Stereotactic Body Radiation Therapy Augmented Checkpoint Inhibitor Immunotherapy Response in Heavily Pretreated...

Area of Science:

• Oncology
• Immunotherapy
• Radiation Oncology

Background:

• Relapsed/refractory (R/R) osteosarcoma has a poor prognosis due to its immunosuppressive tumor microenvironment.
• Stereotactic body radiation therapy (SBRT) possesses immunomodulatory properties beyond local tumor control.
• The combination of SBRT with immune checkpoint inhibitors (ICIs) has not been previously explored in osteosarcoma.

Purpose of the Study:

• To evaluate the efficacy and safety of combining SBRT with ICIs in patients with R/R osteosarcoma.
• To investigate the potential abscopal effect of SBRT in conjunction with ICIs.
• To identify biomarkers predictive of therapeutic response.

Main Methods:

• Retrospective review of 62 R/R osteosarcoma patients treated with ICIs plus SBRT (n=18), conventional radiation therapy (CRT) (n=23), or ICI-only (n=21).
• Assessment of radiological response in radiated and non-radiated lesions to determine systemic efficacy and abscopal effect.
• Analysis of peripheral blood cytometry and intratumoral lymphocyte infiltration as correlative biomarkers.

Main Results:

• ICI+SBRT demonstrated significantly superior systemic tumor response and median overall survival (12.0 months) compared to ICI-only and ICI+CRT groups.
• A notable abscopal effect was observed, with non-radiated lesions responding better in the ICI+SBRT group.
• Higher baseline CD3+ lymphocytes and lower neutrophil-to-lymphocyte ratio correlated with better abscopal effects; increased intratumoral CD8+ T-cell infiltration and PD-L1 expression were observed post-SBRT.

Conclusions:

• SBRT combined with ICIs is a promising strategy to enhance immunotherapy efficacy in R/R osteosarcoma.
• The combination may overcome the immunosuppressive tumor microenvironment and induce systemic anti-tumor immunity.
• Further prospective studies are warranted to validate these findings.