<title>Weanling piglet cerebellum: a surrogate for tolerance to MRT (microbeam radiation therapy) in pediatric neuro-oncology</title>

TLDR

The cerebellum of weanling piglets was used as a surrogate for the radiosensitive human infant cerebellum in a Swiss‑led experimental microbeam radiation therapy program at the ESRF. Five piglets from a 47‑day‑old litter and eight from a 40‑day‑old litter were anesthetized and irradiated with a 1.5 cm × 1.5 cm array of 20–30 µm wide microbeams spaced 210 µm apart, delivering uniform skin‑entrance peak doses of 150, 300, 425, or 600 Gy, with peak and valley doses calculated by GEANT Monte Carlo and validated by film microdosimetry. After 57–66 weeks, the irradiated piglets remained developmentally, behaviorally, neurologically, and radiologically normal, and similar MRT delivered at 625 Gy proved palliative or curative in young adult rats with intracerebral gliosarcomas, underscoring MRT’s potential as an adjunct therapy for infant brain tumors.

Abstract

The cerebellum of the weanling piglet (Yorkshire) was used as a surrogate for the radiosensitive human infant cerebellum in a Swiss-led program of experimental microbeam radiation therapy (MRT) at the ESRF. Five weanlings in a 47 day old litter of seven, and eight weanlings in a 40 day old litter of eleven were irradiated in November, 1999 and June, 2000, respectively. A 1.5 cm-wide x 1.5 xm-high array of equally space approximately equals 20-30 micrometers wide, upright microbeams spaced at 210 micrometers intervals was propagated horizontally, left to right, through the cerebella of the prone, anesthetized piglets. Skin-entrance intra-microbeam peak adsorbed doses were uniform, either 150, 300, 425, or 600 gray (Gy). Peak and inter-microbeam (valley) absorbed doses in the cerebellum were computed with the PSI version of the Monte Carlo code GEANT and benchmarked using Gafchromic and radiochromic film microdosimetry. For approximately equals 66 weeks [first litter; until euthanasia], or approximately equals 57 weeks [second litter; until July 30, 2001] after irradiation, the littermates were developmentally, behaviorally, neurologically and radiologically normal as observed and tested by experienced farmers and veterinary scientists unaware of which piglets were irradiated or sham-irradiated. Morever, MRT implemented at the ESRF with a similar array of microbeams and a uniform skin-entrance peak dose of 625 Gy, followed by immunoprophylaxis, was shown to be palliative or curative in young adult rats bearing intracerebral gliosarcomas. These observations give further credence to MRT's potential as an adjunct therapy for brain tumors in infancy, when seamless therapeutic irradiation of the brain is hazardous.