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Well,
perhaps a "distortion of the authors' message", which isn't quite the
same thing as a "distortion of scientific information".
What
appears to have caught UNSCEAR's attention, more so than that of
the authors, is an elevated risk of thyroid cancer where none had
been observed before (and none would be expected -- 6000 to 10,000 rads for
gawds sake!) But, they also point out the confounding nature of the
hyperthyroid cohort itself; in particular the suspiciously short
cancer occurrence (~5 yrs) after the iodine treatment (e.g. the latency for
external exposure peaks at 15 years). So UNSCEAR is identifying both an
interesting (i.e. unexpected) result and a possible explanation -- a very
scientific thing to do.
The
complaint seems to be based mainly upon what UNSCEAR didn't say -- the
significantly low SMR and SIR for overall cancer. Calling this a
distortion of science is a serious allegation. Maybe UNSCEAR had good
reason to be less enthusiastic than the papers' authors. SMRs and
SIRs are traditionally unreliable in identifying cause and effect, particularly
with a narrow cohort like these hyperthyroidism patients. All kinds
of confounding factors could be contributing. I'll bet that a cohort
of diabetes patients will show a statistically low SMR and SIR for
overall cancer after treatments with insulin -- simply because they
have more dominant medical concerns. Same
thing with gunshot victims. That's not
necessarily what's happening here, but you get my
point.
In any
case, I see little to be gained, and a lot to lose, by casting public
off-the-cuff aspersions on the work of fellow scientists.
Jeremy
Whitlock
"A house divided against itself cannot
stand"
- Abraham Lincoln
-----Original Message-----
From:
Jerry Cuttler [mailto:jerrycuttler@rogers.com]
Sent: February 4, 2004
12:27 AM
To: Whitlock, Jeremy; ANS Member Exchange Listserv;
RAD-SCI-L; cdn-nucl-l
Subject: Re: [cdn-nucl-l] UNSCEAR distorts
scientific info? Fw: My letter to NN, Jan 2000, Re: Dose-response follow-up for
nuclear medicine I-131 therapies
The info is in the reference.
The research was carried out on patients who
had received radioiodine treatment for hyperthyroidism because of
concerns about the subsequent risk of cancer, especially in those treated at a
young age. The scientists found that the relative risk of cancer
incidence and mortality were both decreased. The values were given in
the letter to Nuclear News.
"Incidence of cancers of the pancreas,
bronchus, trachea, bladder, and lymphatic and haemopoietic systems was
lowered."
"There were significant increases in incidence
and mortality for cancers of the small bowel ... and thyroid (SIR 3.25
[1.69 - 6.25], SMR 2.78 [1.16 -6.67]), although absolute risk of these cancers
was small."
"The decrease in overall cancer incidence and
mortality in those treated for hyperthyroidism with radioiodine is reassuring.
The absolute risk of cancers of the small bowel and thyroid remain low,
but the increased relative risk shows the need for long-term vigilance in
those receiving radioiodine."
It should also be pointed out that 300 MB of
radioiodine gives the thyroid a dose of ~50,000 rad, yet "the absolute risk of
cancers of the small bowel and thyroid remain low."
UNSCEAR did not mention the
significant decrease in overall cancer incidence and mortality and did not
state that the absolute risk of thyroid cancer remains low, so the
reader receives the impression that I-131 has a significant carcinogenic
effect on the thyroid.
Dr. Jaworowski MD regards this UNSCEAR paragraph
as a distortion of the authors' message, and I tend to agree.
----- Original Message -----
Sent: Tuesday, February 03, 2004 9:51
PM
Subject: RE: [cdn-nucl-l] UNSCEAR
distorts scientific info? Fw: My letter to NN, Jan 2000, Re: Dose-response
follow-up for nuclear medicine I-131 t herapies
You'll have to provide more info Jerry. From what's been posted
here I see both UNSCEAR and the Lancet article identifying an increase in
thyroid cancer following treatment for hyperthyroidism. You asked "how
can UNSCEAR state in Para. 265 that the risk is elevated?", but I think
you're confusing thyroid cancer with overall cancer incidence &
mortality.
Jeremy Whitlock
"You couldn't fool your mother on the foolingest day of your life if
you had an electrified fooling machine."
-- Homer Simpson
Jeremy,
You state that you do not see the
contradiction, but I do and so does Professor Jaworowski (a former
president of UNSCEAR).
I refer you to the famous quotation below
about fooling people.
----- Original Message -----
Sent: Friday, December 12, 2003 12:51 AM
Subject: Re: Health effects of radiation: Making it
real
You can fool some of the people all of the time, and all of the people
some of the time, but you can not fool all of the people all of the time.
