moons Original Message-----

From: Land, Charles (NCI) [mailto:landc@exchange.nih.gov]

Sent: Monday, November 26, 2001 10:55 AM

To: Elliott, Larry J. (CDC); Neton, Jim (CDC)

Cc: Gilbert, Ethel (NCI); Smith, James M. (CDC); Hoffman, Owen (E-mail);
Duane, Betsy (NCI)

Subject: IREP

Dear Larry and Jim,

I'm writing to you today to give you some insights about our most recent
plans to modify IREP and to express my desire to collaborate in order to
achieve a consensus version of this code.

We plan to submit our PC tables revision report, and program, to NIH and
DHHS in the very near future. Our version of IREP will differ in the
following ways from the NIOSH IREP currently accessible on the web:

1) DDREF: The DDREF uncertainty distribution for breast and thyroid cancer
will be replaced by a closely similar discrete distribution, but with 5% of

the total probability shifted from DDREF values of 1 and above to the value
0.6.

This is in keeping with use of the continuous Grogan et al uncertainty
distribution for DDREF for other solid cancers, which differs from the NCRP
Report 126 uncertainty distribution by having 5% of the probability shifted
from DDREF values of 1 and above, to values between 0.2 and 1.0. By allowing
a small possibility that risk at low doses and dose rates may be higher, per
unit dose, than at high doses and dose rates, the upper uncertainty limit

for assigned share is increased.

2) Skin cancer: We asked Dale Preston, at RERF, to provide likelihood

profile estimates of the uncertainty for excess relative risk of basal cell
carcinoma for different exposure ages, and for the ERR of other non-melanoma
skin cancers, a category that is mostly squamous cell carcinoma. The ERR
estimate for the latter cancer group was negative and, because convergent
estimates could not be obtained for different exposure ages, we settled for

one without variation by exposure age. These uncertainty distributions will

be incorporated into IREP. There are only 10 malignant melanomas in the RERF
series so we did not include an estimate for that cancer. The estimate was

not inconsistent with that for basal cell carcinoma.

3) Thyroid cancer: As you know, David Kocher's report recommended an
uncertain RBE centering on 2.6 for 250 kVp X rays (low-energy photons) vs.
the higher-energy gamma ray photons like those from the Hiroshima and
Nagasaki bombs. Our thyroid cancer risk coefficients for childhood exposures
are based mostly on patients exposed to X rays while the risk coefficients

1



for adults are based mostly on A-bomb survivor data. This would suggest
defining RBE relative to low energy photons for evaluating exposure in
childhood, and relative to high energy photons for evaluating exposure to
adults.That hasn't been done before, and we will probably come up with a
compromise that adds some more uncertainty to the estimates for childhood
exposures related to cancers of the thyroid an other organs. This will not
preclude making changes later, after your public comment has come in.

4) Bone cancer : We will not include estimates for bone cancer. There are
only 15 cases in the RERF tumor registry data set; moreover, a convergent
risk estimate could not be obtained, and we are informed that death
certificate diagnoses of bone cancer in the LSS sample are unreliable (one
of the reasons why the tumor registry series has so few bone cancer cases).

While the 1985 NIH report used the excellent data set from Spiess et al on
bone sarcoma following injection of 224-Ra, this was something of a tour de
force. The risks and dose distribution are very different between this very
atypical exposure and those likely to have been experienced in occupational
and military settings, and there seemed to be no good reason for including
it again.

The current NIOSH IREP provides assigned share estimates for bone cancer and
“residual and ill-defined tumors” that are fairly close for exposure at age

20, but differ by a factor of 2 or so for exposures at age 40. This

discrepancy occurs largely because the residual tumor risk is modeled in

terms of exposure age and age at diagnosis, while bone cancer is not. | can
sympathize with your desire, and the VA's, to have a separate estimate for

bone cancer, but this appears to be beyond us just as it was for the 1985 Ad

Hoc Working Group.

1 doubt that NIOSH will object to 1) or 3), and you would get about the same
result for malignant melanoma as at present if you just used our basal cell
carcinoma risks for malignant melanoma. That's an administrative decision. |
expect that you may not agree with 4), although you would be justified in
using the residual tumor estimates.

In retrospect, we have found that our interaction with NIOSH, and with Mary
Schubauer-Berrigan in particular, was helpful to our report and our version

of IREP. Also, David Kocher's report, which | understand NIOSH commissioned,
is a substantial addition; we plan to include it as an Appendix to our

report, if this is acceptable to you.

On the whole, I think it would be better to have a common version of IREP

than to have two. However, | am also aware that more reasons for having a
separate version of the code may surface, based upon comments you receive in
the next few months. Nevertheless, | would like to extend to you my offer to
collaborate in any way possible to find common ground so as to achieve a
single version of IREP.

Yours sincerely,
Charles