Mini-GRID enhances survival and reduces toxicity in an orthotopic murine model of oral squamous cell carcinoma: A proof-of-concept study.

Background and purpose: Oral squamous cell carcinoma (OSCC) remains a major clinical challenge, with limited therapeutic options and poor outcomes. Among the emerging approaches to address this unmet need, spatially fractionated radiotherapy (SFRT) using mini-GRID patterns has emerged as a promising approach, delivering high radiation doses through narrowly collimated beamlets that spare intervening normal tissue and may enhance the therapeutic index. This study evaluated the efficacy and safety of mini-GRID RT in an orthotopic, syngeneic murine model of OSCC. Materials and methods: C57BL/6 mice bearing MOC1 tumors were randomized to receive conventional radiotherapy (conv-RT; 20 Gy), mini-GRID RT (20 Gy average dose), or no treatment. Endpoints included survival, tumor growth, body weight, and histopathological assessment of tumor and surrounding normal tissues. Results: Mini-GRID RT significantly extended median survival (56 days) compared with controls (36 days; p = 0.0456) and conv-RT (35 days; p = 0.0181). Tumor growth was delayed by approximately 20 days in the mini-GRID group, with long-term survivors regaining baseline body weight within 15 days post-irradiation. Fewer animals in the mini-GRID group required early euthanasia due to acute toxicity compared with the conv-RT group. Histological examination revealed no significant increase in normal tissue damage in mini-GRID-treated mice relative to conv-RT. Conclusion: These findings indicate that mini-GRID RT can improve survival while maintaining a favorable toxicity profile in OSCC, supporting its potential as a novel high-dose radiotherapy approach. Further studies are warranted to elucidate underlying mechanisms, including vascular and immune-mediated responses, and to assess its translational relevance in clinical practice.