Spinal Cord Tolerance to Single-Fraction Partial-Volume Irradiation: A Swine Model

Abstract

Purpose-This study was performed to determine the spinal cord tolerance to single-fraction, partial-volume irradiation in swine.Methods/Materials-A 5 cm long cervical segment was irradiated in 38-47 week old Yucatan minipigs using a dedicated, image-guided radiosurgery linear accelerator. Radiation was delivered to a cylindrical volume approximately 5 cm in length and 2 cm in diameter that was positioned lateral to the cervical spinal cord resulting in a dose distribution with the 90%, 50% and 10% isodose lines traversing the ipsilateral, central and contralateral spinal cord, respectively. Dose was prescribed to the 90% isodose line. Twenty-six pigs were stratified into 8 dose groups from 12-47 Gy. The mean maximum spinal cord doses were 16.9±0.1, 18.9±0.1, 21.0±0.1, 23.0±0.2, and 25.3±0.3 Gy in the 16, 18, 20, 22 and 24 Gy dose groups, respectively. The mean percentage spinal cord volumes receiving >= 10 Gy for the same groups were 43%±3, 48%±4, 51%±2, 57% Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptInt J Radiat Oncol Biol Phys. Author manuscript; available in PMC 2012 January 1. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript ±2 and 59%±4. The study endpoint was motor neurologic deficit determined by a change in gait during a one year follow-up period.Results-A steep dose response curve was observed with an ED 50 (95% CI) for the maximum dose point of 20.0 Gy (18.3-21.7). Excellent agreement was observed between the occurrence of neurologic change and the presence of histological change. All animals with motor deficits showed some degree of demyelination and focal white matter necrosis on the irradiated side with relative sparing of the gray matter while histology was unremarkable in animals with normal neurologic status. Conclusions-Resultsindicate that for a dose distribution with a steep lateral gradient, pigs have a lower ED 50 for paralysis than has been observed in rats and more closely resembles that for rats, mice and guinea pigs receiving uniform spinal cord irradiation.

The role of stereotactic body radiotherapy and stereotactic radiosurgery in the re-irradiation of metastatic spinal tumors

“…Notably, no pigs with a maximum spinal cord dose <18.8 Gy developed gait changes, while all pigs with maximum cord dose >21.3 Gy developed toxicity, suggesting a steep dose complication curve, in which small increases in maximum dose beyond 19 Gy results in high probabilities of spinal cord injury. The radiosurgery ED 50 of the re-irradiated group was 19.7 Gy, practically identical to the radiosurgery ED 50 of 20 Gy in a previously described treatment-naïve swine cohort that underwent radiosurgery alone [39]. There was an estimated 96% recovery of the initial 30 Gy dose by the time of re-irradiation at 1 year.…”

Nonthermal ablation with microbubble-enhanced focused ultrasound close to the optic tract without affecting nerve function

“…36 Note, however, that it is not known whether damage thresholds are the same for the rat and human optic tracts. Differences in the radiosensitivity of nerve structures in different species have been reported, 43 and it is possible that more damage could occur in humans if there are similar differences with this type of ultrasound effect.…”

Molecular Imaging Detects Impairment in the Retrograde Axonal Transport Mechanism After Radiation-Induced Spinal Cord Injury

“…Current literature (reviewed in [12]) suggests 20 Gy as the dose at which 50% of subjects will suffer cord damage for single dose radiation treatment, with similar values for many species: 19 Gy for mice [17], 20 Gy for rats [18] and 20 Gy for pigs [19]. A maximum safe limit of 10 Gy was suggested for clinical stereotactic treatments [15], as a dose limit below which clinical pathology would not be expected to develop.…”

“…While animal models have been used to establish dose-response curves and to investigate the irradiation conditions that modify the response, there is still little known about the human spinal cord tolerance to single-fraction irradiation. Variables such as dose rate, irradiated length, irradiated lateral cross-section, dose to adjacent spinal cord, previous irradiation and age are variables known to influence clinical outcomes [4-6]. Such dosimetric information is valuable for use in the treatment planning process and may predict outcomes when applied to groups of patients.…”