Domain-Specific Cognition-Sparing Stereotactic Radiosurgery: A Novel Planning Approach for Functional Preservation

To introduce a novel cognition-sparing stereotactic radiosurgery (SRS) planning framework that limits dose to the cognitive connectome (10 bilateral white matter tracts, the corpus callosum, and the hippocampi) and to demonstrate its capability to preferentially spare the cognitive domains of memory, language, executive function, attention, and fine motor control.

Three cases representing the spectrum of intracranial disease treated with SRS (intact metastases, postoperative cavity, and arteriovenous malformation) and presenting competing domain-specific priorities based on lesion location were selected from the phase 2 cognition-sparing SRS (COG-SRS) trial. The cognitive connectome was autosegmented using AtlasTrack (white matter tracts) and FreeSurfer/FastSurfer (hippocampi) and registered to the computed tomography simulation scan. For each case, a standard plan, 4-6 domain-optimized plans, and an all-domain composite plan were generated using noncoplanar volumetric modulated arc therapy. All plans were required to meet target coverage and conventional organ-at-risk constraints. Dose to domain-specific structures and plan quality metrics were compared to quantify achievable dose sparing and dosimetric trade-offs.

Domain-optimized plans consistently reduced dose to structures supporting the prioritized domain, with expected cross-domain trade-offs. The all-domain composite plan produced the most balanced reductions across eloquent structures. When lesions abutted cognition-critical structures, D_max reductions were limited. However, substantial D_mean reductions were still achieved. All plans maintained standard target coverage, with generally small differences in plan quality indices relative to standard planning. Plan complexity varied across domain-specific optimizations, reflected by differences in monitor units.

Cognition-sparing SRS that limits dose to the widely distributed cognitive connectome while maintaining target coverage is feasible and allows for a domain-tunable approach applicable across common SRS indications. This flexibility supports a patient-centered paradigm, in which cognitive priorities are incorporated through shared decision-making. Using standard magnetic resonance imaging sequences and automated segmentation, the technique is readily translatable, and an open-access website (www.cogsrs.com) has been created to facilitate dissemination.