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Biomedical subjects

R D Lloyd

Publications and source records attributed to R D Lloyd.

At least 37 records · Page 2Linked to original sources
PubMed1997

Comparison of internal emitter radiobiology in animals and humans.

Investigations of radionuclide metabolism and effects in various mammalian species revealed important similarities between animals and humans and between some animal species. These include skeletal deposition of radium and radiostrontium in bone volume; deposition on bone surfaces of plutonium and other actinides; liver deposition of actinides; induction of skeletal or liver malignancies by these radionuclides; induction of tooth and jaw abnormalities; mammary cancer induction by radium in humans and in the beagle; depression of circulating cells in blood; and induction of bone fractures. There are also inter-species differences that may not have been noted if multiple species (including humans) had not been studied. Some of these are more rapid excretion of radium in humans compared with most other mammals; induction by radium of eye melanomas in animals but not humans; rapid loss of deposited plutonium from liver in many species of mice and rats but not in humans and dog; substantial sex-related differences in skeletal plutonium retention and bone sarcoma induction in mice but not in humans or dog; and induction of head sinus carcinomas by 226Ra in humans but not the beagle. Leukemia and other related neoplasms were not induced in radionuclide-injected lifespan dogs in excess of the occurrence in control animals. Much of our current understanding of skeletal biology and radionuclide behavior in mammals was derived from this and related projects. The primary goal of the Utah experiment of estimating toxicities of bone-seeking radionuclides relative to radium has been accomplished. For 226Ra = 1.0, comparative toxicities (ratios) of a single injection for bone tumor induction in beagles were about 16 +/- 5 for monomeric 239Pu (32 +/- 10 for chronic exposure), 6 +/- 0.8 for 241Am, 8.5 +/- 2.3 for 228Th, 6 +/- 3 for 249Cf, 4 +/- 2 for 252Cf, 6 +/- 2 for 224Ra (16 +/- 5 for 50 weekly injections), 2 +/- 0.5 for 228Ra, and between 0.01 +/- 0.01 and 1.0 +/- 0.5 for 90Sr, depending on the dose-rate, with the lowest dose-rates approaching a ratio of zero. Corresponding ratios in mice for 226Ra = 1.0 were 16 +/- 4 for monomeric 239Pu, 5.4 +/- 2.0 for 224Ra (16 for 50 weekly injections), 4.9 +/- 1.4 for 241Am, 5.0 +/- 1.4 for 249Cf, 2.6 +/- 0.8 for 252Cf, 4.4 +/- 1.8 for 243,244Cm and about 1.0 for 90Sr at high doses, decreasing to near zero for low doses.

Animals↗
PubMed1997

Relationship of natural incidence and radiosensitivity for bone cancer in dogs.

A comparison of the risk coefficients for 239Pu- or 226Ra-induced bone cancer in two canine breeds, one with a relatively low (beagle) and the other with a very high (St. Bernard) natural incidence, indicated only slightly higher risk in the giant breed. The differences in risk for skeletal malignancy in 239Pu and 226Ra dogs were nonsignificant (p > 0.05). Likewise, the values of the 239Pu:226Ra "toxicity ratios" for these respective breeds, using bone cancer as the endpoint, were not significantly different at the 0.05 level. The anatomical distribution of the radiation-induced bone tumors tended to be a function of both the bone mass and the skeletal distribution of the radionuclide, not the site of predilection for naturally occurring bone neoplasia. Although the etiology of the higher natural incidence of bone cancer in the St. Bernard was not determined, several possible factors, including a higher osteoblastic activity level in the St. Bernards, are presented. These data suggest that making extrapolations of radiation-induced bone cancer risk from animals to humans is valid.

Animals↗
PubMed1997

Bone tumor location in dogs given skeletal irradiation by 239Pu or 226Ra.

Statistical analyses have indicated that there was a significant difference between dogs injected with bone volume-seeking 226Ra as compared to those given bone surface-seeking 239Pu with respect to location within the skeleton of 334 radiation-induced primary bone malignancies. Corresponding differences also were evident when dogs given bone volume-seeking 90Sr or bone surface-seeking 241Am, 228Th, (249,252)Cf, or 224Ra (which decays mostly on bone surfaces because of its short, 3.6 d half time) were included along with the 226Ra or 239Pu, respectively (562 total tumors). Further analysis suggested that higher values of percent red marrow (M) and bone turnover rate (R) are correlated with increased probability of tumor appearance at a particular location within the skeleton for the surface seekers. Proportionately higher values of M and R are associated with skeletal sites containing mostly trabecular bone as compared to those with mostly compact (cortical) bone. Coefficients of determination (r2) for the relationship between percent of total tumors vs the combination of percent red marrow and turnover rate (= MR) was about 0.7 for the surface seekers but only about 0.1 for the volume seekers. This indicates that the neoplastic effects of surface seekers, but not volume seekers, are associated with the presence of trabecular bone at the various sites of radionuclide deposition within the skeleton.