Abraham
Lincoln (1809 - 1865), (attributed)
----- Original Message -----
Sent: Tuesday, February 03, 2004
2:14 PM
Subject: [MbrExchange] RE:
[cdn-nucl-l] UNSCEAR distorts scientific info? Fw: My letter to NN, Jan
2000, Re: Dose-response follow-up for nuclear medicine I-131 t
herapies
UNSCEAR is indeed a high-grade scientific
organization, not (one assumes) given to distorting information. I
would look elsewhere for the source of apparent
contradictions.
In this case, based on the information given
below I don't see the contradiction. The UNSCEAR statement about
elevated thyroid cancer appears to be supported by the referenced paper,
as quoted in Jerry's email further down the thread?
Jeremy Whitlock
Can it be that UNSCEAR distorts
scientific information?
The scientists who authored the study
[F13] stated clearly that there was a decrease in overall cancer
incidence and mortality. How can UNSCEAR state in Para.
265 that the risk is elevated? What else did they
distort?
And I thought UNSCEAR is a high-grade
scientific organization.
Jerry Cuttler
265. Two recent studies [F13, R17] found an elevated
risk of thyroid cancer mortality following adult 131I treatment for hyperthyroidism, which is in contrast to
previous studies of hyperthyroid patients [H14] or patients examined
with 131I [H6]. The reason for referral, i.e.
the underlying thyroid disorder, could have influenced the risk, since
the highest risk was seen less than five years after exposure. The
thyroid dose (60-100 Gy)
received by most hyperthyroid patients had previously been considered
as having a cell-killing rather than a carcinogenic
effect.
----- Original Message -----
Sent: Tuesday, February 03, 2004 6:27 AM
Subject: Re: My letter to NN, Jan 2000, Re: Dose-response
follow-up for nuclear medicine I-131 therapies
Dear Jerry,
You may be interested in seeing how
skilfully the consultant of UNSCEAR distorted the information from
the Birmingham study. See paragraph 265, in page 497, Annex J,
UNSCEAR Report 2000.
Best wishes,
Zbigniew
----- Original Message -----
Sent: Saturday, January 31,
2004 12:40 AM
Subject: My letter to NN, Jan
2000, Re: Dose-response follow-up for nuclear medicine I-131
therapies
Jim, see my letter to Nuclear News of
2000 Jan 31:
When I think about the linear
no-threshold (LNT) hypothesis of radiation carcinogenesis, I am
reminded of the famous quotation: "The great tragedy of science is
the slaying of a beautiful hypothesis by an ugly
fact."2
How can the LNT hypothesis continue to be an exception to
this fundamental requirement of science? Are political, social and
economic considerations preventing us from opening our minds to a
different hypothesis?
The University of Birmingham study of
radioiodine treatment of hyperthyroidism, recently published in The
Lancet,3 provides yet another of the hundreds and
hundreds of ugly facts that contradict the LNT
hypothesis.4
This study of 7414 adult patients, treated in Birmingham UK
between 1950 and 1991 with a mean cumulative dose of 308 MBq of
iodine-131, identified 638 cancer diagnoses and 448 cancer deaths in
1971-91 among the treated patients. This was compared with
National Statistics data on cancer incidence and mortality for
England and Wales, specific for age, sex and period: 761 and
499. The standardized
incidence ratio is 0.83 [95% confidence interval 0.77-0.90] and the
standardized mortality ratio is 0.90 [0.82-0.98]. "There were increases in
incidence and mortality for cancers of the small bowel and thyroid,
although the absolute risk of these cancers was small." The scientists concluded,
"The decrease in overall cancer incidence and mortality in those
treated for hyperthyroidism with radioiodine is reassuring."
It certainly is reassuring when we
realize that a dose of 308 MBq corresponds to ~280 mSv (or 28 rem)
to the whole body.5
This is more than ten times the average dose of 15 mSv
(or 1.5 rem) received by the evacuees from the 30-km zone around the
Chernobyl disaster.6 According to the radiation
hormesis model,4 a dose below the NOAEL point stimulates
a protective response and results in overall beneficial
effects. If the dose is
above this point, defense mechanisms are weakened and overall
adverse effects result.
I just can't get over the irony of this
situation. We design,
build and operate each of our nuclear plants to keep its likelihood
of a severe accident below once in a million years. And if this event actually
did occur, the doses to people outside the plant would likely be
beneficial! Yet we
continue to use the LNT hypothesis, and most people associate every
nuclear activity and incident with their likelihood of getting a
cancer, and they are just terrified of cancer.
Can we expect the prospects for
nuclear power to improve as long as LNTH continues to thrive?
Sincerely,
Jerry Cuttler
References:
2.
Huxley TH (1825-95), "Collected Essays 1893-94
Biogenesis and Abiogenesis."
3.
Franklyn JA, Maisonneuve P, Sheppard M,
Betteridge J and Boyle P, "Cancer incidence and mortality after
radioiodine treatment for hyperthyroidism: a population-based cohort
study," The Lancet 353,
1999 June 19, pp 2111.
4.
