Stereotactic Body Radiotherapy Immunological Planning-A Review With a Proposed Theoretical Model

Area of Science:

• Radiation Oncology
• Immunology
• Cancer Therapy

Background:

• The current era of cancer treatment integrates stereotactic body radiotherapy (SBRT) with immunotherapy.
• There is a growing focus on achieving the abscopal effect, where radiation of a tumor leads to the regression of distant tumors.
• Optimizing radiation scheduling and combining it with other therapies is crucial for maximizing treatment efficacy.

Purpose of the Study:

• To propose a theoretical model for enhancing the abscopal effect of SBRT.
• To shift from observing the abscopal effect by chance to achieving it by design.
• To identify key strategies for maximizing tumor cell kill and immune response.

Main Methods:

• Literature review of existing SBRT and immunotherapy strategies.
• Analysis of findings from animal trials.
• Development of a theoretical model focusing on tumor vasculature integrity.
• Exploration of combinatorial approaches including SBRT, immunotherapy, antiangiogenics, and immunoadjuvants.

Main Results:

• Intermediate doses of SBRT (6-10 Gy/fraction) with dose painting and proper immunotherapy timing show improved abscopal effects.
• Animal studies support the proposed model's tenets for enhancing abscopal effects.
• Tumor vasculature integrity is identified as a central theme for consistent abscopal responses.

Conclusions:

• A harmonized combinatorial approach, centered on maintaining tumor vasculature integrity, can convert "abscopal effect by chance" to "abscopal effect by design".
• Integrating SBRT with immunotherapy, cyclical antiangiogenics, and immunoadjuvants can enhance SBRT-induced tumor cell kill and abscopal effects.
• Further convergence research is needed to develop clinical trial protocols based on these strategies.