2023 World Conference on Lung Cancer (Posters)-P2.03. Hybrid Immuno-RT (EclipseRT) for Bulky Tumors: Low-Dose Radiotherapy with Partial Tumor SBRT in Mice and Patients

P2.03. Hybrid Immuno-RT (EclipseRT) for Bulky Tumors: Low-Dose Radiotherapy with Partial Tumor SBRT in Mice and Patients - PDF(Abstract)

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A novel radiotherapy technique called EclipseRT (ERT) has been developed for the treatment of bulky tumors. The technique involves the delivery of low-dose radiation (LDRT) to the entire tumor and stereotactic body radiation therapy (SBRT) to only a part of the tumor. This approach aims to induce immunogenic cell death (ICD) and inflame the tumor microenvironment (TME) by recruiting T cells. The efficacy and safety of ERT combined with PD-1 inhibitors were investigated in mouse models and in patients with advanced lung or liver bulky tumors.<br /><br />The results of the study showed that ERT/αPD-1 therapy was more effective in controlling bulky tumors compared to SBRT/αPD-1 or LDRT/αPD-1 therapy in mouse models. The efficacy of ERT/αPD-1 was dependent on the presence of CD8 T cells. ERT/αPD-1 resulted in complete tumor regression in some mice and induced more CD8 T cells and M1 macrophages in the TME compared to the other therapies. The analysis also revealed that ERT/αPD-1 induced higher infiltration of CD8 T cells into the tumor center and periphery compared to SBRT/αPD-1 and LDRT/αPD-1 therapy. ERT and SBRT irradiation also led to elevated levels of phospho-eIF2α, an ICD marker, and higher dendritic cell infiltration.<br /><br />In the clinical setting, ERT combined with PD-1 inhibitors was shown to be safe and effective in patients with advanced bulky tumors. Grade 1/2 toxicities were observed in some patients, including one case of radiation-induced pneumonitis. The objective response rate was 38.5%, and the median progression-free survival was 5.6 months.<br /><br />In conclusion, ERT/αPD-1 demonstrated superior efficacy in controlling bulky tumors in mouse models and was safe and effective in patients with advanced bulky tumors. This combination therapy has the potential to become a new strategy for the treatment of these patients.

Asset Subtitle

Ren Luo

Meta Tag

Speaker Ren Luo

Topic Metastatic NSCLC: Local Therapies

Keywords

EclipseRT

ERT

bulky tumors

LDRT

SBRT

immunogenic cell death

TME

PD-1 inhibitors

CD8 T cells

combination therapy