Aging↗
PubMed1996

Limits of fetal thyroid risk from radioiodine exposure.

An incident in which a young women became pregnant soon after being treated with 444 MBq 131 I for Graves disease prompted us to search local records for the occurrence of thyroid abnormalities among people exposed in utero to fallout radioiodine. The data base from the Utah Fallout Study (Kerber et al. 1993) indicated that there had been 480 cohort subjects for whom dose to thyroid from fallout radioiodine had been calculated and who could have received any thyroid dose before birth (2473 subjects had been re-examined in 1985-86 of the 4818 examined in 1965-70). Of these 480 subjects in this category, 403 of them could be located in the 1980's and were examined with abnormalities. Although nodules, thyroiditis, hypothyroidism and goiter were seen among the 375 persons with in utero thyroid doses from fallout radioiodine below 0.42 Gy, no thyroid abnormalities of any occurred in the 4 persons with in utero thyroid doses of 0.5 to 2.6 Gy. In addition, no neoplasia was found in any of the 403 subjects examined about 2 decades after in utero fallout exposure. These limited data do not indicate that the fetal thyroid is more sensitive than the postnatal thyroid by more than about a factor of about 4 when thyroid dose is considered and by not much more than unity when the comparison is based on dose equivalent (x ray vs. radioiodine).

Adult↗
PubMed1996

Patterns and risk factors for sprains and strain in Ontario, Canada 1990: an analysis of the Workplace Health and Safety Agency data base.

This study presents the results of analyses performed to generate hypotheses concerning the general patterns of risk factors for occupational sprains and strains, using Ontario workers' compensation data housed in the Workplace Health and Safety Agency (WHSA) data base. Historically, the largest percentage of lost-time injuries in Ontario, Canada, have been sprains and strains. In 1990, there were 171,047 compensated lost-time injuries with a known nature of injury, of which 50.43% were sprains and strains. From cross-tabulations, a number of statistics such as odds ratios (ORs), 95% confidence intervals, P values, attributable risks and number of injuries attributable, were calculated. Results indicate that occupational sprains and strains are related to the time of the day and, in particular, time into the workshift. They occur more frequently than expected (based on the occurrence of non-sprain and non-strain injuries) in the morning hours and in the first 4 hours of the workshift. They are not found to be related to the starting or ending time or the length of the workshift. They occur more frequently than expected during the early part of a week, especially on Mondays, and the early part of a year (January to May). With respect to age, workers 30 to 59 years old have an increased risk of sprains and strains, whereas workers less than 30 years of age, or 60 or more years of age, have a decreased risk. Workers who are not single, and female workers, have a higher risk of sprains and strains than expected. With respect to occupations, nurses and truckers have a higher-than-expected risk. A number of work environments and activities, such as overexertion, bodily reaction from involuntary motions, running and stretching, and slippery surfaces, are associated with a high risk of occurrence of sprains and strains. These results suggest that significant reduction in the number of occupational sprains and strains could be achieved by targeting prevention programs to reduce excess risks encountered in the first 4 hours of the workshift, on Mondays, and during the first 5 months of the year, and by workers 30 to 59 years of age, female workers, and nurses and truck drivers. It is estimated that, with proper interventions to avoid sprains and strains, a large percentage of sprain and strain injuries could be avoided each year: ie 82.49% of injuries due to bodily reaction from involuntary motions, 89.43% of overexertions in lifting objects, 84.64% of running, stretching, and related injuries, and 76.64% of injuries resulting from loss of balance on slippery surfaces. This study uses an internal comparison, ie comparing the risk of sprains and strains to the risk of all other injuries for various risk categories of interest. As a result, an increased OR may mean an increased risk of sprains and strains, or it may mean a decreased risk of all other injuries for a particular risk category. There are also limitations in the use of workers' compensation data base for epidemiologic studies. Therefore, findings in this study are only suggestive for further investigations and should await confirmations before prevention programs are designed.

Accidents, Occupational↗
PubMed1996

The biological effects of radium-224 injected into dogs.

