Commissioning a clinical linac for preclinical research of heterogeneous intratumor irradiation with end‐to‐end tests

Background Although it is not clear how the heterogeneous intratumor irradiation pattern affects the biological effect, investigations of the biological effect dependence on the dose and size of the peak region are essential in the current preclinical research. Purpose This work develops and validates a cone‐equipped clinical linac platform for heterogeneous intratumor irradiation (HII) of small animals, making translationally relevant preclinical radiobiology studies accessible to more clinical centers. Methods Output ratios (ORs) for cones (from 4 mm to 17.5 mm diameters) were measured using Gafchromic EBT3 films on a Varian TrueBeam linac (6 MV FFF beam). Tissue maximum ratios (TMR) and off‐axis ratios (OAR) were incorporated into the Eclipse treatment planning system (TPS) to configure the beam model. End‐to‐end test was performed using both a mouse phantom and tumor‐bearing mice, with dose distributions verified via film dosimetry and γ analysis (3%/3 mm and 3%/2 mm criteria). Results The system achieved millimeter‐scale precision, with γ pass rates ≥ 99% (3%/2 mm). Dose distributions confirmed the feasibility of delivering heterogeneous doses (e.g., 14 Gy via 4 mm cone + 2 Gy via 15 mm cone) while sparing normal tissues. Conclusion This study established a robust preclinical HII platform using clinical linac infrastructure, enabling precise dose delivery for investigating dose‐response relationships and supporting future translational research.