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

PURPOSE: An investigation of the field size effect for the cervical spinal cord of the pig after single doses of gamma-rays. In this study, clinically relevant volumes of the spinal cord were irradiated. METHODS AND MATERIALS: The effects of the local irradiation of different lengths of the spinal cord (2.5 cm, 5.0 cm, and 10.0 cm) have been evaluated in mature pigs (37-43 weeks). Single doses of 25-31 Gy were given using a 60Co gamma-source, at a dose rate of 0.21-0.30 Gy/min. The incidence of radiation-induced paralysis was used as the endpoint. The data were analyzed using probit analysis and a normal tissue complication probability (NTCP)-model. RESULTS: Twenty-five animals out of a total of 53 developed paralysis, with histological evidence of parenchymal and vascular changes in their white matter. The slope of the dose-response curves decreased with the decrease in field size; however, there was no significant difference at the radiation dose associated with a 50% incidence of paralysis (ED50) irrespective of the method of analysis. The ED50 values +/- standard errors (+/- SE) were 27.02 +/- 0.36 Gy, 27.68 +/- 0.57 Gy, and 28.28 +/- 0.78 Gy for field lengths of 10, 5, and 2.5 cm, respectively. Analysis of the data with a normal tissue complication probability (NCTP) model gave similar results. The latent period for paralysis was 7.5-16.5 weeks with no significant differences between dose and field size. CONCLUSION: No significant field size-related differences in response were detectable in the cervical spinal cord of mature pigs after single dose irradiations, specifically at a clinically relevant level of effect (< ED10).

Amelioration of both early and late radiation-induced damage to pig skin by essential fatty acids.

PURPOSE: To evaluate the possible role of essential fatty acids, specifically gamma-linolenic and eicosapentaenoic acid, in the amelioration of early and late radiation damage to the skin. METHODS AND MATERIALS: Skin sites on the flank of 22-25 kg female large white pigs were irradiated with either single or fractionated doses (20 F/28 days) of beta-rays from 22.5 mm diameter 90Sr/90Y plaques at a dose rate of approximately 3 Gy/min. Essential fatty acids were administered orally in the form of two 'active' oils, So-1100 and So-5407, which contained gamma-linolenic acid and a mixture of that oil with eicosapentaenoic acid, respectively. Oils (1.5-6.0 ml) were given daily for 4 weeks prior, both 4 weeks prior and 10-16 weeks after, or in the case of one single dose study, just for 10 weeks after irradiation. Control animals received a 'placebo' oil, So-1129, containing no gamma linolenic acid or eicosapentaenoic acid over similar time scales before and after irradiation. Acute and late skin reactions were assessed visually and the dose-related incidence of a specific reaction used to compare the effects of different treatment schedules. RESULTS: A reduction in the severity of both the early and late radiation reactions in the skin was only observed when 'active' oils were given over the time course of the expression of radiation damage. Prior treatment with oils did not modify the radiation reaction. A 3.0 ml daily dose of either So-1100 or So-5407 given prior to, but also after irradiation with single and fractionated doses of beta-rays produced the most significant modification to the radiation reactions, effects consistent with dose modification factors between 1.06-1.24 for the acute reactions of bright red erythema and/or moist desquamation, and of 1.14-1.35 for the late reactions of dusky/mauve erythema and dermal necrosis. There was the strong suggestion of an effect produced by the 'placebo' oil, So-1129, after higher daily doses of oil. CONCLUSIONS: Essential fatty acids can modulate normal tissue reactions when given over the time when radiation damage is normally expressed. Dose modification factors suggest that a > or = 10% higher dose is required to produce the same level of normal tissue injury. Clinical application of selected essential fatty acids at appropriate doses may lead to a significant increase in the therapeutic gain in patients treated for cancer by radiotherapy.

A new model of radiation-induced myelopathy: a comparison of the response of mature and immature pigs.

PURPOSE: The development of an experimental model of radiation-induced myelopathy in the pig which would facilitate the study of the effects of clinically relevant treatment volumes. METHODS AND MATERIALS: The effects of local spinal cord irradiation, to a standard 10 x 5 cm field, have been evaluated in mature (37-42.5 weeks) and immature (15.5-23 weeks) pigs. Irradiation was with single doses of 60Co gamma-rays at a dose-rate of 0.21-0.65 Gy/min. The incidence of paralysis was used as an endpoint. RESULTS: Irradiation of mature animals resulted in the development of frank paralysis with animals showing combined parenchymal and vascular pathologic changes in their white matter. These lesions, in common with those seen in patients, had a clear evidence of an inflammatory component. The latency for paralysis was short, 7.5-16.5 weeks, but within the wide range reported for patients. However, it was shorter than that reported in other large animal models. The ED50 value (+/- SE) for paralysis was 27.02 +/- 0.36 Gy, similar to that in rats taking into account dose-rate factors. The irradiation of immature pigs only resulted in transient neurological changes after doses comparable to those used in the mature animals, ED50 value (+/- SE) 26.09 +/- 0.37 Gy. The reasons for these transient neurological symptoms are uncertain. CONCLUSION: A reliable experimental model of radiation-induced myelopathy has been developed for mature pigs. This model is suitable for the study of clinically relevant volume effects.

