Probing spatiotemporal fractionation on the preclinical level

Area of Science:

• Radiation oncology
• Preclinical cancer research

Background:

• Conventional radiotherapy delivers uniform doses, limiting the therapeutic window.
• Spatiotemporal fractionation (STF) proposes distinct dose distributions per fraction to enhance tumor control while sparing normal tissues.

Purpose of the Study:

• To develop and validate an experimental setup for preclinical testing of STF's core assumption: treating different tumor parts with varying doses.
• To conduct a proof-of-concept experiment using a reductionist STF model in a murine tumor model.

Main Methods:

• Developed a high-precision, image-guided partial tumor irradiation system (X-RAD SmART) for small animals.
• Utilized a reductionist STF model with two complementary partial irradiations (50% tumor volume each) separated by 24 hours.
• Assessed tumor response in mice with MC38 colorectal adenocarcinoma using daily caliper measurements and CT-volumetry, comparing STF to conventional whole-tumor irradiation.

Main Results:

• The developed system enabled precise partial tumor irradiation in a preclinical setting.
• Reducing the irradiated tumor volume (50% of total) resulted in an intermediate tumor growth response between full irradiation and no irradiation.
• No significant difference in tumor growth was observed between the reductionist STF model and conventional whole-tumor irradiation in this initial experiment.

Conclusions:

• An experimental setup for preclinical STF validation using partial tumor irradiation in small animals was successfully established.
• Initial findings suggest that reducing the irradiated tumor volume yields an intermediate response, supporting the potential of STF.
• Further research with extended follow-up and varied fractionation schemes is necessary to fully support STF's efficacy.