Related Experiment Video
Updated: Jun 27, 2026
Proton Therapy Delivery and Its Clinical Application in Select Solid Tumor Malignancies
Published on: February 6, 2019
Determining Optimal Fractionation of Neoadjuvant Radiation in Low-Risk, Early-Stage Breast Cancer-Randomized SIGNAL
Melanie Spears1,2, Michael Lock3,4, Brian Yaremko3,4
1Ontario Institute for Cancer Research, MaRS Centre, Toronto, ON M5G 1M1, Canada.
Background:
Neoadjuvant partial breast irradiation using stereotactic body radiotherapy (SBRT) has emerged as a strategy to induce tumor and immune responses in early-stage, low-risk breast cancer. While prior studies have demonstrated encouraging response rates and evidence of immune modulation, the optimal radiotherapy regimen for immune priming remains unclear. SIGNAL 2.0 is a randomized phase II trial designed to compare the biological and immunological impact of a single-fraction versus three-fraction neoadjuvant SBRT.
Materials And Methods:
Sixty-one postmenopausal patients ≥ 50 years with unifocal, hormone positive, node-negative invasive ductal carcinoma < 3 cm were randomized 1:1 to receive either 21 Gy in one fraction or 30 Gy in three fractions, delivered to the tumor in the prone position. Core biopsies were collected pre-SBRT and 14-20 days post-SBRT at the time of surgery. Immune markers were assessed using tumor-infiltrating lymphocyte (TIL) scoring, NanoString nCounter PanCancer Immune Profiling, and NanoString GeoMx Digital Spatial Profiling (DSP).
Results:
Available tumor samples from 47 patients underwent paired tissue analysis. Three-fraction SBRT induced 200 differentially expressed genes, including enrichment of pathways related to adaptive immune activation, with significant increases in expression levels of macrophages, dendritic cells, neutrophils and CD8 T-cells. Proteomic profiling also identified a significant increase in the expression levels of neutrophils, Treg cells, macrophages, and NK cells in the tumor microenvironment of the samples from patients receiving the three-fraction regimen.
Conclusions:
Neoadjuvant SBRT induces measurable immune activation, with three-fraction regimens generating more extensive transcriptional, proteomic, and cellular immune changes than a single fraction. Three-fraction neoadjuvant SBRT may provide superior immune priming, providing a foundation for future trials integrating neoadjuvant radiotherapy with immunomodulatory therapies.