Boron neutron capture therapy: a guide to the understanding of the pathogenesis of late radiation damage to the rat spinal cord.

PURPOSE: Before the commencement of new boron neutron capture therapy (BNCT) clinical trials in Europe and North America, detailed information on normal tissue tolerance is required. In this study, the pathologic effects of BNCT on the central nervous system (CNS) have been investigated using a rat spinal cord model. METHODS AND MATERIALS: The neutron capture agent used was 10B enriched sodium mercaptoundecahydro-closododecaborate (BSH), at a dosage of 100 mg/kg body weight. Rats were irradiated on the thermal beam at the Brookhaven Medical Research Reactor. The large spine of vertebra T2 was used as the lower marker of the irradiation field. Rats were irradiated with thermal neutrons alone to a maximum physical absorbed dose of 11.4 Gy, or with thermal neutrons in combination with BSH, to maximum absorbed physical doses of 5.7 Gy to the CNS parenchyma and 33.7 Gy to the blood in the vasculature of the spinal cord. An additional group of rats was irradiated with 250 kVp X rays to a single dose of 35 Gy. Spinal cord pathology was examined between 5 and 12 months after irradiation. RESULTS: The physical dose of radiation delivered to the CNS parenchyma, using thermal neutron irradiation in the presence of BSH, was a factor of two to three lower than that delivered to the vascular endothelium, and could not account for the level of damage observed in the parenchyma. CONCLUSION: The histopathological observations of the present study support the hypothesis that the blood vessels, and the endothelial cells in particular, are the critical target population responsible for the lesions seen in the spinal cord after BNCT type irradiation and by inference, after more conventional irradiation modalities such as photons or fast neutrons.

Modification of late dermal necrosis in the pig by treatment with multi-wavelength light.

Low-level light from a multi-wavelength light source has been used to prevent late X-ray-induced dermal necrosis in the pig. Skin fields, measuring 4 cm x 4 cm on the flank, were irradiated with graded doses of X rays and the incidence of late dermal necrosis at 10-16 weeks after irradiation was scored. The control skin sites were irradiated only with 250 kV X rays but the test skin sites were subsequently exposed to low-level light. Local light exposure was from an array of gallium aluminium arsenide diodes, which produced wavelengths of 660, 820, 880 and 950 nm, pulsating at 5 kHz. Light treatment was given three times a week, from 6-16 weeks after X irradiation. Each treatment session was 1 min, which was equivalent to energy density of 1.08 Jcm-2. Light treatment increased the ED50, the dose which causes dermal necrosis in 50% of the irradiated skin fields, from 20.10 +/- 0.12 Gy to 21.94 +/- 0.30 Gy. This difference, although small, was highly significant (p < 0.001) and was equivalent to a dose modification factor (DMF) of 1.09. The effect of light treatment was minimal at incidence levels of less than the 50% but greater at higher levels of effect. These findings suggest that low-level light, when applied appropriately, may be useful in the prevention of late X-ray-induced damage to the dermis.

Prevention of X-ray-induced late dermal necrosis in the pig by treatment with multi-wavelength light.

Low-level light from a multi-wavelength array of light sources has been used to prevent late X-ray-induced dermal necrosis in the pig. Skin fields, measuring 4 x 4 cm on the flank, were irradiated with a single dose of 23.4 Gy of X-rays. This X-ray dose was associated with the development of a 100% incidence of dermal necrosis, 10-16 weeks after irradiation. These irradiated skin sites were subsequently exposed to light of 660, 820, 880, and 950 nm wavelengths from a gallium aluminium arsenide multiple wavelength multidiode cluster probe (Biotherapy Medical Laser, 3ML), three times a week, from 4 to 16 weeks or 6 to 16 weeks after X-irradiation. The skin fields were exposed to the light pulsating at either 2.5 Hz or 5 kHz. With light pulsating at 5 kHz, energy densities of 0.22, 0.54, 1.08 2.16, 4.32, and 10.8 J/cm2 were used. Treatment with light pulsating at 2.5 Hz, 6-16 weeks after X-irradiation, or treatment with light pulsating at 5 kHz, 4-16 weeks after X-irradiation, did not have a significant effect on the incidence or the latency for the development of ischemic dermal necrosis irrespective of the exposure time to light at each treatment. With light pulsating at 5 kHz, no effect of light dose was observed. However, the overall incidence of dermal necrosis was significantly reduced (P = 0.001) to 52% in the X-irradiated fields receiving treatment with 5 kHz light, 6-16 weeks after X-irradiation.(ABSTRACT TRUNCATED AT 250 WORDS)