Thyroid cancer

[Muckerheide <muckerheide@MEDIAONE.NET>]

Ted,



Re the inquiry about the mortality of thyroid cancer in general and in the

Chernobyl thyroid cancers:



[NOTE: My perspective on thyroid cancer treatment is influenced by my

daughter's thyroid cancer, which initially caused one lobe of her thyroid to

be removed while she was in early pregnancy with her 4th child. This was of

no consequence since the thyroid function is ok with one lobe. The other

lobe was found to have small lesions, so they waited until after her

pregnancy to remove it. She's supposed to take thyroid hormone (usually

Synthroid) regularly (but she's not very good at remembering).  I suspect

her cancer is a result of poor eating habits (hates fruit and most

vegetables) combined with 4 pregnancies, the last ones very close together.

(Joe turns 2 later this month :-) ]



In the UNSCEAR 2000 Report, Annex J on Chernobyl, after discussing the

general monitoring/registry programs, the Intro to this Section is:



V. LATE HEALTH EFFECTS OF THE CHERNOBYL ACCIDENT



259. The studies of late health consequences of the

Chernobyl accident have focussed on, but not been restricted

to, thyroid cancer in children and leukaemia and other cancer

in recovery operation workers and residents of contaminated

areas. Many studies have been descriptive in nature, but until

individual dosimetry is completed, proper controls established,

and methodological requirements satisfied, the results will be

difficult to interpret. Quantitative estimates and projections

will certainly be very unreliable without individual and

reliable dose estimates.



260. The late health effects of the Chernobyl accident are

described in this Chapter. These effects include malignancies,

especially thyroid cancer and leukemia, non-malignant

somatic disorders, pregnancy outcome and psychological

effects. The focus will be on health effects in the most

contaminated areas, but possible effects in other parts of the

world will also be considered.



A. CANCER



1. Thyroid cancer



(a) Epidemiological aspects



261. Thyroid carcinomas are heterogeneous in terms of

histology, clinical presentation, treatment response and

prognosis. Although rare, they are nevertheless one of the

most common cancers in children and adolescents. Thyroid

cancer is known to be more aggressive in children than in

adults, but paradoxically, the prognosis is supposed to be

better in children [V8].



There's a lot of discussion of incidence, with a brief mention of mortality

in older women, not related to Chernobyl, but from other, medical,

exposures. Then there's a brief para:



288. Although rarely fatal, the aggressiveness of the thyroid

cancers found in the Chernobyl area, which is frequently

present with periglandular growth and distant metastases [E1,

K11, W8], argues against the findings being entirely a result

of screening. Although thyroid tumours in adults are usually

tumours of relatively low malignancy, they tend to be more

aggressive in children [S3], so it could be argued that the

growth pattern would have led to the diagnosis of a thyroid

cancer sooner or later.



Then starting the next Section:



(b) Clinical and biological aspects



292. A large proportion of the childhood thyroid cancers in

Belarus and Ukraine were reported to be locally aggressive;

extrathyroidal growth was seen in 48%-61% of the cases,

lymph node metastases in 59%-74% and distant metastases

(mainly lung) in 7%-24% [F5, P2, P6, T4, T18].

Comparisons with characteristics of tumours from other

countries (France, Italy, Japan, the United Kingdom and the

United States) indicate a higher percentage of extrathyroidal

extension for tumours from Belarus and the Russian

Federation but similar percentages of cases with metastases

[N5, P2, P6, V8, Z3].



293. In a recent pooled analysis of 540 thyroid cancers

diagnosed before the age of 20 years (mean age at diagnosis,

14 years) that included nine Western centres, the average

male:female ratio was 1:3.2 and the mean follow-up was 20

years [F7]. Eighty-six percent were papillary thyroid

carcinomas, 79%showed evidence of lymph node metastases,

20%-60% had extracapsular invasion and 23% were

diagnosed with distant metastases. In nearly all cases the

presenting sign was a neck mass. Thirteen of the patients died

as a consequence of the disease.



[This is roughly 2.5% cause-specific mortality for a mean 20 year

follow-up.]



295. A number of thyroid cancer cases in Belarus were

treated with radioiodine at the university clinics of Essen

and Würzburg [R23]. All 145 patients had undergone

operations at the Centre for Thyroid Tumors in Minsk;

lymph node metastases were found in 140 patients and

distant metastases in 74 of them. The mean age at

diagnosis was 12 years. Among 125 children subsequently

followed, 90 were classified as in complete remission and

the others had partial remissions.



296. In a study of 577 Ukrainian thyroid cancer cases

diagnosed in patients less than 19 years of age [T18],

histopathology was evaluated in 296 cases (123 were

analysed by non-Ukrainian pathologists, who confirmed

the initial diagnosis in all cases).Ninety-three percent were

papillary carcinomas, and 65% were found to be of the

more aggressive solid/follicular type. In 55% of cases,

lymph node metastases were found, and in 17% lung

metastases were found either at initial diagnosis or in later

follow-up. Difference in TNM classification [H17] over

time did not show a significant trend towards more

advanced stages (Table 62), as could have been anticipated

if radiation-associated cancers are indeed more aggressive.

