The radiation response of the cervical spinal cord of the pig: Effects of changing the irradiated volume

Aardweg, G.J.M.J. van den; Hopewell, J. W.; Whitehouse, Elizabeth

doi:10.1016/0360-3016(94)e0306-5

Cited by 34 publications

(25 citation statements)

References 19 publications

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“…The histological changes observed in the lateral white matter are very similar to lesions observed in other studies in pigs(10), monkeys(16) and rats(17). As reported for most species, including humans, focal white matter necrosis is the most common histology underlying radiation myelopathy of the spinal cord(18).…”

Section: Discussionsupporting

confidence: 87%

“…A lateral 1mm shift of the spinal cord contour towards the treated isocenter would result in an increase in the maximum spinal cord dose of approximately 1-2% while a 1mm shift in the opposite direction would result in a decrease of the maximum spinal cord dose of 3-4%. The follow-up period of the current study (39-53 weeks) is considered long enough to observe the initial phase of radiation myelopathy as commonly reported for guinea pigs(4), rats(13, 14), mice(15) and pigs(9, 10) (2-6 months). The latent period observed for the onset of motor deficits in the present study (9-24 weeks) is in good agreement with the companion study(9), a previous spinal cord tolerance study using pigs(10) and the case of human myelopathy reported by Sahgal, et.…”

Section: Discussionmentioning

confidence: 99%

“…al. (8) Potentially more cases of radiation myelopathy would have been observed in a longer follow-up period; a previous spinal cord tolerance study(10) reported two late responding pigs at 65 and 75 weeks following irradiation to doses very close to ED 50 . The spinal cords of two pigs (pigs #10 and #12) of the present study were found to have histologic changes including vascular hyalinization accompanied by demyelination and glial scarring 53 weeks following radiosurgery but both pigs maintained normal neurologic status.…”

Section: Discussionmentioning

confidence: 99%

“…Five uniformly distributed axial sections through the irradiated volume of each animal were cut and stained with a Luxol fast blue/periodic acid Schiff combination and were examined for histology. The dose-related incidence of motor deficit was used as an endpoint to obtain quantal data that was analyzed by probit analysis(10) to establish a dose-response curve and to calculate the probability of a deficit at increasing dose levels with the associated 95% confidence bounds.…”

Section: Methodsmentioning

confidence: 99%

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Spinal Cord Tolerance to Reirradiation With Single-Fraction Radiosurgery: A Swine Model

Medin

Foster

Kogel³

et al. 2012

International Journal of Radiation Oncology*Biology*Physics

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Purpose This study was performed to determine the spinal cord tolerance of swine to single-fraction, partial-volume irradiation one year after uniform irradiation to 30Gy in 10 fractions. Materials/ Methods A 10cm length of spinal cord (C3-T1) was uniformly irradiated to 30Gy in ten consecutive fractions and reirradiated one year later with a single radiosurgery dose centered within the previously irradiated segment. Radiosurgery was delivered to a cylindrical volume approximately 5cm in length and 2cm 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. Twenty-three pigs were stratified into six dose groups with mean maximum spinal cord doses of 14.9±0.1 (n=2), 17.1±0.3 (n=3), 19.0±0.1 (n=5), 21.2±0.1 (n=5), 23.4±0.2 (n=5), and 25.4±0.4 (n=3)Gy. The mean percentage spinal cord volumes receiving >=10Gy for the same groups were 34%±1, 40%±1, 46%±3, 52%±1, 56±3, and 57%±1. 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 ED50(95% CI) for the maximum point dose of 19.7Gy (17.4-21.4). With two exceptions, histology was unremarkable in animals with normal neurologic status while 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. Histologic comparison with a companion study of de novo irradiated animals revealed retreatment responders have more extensive tissue damage, including infarction of the gray matter, only at prescription doses >20Gy. Conclusion Pigs receiving spinal radiosurgery one year following 30Gy in 10 fractions are not at significantly higher risk of developing motor deficits than pigs that have received radiosurgery alone.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Spinal Cord Tolerance to Reirradiation With Single-Fraction Radiosurgery: A Swine Model

Medin

Foster

Kogel³

et al. 2012

International Journal of Radiation Oncology*Biology*Physics

View full text Add to dashboard Cite

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“…Chronic progressive radiation myelopathy developed in patients after 0.5 to 2 years of treatment (13)(14)(15)(16)(17). Van den Aardweg et al previously evaluated the effects of local irradiation on various lengths of the spinal cord in mature pigs (37-43 weeks) (18). In that study, the effective dose 50 (ED50) values for chronic progressive radiation myelopathy were found to be 27.02±0.36, 27.68±0.57 and 28.28±0.78 Gy on a field length of 10, 5 and 2.5 cm, respectively, with a single high dose of radiation (25-32 Gy).…”

