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Nasopharyngeal Radium Irradiation

Between the 1920s and 1960s, two types of radiation therapy, external beam and nasopharyngeal (NP) radium, were considered good medical practice and effective treatment for a number of medical problems of the head and neck. In the 1960s and 1970s, concerns were raised that these treatments may have inadvertently exposed people to an excess risk for head and neck cancers. Information about these two types of radiation therapy follows:

External Beam Radiation Therapy

Between the early 1920s and the 1960s, external beam radiation therapy had been considered good medical practice and effective treatment for such conditions as ringworm of the scalp, enlargement of the thymus gland, deafness due to lymphoid tissue around the eustachian tubes, enlargement and inflammation of the tonsils and adenoids, and acne. Radiation was often the only method of treatment for some of these conditions before antibiotics became available. It was estimated that more than a million people might have been exposed, as children or young adults, to these treatments.

In the 1960s, a link was recognized between this form of radiation therapy and thyroid cancer. As a result, in 1977, the National Cancer Institute (NCI) conducted a nationwide campaign to inform physicians and the public about the risks of irradiation related thyroid cancer and how exposed patients should be monitored, examined, and treated, if tumors developed.

Nasopharyngeal Radium Therapy

NP radium radiation, introduced in the United States in 1926, was a treatment used to shrink swollen lymphoid tissue in the nasopharynx region near the back of the nose, especially in children. Typically, treatment in the United States consisted of inserting two cylinders, each containing 25 milligrams of radium sulfate, in nasopharyngeal openings for three sessions of 8.5 minutes each.

Many physicians during the 1940s and 1950s thought that conditions such as hearing loss, chronic ear infections, and middle ear problems could be treated more effectively with NP radium therapy than with surgery. It has been estimated that anywhere from 500,000 to 2 million people may have received NP radium treatment, many of them military submariners and aviators with aerotitis, a condition produced by air pressure changes in the middle ear.

By the 1960s, reports by both the National Academy of Sciences Committee on the Biological Effects of Atomic Radiation and the British Medical Research Council had raised general concerns that use of radiation therapy might have adverse, long-term effects such as increased cancer risk. Also, effective antibiotic regimens and better surgical methods reduced the demand for all types of radiation treatment for head and neck conditions. Use of NP radium treatments stopped when side-effects and concerns about cancer arose. Reports of cancer due to treatments with external doses of X-rays had started to emerge and concern grew that NP radium treatments might also cause cancer.

Worldwide studies conducted during the past two decades are somewhat contradictory on the effects of NP radium irradiation, but no studies have definitively linked NP radium exposure to any disease. A professional panel convened in 1996 concluded that, based on all available evidence, screening or testing of asymptomatic persons who had been exposed to NP radium treatments is not warranted, because the evidence did not suggest a very high level of radiation-related disease and because the effect of medical intervention for false-positive results might be more harmful than NP radiation.

Given the concern and lack of definitive findings regarding adverse effects of NP radium irradiation, new data are being gathered to try and resolve some of the complexities surrounding the possible link between NP radium irradiation and disease. These studies focus on patients treated as children, who are thought to be the most vulnerable group. One study is a longer follow-up of a group of people previously studied at the John Hopkins University in Baltimore. A second study is following a group of patients in the Netherlands for an additional 10 years, with support and collaboration from the NCI and the Centers for Disease Control and Prevention (CDC). The NCI/CDC study should complete its data gathering phase in 1999 with analysis and results available by the year 2000.

Nasopharyngeal radium studies: A selected literature overview

From studies of various populations exposed to high levels of ionizing radiation, it is well established that many tissues and organs are susceptible to cancer induction associated with radiation exposure (NAS 1990, UNSCEAR 1994, Boice et al, 1996). These include the brain, salivary glands, and thyroid gland, which are located close enough to the region of nasopharyngeal irradiation to receive non-negligible doses, although vastly smaller than those to the intended target tissue. In addition to case reports (Sandler et al., 1982; Katz & Preston-Martin, 1984; Soffermann & Heisse, 1985), three epidemiological studies evaluated cancer risk associated with this treatment. Hazen et al. (1966) reported on 417 children who had been treated for lymphoid hyperplasia of the nasopharynx (65 percent), deafness (22 percent), ear infection (8 percent), and other conditions (5 percent) using 25 mg of radium (300-600 mg-min), compared to an X-ray treated group of 971 children and a control group of 2,746 non-exposed siblings of children in the two exposed groups. In a follow-up period averaging 14.6 years, two malignant and five benign tumors were diagnosed in the radium-treated group, about what would have been expected from the 10 malignant and 23 benign tumors in the control group; eight malignant and six benign tumors were observed in the group treated by X-ray.

Sandler et al. (1982) reported four malignant and 19 benign incident tumors of the head and neck among 904 radium-treated children (50 mg in each applicator, 12 minutes, three treatments; usual exposure 4,208 mg-min) in an average follow-up time of 25 years, compared to no malignant and 23 benign tumors in 2,021 non-irradiated controls. Three of the four malignant tumors in the irradiated patients were in the brain (two astrocytomas and one unknown), and the other was an undifferentiated anaplastic cancer of the soft palate. Sandler et al (1982) estimated that doses in mGy (Gy is an abbreviation for gray, a unit of absorbed radiation dose equivalent to 100 rads) to the sites of observed tumors were 440-780 for the brain, 100-200 for the soft palate, and 60-90 for the thyroid gland. Doses to the pituitary and salivary glands were estimated to be 440-1,770 and >100 mGy, respectively.

