The Role of Biological Effective Dose in Gamma Knife Radiosurgery: A Systematic Review Across Multiple Indications.

Background: Gamma Knife radiosurgery (GKS) is widely used for the management of intracranial disorders. Emerging evidence suggests that incorporating the biological effective dose (BED) into GKS planning may improve the prediction of treatment efficacy and toxicity. This review aims to evaluate the role of BED in GKS across multiple intracranial indications. Methods: A qualitative review of published clinical studies was performed to assess the application of BED models in GKS for pituitary adenomas, vestibular schwannomas, meningiomas, arteriovenous malformations (AVMs), trigeminal neuralgia, and other disorders. The relationships between BED, treatment outcomes, and adverse effects were compared across indications. Results: The association between BED and clinical outcomes was most consistent in AVMs, where higher BED correlated closely with obliteration rates. In other diseases, BED-based analyses showed promising but variable predictive value. Notably, BED-derived parameters demonstrated improved prediction of post-GKS hypopituitarism in pituitary adenomas and AVM obliteration compared with physical dose alone. However, most available evidence was derived from retrospective studies. Conclusions: BED may serve as a valuable complement to conventional physical dose metrics in GKS planning, but its ability to replace physical dose remains uncertain. Prospective studies and histology-specific radiobiological parameter validation are required to establish the routine clinical utility of BED.