Journal of the American Medical Association, Vol. 274, No. 11, p 858-859, Sept. 20, 1995.

Medical News & Perspectives - September 20, 1995


Government Is in No Rush to Study Thousands of Veterans Who Received Nasal Radiation Therapy

DESPITE LARGE gaps in the knowledge of the risks of head and neck cancers from ionizing radiation, federal authorities are in no rush to conduct an epidemiologic study of a large cohort of US veterans and others who were treated with nasopharyngeal radium irradiation from 1943 until the mid 1960s.

Some authorities estimate that during this period tens of thousands of servicemen and hundreds of thousands of children and other civilians received high doses of radiation from radium capsules inserted into their nasal passages to shrink adenoid and lymphoid tissues.

On August 29, 1994, in response to an increasing number of requests for a federal study by some scientists and veterans, the US Senate Subcommittee on Clean Air and Nuclear Regulation held a hearing on the effects of nasopharyngeal radium treatments.

To collect information to help determine what, if any, public health assessments are needed for populations who were exposed to these treatments, the Centers for Disease Control and Prevention (CDC), Atlanta, Ga; US Department of Veterans Affairs, Washington, DC; and Yale University School of Medicine, New Haven, Conn, are holding a workshop on "The Public Health Response to Nasopharyngeal Radium Irradiation" in New Haven, September 27 and 28.

Submariners and Aircrews Treated

Many who served in the US Army Air Force during World War II experienced difficulties in equalizing air pressure in their eustachian tubes when ascending or descending in the then-unpressurized cabins of military planes. US Navy submarine trainees also experienced ear pressure problems while practicing underwater escapes. The resulting trauma frequently led to otitis media. Otic barotrauma was reported in 27% of the trainees at the submarine training facility near New London, Conn, and 31% of US Army Air Force trainees tested during 1944 and 1945, says Stewart A. Farber, MPH, a consulting scientist in Pawtucket, RI, who works in environmental and radiation risk assessment.

"Radium treatment of the adenoids at the nasopharyngeal orifice of each eustachian tube was said to reduce the rate of recurrence of symptomatic otitis media among these trainees from 100% to less than 20%," he says.

Farber has been one of the most outspoken advocates for a comprehensive federal study of veterans who received these treatments.

He recently presented a poster on the need for such a study at the joint annual meeting of the Health Physics Society and American Association of Physicists in Medicine, Boston, Mass. According to Farber, servicemen typically received two to eight bilateral treatments, each lasting 8 to 10 minutes, with approximately 50 mg of the sodium salt of radium 226. The radium was contained in two commercially supplied Monel metal capsules that were inserted through the nasal passages and positioned at the pharyngeal openings of the eustachian tubes.

Farber estimates that four 10-minute irradiations resulted in a total radium exposure equivalent to 1 Ci of radium 226 in both the left and right nasal passages for 2 minutes (2 g-min). In a published letter (N Engl J Med. 1992;326:71-72), Farber and Alan M. Ducatman, MD, MSc, a former navy epidemiologist now at West Virginia University School of Medicine, Morgantown, estimated that the average radiation dose received with this protocol totaled more than 20 Gy (2000 rem), with tissues 1 cm deep receiving approximately 2 Gy (200 rem) of gamma radiation and 0.68 Gy (68 rem) of beta radiation. They similarly calculated that tissues at 2 cm received approximately 60 rem of gamma radiation and 28 rem at 3 cm.

According to a study of 6149 navy submarine trainees, 732 (12%) had received nasal radium treatment (Ann Otol Rhinol Laryngol. 1946;55:347-371). Available records indicate that nasal radium treatments of navy personnel continued through the mid 1960s, and that more than 5000 submariners may have been treated in New London alone, Farber says.

