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Volume effects on canine spinal cord function
156
Radiation Oncology, Biology, Physics October 1990, Volume 19, Supplement 1
64 VOLUME
EFFECTS
E.L. Gillette, Radiology
ON CANINE
SPINAL
CORDFUNCTION
S. McChesney Gillette,
and Radiation
Biology,
VOLUME
G. Childs,
Colorado
EFFECTS
M. Ritt,
B. Powers
State University
ON CANINE SPINAL CORD FUNCIION
EL. Gillette, S. McChesney Gillette, G. Childs, M. Ritt, B. Powers Radiation myelopathy is one of the most serious late effects of radiotherapy. The length of spinal cord irradiated is suspected to influence the incidence of myelopathy, however, little is known of the magnitude or mechanism of this effect. The functional effects of irradiation of canine thoracic spinal cord to a length of 20 cm versus 4 cm is the subject of this presentation. The 20 cm field encompassed nearly the entire thoracic cord (Tl-T12). The 4 cm field was positioned at the mid thoracic cord (T6). Irradiation was given in 4 Gy fractions over 4 weeks. Total doses of 44 to 68 Gy were given to the 20 cm field while dogs irradiated with a 4 cm field received doses between 48 to 80 Gy. The functional response was evaluated by monthly physical neurologic examinations and by electrophysiologic studies. Electrophysiology was done at the end of irradiation and at 6 months and 1 year after irradiation. Dogs were evaluated for pain in the thoracic or low cervical region following neck flexion. Moderate to severe pain over the thoracic cord was a common occurrence and first appeared at 2 to 3 months. The ED5 for pain was approximately 55 Gy for the 20 cm field and 66 Gy for the 4 cm field. This early delayed response is thoug g t to be similar to Lhermitte’s sign of humans. At 6 months only three dogs had shown delayed radiation myelopathy. This occurred at doses of 68 Gy given over a 20 cm length of spinal cord. Two of these dogs had bilateral hind limb paralysis, the third had paresis. Spinal cord evoked potentials were evaluated for conduction velocity and wave amplitude and configuration. Recordings were made from irradiated and nonirradiated portions of spinal cord. No abnormalities in spinal cord evoked potentials were found immediately after treatment in any dogs. One dog with bilateral paralysis and one dog with paresis had decreased conduction velocities at the time of onset. Evoked potentials were not measured in the second dog with paralysis because it was a control for this procedure. In previous studies myelopathies continued to develop to 1 year. The EDSO for radiation myelopathy for the entire thoracic cord given in 4 Gy fractions over four weeks was 56 Gy at one year. The latent period for radiation myelopathy tends to decrease with increasing dose. These preliminary observations indicate a volume effect on the response of spinal cord to irradiation. A dose of approximately 11 Gy greater was required for evidence of an early delayed response when the irradiated length has reduced from 20 to 4 cm. This study is continuing to observe for the influence of irradiated length on later developing myelopathies.
65 EFFECTS
OF IRRADIATION
R.M. VIGNEULLEI,
H.M.
OF EXTERIORIZED VRIESENDORP12,
SMALL
INTESTINE
G. KITTOI, Institute 1 ,
T. PELKEYl,
P. TAYLOR3,
AND J. SMITHI.
Armed Research orces Radiobiology Bethesda, Maryland, Johns Hopkins Oncology Center f Baltimore, Maryland and Department of Radiation Medicine, Georgetown University Hospitai3, Washington, D.C. 20007. Small intestine of Sprague-Dawley rats can be exteriorized and irradiated in a homogeneous manner with 18 MVp photons. Survival times after irradiation of the exteriorized small intestine are longer than after total body irradiation by about 4 days. The LD50 after irradiation of the exteriorized small intestine is approximately 6 Gy higher than after total body irradiation. The addition of a 5 X 5 cm abdominal radiation field to the radiation field used for the exteriorized intestine reduces survival times to the values found after total body irradiation. The higher the amount of radiation received by the abdomen, the closer the survival time will be to the one observed after total body irradiation. The addition of radiation fields to the thoracic or pelvic areas does not alter the survival time observed after radiation of the exteriorized intestine. No influence of irradiation received by the bone marrow is observed on intestinal mortality. Results are best explained by postulating the release of humoral factors in the irradiated abdomen that have an abscopal effect on small intestinal structures. This hypothesis is corroborated by morphometric analysis of the small intestine after irradiation. Specimens obtained 3, 5, 8 and 11 days after irradiation of the abdomen only indicate that in the shielded intestine an increase in the intestinal circumference occurs as well as cell loss and shrinkage of villi of the proximal small intestine, and elongation and increased cell number in the villi of the distal small intestine. The radiation response develops faster in the proximal small intestine and is predominantly expressed in villus length. In the distal small intestine, the most pronounced radiation effect is a decrease in the number of crypts per millimeter. Overall, the results point out the unsuspected complexity of the radiation response of the small intestine. After radiation accidents, the dose received by proximal small intestine, distal small intestine and abdomen need to be determined separately for an accurate assessment of the anticipated morbidity or mortality. The results again emphasize that, in addition to the small intestinal crypt stem cell, other factors do influence radiation-induced intestinal mortality and morbidity, and that bone marrow is not one of these factors. The chemical identification of humoral factors involved in the radiation response of the small intestine will be of great relevance to improving the therapeutic ratio of new radiation oncology protocols that incorporate significant volumes of small intestine in the field.