Calabrese EJ, Baldwin LA. "Radiation hormesis:
origins, history, scientific foundations," BELLE Newsletter 8:2, University of
Massachusetts, School of Public Health, Amherst, MA 01003, 1999
December. See also
http://www.belleonline.com/home82.html
5.
Eisenbud M, "Environmental Radioactivity,
2nd Edition," Academic Press, New York, 1973, pp 421-425.
6.
"Chernobyl - ten years on: radiological and
health impact," an appraisal by the NEA Committee on Radiation
Protection and Public Health, Nuclear Energy Agency, Organisation
for Economic Co-operation and Development, 1995 November, pp
47.
-----------------------------------------
----- Original Message -----
Sent: Friday, January 30,
2004 11:05 AM
Subject: Dose-response
follow-up for nuclear medicine I-131 therapies
Friends,
Please
review the following abstract for the significance of measured
acute and late effects, as chromosomal damage, of I-131
therapies.
What
are dose conversion estimates (whole body, not thyroid) for
300-3700 MBq doses?
This
study is one of the very few studies that have been conducted to
measure human biological responses in the 10s of millions of
patients that are exposed to nuclear medicine procedures. (The
primary interest is in diagnostic procedures. I have not
distributed various papers on P-32 for polycythemia vera because
it is fundamentally high-dose therapy. I-131 is also, but the
high dose is to the thyroid with a low to moderate dose to the
whole body - with epi follow-up as reported in our early studies
by Rosalyn Yalow and others, primarilty from work by Las-Erik Holm
and others from Swedish data.)
The failure to conduct dozens of such studies to
follow human biological responses from injection and ingestion of
radionuclides in the face of the "LNT debate" is unfortunate, if
not unforgivable. I invited Dr. Carretta, as past president
of the SNM, to address this in our Nov 2000 sysmposium on medical
applications, but he then did not do so.
Do you
know of any other such studies that are being
conducted?
I do
not have access to this journal. I would appreciate a copy and any
comments on the significance of this study to the assessment
low-dose response.
Thank
you.
Regards, Jim Muckerheide
====================
Eur J Nucl Med Mol Imaging. 2004 Jan 28 [Epub ahead of
print]
Iodine-131 treatment and chromosomal
damage: in vivo dose-effect relationship.
Erselcan
T, Sungu S, Ozdemir S, Turgut B, Dogan D, Ozdemir
O.
Department of Nuclear Medicine, Cumhuriyet
University School of Medicine, P.K. 806, Sivas,
Turkey.
Although it is well known that radiation induces
chromosomal aberrations, there is a lack of information on the in
vivo dose-effect relationship in patients receiving iodine-131
treatment, and the results of previous studies are controversial.
In this study, the sister chromatid exchange (SCE) method was
employed to investigate acute and late chromosomal damage (CD) in
the peripheral lymphocytes of 15 patients who received various
doses of (131)I (259-3,700 MBq), either for thyrotoxicosis (TTX)
or for ablation treatment in differentiated thyroid cancer (DTC).
The SCE frequencies in cultured peripheral lymphocytes were
determined before treatment (to assess basal SCE frequencies), on
the 3rd day (to assess acute SCE frequencies) and 6 months later
(to assess late SCE frequencies). The basal, acute and late SCE
frequencies (mean+/-SD) were 3.19+/-0.93, 10.83+/-1.72 and
5.75+/-2.06, respectively, in the whole group, and these values
differed significantly from each other ( P<0.001). In order to
perform a quantitative evaluation of the present data and a
comparative analysis with the results of previous studies reported
in the literature, we defined acute and late effects using a
"damage ratio" (DR) and a "recovery ratio" (RR), based on the
basal, acute and late data for individual patients. No
statistically significant difference was found in the DR between
DTC and TTX patients (76.4%+/-11.5% vs 67.6%+/-9.0%), while the
mean RR was higher in TTX patients than in the DTC group
(75.2%+/-24.4% vs 36.8%+/-13.7%). The DR on the 3rd day was not
related to the administered (131)I dose in the whole group, but a
negative correlation was found between the (131)I dose and the RR
at the 6th month ( r=-0.60, P=0.04). The best fit for this
relationship was obtained by a linear-quadratic model, as y=104.89
x-28.4 x(2)+38.1 ( R(2)=0.51, P=0.04). On the other hand,
comparative analysis with the results of previous studies with
comparable sampling times revealed that the best fit for the
relationships between the administered dose of (131)I and DR and
RR were obtained with a linear-quadratic model ( Y=alpha D+beta
D(2)) rather than a linear one. However, there was an interesting
difference in comparison with in vitro studies, in that we found
the coefficient beta to have a negative value, suggesting the
disappearance of damaged lymphocytes from the peripheral
circulation in a dose-dependent manner following (131)I treatment.
Further studies are therefore needed to clarify the effect of the
negative beta value on the biological dosimetry approach in
continuous internal low LET radiation, as in the case of (131)I
treatment.
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