Revision 1
March 19, 1998
by Radiation, Science, and Health, Inc.,
Edited by J. Muckerheide

1.2.3
Medical

1.2.3.2
Medical Patients

References

Dr. Luckey also reports (1991) on the effect of radiation on reproduction, that Female mice exposed to low doses of ionizing radiation produced more young than controls. It was found that 1458 women who had been exposed to diagnostic X-rays had 10 to 15% greater fertility than 1458 matched controls, p=0.01. The exposed women had more fetal deaths which was compensated by the fewer deaths following the live births, p<0.01. A study with over 1000 carefully matched controls showed young women who had been exposed to X-rays in utero produced significantly more babies, more living children, and more sterilizing operations than controls, p<0.001. I-131 thyroid cancer therapy did not impair subsequent fertility or cause miscarriages during adulthood.

Senior Medical Investigator Emeritus Nobel Laureate (Physiology or Medicine 1977) Dr. Rosalyn Yalow, Bronx VA Medical Center, and Solomon A. Berson Distinguished Professor-at-Large, Mt. Sinai School of Medicine, reports (1994) that: "Hyperthyroid patients treated with I-131 have about 10 rem whole-body (bone marrow) irradiation. In a study of 36,000 patients, 22,000 received I-131, with 14,000 mostly receiving surgical treatment. At 7- and 10-yr follow-ups, sufficient for leukemia effects, no difference exists in the two groups." (Saenger 1968; 1971) Another study of 10,000 patients followed for 15 yr is also negative." (Holm 1991)

Dr. Yalow reports also (1994) that: "A case control study by Linos et al (1980) of 138 cases of leukemia, which represent all known cases in Olmstead County, Minnesota between 1955 and 1974 and matched controls, revealed that there was no statistically significant increase in the risk of developing leukemia after radiation doses up to 300 rads to the bone marrow when these doses were administered in small doses over long periods of time, as in the case of routine medical care. Virtually all medical care is provided by the Mayo Clinic and one other private medical group practice and the record keeping and estimations of bone marrow dose is very reliable."

BEIR V (1990) states (p 212) in "Dose-Response Relationships", that "There is strong evidence for a flattening of the dose-response curve at high doses in all of the cohorts except the CAN-TB series [Miller 1989], in which the curvature appears to be in the opposite direction, i.e, concave upward. It has been suggested that the flattening in the dose-response function at doses in excess of 4 Gy or so is the result of cell-killing effects. However it is unlikely that this curvature is solely a result of cell-killing since ... For the fluoroscopy cohorts (MASS-TB and CAN-TB) the doses were highly fractionated and it is unlikely that any single exposure involved doses which were high enough to cause appreciable cell-killing. Even when the women who received the highest doses are excluded, it is difficult to reach firm conclusions about the shape of the dose-response function at low doses. The incidence data provide weak evidence for a negative quadratic response (p= 0.1), while the Canadian mortality data indicate evidence for a positive quadratic component when the Nova Scotia data are included in the analyses. However, after allowing for this nonlinearity, a significant difference between the risk per unit dose in the two Canadian subcohorts remains. In contrast, if one allows for this subcohort difference, the quadratic component of the dose response is not statistically significant (p = 0.5). Based upon these analyses the Committee’s preferred models for breast cancer incidence and mortality are linear dose-response models."

Professor Emeritus Myron Pollycove, MD, Laboratory Medicine and Radiology, U. California San Francisco, reports (1994, 1996) on fluoroscopy effects, that "From BEIR V 1990, breast cancer, pp 253-254: ‘The epidemiological data reveal little or no decrease in the yield of tumors when the total radiation dose is received in multiple exposures rather than in a single, brief exposure.’

Dr. Pollycove also states (1994) that in 31,710 women tuberculosis patients exposed to fluoroscopies between 1930 and 1952, the authors state ‘that the most appropriate form of dose response relation is a simple linear one.’ However, compared to the controls receiving 0 to 0.09 Gy, patients who received 0.1 to 0.19 Gy and 0.2 to 0.29 Gy had relative risks (RR) of 0.66 (p<.01) and 0.85 (p<.38). The data showing lower breast cancer with low dose, low dose rate radiation were rejected a priori by extrapolating from high dose exposures to zero despite the data. The data were rejected since the possibility of a measurable decreased risk associated with low exposures is simply claimed to be inconceivable. The highly significant decreased RR, with the highest confidence limits of the study, are not discussed, but the authors predict 900 excess breast cancer deaths from one million women exposed to 0.15 Gy. However, the data shows, with better than 99% confidence limits, that instead of causing 900 deaths, a dose of 0.15 Gy would prevent 10,000 breast cancer deaths in these one million women.

