DISCLAIMER

The following is a staff memorandum or other working document 
prepared for the members of the Advisory Committee on Human
Radiation Experiments.  It should not be construed as representing
the final conclusions of fact or interpretation of the issues. 
All staff memoranda are subject to revision based on further 
information and analysis.  For conclusions and recommendations of
the Advisory Committee, readers are advised to consult the Final
Report to be published in 1995.


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MEMORANDUM

TO:       Advisory Committee on Human Radiation Experiments

FROM:     Advisory Committee Staff 

DATE:     March 27, 1995

RE:       Nasopharyngeal Radium Treatment
______________________________________________________________________


     The attached material is intended to provide Committee members 
with information and documentation needed to prepare for a discussion 
of nasopharyngeal radium treatment at the April Committee meeting.  
The following memorandum is a capsule description of the issue:  

     In the early 1940s seven-hundred and thirty-two submariners were 
subjects of a controlled experiment designed to test whether radium 
could be used to shrink lymphoid tissue surrounding the eustachian 
tubes thereby equalizing external and middle ear pressure.  In a 
February 23, 1994 memorandum the Navy characterized this experiment as 
"research evaluations of radium in the prevention and treatment of 
aerotitis media in submariners."1 [Memorandum from Commanding Officer, 
Naval Submarine Medical Research Laboratory, to Chief, Bureau of 
Medicine and Surgery, February 23, 1994. Subject: "Human Radiation 
Research Review."] (Attachment 1) The treatment, which had previously 
been used among other things to treat deafness in children, was 
successful in nine of ten cases.2 [Haines, HL, Harris, JD. "Aerotitis 
Media in Submariners,"  Annals of Otology, Rhinology and Laryngology, 
1946; 55:347-371.] (Attachment 2). Similar treatment was administered 
to 6,881 airmen.  In a 1945 journal article it was noted that a 
controlled study was considered by the Army Air Forces, but rejected 
because of the urgent need to treat fliers immediately and keep them 
flying.3 ["The use of radium in the aerotitis control program of the 
Army Air Forces.  A combined report by the officers participating,"  
Annals of Otology, Rhinology and Laryngology, 1945; 54: 650-724.] 
(Attachment 3) Tens of thousands of servicemen were subsequently 
given this nasopharyngeal radium treatment.  

     Nasopharyngeal irradiation using intranasal radium applicators 
(or glass ampules of radon) was employed  from 1924 on as a means of 
shrinking lymphoid tissue at the entrance to the eustachian tubes to 
treat middle ear obstructions, infections and deafness.  The treatment 
was introduced by Crowe and Baylor and over a quarter century came to 
constitute standard treatment.  It was used as a prophylaxis against 
deafness, for relieving children with recurrent

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adenoid tissue following tonsillectomy and adenoidectomy, and for 
children with chronic ear infections.  Others considered candidates 
for irradiation were asthmatic children with frequent upper 
respiratory infections.

     At Johns Hopkins Otolaryngology clinic 150 patients (mostly 
children) a month were treated with radium applicators over several 
years.4 [Crowe, Samuel J.  "Irradiation of the Nasopharynx," Annals of 
Otology, Rhinology and Laryngology, 1946; 55: 779-788; Sandler, Dale 
P. et al. "Neoplasms Following Childhood Radium Irradiation of the 
Nasopharynx," JNCI, 1982; 68: 3-8.] (Attachment 4) Treatments 
extended over a total span of about 25 years.  Many children received 
treatment more than once as recurrent lymphoid tissue was considered 
an indication for treatment.  In 1948 Crowe observed that more than 
1,000 radium applicators were in use throughout the United States.  
Carcinogenesis was not considered a long-term risk of nasopharyngeal 
radium treatments at this time.  It is likely that the use of this type 
of therapy was discontinued because of newly available antibiotics and 
the use of transtympanic drainage tubes.

     Efficacy:  Crowe and colleagues in various review articles 
reported that about 85 per cent of treated patients responded with 
decreased numbers of infections and/or improved hearing when treated 
at young ages.  Staff has been unable to find a controlled study 
showing these results.