Cancers diagnosed in 1996 and 1997 were more likely to

be locally aggressive, stage T4, but they revealed the same

pattern of lymph node metastases and distant spread. The

male:female ratio was found to be influenced by age at the

time of diagnosis (Table 63): the ratio was 1.1:1 for those

less than 5 years of age at time of diagnosis and 1:2.7 for

those 15
18 years. However, age at time of the accident

did not seem to influence the male:female ratio (Table 63).

A possible sex difference in the susceptibility of the thyroid

tissue to ionizing radiation did not seem to influence the

gender ratio, since age at diagnosis and not age at exposure

influenced the distribution.



297. In a study in the United States of 4,296 patients

previously irradiated for benign disorders, 41 childhood

(mean age at diagnosis, 16 years) and 77 adult (mean age

at diagnosis, 27 years) thyroid cancers were found [S4].

The childhood cancers more often presented themselves

with lymph node metastases and vessel invasion but were

significantly smaller in adults and found incidentally when

benign nodules were operated. Of the childhood cancers,

95%were papillary carcinomas compared with 84%of the

adult cancers. Thirty-nine percent of the childhood cancers

relapsed compared with 16% of the adult cancers. After a

mean follow-up of 19 years, there was only one death due

to thyroid cancer, and this was in the adult group.



The report then goes in to molecular biology (again making clear that issues

of cellular signaling etc. are the critical factors with no clear

association of cancer with specific deletions, etc.  The end of the section

has 2 paras:



(c) Summary



308. There can be no doubt about the relationship between

the radioactive materials released from the Chernobyl

accident and the unusually high number of thyroid cancers

observed in the contaminated areas during the past 14 years.

While several uncertainties must be taken into consideration,

themain ones being the baseline rates used in the calculations,

the influence of screening, and the short follow-up, the

number of cases is still higher than anticipated based on

previous data. This is probably partly a result of age at

exposure, iodine deficiency, genetic predisposition, and

uncertainty that surrounds the role of 131I compared with that

of short-lived radioiodines. The exposure to short-lived

radioiodines is entirely dependent on the distance from the

release and themode of exposure, i.e. inhalation or ingestion.

It was only in the Gomel region, the area closest to the

Chernobyl reactor, that Astakhova et al. [A6] found a

significantly increased risk of thyroid cancer. It has been

suggested that the geographical distribution of thyroid cancer

cases correlates better to the distribution of shorter-lived

radioisotopes (e.g. 132I, 133I and135I) than to that of 131I [A7].



309. The identification of a genomic fingerprint that

shows the interaction of a specific target cell with a defined

carcinogen is a highly desirable tool in molecular

epidemiology. However, a specific molecular lesion is

almost always missing, probably because of the large

number of factors acting on tumour induction and progression.

Signalling via protein tyrosine kinases has been

identified as one of the most important events in cellular

regulation, and rearrangements of the tyrosine kinase

domain of the RET proto-oncogene have been found in

thyroid cancers thought to be associated with ionizing

radiation [F2, I21, K14]. However, the biological and

clinical significance of RET activation remains controversial,

and further studies of the molecular biology of

radiation-induced thyroid cancers are needed before the

carcinogenic pathway can be fully understood.



2. Leukaemia



There's more, but if there's further interest I'd recommend downloading the

UNSCEAR 2000 Annex J, from:

http://www.unscear.org/

Go to "Reports," then "2000," then "Annex J" which is the pdf file.

Also go to the "Chernobyl" link, and see the report of the follow-on June

2001 Kiev Conference responding to the countries/interests in claiming major

consequences of Chernobyl for financial aid purposes. Note the attendees.

 

Many specific papers can also be found.



As a footnote, I went back to pull out the following data to consider:



277. In a study of Ukrainian thyroid cancer patients less

than 15 years old at diagnosis, registered at the Institute of

Endocrinology and Metabolism, Kiev, the thyroid cancer

rate for 1986-1997 exceeded the pre-accident level by a

factor of ten [T18]. A total of 343 thyroid cancers occurred

in patients born between 1971 and 1986, and the thyroid

cancer rate for this age cohort was 0.45 per 100,000

compared with 0.04-0.06 per 100,000 before the accident.

For the slightly older group of patients 15-18 years old at

diagnosis in 1986-1997, 219 cases of thyroid cancers were

found, and the average incidence was three times higher

than that in the group diagnosed before the accident.



It would seem that the 0.45 rate here, under these relatively large and

instantaneous releases without protective actions, and endemic problems of

iodine deficiency, etc., this tragedy produces 1 thyroid cancer in 220,000

children, eminently treatable, with NO reported mortality. The slightly

older children had about 1 case in 660,000 children. In the highest dose

area I think I saw the rate was also up about a factor of a little more than

10, to 2.5 per 100,000, or about 1 case in 40,000 children.



Now, we should talk about releasing radioiiodines from a water reactor

accident!?  Even with a cracked containment, thousands of times less

radioiodine, and evacuate and interdict milk and food from the garden! :-)



Regards, Jim



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