First Measurement: Proactive Immune Cell Sparing in Radiation Therapy

Area of Science:

• Oncology
• Immunology
• Radiation Oncology

Background:

• Radiation therapy (RT) can stimulate anti-tumor T cells but also cause immunosuppression.
• Radiation-induced immunosuppression (RIIS) can limit the effectiveness of RT.
• The benefit of sparing RT dose to immune organs is not well-established.

Purpose of the Study:

• To evaluate the clinical advantages of proactively sparing RT dose to immune-rich organs.
• To assess the impact of dose reduction to blood, bone marrow, and lymph nodes on RIIS.
• To compare RIIS-optimized treatment with standard treatment in early-stage lung cancer patients.

Main Methods:

• A phase II randomized trial involving 51 early-stage lung cancer patients treated with SBRT.
• Two arms: RIIS-optimized-treatment (dose reduction to immune organs) and standard-treatment.
• Peripheral blood collected at baseline and at multiple time points post-treatment to assess Absolute Lymphocyte Count (ALC).

Main Results:

• The optimized arm showed significantly less ALC reduction post-SBRT compared to the standard arm (13.4% improvement, p=0.01).
• Central tumors demonstrated a greater ALC improvement in the optimized arm (29.5% improvement, p=0.004).
• Grade 3 lymphopenia was absent in the optimized arm, and a trend towards improved Event-Free Survival and Overall Survival was observed.

Conclusions:

• Reducing RT dose to immune-rich organs significantly mitigates RIIS.
• This strategy holds potential for enhancing immune-mediated anti-tumor activity.
• Optimized RT planning may improve clinical outcomes in lung cancer patients.