatment that utilizes low intensity (1-3 V/cm) alternating electric fields in the intermediate frequency (100-300 kHz) that are delivered in two orthogonal directions using 2 pairs of transducer arrays. TTFields are currently approved for Glioblastoma Multiforme (GBM). A phase II clinical trial (EF-20) showed that TTFields in combination with gemcitabine was safe in patients with locally advanced pancreatic cancer.
Preclinical studies show that the effect of TTFields is intensity-dependent with a therapeutic threshold of 1 V/cm. Simulation-based studies show that the field distribution changes with array placement. Treatment planning with arrays positioned on the scalp to maximize field intensity to the tumor is standard of practice when treating GBM. Studies to examine array layout on the abdomen to maximize the field distribution in this region have not been done. In the EF-20 study, a generic layout was used. We used computer simulations to test how altering the transducer array layout on the mid-body alters the field distribution within the abdomen and pancreas.
Methods
To simulate delivery of TTFields to the abdomen, we used a realistic computerized model of a human male (DUKE 3.0 from ZMT-Zurich). Eight different layouts utilizing combinations of arrays with either 13 or 20 disks placed at different locations on the abdomen were simulated. In order to generate TTFields, an alternating voltage difference with a peak to peak magnitude of 100V and a frequency of 150 KHz was imposed on the outer surfaces of the disks of each pair of arrays. The simulations were performed using ZMT's Sim4Life V3.0 electro-quasi-static solver. For each pair of transducer arrays, the mean field intensity in the abdomen and chest, and in the pancreas and liver, was calculated.
Results
All eight layouts delivered fields with mean intensities of about 2 V/cm to the abdomen. The average field intensity delivered to the pancreas and the liver exceeded the therapeutic threshold of 1 V/cm for all layouts. The highest intensities were delivered to the pancreas by layouts in which a 20-disk array was placed at the middle of the back, and either a 20 disk array placed at the middle of the abdomen or a 13 disk array placed on the front-left side of the abdomen over the pancreas. Generally, field intensities in the pancreas are lower than in the rest of the abdomen because of the high electric conductivity of this organ.
Conclusion
This work shows that TTFields can be delivered to the pancreas with intensities well above the therapeutic threshold of 1 V/cm, and that altering the location of the arrays on the abdomen can influence the field intensity and distribution within the body. This work forms the basis for developing optimal strategies for delivering TTFields to the pancreas.
Citation Format: Ariel Naveh, Ze'ev Bomzon, Noa Urman, Ofir Yesharim, Eilon D. Kirson, Uri Weinberg. Optimizing transducer array configuration for treatment of pancreatic cancer using Tumor Treating Fields (TTFields) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1569. doi:10.1158/1538-7445.AM2017-1569</jats:p
Abstract 4528: A novel transducer array design optimizing TTFields delivery to the thorax
No full textAbstract
Objective: The purpose of this study was to design transducer arrays for the delivery of Tumor Treating Fields (TTFields) to the thorax, generating high intensity in the upper torso while potentially improving patient comfort.
Background: TTFields are low intensity, intermediate frequency, alternating electrical fields that disrupt cell division. The ongoing Phase II STELLAR trial [NCT02397928] is investigating the efficacy and safety of TTFields in combination with chemotherapy for the treatment of mesothelioma. A pivotal study to evaluate the efficacy of TTFields in treating NSCLC is planned for 2017. TTFields are delivered via capacitive transducer arrays, comprising ceramic disks covered with a thin layer of conductive medical-grade gel, which are arranged in an almost rectangular order. Two orthogonal pairs of arrays are placed on the skin in the vicinity of the treated region. One pair is placed on the anterior and posterior sides of the thorax. The other pair is placed on the lateral and contralateral sides of the thorax. This configuration has limitations: (a) Sub-optimal electric contact may be caused by poor attachment of the arrays on the chest due to body curvature; (b) TTFields intensity generated by anterior-posterior arrays may be attenuated in the thorax of females and obese individuals, due to high resistivity of the thick adipose layers in the breast; (c) the current lateral-contralateral arrays generate lower field intensities in the lung’s apex. This study presents novel array designs to overcome these limitations.
Methods: Various concepts for array designs that avoid placement over regions of thick sub-cutaneous fat were designed. To evaluate the field distribution generated by these arrays and optimize their design, numerical simulations using realistic computational phantoms were used.
Results: Novel array designs were developed for the delivery of TTFields to the lungs. These arrays consist of sets of interconnected small patches that adhere to the natural contours of the human body. Simulations showed that the proposed arrays deliver uniformly distributed, high electrical field to the lungs. One notable design is a pair of arrays shaped as circular rings, in which one array is placed around the neck and shoulders, whereas the second array is placed on the lower torso. This design yielded a highly uniform field directed longitudinally throughout the torso.
Conclusion: The array designs presented in this study are expected to maintain patient comfort and will ensure high field intensity delivered to the thorax. Compliance and TTFields treatment delivery could both be improved by using these designs.
Citation Format: Hadas S. Hershkovich, Sholi Strauss, Uri Weinberg, Eilon D. Kirson, Ze'ev Bomzon. A novel transducer array design optimizing TTFields delivery to the thorax [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4528. doi:10.1158/1538-7445.AM2017-4528</jats:p
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