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I looked again at the Lancet paper after receiving
the note below from Dr. Jaworowski.
Of the 634 cancer cases diagnosed (from the 7417
patients), only 9 thyroid cancer cases were observed and 2-8 were
expected. Of the 448 cancer deaths, only 5 thyroid cancer deaths were
observed and 1-8 were expected. There is no discussion of occult thyroid
cancer.
UNSCEAR and others seem to be trying very hard
to link thyroid cancer to I-131 radiation. Why?
Jerry
-----------------------
I would like to add, that the
statistics in UNSCEAR ref. F13 is based on 9 thyroid cancer cases. The authors
stated: "it is not posible to establish a relation between [thyroid] cancer
incidence or mortality and a radioiodine dose ... and that findings for thyroid
cancer may reflect an association with thyrotoxicosis rather than radioiodine
exposure".
The problem of thyroid cancer
epidemiology is complicated by a very high normal incidence of occult thyroid
cancers, which ranges in various countries from about 5% in Colombia, 9% in
Poland, 15% in the USA, to 35% in Finland. Any discussion of epidemiology of
radiation induced thyroid cancers which ignores the occult thyroid cancers, and
the screening effect involved, is improper.
Best wishes,
Zbigniew
----- Original Message -----
Sent: Thursday, February 05, 2004 12:39
AM
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
I
think the main reason why the UNSCEAR text mentions the elevated risk of
thyroid cancer and not the decreased overall cancer risk, is that it is
excerpted from a section (pg. 497, Annex J, UNSCEAR 2000) dealing
specifically with the elevated incidence of thyroid cancer in the
Chernobyl-affected regions of the former USSR. There ain't no
conspiracy or misconduct here.
Even
so, as I've mentioned, they point out the non-conclusive nature of SMRs and
SIRs. Thus those studies do not prove an elevated risk of thyroid cancer
due to I-131 exposure, nor do they prove a decreased risk of overall
cancer. You would need a case-control study within the hyperthyroidism
cohort to demonstrate this, and as far as I can see this was not
done.
Jeremy Whitlock
We should split hairs on this very important
matter. It is crucial to public acceptance of all nuclear
technologies.
In my view, it is
improper for scientists to mislead the public about the
health effects of radiation. If a significant reduction in cancer
incidence and mortality is observed and reported by credible scientists,
then UNSCEAR should include this information in its publications, especially
in publications that comment on and reference publications that
contain this information. Mentioning only an increase in a small
cancer effect while ignoring a decrease in a much larger cancer effect,
seems like misconduct. It seems to be a very common practice --
reflecting perhaps a very strong desire -- to tie any amount of radiation to
cancer. It must stop.
In the view of Dr. Jaworowski, too much is
being made of thyroid cancer. The link to I-131 is not that
strong.
----- Original Message -----
Sent: Wednesday, February 04, 2004
3:37 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 therapies
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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