A life-span study was conducted in 128 beagle dogs to determine the biological effects of intravenously injected 224Ra chloride. The 224Ra chloride was prepared by the same method used for intravenous injections in humans who were treated for ankylosing spondylitis and tuberculosis. Thus the results obtained from dogs can be compared directly to the population of treated humans, both for the elucidation of the effect of exposure rate and for comparison with other radionuclides for which data for humans are unavailable. Using equal numbers of males and females, the dogs were injected with one of four levels of 224Ra resulting in initial body burdens of approximately 13, 40, 120 or 350 kBq of 224Ra kg-1 body mass. A control group of dogs was injected with diluent only. All dogs were divided further into three groups for which the amount of injected 224Ra (half-life of 3.62 days) or diluent was given in a single injection or divided equally into 10 or 50 weekly injections. As a result of these three injection schedules, the accumulation of dose from the injected 224Ra was distributed over approximately 1, 3 or 12 months. Each injection schedule included four different injection levels resulting in average absorbed alpha-particle doses to bone of 0.1, 0.3, 1 and 3 Gy, respectively. The primary early effect observed was a hematological dyscrasia in the dogs receiving either of the two highest injection levels. The effect was most severe in the dogs receiving a single injection of 224Ra and resulted in the death of three dogs injected at the highest level. The late-occurring biological effects were tumors. Bone tumors were the most common followed by tumors in the nasal mucosa. The occurrence of bone tumors was highest in the dogs given the highest dose in 50 injections. The age-specific incidence rate for mammary tumors was increased in all three injection groups. The results of this study revealed two important exposure-rate effects. Hematological dyscrasia was amplified by delivery of relatively high doses at a high exposure rate. In contrast, bone tumors were amplified by delivery of relatively high doses at a lower exposure rate (i.e. dose delivered over 1 year rather than 1-3 months). There was a dose-response relationship for the induction of nasal mucosal tumors and mammary tumors. These findings in dogs are similar to those in humans injected with 224Ra, except for the nasal tumors. The calculated risk of developing a bone tumor was about 40 times higher in dogs than reported for humans.

Animals↗
PubMed1995

Soft tissue tumors in beagles injected with 241Am citrate.

The occurrence of soft tissue tumors has been studied in 117 beagles assigned to 8 dosage groups of between 2 and 26 animals each and injected with 0.07 to 104 kBq 241Am kg-1 as the citrate. In addition, 133 control beagles given no radioactivity were used as a comparison group. All 250 dogs were maintained under identical conditions and were observed for their entire lifespans. An important competing risk for the appearance of soft tissue tumors appeared to be the occurrence of skeletal malignancy, and at the highest injected activity (104 kBq kg-1), kidney and liver failure brought about the death of both of the two dogs in this group. Thyroid and liver were the only soft tissues that exhibited greater concentrations of 241Am than the skeleton. Liver tumors were associated with 241Am exposure (p < 0.001), but the thyroid tumor rate was not increased significantly in the irradiated animals (p > 0.10) as compared with the occurrence in controls. There was a greater relative occurrence of all vaginal tumors in control animals than in dogs given 241Am, a situation also found for all tumors of the pancreas, skin, testis, and mammary glands and for malignant ovarian tumors. All of these differences were statistically significant. The survival of animals given 0.07 to 0.59 kBq 241Am kg-1 could not be established (p > 0.10) as significantly different from controls, but the survival of all groups given 1.8 to 104 kBq kg-1 was decreased (p < 0.05). There was no indication in our studies of a positive association between relative exposure to 241Am and the occurrence of mammary tumors, mast cell sarcomas originating outside the liver, lymphosarcoma or tumors of marrow, including leukemia.

Americium↗
PubMed1995

The Utah Leukemia Case-Control Study: dosimetry methodology and results.

This paper discusses the dosimetry methodology used to estimate bone marrow dose and the results of dosimetry calculations for 6,507 subjects in an epidemiologic case-control study of leukemia among Utah residents. The estimated doses were used to determine if a higher incidence of leukemia among residents of Utah could have been attributed to exposure to radioactive fallout from above-ground nuclear weapons tests conducted at the Nevada Test Site. The objective of the dosimetry methodology was to estimate absorbed dose to active marrow specific to each case and each control subject. Data on the residence of each subject were available from records of the Church of Jesus Christ of Latter-day Saints. Deposition of fallout was determined from databases developed using historical measurements and exposure for each subject from each test was estimated using those data. Exposure was converted to dose by applying an age-dependent dose conversion factor and a factor for shielding. The median dose for all case and control subjects was 3.2 mGy. The maximum estimated mean dose for any case or control was 29 +/- 5.6 mGy (a resident of Washington County, UT). Uncertainties were estimated for each estimated dose. The results of the dosimetry calculations were applied in an epidemiological analysis.

