Advancing Intracranial Tumor Treatment Through Gyroscopic Radiosurgery-Based Lattice Therapy: Evidence From a Case Series Study.

Lattice radiotherapy (LRT), a modern form of spatially fractionated radiation therapy, introduces a novel therapeutic strategy by delivering high-dose vertices interspersed within the gross tumor volume (GTV), leveraging both direct cytotoxicity and immune-mediated effects. While this technique has been explored in extracranial malignancies, its clinical application in intracranial tumors remains scarce. This study presents a preliminary case series assessing the feasibility, safety, and early clinical outcomes of LRT delivered via the gyroscopic radiosurgery platform ZAP-X® (ZAP Surgical Systems, Inc., San Carlos, USA) in patients with recurrent glioblastoma multiforme (GBM) who had already undergone multiple courses of radiotherapy. Between December 2024 and February 2025, four patients with histologically confirmed GBM received single-fraction LRT with a prescribed dose of 20 Gy to each lattice vertex. Patient-specific lattice geometries were generated using a custom Python-based software tool, ensuring high-dose spheres were fully confined within the GTV and spaced to achieve a peak-to-valley dose ratio of 4. Treatment plans were created on the ZAP-X system using multi-isocenter targeting and optimized to deliver a mean GTV dose exceeding 5 Gy. The tumor volumes of the four presented cases were 186 cc, 68 cc, 75 cc, and 293 cc. Treatment delivery times ranged between 44 and 46 minutes. All patients were evaluated clinically and radiologically at 1 and 3 months post-treatment. LRT was successfully delivered in all cases with favorable treatment tolerability and no acute neurotoxicity. Early imaging revealed radiological response or disease stabilization in three patients. One patient demonstrated significant cystic transformation and maintained stable neurological status; another exhibited partial response prior to disease progression at a distant intracranial site. The third patient remained clinically and radiologically stable without requiring systemic therapy. The fourth patient, who had a poor baseline status, experienced local progression and was hospitalized due to aspiration pneumonia. Across the cohort, steroid requirements were stable or reduced post-treatment. These early findings suggest that ZAP-X-based LRT is a feasible and well-tolerated reirradiation option in heavily pretreated GBM patients. By integrating high-dose and low-dose regions within the tumor, LRT may stimulate immunologic effects and improve local control without increasing toxicity. Although limited by small sample size and short follow-up, this study supports the potential of LRT as a palliative strategy and sets the foundation for future prospective trials exploring its clinical efficacy and immunomodulatory role in neuro-oncology.