Appeals to President's Committee

In March 1995, Farber brought the US military studies on the effectiveness of nasal irradiation in treating and preventing aerotitis media in servicemen to the attention of the President's Advisory Committee on Human Radiation Experiments. The committee was established by President Clinton to investigate all radiation experiments involving human subjects sponsored or supported by the federal government from 1944 to 1974. However, the advisory committee has decided not to include these clinical trials in its list of human radiation experiments.

"American veterans have a right to know of their exposure," he says. "They may be at risk for head and neck cancers and other disorders resulting from the radiation exposure. The only long-term health study of nasal radium irradiation as practiced in the United States is not reassuring."

The study, a follow-up survey of 902 children who had received similar nasal radium treatment at a hearing loss clinic between 1943 and 1960, found that four had died of malignant head and neck tumors by 1980. Three had brain cancer and one had soft-palate cancer. According to Dale Sandler, PhD, now an epidemiologist at the National Institute of Environmental Health Sciences, Research Triangle Park, NC, and her coauthors, no such tumors were detected in the untreated clinic population (J Natl Cancer Inst. 1982;68:3-8).

Using the BIER V risk estimate derived from the study in the Journal of the National Cancer Institute, Farber says the findings suggest a 5.3-fold excess in observed brain cancer deaths (P=.014). Although there were no thyroid tumors, there was a highly statistically significant, 8.6-fold increase in Graves' disease. The increase in this disease, but not in thyroid cancer, may be due to the relatively large distance between the thyroid and the irradiation site, which was much closer to the pituitary gland, say the authors, who estimate that the pituitary would receive 51 to 207 rems in a three-treatment course.

Sandler and colleagues hypothesize that the increased incidence of thyroid disease may be related to damage to the control of thyroid-stimulating hormone resulting from pituitary irradiation. "That point alone is what makes this study so fascinating from a medical-scientific point of view," Farber speculates. "There's likely to be pituitary involvement that has other health effects besides thyrotoxicosis. When the pituitary is disturbed, you affect other things, like female sex hormones. Ovarian production of FSH [follicle-stimulating hormone] and LH [luteinizing hormone] are related to pituitary control."

Farber recognizes that the number of subjects in the study published in the Journal of the National Cancer Institute is too small to generalize the increased brain cancer risk with any confidence. However, if the study's findings as to excess risk, as stated in the BIER V report, are valid, it would predict hundreds of excess brain cancer deaths among Americans who received nasopharyngeal radium irradiation. "The number of excess brain cancer deaths predicted for any size of cohort of nasal radium-irradiated Americans would slightly exceed all excess cancer deaths due to radiation exposure observed among an equal population of atomic bomb survivors of Hiroshima and Nagasaki," he says.

"Radium nasal irradiation represents a unique biomedical issue which has been essentially ignored by government bureaucracies and the medical and scientific communities," Farber says. He estimates that at least 10 000 submariners, 10 000 US Army Air Force veterans, and 1000 family dependents of veterans received this treatment from military physicians. In addition, between 1943 and the mid 1960s, from 100 000 to as many as 400 000 other Americans received nasopharyngeal radium irradiation, mostly during childhood, from private physicians.

Indeed, during the 1960s textbooks were still recommending nasal radium irradiation to shrink adenoid tissues in children. In one such textbook, Donald F. Proctor, MD, now emeritus professor of otolaryngology, Johns Hopkins University School of Medicine, Baltimore, Md, states that hundreds of thousands of patients had been treated over more than a quarter century with no damage from irradiation ever reported. Nevertheless, "to eliminate any possible danger from excess irradiation," he recommended no more than two series of treatments (The Tonsils and Adenoids in Childhood. Springfield, Ill, Charles C Thomas; 1960:18).

Other Reasons for Study

There are other good reasons to identify and study the exposed population, Farber says. "Many veterans of nuclear submarine service may have gone on to work in the nuclear industry, for which several highly publicized epidemiologic studies suggest there is an increased prevalence of brain cancer without a clear relation to occupational dose. Radiation exposure to the head and neck from nasal radium irradiation would have been higher than from all occupational exposure. Ongoing studies of head and neck cancers among workers at nuclear facilities may be confounded by including workers who had been treated during military service."