Dr. Pollycove (1996) further quotes from Miller 1989 that ‘Women exposed to 10 cGy of radiation had a relative risk of death from breast cancer of 1.36, as compared with those exposed to less than 10 cGy (95 percent confidence interval, 1.11 to 1.67; P=0.001). The data were most consistent with a linear dose-response relation. …Our additive model for lifetime risk predicts that exposure to 1 cGy at the age of 40 increases the number of deaths from breast cancer by 42 per million women.’

Dr. Pollycove also reports (1996) that in the Final Draft of UNSCEAR/Annex B submitted for approval in March 1994, paragraph 252 and the Table from Miller 1989, were subsequently deleted from Annex B, to refer to Annex A; and that Annex A includes statements that directly contradict, and misrepresent, the actual data.

Finally, Dr. Pollycove notes that NCRP 121 (1995) reports that breast cancer among Japanese atomic-bomb survivors has indicated that the dose-response curve is essentially linear. In the irradiated group with <0.5 Gy, 179 breast cancers were observed as compared with 163 expected. A statistically significant dose-response trend is seen over the range 0.2 to 0.5 Gy, and the trend was suggestive, but not statistically significant for the dose range up to 0.2 Gy. …and that ‘similar results were found in a large multiple fluoroscopy study of 31,700 women in Canada, where a linear dose-response provided a good fit with a risk estimate comparable with other breast-irradiation studies. An excess was evident over the entire dose range, including doses below 0.4 Gy. The data are supportive of an interpretation that low doses or fractionated doses have a substantial degree of additivity of their effects upon breast cancer risk. The data for breast cancer from x-ray irradiation, perhaps more than any other human cancer, supports the notion of a dose-response relationship that is a linear function of dose and largely independent of dose rate or fractionation, thus supporting the concept of collective dose.’ These conclusions are unsupported by, contrary to, and substantially misrepresent, the actual data.

BEIR V (1990) states (p 288) in "Cancer at Specific Sites, Thyroid Cancer" reports on patients given I-131 in therapeutic applications: and for patients given I-131 in diagnostic applications, that do not support the linear model, concluding: "In summary, the results of these studies do not support the conclusion that diagnostic doses of I-131 significantly increases the risk of thyroid cancer. (Holm 1988)"

Senior Medical Investigator Emeritus Nobel Laureate (Physiology or Medicine 1977) Dr. Rosalyn Yalow, Bronx VA Medical Center, and Solomon A. Berson Distinguished Professor-at-Large, Mt. Sinai School of Medicine, further states (1994) that "Before 1968, 1 to 3 million US patients received I-131 thyroid diagnosis. A Swedish 20-yr follow-up of about 35,000 patients, 5% exposed at <20 yr old, with a mean thyroid dose of 50 rem, found that patients diagnosed for reasons other than a suspected tumor, had thyroid cancers at 62% of controls ([statistically] significant)."

Professor Emeritus Myron Pollycove, MD, of Laboratory Medicine and Radiology, UCSF, also on thyroid cancer, reports (1995) that: ICRP 60, UNSCEAR 1988 and BEIR V agree that NCRP 80 presents current thyroid risks. ICRP 1990 states that cancer risk from external radiation is estimated for high doses and extrapolated to low doses by presuming the linear response, and I-131 thyroid cancer risk is about one-fourth to one-third as effective as external radiation. However, UNSCEAR states that for ‘A combined analysis of nearly 47,000 Swedish patients given I-131 for thyroid cancer, for hyperthyroidism or for diagnostic purposes no clear association of cancer induction by radiation was evident in the analysis.’ NCRP 80 concludes, ‘I-131 has not been shown to be carcinogenic in people.’ ICRP circumvented this ‘problem’ by assuming the number of thyroid cancer cases at the upper limit value of uncertainty. A decade later these studies continue to show no excess cancer or leukemia in 35,074 patients given diagnostic doses, including 2,000 under the age of 20, and another 12,000 patients given therapeutic doses of I-131. This larger number of patient-years has reduced the upper limit of relative effective carcinogenicity of I-131 compared to external radiation from 1/3 to 1/17. However, to reach zero in this manner, an infinite number of patients is required.

