从模拟到现实:支持LB10000安全递送高剂量TTFields的证据

Introduction: Tumor Treating Fields (TTFields) are a noninvasive cancer therapy that employ alternating electric fields in the 100-500 kHz range to disrupt tumor cell division. TTFields are clinically approved for glioblastoma, mesothelioma, and non-small cell lung cancer. The LB10000 is a novel TTFields device designed to deliver high-dose fields adaptively across large body regions. Unlike existing systems that use four fixed transducer arrays, the LB10000 employs a large matrix of programmable transducers whose phases can be dynamically switched between 0°, 180°, and off. This enables dynamic field shaping, targeted delivery to multiple anatomical sites, and effective thermal management. We present both in-vivo and in-silico evidence demonstrating the safety of this new system. Methods: Six female Yucatan pigs were treated with the LB10000. Arrays were removed daily between 7-9 a.m. and reapplied between 12-3 p.m., targeting ≥16 hours of active treatment per day for 24-32 days within a period of 40 days from treatment initiation. If a pig reached the desired quota of per-protocol days, treatment was stopped and the animal euthanized. During treatment, skin temperature, treatment duty cycle, current, and voltage were continuously monitored, and animal well-being was evaluated daily by a veterinarian. Following euthanasia, gross examination of major organs was performed. To assess safety in humans, computational modeling was performed using the Sim4Life (ZMT Zurich, Switzerland) ohmic solver. Virtual LB10000 arrays were applied to anthropomorphic phantoms-DUKE (adult male), ELLA (adult female), and FATS (obese male)-and electric field delivery simulated at 200 Vpp, the device's maximum output. Specific Absorption Rate (SAR) distributions were calculated to evaluate potential heating. Results: In vivo, the LB10000 delivered fields continuously at 130 V and 6 A (~100 W) with 78-90 % on-time per animal. Five of six pigs completed the full protocol(24-32 day with 16hr/day treatment), totaling 2,780 hours of treatment without adverse events or tissue injury. Gross examination revealed no abnormalities. In silico, SAR values in superficial skin layers were 10-100× higher than in internal organs, indicating that any potential heating is localized beneath the transducers. The risk of thermal damage to tissues increases drastically when tissue temperatures exceed 109°F (43°C). The LB10000 continuously monitors skin temperature below the transudcers and controls delivered power to maintain skin temperature below a safety threshold of 105 °F. Together, these findings demonstrate that the LB10000 operates safely at high doses in vivo and that the risk that the device will cause thermal damage in humans is negligible. Conclusion: These results provide key evidence supporting advancement toward first-in-human clinical evaluation.