Abstract 2396: Tumor treating fields (TTFields) for spinal metastasis: Clinical trial concept for use of conductive implants as waveguides to enhance TTFields strength

Abstract

Abstract Tumor treating fields (TTFields) is a FDA-approved electric fields-based therapy for glioblastoma (GBM) and malignant pleural mesothelioma. We describe a novel approach to increase the strength and therapeutic effect of TTFields at vertebral tumor targets, using spinal implants as electrically-conductive waveguides. In vivo anti-cancer efficacy is achieved with TTFields strength >1 V/cm. If the tumor is surrounded by tissues of lower conductivity (e.g., the skull in the case of GBM), then the TTFields strength reaching the tumor is decreased. Surgical treatment of radiation-refractory spinal metastases is difficult and provides a short-term benefit at the expense of a lengthy recovery. Such resections require bone removal that disrupts the spinal stability, necessitating reconstruction with titanium (Ti) pedicle screw constructs that are electrically conductive. We theorize that astute placement of Ti hardware in the proximate spinal levels post-resection would have a waveguiding effect of electrical current from the surrounding muscle towards the tumor. This would in turn boost TTFields strength achieved around the resection cavity, decreasing the chances of tumor recurrence. Bomzon et al. described a computational model of the distribution of TTFields in a realistic human torso. The simulation demonstrated that a TTFields strength of 3 V/cm can be achieved, which is approximately 3-fold greater than what is achieved in the brain parenchyma in the context of TTFields for GBM. In a more generic simulation using a 0.5 × 100 mm waveguide targeting a tumor deeper in the torso (480 mA), we found 21.8 vs. 61.2 cm3 volumes achieving ≥ the 1.0 V/cm efficacy floor, without and with the waveguide, respectively, a 2.8-fold increase. At a higher amplitude (550 mA) and stronger TTFields strength threshold of ≥1.5 V/cm, a negligible volume was attained with no waveguide (0.1 cm3), whereas a volume of 17.6 cm3 was attained around the tip of the waveguide when present. Based on compelling pre-clinical data, a prospective clinical trial is being designed in which patients with radiation-refractory spinal metastasis from any number of primary sites will undergo resection. Next, primary cultures of their tumor cells will be made and evaluated for the TTFields frequency that maximizes cell death on a per-patient basis. Patients will then undergo postoperative local TTFields therapy ± systemic therapy. The primary endpoint will be safety and efficacy of such an approach, with future aims focusing on local control rates. The application of TTFields as an adjunct to surgery may offer a new therapeutic option for patients with spinal metastasis who would otherwise not be considered surgical candidates. Similarly, waveguides may be used throughout the head and body to increase TTFields efficacy. Citation Format: Claudio E. Tatsui, Kristen W. Carlson, Chirag B. Patel. Tumor treating fields (TTFields) for spinal metastasis: Clinical trial concept for use of conductive implants as waveguides to enhance TTFields strength [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2396.