     Radiation Risk:  Relying on a risk estimate by Dale P. Sandler 
et al5[Sandler, Dale P. et al. "Neoplasms Following Childhood Radium 
Irradiation of the Nasopharynx," JNCI, 1982; 68: 3-8.] (Attachment 5) 
Stewart Farber, a radiation-monitoring specialist with a background in 
public health, has  projected 51.4 excess brain cancers over a 50-year 
period in the 7613 servicemen irradiated in the Navy and Army Air 
Forces studies noted above.6 [Letter to Stephen Klaidman from Stewart
Farber, March 8, 1995.] (Attachment 6) Alan Ducatman, MD, of the 
University of West Virginia School of Medicine, who coauthored a 
letter with Farber to New England Journal of Medicine regarding the 
radium exposure of military personnel,7 [Ducatman, Alan M. and Farber, 
Stewart A. "Radium Exposure in U.S. Military Personnel," New England 
Journal of Medicine, 1992; 326: 71+72.] (Attachment 7), wrote to 
Committee Staff that he found "no convincing evidence of excess 
cancer in the exposed population."  He added, however, "there is
also no good evidence for the null hypothesis."8 [Letter to Duncan T
homas from Alan Ducatman, February 22, 1995.] (Attachment 8) 
E. W. Webster, also a health physicist and a  consultant to the

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Advisory Committee, offers the following analysis of the Sandler 
study and a larger Dutch study9 [Memorandum to Ron Neumann from 
E. W. Webster, August 6, 1994. Subject:  "S. Farber investigation 
of Nasopharyngeal radium applicators for treatment of aerotitis
media in military personnel."] (Attachment 9):

     1.   The number of brain tumors found was not significantly 
          elevated at the 95 perent confidence level.  The adjusted 
          relative risk is noted by Sandler as 0.87 > infinity.  The 
          lower limit is less than 1.

     2.   The subjects of Sandler's study were children, average age 
          11, whereas the military personnel were adult.  There is 
          epidemiologic data indicating that the relative risk of 
          cancer following irradiation is higher in children than in 
          adults.  Commonly a factor of two or more is given.

     3.   There is no significant elevation of brain cancer in 
          Japanese A-bomb survivors inboth mortality and incidence 
          studies.  For example, in the 1994 Thompson study among 
          males of all ages the excess relative risk is 0.26 with 95 
          per cent confidence limits -0.23 to +1.27.  For males in the 
          20-39-year age group the excess relative risk (ERR) was zero 
          for 10 cases found.  However, for children up to 9 years 
          old, the ERR was 1.72. 

     4.   In the Verduijn (Dutch) study of 2500 children irradiated 
          with radium applicators no cases were found.10 [Verduijn, 
	  Peter G. et al. "Mortality After Nasopharyngeal Nasal 
   	  Irradiation for Eustachian Tube Dysfunction," Annals of 
	  Otology, Rhinology and Laryngology, 1989; 98: 839-844.] 
	  (Attachment 10) Allowing for the smaller radiation doses 
	  (20 mg. hrs. vs. 70 mg. hrs), the larger study group and 
	  the longer follow up, 2.65 brain deaths would be expected 
	  based on Sandler instead of the zero actually found.  
	  However, there is no significant difference from zero in 
	  this expectation either.

     5.   In BEIR V11 ["Health Effects of Exposure to Low Levels of 
	  Ionizing Radiation," BEIR V, 1990, 324-325 and 310-313.] 
	  (Attachment 11) there are seven studies reported, six of 
	  which relate to children.  The largest studies are two of 
	  Israeli children whose scalps were irradiated for ringworm 
          treatment. The excess risk in these two studies are listed 
          as 1.0 +  0.4 per 10,000 P-Y-GY and 0.71 + 0.2 per 10,000 
          P-Y-Gy, both considerably smaller than the range 3.4 to 9.0 
          for the Sandler study in BEIR V.


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     Webster concluded that an epidemiologic study would help define 
the risk of the treatment. Attached is a proposal from Han K. Kang, 
with the Environmental Epidemiology Service of the Veterans Health 
Administration, to conduct an epidemiologic study of Navy veterans 
who received radium treatments.12 [Kang, Han K. "Feasibility of an 
Epidemiologic Study of a Cohort of Submariners Who Received Radium 
Irradiation Treatment," August 23, 1994.] (Attachment 12) It is not 
clear, however, that sufficient numbers of treatment-documented 
personnel can be identified. (A group representing submariners has 
apparently been unable to locate more than a handful of men whose 
records indicate they received radium treatment.)  However, the 
Veterans of Foreign Wars organization apparently is now processing 
hundreds of surveys filled out by veterans who say they underwent 
nasopharyngeal radium treatment.  Once this task is completed 
Senator Joseph Lieberman of Connecticut plans to present the data 
to the Department of Veterans Affairs with a recommendation that 
an epidemiologic study be conducted.




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