Verduijn et al (1988, 1989) studied cancer mortality among subjects who had been treated in five Dutch ear, nose, and throat (ENT) clinics, including 2,510 treated by the Crowe method (Crowe and Baylor, 1939) and 2,199 matched controls who did not receive radiation therapy. The average follow-up period was 25.3 years for the irradiated patients and 26.8 years among the controls; average radiation exposure was 1,198 mg-min (unilateral treatment was the standard in the Netherlands, whereas bilateral treatment was used on the subjects studied by Saddler et al.). Verduijn et al estimated absorbed doses of 20-70 mGy to the thyroid gland, 40-190 mGy to the parotid gland, and 100-360 mGy to the pituitary gland, almost all from gamma rays, but 36-230 Gy, mainly from beta particles, to tissue adjacent to the radium capsules.

Ninety-one percent of the subjects could be traced, and of them 150, or 3 percent of the entire cohort, had died. It was possible to trace the cause of death in 144 (96 percent) of deceased subjects. One death from head and neck cancers (including benign brain tumors) was observed in the irradiated patients and two in the controls (all three were brain tumors, of which one was benign); there were three leukemia deaths among the exposed, vs. two among the controls (Verduijn et al, 1989). In all, there were 21 cancer deaths among the exposed, and 15 among the controls.

Questionnaires were completed by 86.5 percent of subjects found alive. Sixty percent of completed questionnaires were returned after the first request, 23 percent after the second, and the remaining 17 percent were obtained by telephone or home interview (Verduijn, 1988). Tumors or suspected tumors indicated in the questionnaire were classified by the investigator as to probable malignancy, and subjects were asked for permission to verify reported tumors whose likelihood of malignancy was rated as "possible" or higher. Verification was sought from the treating physician or from hospital records. Twenty-one cancers (two brain, six other head and neck, one lymphatic and hematopoietic (L&H), four breast, and eight other) were found among the exposed, vs. 10 (two brain, one other head and neck, two L&H, two breast, and three other) among the non-exposed. The head and neck cancers included two larynx, two skin, and two thyroid cancer among the exposed, and one skin cancer among the nonexposed. Combining mortality and incidence data, estimated relative risks for the exposed subjects were 1.7 (95 percent confidence interval (CI) 1.0-2.8) for all cancers, 0.8 (0.2-10.6) for brain, 5.3 (0.6-109.) for other head and neck, 1.1 (0.3-5.1) for L&H, 1.3 (0.2-4.2) for breast, and 1.9 (0.9-4.1) for other sites.

It has been speculated (Saddler et al, 1982; Verduijn et al, 1989) that an apparent deficit of female breast cancer observed among the exposed in all three epidemiological studies may reflect effects of radiation on pituitary gland function.

References And Additional Resources:

Block, M.A., Miller, M.J., Horn, R.C. Carcinoma of the thyroid after external radiation to the neck in adults. Am Jrnl. Surg 1969;118:764-769.

Boice, J.D., Jr., Land, C.E., Preston, D.L.: Ionizing radiation. In: Schottenfeld, D., Fraumeni, J.F., Jr., Eds., Cancer Epidemiology and Prevention, 2nd. Edition, Philadelphia, J.F. Saunders, 1996, 319-354.

Bumgarner RL. Radium exposure in U.S. military personnel. NEJM 1992;326:71-72.

Clark, D.E. Association of irradation with cancer of the thyroid in children and adolescents. JAMA 1955;159:1007-1009

Crowe S.J., Baylor J.W. The prevention of deafness. JAMA 1939;112:585-590.

Ducatman A.M., Farber S.A. Radium exposure in U.S. military personnel. NEJM 1992;326:71.

Hazen R.W., Pifer J.W., Toyooka E.T., Livingood J., Hempelmann L.H. Neoplasms following irradiation of the head. Cancer Res 1966;26:305-311.

Katz AD & Preston-Martin S. Salivary gland tumors and previous radiotherapy to the head or neck. Report on a clinical series. Amer Jrnl. Surg 1984;147:345-348.

Lindsay, S., Chaikoff, I.L. The effects of irradiation in the thyroid gland with particular reference to the induction of thyroid neoplasms: a review. Cancer Res 1964;24:1099. Committee on the Biological Effects of Ionizing Radiation. 1990. Health Effects of Exposure to Low Levels of Ionizing Radiation. BEIR V., Washington, D.C., National Academy Press, 1990.

Saddler D.P., Comstock G.W., Matanoski G.M. Neoplasms following childhood radium irradiation of the nasopharynx. Jrnl. Natl. Cancer Inst. 1982,68:3-8.

Skolnick A.A., Government is in no rush to study thousands of veterans who received nasal radiation therapy. JAMA 1995;274:858-859.

Soffermann R.A. & Heisse J.W., Adenoid cystic carcinoma of the nasopharynx after previous adenoid radiation. Laryngoscope 1985;95:458-461.

United Nations Scientific Committee on the Effects of Atomic Radiation. 1994. Sources, Effects and Risks of Ionizing Radiation. Annex A. Epidemiological Studies of Radiation Carcinogenesis. E.94.IX.11 New York: United Nations.

Verduijn P.G., Late health effects of radiation for eustachian tube dysfunction. Thesis. 1988: Erasmus University Rotterdam.

Verduijn P.G., Hayes R.B., Habbema J.D.F., Looman C., van der Maas P.J., Mortality after nasopharyngeal radium irradiation for eustachian tube dysfunction. Ann Otol Rhinol Laryngol 1989;98:839-843.

Wilson, E.H., Asper, S.P., The role of X-ray therapy to the neck region in the production of thyroid cancer in young people. Arch. Intern Med. 1960;105:244-251.