Biologically Driven Shot Sequence Optimization for Multi-Metastasis Gamma Knife Radiosurgery
Abstract
Purpose
In multi-target Gamma Knife (GK) radiosurgery, the clinical default plan typically sequences shots based on geometric efficiency to minimize treatment duration. However, this approach ignores the time-dependent biological effects of sublethal damage repair. This study investigates the potential of shot sequence optimization based on Biologically Effective Dose (BED) to improve the therapeutic ratio in single-fraction brain metastasis treatments compared to the standard clinical workflow.
Methods
A clinical case with 7 brain metastases was analyzed using a bi-exponential BED model that accounts for two repair rates. The normal tissue constraint was defined as a Ring Structure surrounding the targets. We compared two shot sequencing strategies while keeping isocenter positions and beam-on times fixed: Default Sequence: A standard clinical ordering traversing isocenters along the z-axis (superior-to-inferior). Biological Optimization: A Genetic Algorithm (GA) designed to optimize the shot delivery order to maximize the Therapeutic Ratio (GTV BED D95/OAR Mean BED). Model parameters were set to alpha beta ratio = 10 Gy for tumors and 2.47 Gy for the Ring structure.
Results
The default sequence, which traverses shots from superior to inferior to ensure time efficiency, resulted in a suboptimal biological profile. In contrast, the biologically optimized shot sequence yielded a 10.6% improvement in the Therapeutic Ratio (0.94 vs. 0.85) compared to the default baseline. The optimizer prioritized a specific delivery order that leveraged the differential repair kinetics between the tumor and the Ring structure, reducing normal tissue toxicity without compromising target coverage.
Conclusion
For multi-metastasis GK SRS, the standard geometrically driven sequence is not biologically optimal. Implementing shot sequence optimization incorporating BED kinetics offers a clinically significant therapeutic gain (>10%) without altering the physical dose distribution. This suggests that the sequence of shots is a critical, yet underutilized, degree of freedom in treatment planning.