Section: A B C Dmentioning

confidence: 99%

Changes in cell cycle, apoptosis and necrosis following the establishment of a 125I brachytherapy model in the spinal cord in Banna mini-pigs

et al. 2011

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Abstract. Brachytherapy is regarded as the most effective method in the treatment of metastatic spinal tumors since little damage is caused to surrounding healthy tissue. However, this method may cause radiation myelopathy if an overdose occurs. In the present study, we established a Banna mini-pig 125 I spinal cord implantation model to provide a tool for the study of how to reduce these types of side effects. Cell cycle alteration, apoptosis and necrosis of spinal cord neurons in the presence of various doses and durations of 125 I brachytherapy were also investigated. The pigs were randomly divided into four groups, A, B, C and D. In group A, four 125 I seeds (total radioactivity, 4.0 mCi) were implanted into the dura mater of the spinal canal at the level of T13. In groups B and C, eight 125 I sources (total radioactivity, 8.0 mCi) were inserted at the same location. Groups A and C were raised for up to 8 months and group B for only 2 months. Neurons from the swine spinal cord at the T13 level were collected and cell cycle analysis was performed. Apoptosis and necrosis were tested by a terminal deoxynucleotidyl transferase dUTP nick endlabeling (TUNEL) assay. The Banna mini-pig brachytherapy model was successfully established. Radiation myelopathy was closely associated with radiation dose and duration, more neurons were blocked in the G2 and S phases as dose and time increased, and an increase in apoptosis and necrosis was detected. Ratios of apoptosis and necrosis were reduced as lower doses and shorter durations of radiation were applied. Our results demonstrate that the Banna mini-pig is an ideal animal to study 125 I brachytherapy. Low-dose and short-term brachytherapy may effectively decrease apoptosis and necrosis in spinal cord cells in Banna mini-pigs.

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Optimization of hexagonal‐pattern minibeams for spatially fractionated radiotherapy using proton beam scanning

et al. 2020

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In this study, we investigated computationally and experimentally a hexagonal-pattern array of spatially fractionated proton minibeams produced by proton pencil beam scanning (PBS) technique. Spatial fractionation of dose delivery with millimeter or submillimeter beam size has proven to be a promising approach to significantly increase the normal tissue tolerance. Our goals are to obtain an optimized minibeam design and to show that it is feasible to implement the optimized minibeams at the existing proton clinics. Methods: An optimized minibeam arrangement is one that would produce high peak-to-valley dose ratios (PVDRs) in normal tissues and a PVDR approaching unity at the Bragg peak. Using Monte Carlo (MC) code TOPAS we simulated proton pencil beams that mimic those available at the existing proton therapy facilities and obtained a hexagonal-pattern array of minibeams by collimating the proton pencil beams through the 1-3 mm diameter pinholes of a collimator. We optimized the minibeam design by considering different combinations of parameters including collimator material and thickness (t), center-to-center (c-t-c) distance, and beam size. The optimized minibeam design was then evaluated for normal tissue sparing against the uniform pencil beam scanning (PBS) by calculating the therapeutic advantage (TA) in terms of cell survival fraction. Verification measurements using radiochromic films were performed at the Emory proton therapy center (EPTC). Results: Optimized hexagonal-pattern minibeams having PVDRs of >10 at phantom surface and of >3 at depths up to 6 cm were achieved with 2 mm diameter modulated proton minibeams (with proton energies between 120 and 140 MeV) corresponding to a spread-out-Bragg-peak (SOBP) over the depth of 10-14 cm. The results of the film measurements agree with the MC results within 10%. The TA of the 2 mm minibeams against the uniform PBS is >3 from phantom surface to the depth of 5 cm and then smoothly drops to~1.5 as it approaches the proximal edge of the SOBP. For 2 mm minibeams and 6 mm c-t-c distance, we delivered 1.72 Gy at SOBP for 7.2 9 7.2 9 4 cm 3 volume in 48 s. Conclusions: We conclude that it is feasible to implement the optimized hexagonal-pattern 2 mm proton minibeam radiotherapy at the existing proton clinics, because desirable PVDRs and TAs are achievable and the treatment time is reasonable.

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The radiation response of the cervical spinal cord of the pig: Effects of changing the irradiated volume

Cited by 34 publications

References 19 publications

Spinal Cord Tolerance to Reirradiation With Single-Fraction Radiosurgery: A Swine Model

Spinal Cord Tolerance to Reirradiation With Single-Fraction Radiosurgery: A Swine Model

Changes in cell cycle, apoptosis and necrosis following the establishment of a 125I brachytherapy model in the spinal cord in Banna mini-pigs

Optimization of hexagonal‐pattern minibeams for spatially fractionated radiotherapy using proton beam scanning

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