Abstract
<title>Abstract</title> <p>Purpose: Fractionation regimens for stereotactic partial breast irradiation (SBRT-PBI) vary substantially, and the optimal regimen remains uncertain. This radiobiological modeling study compared commonly used and exploratory SBRT-PBI regimens using uncomplicated tumor control probability (UTCP) and excess absolute risk (EAR) to identify a model-based dose window with a favorable benefit--risk balance. Methods: Fourteen patients with early-stage breast cancer who met the ASTRO 2023 guideline criteria for APBI were included. For each patient, a benchmark plan of 30 Gy in 5 fractions was generated, and the absolute dose was proportionally scaled to simulate eight fractionation regimens while keeping beam geometry and relative dose distribution unchanged. Tumor control probability (TCP), normal tissue complication probability (NTCP), UTCP, and EAR were calculated from the derived dose distributions. Paired statistical comparisons and cubic spline fitting were used to evaluate regimen-specific differences and estimate the population-optimal total dose. Results: All benchmark plans met the ASTRO dose--volume constraints. UTCP showed a non-monotonic relationship with total dose, increasing with improved tumor control at lower doses and decreasing at higher doses because of rising fibrosis risk. The highest UTCP values were observed for 28 Gy in 4 fractions and 30 Gy in 5 fractions, whereas 40 Gy in 5 fractions achieved the highest TCP but showed a marked reduction in UTCP due to increased fibrosis NTCP. For secondary cancer risk, ipsilateral breast EAR decreased slightly with increasing dose, consistent with high-dose cell killing, whereas EAR for the contralateral breast and both lungs increased with total dose. NTCPs for other organs at risk were extremely low and had negligible influence on UTCP. Conclusion: The ASTRO-recommended 30 Gy in 5 fractions regimen remains the most clinically supported reference option for SBRT-PBI. The 28 Gy in 4 fractions regimen showed a comparable model-estimated benefit--risk balance and may represent a promising shortened regimen requiring prospective validation. Higher-dose regimens may be less favorable because of increased model-estimated late toxicity and secondary cancer risk, and should therefore be interpreted cautiously. Keywords: Stereotactic partial breast irradiation; Fractionation regimens; Uncomplicated tumor control probability; Excess absolute risk; Radiobiological modeling</p>