Adolescent↗
PubMed1995

The Utah Thyroid Cohort Study: analysis of the dosimetry results.

Above ground testing of nuclear weapons at the Nevada Test Site (NTS) during the 1950s created radioactive fallout that was dispersed into the atmosphere and deposited over a large geographical area of the U.S. One area believed to have received a considerable amount of exposure to radioiodines (131I and 133I) in the fallout was southwest Utah and southeast Nevada. This paper describes the estimates of doses to the thyroid for a cohort of 3,545 subjects who were children during the atmospheric testing period. This group of children was examined for thyroid disease during 1965-1970 and again in 1985-1986. The cohort was made up of children who lived in three counties in 1965: Washington County, Utah; Lincoln County, Nevada; and Graham County, Arizona (originally thought to be an unexposed group). Pathway analysis was used in the dosimetry, considering exposures through the ingestion of milk and vegetables, inhalation of iodine during the passage of the fallout cloud, and external exposure. Specific data were obtained on diet (including sources and levels of milk and vegetables consumed, residence history, and lifestyle) by interviewing the parents or nearest living relative of subjects. The final dosimetry file for each member of the cohort contained specific doses to the thyroid glands and uncertainties (reported as geometric standard deviations, GSD) related to each dose estimate. The mean absorbed dose to the thyroid for subjects living in Washington County, Utah, was 170 mGy; for Lincoln County, Nevada, 50 mGy; and for those living in Graham County, Arizona, 13 mGy. The maximum dose to any subject was 4,610 mGy. There were 10 subjects who had doses greater than 1 Gy. The majority of uncertainty values calculated in this study were GSD values between 2.0 and 4.0. The results of the dosimetry were combined with the results of clinical examinations of the cohort to determine if a causal relationship exists between dose to thyroid from NTS generated radioactive iodines and the incidence of thyroid disease.

Adult↗
PubMed1995

Fission fragment relative biological effectiveness for liver tumor induction.

The risk coefficients for liver tumors as derived from 60 beagles with body burdens of 249Cf or 252Cf were used to determine the relative biological effectiveness of fission fragments relative to alpha particles. For liver malignancies the relative biological effectiveness was calculated to be about 2 +/- 3. The estimate based on the combined benign and malignant liver tumors was about 7, with a proportionately larger standard deviation of about +/- 14. Although the confidence intervals were wide, it is possible that the relative biological effectiveness of fission fragments relative to alpha particles, using liver neoplasia as the endpoint, is greater than 1.0 as compared to a value only slightly above zero when bone cancer was the lesion of interest.

Alpha Particles↗
PubMed1995

Soft tissue tumors among beagles injected with 90Sr, 228Ra, OR 228Th.

The occurrence of soft-tissue tumors in beagles given 90Sr (88 dogs), 228Ra (76 dogs), or 228Th (81 dogs) as young adults and followed throughout their lifespans was compared with that of 133 control beagles given no radioactivity. For animals injected with 228Ra, tumors of the eye were more prominent (p < 0.05) than in the controls, and soft-tissue tumors of cavities in the head (excluding the brain, mouth, and eye) were more prominent in dogs given 90Sr than in the controls (p < 0.05). There was some indication that eye tumors in animals given about 0.56 kBq 228Th kg-1 were associated with their radionuclide exposure. For tumors at a few other locations, the relative occurrence was greater (p < 0.05) in the controls. These included malignant tumors of the testis and malignant plus benign tumors of the mammae and vagina in 228Th dogs; both malignant and malignant plus benign tumors of the mouth and testis, and malignant plus benign tumors of the mammae and vagina in 228Ra dogs; and malignant plus benign tumors of the mammae in 90Sr dogs (p > 0.05 by Odds Ratio Chi Square analysis but p < 0.05 by Fisher's Exact Test). Differences in relative occurrence between radioactive dogs and controls of all other tumor types that appeared in any of the animals (notably lymphosarcoma, lymph node tumors, leukemia, mast cell tumors, liver tumors, etc.) were not statistically significant (p > 0.05). Intercurrent mortality, mainly from bone cancer, was higher in the radioactive dogs than in the controls. Mean survival was reduced in the dogs given 90Sr, 228Ra, or 228Th (13.17 +/- 2.64 y in controls, 10.95 +/- 4.06 y in 90Sr dogs, 9.07 +/- 3.61 y in 228Ra dogs, and 9.20 +/- 4.15 y in 228Th dogs). Attenuated lifespans could account, at least in part, for the relative paucity of soft-tissue tumors not induced by radiation among the groups of dogs given radioactivity and occurring near the end of life for control animals.

