Multimodal spatially fractionated radiotherapy (SFRT) achieved 65.63% objective response in bulky solid tumors with favorable safety

Bulky solid tumors present significant therapeutic challenges due to their size, heterogeneity, and resistance to conventional treatments. Standard-of-care often falls short in achieving durable responses, necessitating novel approaches. Spatially fractionated radiotherapy (SFRT) is an emerging technique that delivers alternating high- and low-dose radiation subvolumes, aiming to alter the tumor microenvironment and enhance anti-tumor immunity while minimizing toxicity to surrounding healthy tissue. This phase II trial investigates SFRT's potential when combined with immune checkpoint inhibitors (ICIs) and anti-angiogenic agents to improve outcomes in advanced malignancies.

This prospective phase II trial enrolled 34 patients with bulky solid tumors between October 2024 and July 2025. All patients received SFRT using GRID, LATTICE, or Stereotactic central/core ablative radiation therapy techniques. The multimodal therapy included pre-radiotherapy administration of granulocyte-macrophage colony-stimulating factor and thymalfasin, along with concurrent ICIs and anti-angiogenic agents during SFRT, tailored to clinical recommendations and patient preferences. Primary endpoints were treatment-related adverse events and objective response rate (ORR). A prognostic analysis also identified factors associated with clinical outcomes.

Among 37 treatment courses administered to 34 patients, 4 patients did not complete therapy, and 1 was lost to follow-up. The median follow-up duration was 6.0 months. Of the 32 evaluable lesions from patients who completed the study, the objective response rate (ORR) was 65.63% (21/32). Notably, among 22 evaluable patients, 5 (22.73%) exhibited abscopal effects, indicating systemic anti-tumor immunity beyond the irradiated field. Common adverse events included anemia (18.92%), followed by skin/mucositis and pneumonia, each occurring in 10.81% of patients. The multimodal approach of SFRT combined with ICIs and anti-angiogenic agents demonstrated a 65.63% objective response rate in bulky solid tumors, with 22.73% of evaluable patients experiencing abscopal effects.