From the Abstract, in Radiation Research, Lundell and Holm, 1996, report that 14,624 infants irradiated for skin hemangiomas located all over the body, had a weighted bone marrow dose average of 0.13 Gy. From 1920-1986, 20 leukemia deaths were observed vs. 17 expected, with no significant associations between childhood leukemia and radiation dose. Despite the relatively large number of infants, the low average dose to bone marrow limited the possibility of detecting a small radiation risk as might be predicted from other radiation studies.

From the Abstract, in the Journal of the American Medical Association, Boice et al, 1991, report on medical X-rays and the risk of leukemia, non-Hodgkin’s lymphoma (NHL), and multiple myeloma. Adults with leukemia, NHL, and multiple myeloma were matched to controls, with over 25,000 x-ray procedures abstracted from medical records. X-ray exposure "was not associated with" chronic lymphocytic leukemia, which has never been linked to radiation, a relative risk (RR) of 0.66, [indicating a possible beneficial effect.] Other leukemia combined had a slight risk (RR, 1.17) but no dose-response relationship. Patients with NHL had an RR of 0.99 with a 2-year lag. For multiple myeloma, overall risk was not significantly high (RR, 1.14), with increasing risk with increasing numbers of diagnostic x-ray procedures. Persons with leukemia and NHL undergo x-ray procedures frequently just prior to diagnosis related to their disease. There was little evidence that diagnostic x-ray procedures were causally associated with leukemia or NHL, but multiple myeloma was increased among patients frequently exposed to x-rays.

From the abstract, Dr. Michael Hawkins et al report on childhood cancer radiotherapy effects, in the Journal of the National Cancer Institute, 1996, that individuals with childhood cancer are at higher risk of developing bone cancer than any other type of second primary cancer. In 13,175 3-year survivors of childhood cancer diagnosed between 1940 and 1983, there were 55 subsequent bone cancers. The cumulative dose of radiation received at the site of the second bone cancer in the case subject and at the corresponding anatomic site in the matched control subjects, and the cumulative dose of alkylating agents and vinca alkaloids received by case and control subjects were studied. The 3-year survivors developing bone cancer within 20 years did not exceed 0.9%, except following heritable retinoblastoma (7.2%), Ewing’s sarcoma (5.4%), and other malignant bone tumors (2.4%). The risk of bone cancer increased substantially with increased cumulative dose of radiation to the bone (P <0.001, linear trend). At the highest levels of exposure, however, the risk appeared to decline somewhat (P=.065, nonlinearity). Exposure to <10 Gy was, at worst, associated with only a small increased relative risk (RR) of bone cancer (RR = 0.7; 95% CI= 0.2-2.2). Bone cancer risk increased linearly (P=0.04, one-tailed test) with increased cumulative dose of alkylating agents. This population-based study provides grounds for reassurance of the majority of survivors in that their risk of developing bone cancer within 20 years of 3-year survival did not exceed 0.9%.

Dr. Y. Ishikawa, Dept. of Pathology, Cancer Institute; Dr. Y. Kato and Dr. T. Mon of the National Institute of Radiological Sciences and Dr R. Machinami of the Deptartment of Pathology at the University of Tokyo report (1997) on thorotrast patient health effects that the widely accepted concept that radon (Rn-222, Rn-220) induces lung tumors in humans is based on excess lung cancers observed in underground miners. However, such miners were also heavily exposed to mine dusts including silicates, diesel exhaust, etc. in their environment. Patients to whom Thorotrast was administered continuously exhale radon (Rn-220) derived from Th-232 in the body and therefore provide a model for lung carcinogenesis by radon without dust exposure. We measured both body Th-232 burden and exhaled Rn-220 in Thorotrast patients, and analyzed lung tumors in Thorotrast patients histopathologically. The radioactivity of Rn-220 in the breath of a standard Thorotrast patient (25 cGy/yr to the liver) is 28,000 Bq/m³. The ratio of death due to lung cancer was only 1.8, with no statistically significant increase.