Animals↗
PubMed1995

Mammary tumor occurrence in beagles given 239Pu.

Comparison of 120 young adult female beagles given 0.026 to 106 kBq 239Pu kg-1 by intravenous injection and 63 comparable female control beagles showed that there were no significant differences in the risk of mammary tumor appearance between the two groups. This was the case for benign tumors only, for malignant tumors only, and for both malignant and benign tumors considered together. For malignant tumors the observed number was 73 as compared with 69 expected; for benign tumors, there were 131 observed and 126 expected; for all tumors (separate analysis, not just the addition of malignant plus benign), there were 199 observed and 199 expected. Chi-square analysis indicated that the p values for all these comparisons were > 0.05. There were 45 controls (71.4%) with any tumor vs. 67 dogs (55.8%) given Pu (95% C. I. = 46.9% to 86.2%). No significant differences could be established (Kaplan-Meier analysis) between these two groups for survival age at diagnosis of the first mammary tumor, 11.75 +/- 0.30 y for dogs given Pu vs. 11.90 +/- 0.36 y for controls. We reported previously that differences in mammary cancer occurrence had been identified between this same group of control dogs and 57 female beagles given 226Ra as young adults. The present study appears to support the earlier conclusion that something other than alpha irradiation of the skeleton (both 226Ra and 239Pu deposit in bone) seems to affect the appearance of mammary cancers, since internally deposited 226Ra does appear to induce these malignancies, possibly from initial deposition in mammary tissue of the parent radionuclide or the subsequent concentration in sensitive tissue of its radioactive progeny, 22Rn or isotopes of polonium, lead, and bismuth, which are absent in the case of 239Pu.

Animals↗
PubMed1995

Soft tissue tumors induced by monomeric 239Pu.

Individual records of soft tissue tumor occurrence (lifetime incidence) among 236 beagles injected with 239Pu citrate as young adults and 131 comparable control beagles given no radioactivity enabled us to analyze the possible effects on soft tissue tumor induction resulting from internal exposure to 239Pu. A significant trend was identified in the proportion of animals having malignant liver tumors with increasing radiation dose from 239Pu. There was also a significant difference in the relative numbers of both malignant liver tumors (3.2 expected, 22 observed) and benign liver tumors (18.1 expected, 66 observed). Malignant tumors of the mouth, pancreas, and skin were more frequent among controls than among the dogs given 239Pu as were all tumors (malignant plus benign) of the mouth, pancreas, testis, and vagina. For all other tumor sites or types, there was no significant difference for both malignant and all (malignant plus benign) tumors. Mammary tumor occurrence appeared not to be associated with 239Pu incorporation. We conclude that the only soft-tissue neoplasia induced by the intake of 239Pu directly into blood is probably a liver tumor.

Age Factors↗
PubMed1994

Skeletal malignancies among beagles injected with 241Am.

Seventy skeletal malignancies in 44 dogs were identified among 117 beagles injected as young adults with graded dosages of approximately 0.07 to 104 kBq 241Am kg-1 and maintained for lifetime observation. All of these tumors were osteosarcomas except four fibrosarcomas of bone and four chondrosarcomas of bone. Of these 117 animals, 114 survived beyond the minimum age (of 2.79 y) for radiation-induced bone cancer, and all are now dead. An expression was derived that described the dependence of percent occurrence of bone sarcoma on skeletal radiation dose of A = 0.76 + 30D, where A = percent of dogs with skeletal malignancy within any dosage group, D = average skeletal dose (< 3 Gy) at 1 y before death (average skeletal dose was calculated to the presumed start of tumor growth, which we have taken to be 1 y before death), and 0.76 represents the lifetime percent malignant bone tumor response among 132 suitable control dogs in our colony not given any radioactivity. All dosage groups with skeletal doses of > 3 Gy at 1 y before death exhibited close to 100% occurrence and appeared to be beyond the region of linearity. Therefore, they were excluded from the derivation of this expression. Similar analysis of corresponding data for beagles given 226Ra as young adults, excluding the two highest dosage groups in which the bone tumor response was approximately 100%, yielded the expression, A = 0.76 + 4.7D, (D < 20 Gy). A ratio of the coefficients in these two expressions indicates the effectiveness at low radiation doses for bone-cancer induction of 241Am relative to 226Ra, or (30 +/- 2.6)(4.7 +/- 0.47)-1 = 6 +/- 0.8. This compares to the relative effectiveness at low radiation doses that was obtained earlier for a 239Pu:226Ra toxicity ratio of about 16 +/- 5.

