Spinal Cord Tolerance Guided by Stereotactic Radiosurgical Treatment of Intramedullary Arteriovenous Malformations

Abstract

Spinal cord toxicity resulting in neurological deficits remains the most feared complication of spinal region stereotactic radiosurgery (SRS). In treating vertebral body disease, a radiation dose gradient can typically be established between tumor and spinal cord. This is difficult for intramedullary spinal cord arteriovenous malformations (iSCAVMs), which can be integrated throughout the cord. Here we report outcomes of cord tolerance in treatment of integrated iSCAVMs. A retrospective cohort of 17 consecutive patients with integrated iSCAVMs treated once with frameless robotic surgery, SRS between 2007 and 2018 was accrued. Clinical outcomes, dose prescriptions, and target dose-volume histogram (DVH) parameters were acquired. Volumes of interest (VOIs) comprising the proper AVM and cord were registered on treatment planning software. A cord minus AVM (CmA) structure representing independent spinal cord was generated by Boolean subtraction of the respective proper AVM from the cord. Various dose quantifiers were extracted from DVHs, statistical univariate analysis was performed, and Task Group 101 (TG101) constraints were interpolated to two-fraction regimens with α/β of 2-3 Gray (Gy) using Wolfram Mathematica (Wolfram Research, Champaign, IL). Among the 17 patients analyzed (eight male and nine female), all had CmA volumes smaller than cord, confirming the integrated nature of their iSCAVMs. Nine had a nidus in the C-spine; six in the T-spine; and two in the L-spine or lower. Median age at diagnosis was 23, ranging from 9 to 56 years. Nine patients had no prior intervention, while eight had prior embolization(s) and/or microsurgery. Median follow-up time was 40 months. Ten patients (59%) experienced Grade (G) 0 neurological toxicity post-treatment, seven (41%) experienced G1, and zero experienced G2+. Three patients were prescribed three fractions to 21 or 24 Gy. The rest received two fractions (20-22 Gy). Max dose (Dmax) to cord and CmA ranged from 2278-2874 cGy and 2000-2659 cGy, respectively. All patients had Dmax to cord and CmA greater than TG101 constraints. All patients received minimum dose to hottest 0.03 cc volume (D0.03) to cord greater than constraints; 15 patients (88%), to CmA. All patients received minimum dose to hottest 0.35 cc volume (D0.35) to cord greater than threshold; 13 patients (76%), to CmA. At significant level of 0.05, one-tailed binomial test suggests max monthly G2+ toxicity rate of 0.4% in exceeding tolerances. No neurologic toxicity beyond Grade 1 was experienced by any patient, all of whom received Dmax to spinal cord tissue (both independent and integrated with AVM) beyond recommended constraints. Further, all patients exceeded volumetric constraints to cord. Most exceeded volumetric constraints to CmA, as well. Novel tolerance data from rare iSCAVMs may influence current cord constraints to avoid limiting appropriate treatment of more common vertebral metastases.