Balancing Conformity and Low-Dose Brain Exposure Across Gamma Knife and Linac-Based Stereotactic Radiosurgery...

Background/Objectives: LINAC-based single-isocenter (SIT) stereotactic radiosurgery (SRS) enables efficient treatment of multiple brain metastases but may compromise target conformity and increase low-dose brain exposure, particularly for spatially distributed lesions. Dual-isocenter techniques (DITs) may mitigate these limitations, while Gamma Knife (GK) remains the reference standard for high-selectivity radiosurgery. This study compares SIT- and DIT LINAC-based SRS with GK, focusing on target conformity and low-dose brain exposure under equivalent, zero-margin targeting assumptions. Methods: Twenty-eight patients with multiple brain metastases (197 lesions) were included in this retrospective planning study. For each patient, three plans were generated: a GK plan and LINAC-based SIT and DIT plans using automated dynamic conformal arc optimization (Elements Multiple Brain Metastases). All plans were generated using a zero-millimeter GTV-to-PTV margin strategy. For DIT, lesions were automatically clustered and assigned to two isocenters. Target coverage required ≥99% of each GTV to receive the prescription dose. Plan quality was evaluated using the Paddick Conformity Index (PCI) on a per-lesion basis and low-dose brain volumes (V12, V10, V5, V4, and V3 Gy) on a per-patient basis. Paired non-parametric tests and multivariable models were used to assess technique-related differences and associations with total target volume and lesion count. Results: GK achieved the highest median PCI (0.83), followed closely by DIT (0.77), while SIT plans demonstrated significantly lower conformity (0.73). Compared with GK, the median PCI difference was -0.05 for DIT and -0.08 for SIT. Conformity for DIT remained stable across lesion volumes and lesion counts, whereas GK conformity increased modestly with lesion size. Low-dose brain exposure differed significantly between techniques at all dose levels (p < 0.001). GK consistently yielded the lowest Vx volumes, SIT the highest, and DIT intermediate values. Relative to GK, SIT plans showed progressively larger increases in low-dose exposure at lower dose levels (mean ΔV3 ≈ +149 cc), while DIT reduced this low-dose spread (mean ΔV3 ≈ +117 cc). Total target volume was the dominant predictor of low-dose brain exposure across all techniques, with a smaller additional contribution from lesion count. Conclusions: DIT LINAC-based SRS significantly improves target conformity and reduces low-dose brain exposure compared with SIT delivery, achieving dosimetric performance that closely approximates Gamma Knife under equivalent zero-margin targeting assumptions. While Gamma Knife remains the reference standard for low-dose sparing, dual-isocenter planning represents a clinically robust and scalable alternative that effectively balances plan quality and treatment efficiency in patients with multiple brain metastases.