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Uri Weinberg
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-088d - TTFields Combined with PD-1 Inhibitors or Docetaxel for 2nd Line Treatment of Non-Small-Cell Lung Cancer (NSCLC): Phase 3 LUNAR Study (ID 7563)
09:30 - 09:30 | Presenting Author(s): Uri Weinberg
- Abstract
Background:
Tumor Treating Fields (TTFields) are a non-invasive, anti-mitotic treatment modality. TTFields disrupt the formation of the mitotic spindle, and dislocation of intracellular constituents. TTFields significantly extend the survival of newly diagnosed glioblastoma patients when combined with temozolomide. Efficacy of TTFields in NSCLC has been shown preclinically and in a phase I/II pilot study with pemetrexed, where overall survival (OS) improved by > 5 months vs historical controls. We hypothesize that adding TTFields to 2nd line therapies in advanced NSCLC will increase OS.
Method:
Patients (N=512) with squamous or non-squamous NSCLC are enrolled in this Phase 3 study LUNAR [NCT02973789]. Patients are stratified by 2[nd] line therapy (PD-1 inhibitor or docetaxel), histology (squamous vs. non-squamous) and geographical region. Key inclusion criteria are 1st disease progression (RECIST 1.1), ECOG 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) are given at standard doses. TTFields are applied to the upper torso for at least 18 hours/day, allowing patients to maintain daily activities. TTFields are continued until progression in the thorax and/or liver according to the immune-related response criteria (irRC). Follow up is performed once q6 weeks, including CT scans of the chest and abdomen. On progression in the upper torso, patients are followed monthly for survival. The primary endpoint is superiority in 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 compares 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 HR of 0.75 in TTFields-treated patients versus control group.
Result:
Section not applicable
Conclusion:
Section not applicable
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P3.01-088e - TTFields Delivery to the Brain: An Overview of Computational Studies and Implications When Treating Brain Metastases (ID 8773)
09:30 - 09:30 | Presenting Author(s): Uri Weinberg
- Abstract
Background:
TTFields is an antimitotic cancer treatment that utilizes alternating electric fields in the intermediate frequency range . TTFields are approved for treating Glioblastoma Multiforme (GBM), and a pivotal trial testing the efficacy of TTFields for treating brain metastases (METIS) is currently underway. TTFields are delivered in two orthogonal directions using 2 pairs of transducer arrays placed on the patient’s scalp. The field distribution within the brain depends on the position of the arrays on the head. Therefore, personalizing array placement to optimize field delivery to the tumor requires a deep understanding of how brain anatomy, tumor position and array position influence the field distribution within the brains of patients. Here we present an overview of computational studies investigating TTFields distribution within the brain
Method:
In order to simulate the delivery of TTFields to the head realistic computational models are constructed by segmenting MRI datasets of both healthy individuals and brain tumor patients. Both healthy and pathological tissues are identified and assigned appropriate dielectric properties. Virtual transducer arrays are placed on scalps of the models and TTFields are created within the models.
Result:
Studies show that the field distribution within the brain is heterogeneous and depends on the anatomy of the model and the location of the arrays on the scalp. By shifting the arrays on the head it is possible to increase the field intensity in the tumor bed by a factor of two or more relative to a generic layout in which arrays are geometrically centered on the head. Optimizing array position, it is possible to guarantee that field intensities within the tumor bed and large portions of the brain exceed the therapeutic threshold of 1 V/cm. One particular layout worth noting is a layout in which each array of one pair are laterally placed superficially to the lower region of the occipital lobe, and the two arrays of the second pair are placed on the calvarium and the superior aspect of the neck. This layout delivers fields above the therapeutic threshold to both the supratentorial and infratentorial regions of the brain, making it suitable for treating multi-focal disease with tumors or metastases in both these regions.
Conclusion:
Optimal delivery of TTFields is layout dependent. The study suggests that TTFields can be used to treat brain tumors and metastases throughout the brain, as well as multi-focal disease encompassing both the supratentorial and infratentorial regions of the brain.
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P3.07 - Immunology and Immunotherapy (ID 723)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.07-013c - Computational Simulations for Investigating Electric Field Distributions When Delivering Tumor Treating Fields (TTFields) to the Lungs (ID 8776)
09:30 - 09:30 | Presenting Author(s): Uri Weinberg
- Abstract
Background:
Tumor Treating Fields (TTFields) are low intensity, alternating electric fields in the intermediate frequency range. TTFields disrupt mitosis, and are FDA approved for the treatment of glioblastoma. A study testing the efficacy of TTFields in combination with chemotherapy for the treatment of mesothelioma [NCT02397928] is ongoing , and a pivotal study testing the efficacy of TTFields in treating NSCLC was recently launched [ NCT02973789]. TTFields are delivered through two pairs of transducer arrays placed on the patient's skin. Preclinical research shows that treatment efficacy increases with the intensity of the field. Therefore, optimizing treatment requires a deep understanding of how TTFields distribute within the body. . Here we present a computational simulations-based study investigating the field distribution in male and female realistic computational phantoms when arrays are placed on the thorax
Method:
Simulations were performed using the Sim4Life software package realistic computational phantoms of a male, female and obese male (ZMT, Zurich, Switzerland). Arrays with a geometry similar to that used to deliver TTFields to the thorax with the NovoTTF-100L were placed on the chests of the models, and delivery of TTFields was applied by imposing boundary conditions simulating a 4 ampere peak to peak current at 150 kHz. The field intensities within the lungs of the models were then evaluated.
Result:
The highest field intensities within the lungs were obtained when the arrays were axially-aligned with the parenchyma as much as anatomically possible. Under these conditions, field intensities throughout the lungs exceeded the therapeutic threshold of 1 V/cm in all models. Array layouts in pairs delivered electric fields from the anterolateral to the posterior-contralateral aspect of the patient and from the antero-contralateral to the posterolateral aspect of the patient, respectively, resulted in high intensity relatively uniform field intensities through the lungs. These types of layouts could be used on male subjects. However, due to body contours, these cross-body layouts may not adhere well to females, potentially hampering the efficient delivery of TTFields. For the female phantom, a layout in which one pair of arrays is placed on the lateral and contralateral aspects , and the second set of arrays placed on the anterior and posterior aspects may be the preferred layout.
Conclusion:
This study provides insights into how transducer array layouts influence TTFields distribution in the lungs. These results should be accounted for when treating lung cancer with TTFields.