Radiation Oncology, Biology, Physics October 1990, Volume 19, Supplement 1
64 VOLUME
EFFECTS
E.L. Gillette, Radiology
ON CANINE
SPINAL
CORDFUNCTION
S. McChesney Gillette,
and Radiation
Biology,
VOLUME
G. Childs,
Colorado
EFFECTS
M. Ritt,
B. Powers
State University
ON CANINE SPINAL CORD FUNCIION
EL. Gillette, S. McChesney Gillette, G. Childs, M. Ritt, B. Powers Radiation myelopathy is one of the most serious late effects of radiotherapy. The length of spinal cord irradiated is suspected to influence the incidence of myelopathy, however, little is known of the magnitude or mechanism of this effect. The functional effects of irradiation of canine thoracic spinal cord to a length of 20 cm versus 4 cm is the subject of this presentation. The 20 cm field encompassed nearly the entire thoracic cord (Tl-T12). The 4 cm field was positioned at the mid thoracic cord (T6). Irradiation was given in 4 Gy fractions over 4 weeks. Total doses of 44 to 68 Gy were given to the 20 cm field while dogs irradiated with a 4 cm field received doses between 48 to 80 Gy. The functional response was evaluated by monthly physical neurologic examinations and by electrophysiologic studies. Electrophysiology was done at the end of irradiation and at 6 months and 1 year after irradiation. Dogs were evaluated for pain in the thoracic or low cervical region following neck flexion. Moderate to severe pain over the thoracic cord was a common occurrence and first appeared at 2 to 3 months. The ED5 for pain was approximately 55 Gy for the 20 cm field and 66 Gy for the 4 cm field. This early delayed response is thoug g t to be similar to Lhermitte’s sign of humans. At 6 months only three dogs had shown delayed radiation myelopathy. This occurred at doses of 68 Gy given over a 20 cm length of spinal cord. Two of these dogs had bilateral hind limb paralysis, the third had paresis. Spinal cord evoked potentials were evaluated for conduction velocity and wave amplitude and configuration. Recordings were made from irradiated and nonirradiated portions of spinal cord. No abnormalities in spinal cord evoked potentials were found immediately after treatment in any dogs. One dog with bilateral paralysis and one dog with paresis had decreased conduction velocities at the time of onset. Evoked potentials were not measured in the second dog with paralysis because it was a control for this procedure. In previous studies myelopathies continued to develop to 1 year. The EDSO for radiation myelopathy for the entire thoracic cord given in 4 Gy fractions over four weeks was 56 Gy at one year. The latent period for radiation myelopathy tends to decrease with increasing dose. These preliminary observations indicate a volume effect on the response of spinal cord to irradiation. A dose of approximately 11 Gy greater was required for evidence of an early delayed response when the irradiated length has reduced from 20 to 4 cm. This study is continuing to observe for the influence of irradiated length on later developing myelopathies.
65 EFFECTS
OF IRRADIATION
R.M. VIGNEULLEI,
H.M.
OF EXTERIORIZED VRIESENDORP12,
SMALL
INTESTINE
G. KITTOI, Institute 1 ,
T. PELKEYl,
P. TAYLOR3,
AND J. SMITHI.
Armed Research orces Radiobiology Bethesda, Maryland, Johns Hopkins Oncology Center f Baltimore, Maryland and Department of Radiation Medicine, Georgetown University Hospitai3, Washington, D.C. 20007. Small intestine of Sprague-Dawley rats can be exteriorized and irradiated in a homogeneous manner with 18 MVp photons. Survival times after irradiation of the exteriorized small intestine are longer than after total body irradiation by about 4 days. The LD50 after irradiation of the exteriorized small intestine is approximately 6 Gy higher than after total body irradiation. The addition of a 5 X 5 cm abdominal radiation field to the radiation field used for the exteriorized intestine reduces survival times to the values found after total body irradiation. The higher the amount of radiation received by the abdomen, the closer the survival time will be to the one observed after total body irradiation. The addition of radiation fields to the thoracic or pelvic areas does not alter the survival time observed after radiation of the exteriorized intestine. No influence of irradiation received by the bone marrow is observed on intestinal mortality. Results are best explained by postulating the release of humoral factors in the irradiated abdomen that have an abscopal effect on small intestinal structures. This hypothesis is corroborated by morphometric analysis of the small intestine after irradiation. Specimens obtained 3, 5, 8 and 11 days after irradiation of the abdomen only indicate that in the shielded intestine an increase in the intestinal circumference occurs as well as cell loss and shrinkage of villi of the proximal small intestine, and elongation and increased cell number in the villi of the distal small intestine. The radiation response develops faster in the proximal small intestine and is predominantly expressed in villus length. In the distal small intestine, the most pronounced radiation effect is a decrease in the number of crypts per millimeter. Overall, the results point out the unsuspected complexity of the radiation response of the small intestine. After radiation accidents, the dose received by proximal small intestine, distal small intestine and abdomen need to be determined separately for an accurate assessment of the anticipated morbidity or mortality. The results again emphasize that, in addition to the small intestinal crypt stem cell, other factors do influence radiation-induced intestinal mortality and morbidity, and that bone marrow is not one of these factors. The chemical identification of humoral factors involved in the radiation response of the small intestine will be of great relevance to improving the therapeutic ratio of new radiation oncology protocols that incorporate significant volumes of small intestine in the field.