Radiation and Cancer Biology
SS 19 - Biology 4 - Normal Tissue Radiobiology
147 - The Dose-Length Effect in Spinal Nerves Receiving Single-Session Stereotactic Ablative Radiation Therapy (SAbR)
Tuesday, October 23
8:05 AM - 8:15 AM
Location: Room 008
Paul Medin, PhD
University of Texas Southwestern Medical Center
University of Texas Southwestern Medical Center: Professor: Employee
Brainlab Inc: Honoraria
The Dose-Length Effect in Spinal Nerves Receiving Single-Session Stereotactic Ablative Radiation Therapy (SAbR)
P. M. Medin1, B. A. Hrycushko1, L. Phillips1, J. Sayre2, M. R. Folkert3, S. Vernino1, R. D. Foster4, N. Hassan Rezaeian1, Y. Yamada5, and A. J. Van Der Kogel6; 1University of Texas Southwestern Medical Center, Dallas, TX, 2University of California Los Angeles, Los Angeles, CA, 3Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, 4Levine Cancer Institute: Atrium Health, Charlotte, NC, 5Memorial Sloan Kettering Cancer Center, New York, NY, 6University of Wisconsin, Madison, WI
Purpose/Objective(s): SAbR is a rapidly expanding treatment modality utilized for an increasing number of cancers. The radiosensitivity of healthy neural structures is poorly understood in the setting of SAbR and numerous cases of peripheral neuropathy following SAbR have been reported at a range of doses. A study is underway in a pig model to define the dose-related incidence of neuropathy resulting from single-session SAbR to the spinal nerves, and to test the hypothesis that the probability of toxicity depends on the length of nerve irradiated.
Materials/Methods: A 2-armed study is underway using 50 Yucatan minipigs. Every pig underwent treatment planning CT and MRI imaging followed by single-session SAbR using a clinical accelerator. The left-sided C6, C7 and C8 spinal nerves were irradiated in all pigs, and the length of nerve irradiated was the only difference between study arms. For pigs in Arm 1, a nerve length of 15mm was targeted with the following Rx doses (N): 16(7), 18(5), 20(5), 22(5) or 24(3) Gy with corresponding maximum nerve doses of (17.3, 19.5, 21.6, 23.9, 26.1 Gy). For pigs in Arm 2, a nerve length of 5mm was targeted with the following Rx doses (N): 16(5), 18(5), 20(5), 22(5) or 24(3) Gy with corresponding maximum nerve doses of (16.7, 19.1, 21.3, 23.1, 25.5 Gy). The neurologic status of all animals is followed by electrodiagnostic (EDX) exam at (-1, 2, 10, 20, 36 and 52) weeks following SAbR, and daily observation of gait. Current followup ranges between 1-56 weeks following SAbR. Animals are evaluated with EDX exams and gait observation until neurologic deficits occur or the 52-week planned followup period is reached. Histopathologic examination of paraffin-embedded sections with luxol fast blue/periodic acid-Schiff’s staining is performed on bilateral spinal nerves and the spinal cord.
Results: For Arm 1, responders/pigs by dose group are: 16 (0/7), 18 (2/5), 20 (5/5), 22 (5/5), and 24 (3/3) Gy. For Arm 2, responders/pigs by dose group are: 16 (0/5), 18 (0/5), 20 (1/5), 22 (2/5), and 24 (3/3) Gy. Probit analysis yields ED50(95% CI) values of 19.7 Gy(18.5-21.1) for Arm 1 and 23.0 Gy (21.9-24.4) for Arm 2. Responding animals presented with a limp in their left forelimb only and electromyography (EMG) demonstrated evidence of denervation in C6 and C7 innervated muscles in these animals. Increased insertional activity and denervation were noted in some non-responders. Gait change was first observed 9-15 weeks following irradiation. Histopathologic observation of left-sided spinal nerves revealed some degree of vascular and myelin degeneration with fibrosis in all symptomatic pigs. The severity of change is dose dependent. Right-sided (untreated) spinal nerves and spinal cords have all been normal.
Conclusion: In this interim analysis, the toxicity response of spinal nerves to single-session SAbR appears to depend on the length irradiated. This study is not yet complete, additional followup is ongoing.
Author Disclosure: P.M. Medin: Honoraria; Brainlab Inc. B.A. Hrycushko: None. L. Phillips: Consultant; ACI Clinical. J. Sayre: None. M.R. Folkert: Research Grant; Medtronic, Inc, Augmenix, Inc. Travel Expenses; Varian, Inc. S. Vernino: Consultant; Quest Diagnostics. Speaker's Bureau; Lundbeck. Advisory Board; Lundbeck. member; American Autonomic Society, Dysautonomia International. R.D. Foster: None. N. Hassan Rezaeian: None. Y. Yamada: Speaker's Bureau; Institute for Medical Education, Varian Medical Systems, BrainLab.