A prospective study of immune responses in patients with lung metastases treated with stereotactic body radiotherapy with or without concurrent systemic treatment

Background and purpose: We evaluated the longitudinal effects of stereotactic body radiotherapy (SBRT) on circulating immune cells. Materials and methods: Patients with oligometastatic/oligoprogressive pulmonary lesions were treated with ablative SBRT with (cSBRT) or without (SBRT group) concurrent systemic treatment (chemotherapy or immune checkpoint blockade, ICB) using different fractionation regimes. Immunoprofiling of peripheral blood cells was performed at baseline, during, and at the end of SBRT, and during the first (FU1) and second follow-ups (FU2). The primary endpoint was the increase in CD8⁺ T cells at FU1 compared to baseline. Results: The study accrued 100 patients, 80 with evaluable samples. At FU1 12 % and 20 % of the patients experienced an increase in CD8⁺ T-cell counts in the SBRT and cSBRT groups, respectively. With a median follow-up of 30 months, the median OS was 30 months in the SBRT group and 53 months for the cSBRT group. Lower doses per fraction led to a significant increase in the proportion of proliferating CD4⁺ and CD8⁺ T cells. The effect size of standardized changes from baseline in proliferating T cells was considerably more significant in the SBRT group. The increased T-cell proliferation was prominent at the end of treatment and maintained at FU1 (SBRT, cSBRT) and FU2 (SBRT). The addition of ICBs did not lead to an augmentation of this systemic immunomodulatory effect. Conclusion: In oligometastatic/oligoprogressive disease, the optimal dose and fractionation for ablative SBRT might be with less than 10 Gy per fraction and the optimal timing of systemic treatment may be post-SBRT to leverage the immune-modulating effects of SBRT.