Americium↗
PubMed1994

Soft-tissue tumors among beagles injected with 226Ra.

A total of 409 primary soft-tissue tumors (189 malignant) occurred among 87 of 120 young adult beagles (72.5%) injected with 226Ra in eight dose levels ranging from 0.2-440 kBq kg-1 body mass, while a total of 565 primary soft-tissue tumors (208 of them malignant) were seen among 117 of 133 control beagles not given radioactivity (88%). Because the p-value for the difference in these two percentages was > 0.05, further comparisons were not made of all tumor locations or types taken together but only of the individual tumor locations or types. There was a clear excess of malignant tumors and all tumors (benign plus malignant) in the eye among dogs injected with radium (p < 0.05, p < 0.01, respectively), but the occurrence of all the other types of soft-tissue tumors was not greater in irradiated vs. control dogs (p > 0.05). This was also true for hematopoietic tumor types (including just one leukemia in a control and none in irradiated dogs) in which there was no difference between controls and dogs given radium. The following total tumors (benign plus malignant) occurred in control dogs but not in radium dogs: brain = 3, peritoneum = 1, and pituitary = 4. Malignant tumors other than leukemia appearing in control animals and not among radium dogs were brain = 2, lymph nodes = 1, adrenal = 3, uterus = 1, and pancreas = 5. Tumors that occurred in dogs given radium and not in controls were 3 mast cell sarcomas and 2 tumors of the thymus (1 malignant). Age at first tumor diagnosis for corresponding tumor types did not seem to differ (p > 0.10 or p > 0.05) between radium dogs and controls except for the eye (p < 0.05), with radium dogs being somewhat younger than controls at first diagnosis, at death, or at loss from the colony. Cox regression indicated differences between radium dogs and controls in risk of dying with specific tumors. The following tumors had p values of < 0.05 and risk ratios of > 2.2:eye, mouth (mostly melanomas), and thyroid for malignant tumors and for malignant and benign tumors together. When all sarcomas were considered as a group, there was no difference between controls and radium dogs but there was a difference for all carcinomas taken together, even when mammary tumors and eye tumors were excluded and when eye tumors alone were excluded.

Animals↗
PubMed1994

Occurrence of metastases in beagles with skeletal malignancies induced by internal irradiation.

Metastases from malignant bone tumors often are responsible for the fatal effects of these cancers. Characteristics of primary skeletal malignancies in beagles injected with bone-seeking radionuclides were studied by Thurman (1971) and summarized by Thurman et al. (1971). There were 212 tumors in 186 of these dogs for which we subsequently received information on bone tumor metastases. Evaluation of bone and soft tissue slides from these animals allowed us to compare parameters reported previously with the occurrence of grossly apparent bone tumor metastases. Data included growth-rate of the primary tumor, volume of the primary tumor at death, sex of the animal, growth period of the primary tumor, degree of calcification of the primary tumor, skeletal location of the primary tumor, cumulative radiation dose to the skeleton, dose equivalent to the skeleton, and year of death. For most of the comparisons, no significant differences could be established between dogs with and without metastases. However, tumor volume at death appeared to be correlated with probability of metastasis (p < 0.05), with the larger tumors being associated with higher rates of metastasis. Comparisons of dogs with and without metastases as a function of tumor growth-rate did not, for the most part, yield significantly different results between groups. Exceptions were when only one tumor per dog was considered for animals with multiple primary tumors and when only the tumor with the longest doubling time was included for all dogs with multiple primary tumors (p < 0.02). This effect was a result of only two tumors with doubling times > 45 d. Both had been characterized by Thurman (1971) as among the tumors with the least uncertainty in calculated doubling times. Rates of metastasis in dogs with primary tumors in paired bones were significantly higher than corresponding values of dogs with primary tumors in unpaired bones. Metastases in dogs with primary tumors in the ribs appeared to be more pronounced and those in the thoracic vertebrae appeared to be less pronounced than for animals with primary tumors in other bones as compared with the average for the whole skeleton.

Animals↗