In Regard to Prabhu et al

We thank Prabhu et al¹ for their impactful international multicenter analysis comparing standard-dose versus reduced-dose single-fraction preoperative stereotactic radiosurgery (SRS) for resected brain metastases. Their results demonstrate that both the standard and reduced dosing regimens achieved excellent local control rates and showed no significant differences in adverse radiation effects, meningeal disease, or overall survival. This study provides important clarity on the safety of both the reduced and standard dosing regimens and lays the foundation for future dose optimization strategies.

As we aimed to refine outcomes for brain metastases using preoperative SRS, we believe that there is growing rationale for considering multifractionated preoperative SRS. Fractionated regimens have been shown to allow safer dose escalation and better address local control concerns for larger brain metastases. For example, Prabhu et al² previously reported favorable outcomes with a 3- to 5-fraction preoperative SRS regimen (median dose of 24 Gy in 3 fractions), demonstrating significantly reduced rates of local recurrence compared with single-fraction preoperative SRS (P = .004) without increasing the risk of adverse radiation effects or meningeal disease. Similarly, in a multi-institutional retrospective analysis, Palmer et al³ evaluated 55 brain metastases treated with preoperative fractionated SRS (24-25 Gy in 3-5 fractions) and reported 0 local failures, 3 cases of symptomatic radionecrosis, and 1 case of meningeal spread. These outcomes corresponded to a lower per-patient event rate of 8% compared with higher event rates of 20% to 60% in postoperative SRS studies.³ In fact, there is a theoretical advantage in reducing the incidence of leptomeningeal disease (LMD) by irradiating the tumor prior to inadvertent inoculation of tumor cells into the cerebrospinal fluid (CSF) during tumor resection. Hypofractionated schemes allow for higher doses to larger tumors and may have an advantage with regard to LMD rates, leading to the idea that dose de-escalation may be inferior.

In summary, the current study importantly reinforces the safety of single-fraction preoperative SRS and highlights that dose reduction may not be necessary. At the same time, we advocate for greater exploration of preoperative approaches as a promising strategy to enhance outcomes for select patients with larger lesions at risk for LMD or other adverse radiation effects, such as the currently enrolling clinical trial NRG-BN012 (NCT05438212), which compares preoperative with postoperative SRS. The trial uses an alternate reduced-dose single-fraction preoperative strategy.⁴ Additionally, the ongoing Radiation One And Done Study (ROADS) trial (NCT04365374) is comparing intraoperative GammaTile brachytherapy with postoperative SRS, highlighting another evolving strategy to integrate radiation with surgery.⁵ This encapsulates the broader movement toward optimizing the timing and modality of radiation in the management of brain metastases.

We congratulate the authors for advancing the discourse on preoperative radiosurgery and look forward to more prospective studies that address optimal fractionation and dosing paradigms.

Disclosures

Rodney E. Wegner has received grant funding from Elekta. The other authors have nothing to disclose.