Existence of a dose-length effect in spinal nerves receiving single-session stereotactic ablative radiation therapy Journal Article


Authors: Hrycushko, B.; van der Kogel, A. J.; Phillips, L.; Folkert, M.; Sayre, J. W.; Vernino, S.; Hassan-Rezaeian, N.; Foster, R. D.; Yamada, Y.; Timmerman, R.; Medin, P. M.
Article Title: Existence of a dose-length effect in spinal nerves receiving single-session stereotactic ablative radiation therapy
Abstract: Purpose: The spinal nerves have been observed to have a similar single-session dose tolerance to that of the spinal cord in pigs. Small-animal studies have shown that spinal cord dose tolerance depends on the length irradiated. This work aims to determine whether a dose-length effect exists for spinal nerves. Methods and Materials: Twenty-seven Yucatan minipigs underwent computed tomography and magnetic resonance imaging for treatment planning, followed by single-session stereotactic ablative radiation therapy. A 0.5 cm length of the left-sided C6, C7, and C8 spinal nerves was targeted. The pigs were distributed into 6 groups with prescription doses of 16 Gy (n = 5), 18 Gy (n = 5), 20 Gy (n = 5), 22 Gy (n = 5), 24 Gy (n = 5), or 36 Gy (n = 2) and corresponding maximum doses of 16.7, 19.1, 21.3, 23.1, 25.5, and 38.6 Gy, respectively. Neurologic status was assessed with a serial electrodiagnostic examination and daily observation of gait for approximately 52 weeks. A histopathologic examination of paraffin-embedded sections with Luxol fast blue/periodic acid-Schiff's staining was also performed. Results: Marked gait change was observed in 8 of 27 irradiated pigs. The latency for responding pigs was 11 to 16 weeks after irradiation. The affected animals presented with a limp in the left front limb, and 62.5% of these pigs had electrodiagnostic evidence of denervation in the C6 and C7 innervated muscles. A probit analysis showed the dose associated with a 50% incidence of gait change is 23.9 Gy (95% confidence interval, 22.5-25.8 Gy), which is 20% higher than that reported in a companion study where a 1.5 cm length was irradiated. All symptomatic pigs had demyelination and fibrosis in the irradiated nerves, but the contralateral nerves and spinal cord were normal. Conclusions: A dose-length effect was observed for single-session irradiation of the spinal nerves in a Yucatan minipig model. © 2019 Elsevier Inc.
Keywords: histopathology; nonhuman; treatment planning; nuclear magnetic resonance imaging; magnetic resonance imaging; animal tissue; computer assisted tomography; radiotherapy; incidence; animal experiment; confidence interval; fibrosis; limb; computerized tomography; spinal cord; staining; irradiation; motor dysfunction; stereotactic body radiation therapy; mammals; radiation dose distribution; data analysis software; paraffin; radiation tolerance; acid; latent period; demyelination; maximum permissible dose; cervical spine; electrodiagnosis; periodic acid schiff stain; denervation; gait; methods and materials; female; priority journal; article; spinal nerve; probit analysis; yucatan mini-pigs; radiation dose response; length effects; mini-pig model; small animal study; fast blue; yucatan micropig
Journal Title: International Journal of Radiation Oncology, Biology, Physics
Volume: 106
Issue: 5
ISSN: 0360-3016
Publisher: Elsevier Inc.  
Date Published: 2020-04-01
Start Page: 1010
End Page: 1016
Language: English
DOI: 10.1016/j.ijrobp.2019.11.417
PUBMED: 31953062
PROVIDER: scopus
DOI/URL:
Notes: Article -- Source: Scopus
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  1. Yoshiya Yamada
    479 Yamada