According to Farber, the US government has failed to behave in an honest and ethical manner regarding the likely health effects on veterans that were irradiated. "A comprehensive program for the identification and medical surveillance of the radium-exposed veteran cohort is an absolute minimum federal obligation," he says. "An immediate general advisory to the nation's physicians by the CDC of potential health problems in nasal radium-exposed military and civilians is long overdue."

Government Disagrees

In a published reply to the letter in the New England Journal of Medicine, Robert L. Bumgarner, MD, then at the US Navy's Bureau of Medicine and Surgery, Washington, DC, wrote, "Although I agree that it would be ideal to follow all patients who received nasopharyngeal irradiation, a fruitful study would be difficult at best to complete."

Among the problems he cited was concern for the veterans' "rights to privacy" and the great difficulty in obtaining patient identification and exposure data. Bumgarner called the risks from these treatments relatively small and cited a follow-up study, involving 2500 patients in the Netherlands who received nasopharyngeal irradiation, that failed to find a significant overall increased risk of cancer. However, Bumgarner failed to note that the Dutch study involved patients who were treated with one-sixth the average radiation dose given to children and servicemen in the United States.

Speaking last year at the Senate subcommittee hearing, Sen Joseph I. Lieberman (D, Conn), said, "To me, the best evidence of the danger of this radium treatment is the fact that no doctor in his right mind would think of performing such a procedure today. It is our job now to correct mistakes of the past, and do all we can to warn and treat the former patients whose health and/or lives now may be at risk."

Lieberman said it is important to get the word out to former radium treatment patients and to the nation's health care providers to watch for possible health effects of the treatment. It is equally important to conduct an unbiased epidemiologic study of the long-term health consequences of radium treatment "to provide those individuals who underwent such treatments with honest, reliable information about any health effects that they may face."

RADM Harold M. Koenig, MC, USN, deputy surgeon general of the navy--who as a child received the same radiation treatment for chronic tonsillitis--testified at the hearing that he always tells his physicians about the treatment when he goes for his annual medical examination "so that they will take extra care checking out my nasopharynx to make sure that there's nothing in there that shouldn't be there."

While Koenig says the degree of risk, if any, is not yet known, he recommends that the public be informed of the need to tell their physicians if they received nasopharyngeal radiation. Health care providers should be educated about the need to look more carefully for health problems that might be caused by the radiation exposure, he says.

However, at least one radiation expert disagrees. James Smith, PhD, chief of the CDC's National Center for Environmental Health and Injury Control's Radiation Studies Branch, testified against informing the public or investing in a study at this time. Although he said that there are concerns "that need some further discussion and elaboration," he did not agree that there is sufficient information to alert medical colleagues throughout the country about any potential problem. "The studies that have been done [the Dutch study and the study in the Journal of the National Cancer Institute], are conflicting and based upon very few numbers," Smith said. "So we really can't be sure, at least for cancer, that there is a problem."

Smith warned the subcommittee about the great expense and difficulty in conducting epidemiologic studies of people exposed to "low doses" of radiation that are hard to estimate. He recommends that a feasibility assessment be conducted before committing major resources to a comprehensive study.

Doses Far From Low

However, according to Farber and Ducatman, patients who received nasal radium treatment had relatively easy-to-estimate doses that were anything but low. The total doses were near and sometimes above doses routinely used to destroy tumors.

Some government experts are arguing that it will be much too difficult to conduct a meaningful epidemiologic study. Says Farber, "If a decent study can't be done with tens of thousands of veterans and hundreds of thousands of civilians who received intense, focused radiation to the base of the brain--with localized dosimetry that's reconstructable--how can any meaningful epidemiologic radiation study be done on any cohort?"

--by Andrew A. Skolnick