Spatially fractionated radiation therapy: A powerful and low-toxicity technique for cancer treatment

GRID and LATTICE radiation therapy, officially known as spatially fractionated radiation therapy (SFRT), treat tumors by delivering a spatially modulated radiation dose with highly heterogeneous dose distributions. SFRT represents a rapidly evolving frontier in radiation oncology, physics, and tumor biology, attracting significant interest. Increasing clinical experience with SFRT suggests high tumor response and low toxicity, particularly in therapy-refractory and advanced tumors. Meanwhile, preclinical data from cell and animal studies are accumulating rapidly, alongside continuous advancements in SFRT technologies and techniques. These innovations have expanded SFRT applications across various radiation therapy platforms, including synchrotron, proton, carbon, electron, and photon beams. Despite its potential, SFRT remains challenging for many clinicians. The dosing principles are not well known, dose metrics are unfamiliar, and treatment planning techniques can seem daunting, all these factors may hinder the broader and correct adoption of this unique modality. This review article explores the principles of SFRT, conventional dose-rate GRID and LATTICE SFRT techniques, consensus SFRT dose metrics, and approaches for clinical implementation. While the primary focus is on the physics aspects of SFRT, key clinical data are also reviewed.