Biologically Guided Gamma Knife Dose Painting for Recurrent High-Grade Gliomas: A Retrospective Study Using Functional MRI Techniques

BACKGROUND This study examines the efficacy of biologically guided dose painting in Gamma Knife stereotactic radiosurgery (GKSRS) to improve radiographic response in patients with recurrent high-grade gliomas by increasing radiation dosage in functionally active tumor subregions identified through magnetic resonance spectroscopy (MRS) and T1-weighted perfusion magnetic resonance imaging (T1-PMRI). MATERIAL AND METHODS In this single-arm cohort of patients (n=23) with recurrent high-grade glioma, all patients previously treated with surgery, chemotherapy, and fractionated radiotherapy underwent GKSRS. Functional imaging (MRS and T1-weighted PMRI) delineated metabolically active ("aggressive") and less active ("passive") tumor regions. A modified radiosurgery plan prescribed 18 Gy to aggressive and 15 Gy to passive zones. For intra-patient comparison, a uniform-dose plan (plan 1, 16 Gy) was generated but not delivered. All statistical analyses were performed in Python 3.11 (SciPy-v1.11, statsmodels-v0.14, lifelines-v0.28) executed in Visual Studio Code 1.88 (Microsoft). RESULTS Across 23 patients, plan 2 vs plan 1 showed no significant change in whole-brain mean dose (P=0.716), integral dose (P=0.792), or V12 (P=0.583). Among 11 patients with follow-up imaging, K-trans decreased significantly (median, -18%; P=0.028; Wilcoxon) with a trend for initial area under the gadolinium concentration-time curve (IAUC; median, -22%; P=0.031 for table; overall P=0.08 for initial under curve analysis). Higher baseline K-trans correlated with greater K-trans reduction (r=-0.84, P=0.0012). CONCLUSIONS Using advanced MRI techniques (accounting for K-trans and IAUC on T1-PMRI, and MRS) to determine aggressive zones in salvage treatment for recurrent high-grade gliomas, and then focusing radiotherapy on these zones, can increase Gamma Knife efficiency without increasing the morbidity rate.