EXTH-17. Tumor Treating Fields suppress tumor growth and improve neurologic outcomes in spinal metastasis models—highlighting a translational strategy for patients with radiation refractory spinal metastases

Abstract Spinal metastases are the most common tumors of the spine, which have been observed in approximately 70% of patients with metastatic disease at autopsy. Despite advances in surgical techniques and spine stereotactic radiotherapy, spinal metastases often progress after upfront therapy. Due to limited treatment options, these patients frequently encounter permanent neurological deficits and impaired oncologic outcomes. Tumor treating fields (TTFields) exert multi-modal anti-tumor properties including cellular cytotoxicity through disruption of mitotic spindle assembly and subsequent immunogenic cell death. This study investigated TTFields’ anti-tumor effect across various tumor histologies that metastasize to the spine using in vitro, ex vivo bone scaffold, and syngeneic orthotopic spine metastasis models. Histologies included murine breast, lung, renal, melanoma, and prostate cancer cell lines. Monolayer cell cultures were treated with inovitro TTFields to determine optimal treatment frequency. Frequency scanning revealed that TTFields had the most significant cytotoxicity at 100–200 kHz for most cell lines. We further evaluated the effect of TTFields ex vivo by growing cells on bone scaffolds and applying TTFields at 150kHz. Cell growth was monitored using bioluminescent imaging (BLI). BLI data showed TTFields significantly inhibited growth of B16F10Fluc3 (melanoma), Renca (renal), and RM-1 (prostate) cells, which were further confirmed by CellTiter-Glo assays. Finally, we orthotopically implanted B16F10Fluc3 murine melanoma into the spine of immunocompetent mice followed by TTFields treatment. BLI and MRI analyses demonstrated that TTFields inhibited early tumor growth, while behavioral assessments showed a delay in the onset of neurological deficits compared to controls. Our findings highlight that TTF may facilitate local disease control and associated functional preservation in murine spine metastasis models, while establishing the foundation for integrating with combinatorial cancer therapies. Lasty, these data provide further support for the upcoming Phase I study (NCT06906900) exploring the safety and feasibility of TTFields for patients with treatment refractory spinal metastases.