Posted: Monday, November 6, 2023
“Immune education” fomented by comprehensive metastasis-directed radiation therapy (MDRT) may prove to be a complementary mechanism of micrometastatic control in oligometastatic prostate cancer, in conjunction with cytoreduction of macroscopic disease, according to an analysis of the 174-patient, phase II EXTEND trial, presented at the 2023 American Society for Radiation Oncology (ASTRO) Annual Meeting (Abstract 157). Adding MDRT to hormone therapy induced systemic T-cell activation, proliferation, and clonal expansion, which was not observed with hormone therapy alone, noted Alexander D. Sherry, MD, of The University of Texas MD Anderson Cancer Center, Houston, and colleagues. In addition, this systemic immune response seemed to be independently associated with improved progression-free survival.
The investigators had already found that MDRT extended progression-free survival and the time to new lesion formation in the intermittent hormone therapy basket of EXTEND. In this analysis, the investigators pooled the intermittent [6 months; n = 87] and continuous [indefinitely; n = 87] hormone therapy baskets of EXTEND to see if adding MDRT to hormone therapy would program systemic T cells to control micrometastatic disease, Dr. Sherry and co-investigators explained.
MDRT plus hormone therapy was associated with T-cell receptor clonal expansion, remodeling of the T-cell receptor repertoire, and changes in dominant T-cell receptor motifs at the end of MDRT and at 3-month follow-up (all P < .05). Observed T-cell priming may be driven by signaling networks of canonical T-cell stimulatory cytokines, they continued. Further, at the end of MDRT, systemic T-cell responses were associated with improved progression-free survival.
The mechanisms and biomarkers predicting patient responses are not well understood. However, these results may provide a potential direction for studies to combine immunotherapies with radiation and hormone therapies and to personalize treatments based on individual patients’ immune systems.
Disclosure: Dr. Sherry reported no conflicts of interest.