Preliminary results from a phase II trial of spatially fractionated radiotherapy combined with immunotherapy and anti-angiogenic therapy in patients with bulky solid tumors: early evidence of promising efficacy and favorable safety

BACKGROUND AND PURPOSE: Bulky solid tumors present significant therapeutic challenges. Spatially fractionated radiotherapy (SFRT), a technique delivering alternating high- and low-dose subvolumes, alters the tumor microenvironment while minimizing toxicity. This phase II trial assesses the efficacy and safety of SFRT combined with immune checkpoint inhibitors (ICIs) and anti-angiogenic agents in advanced malignancies. METHODS AND MATERIALS: This prospective phase II trial enrolled 34 patients with bulky solid tumors between October 2024 and July 2025. All patients underwent SFRT using GRID, LATTICE, or Stereotactic central/core ablative radiation therapy techniques. Multimodal therapy, incorporating pre-radiotherapy administration of granulocyte-macrophage colony-stimulating factor and thymalfasin, as well as concurrent ICIs and anti-angiogenic agents during SFRT, was administered according to clinical recommendations and patient preferences. The endpoints were treatment-related adverse events and the objective response rate (ORR). In addition, a prognostic analysis was performed to identify factors associated with clinical outcomes. RESULTS: Among the 37 treatment courses in 34 patients, 4 patients did not complete the planned 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 ORR was 65.63% (21/32). Of the 22 evaluable patients, 5 (22.73%) exhibited abscopal effects. Common adverse events included anemia (18.92%), followed by skin/mucositis and pneumonia, each occurring in 10.81% of patients. CONCLUSIONS: This phase II trial demonstrates that the multimodal approach of SFRT combined with ICIs and anti-angiogenic agents is a promising strategy for bulky solid tumors, while highlighting the need for larger trials to validate long-term efficacy and refine personalized treatment protocols. (Registry: ClinicalTrials.gov, TRN: NCT06775678, Registration date: 1 October 2024)