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Fukushima Thyroid Examination February 2017: 184 Thyroid Cancer Suspected/Confirmed (1 Additional Case)


Highlights:
  • One more case of suspected thyroid cancer was diagnosed by cytology since the last report.
  • No additional surgeries since the last report: the number of confirmed cancer cases remains at 145 (101 in the first round and 44 in the second round)
  • Total number of confirmed/suspected thyroid cancer diagnosed (excluding a single case of benign tumor) is 184 (115 in the first round and 69 in the second round)
  • The second round screening data is still not final (confirmatory examination still ongoing).
  • Thyroid Examination Evaluation Subcommittee will be convened in May or June 2017 to evaluate the results of the second round screening.
On February 20, 2017, less than two months since the last report, the 26th Oversight Committee for Fukushima Health Management Survey convened in Fukushima City, Fukushima Prefecture. Among other information, the Oversight Committee released the latest results (as of December 31, 2016) of the second and third rounds of the Thyroid Ultrasound Examination (TUE). Official English translation of the results is posted here. The narrative below presents basic facts of TUE and its current results in perspective, including information covered during the committee meeting and the subsequent press conference.

Overview
As of December 31, 2016, there is only 1 more case with cancer or suspicion of cancer from the second round, making a grand total of 184 (185 including the single case of post-surgically confirmed benign nodule) for the first and second round screening results combined. The number of surgically confirmed cancer cases, excluding the aforementioned case of benign nodule, did not change from the previous report (101 from the first round and 44 from the second round), and the remaining 38 (14 from the first round and 24 from the second round) continue to be under observation. 

The second round screening (the first Full-Scale screening) was originally scheduled to be conducted from April 2014 through March 2016, and the primary examination (with the participation rate of 70.9% and the progress rate of 100.0%), is essentially complete. But the confirmatory examination (with the participation rate of 79.5% and the progress rate of 95.0%) is still ongoing. 

The third round screening (the second Full-Scale Screening) began on May 1, 2016 and is scheduled to run through March 2018--the end of Fiscal Year 2017. As of December 31, 2016, 87,217 out of the survey population of 336,623 residents have participated in the ongoing primary examination at the participation rate of 25.9%. The confirmatory examination began on October 1, 2016, with the participation rate of 29.6% so far. 

Full-Scale Screening (first and second)
To be conducted every 2 years until age 20 and every 5 years after age 20, the Full-Scale screening began with the second round screening (the first Full-Scale Screening) in April 2014, including those who were born in the first year after the accident. There are 381,282 eligible individuals born between April 2, 1992 and April 1, 2012. As of December 31, 2016, 270,489 actually participated in the primary examination. 

The participation rate remained the same as 3 months earlier at 70.9% but lower than 81.7% from the first round screening. Results of the primary examination have been finalized in 270,468 participants, and 2,226 (increased by 4 since the last Oversight Committee meeting) turned out to require the confirmatory examination. 

The confirmatory examination is still ongoing for the second round. Of 2,226 requiring the confirmatory examination, 1,770 have participated at the participation rate of 79.5% (increased from the previous 75.8% but still lower than 92.8% from the first round screening). So far 1,681 have received final results including 195 that underwent fine needle aspiration cytology (FNAC) which revealed 69 cases suspicious for cancer. 

Confirmation of thyroid cancer requires pathological examination of the resected thyroid tissue obtained during surgery. There has been no additional surgical case since the last reporting. As of December 31, 2016, 44 underwent surgery and 43 were confirmed to have papillary thyroid cancer. One remaining case was confirmed to have "other thyroid cancer" according to the classification in the seventh revision of Japan's unique thyroid cancer diagnostic guidelines. A specific diagnosis was not revealed, but it has been reported as a differentiated thyroid cancer that is not known to be related to radiation exposure and it is allegedly neither poorly differentiated thyroid cancer nor medullary cancer. 

The third round screening or the second Full-Scale Screening has covered 87,217 or 25.9% of the survey population of 336,623. The primary examination results have been finalized in 71,083 or 81.5% of the participants, revealing 483 to require the confirmatory examination. Results of the confirmatory examination have been finalized in 64 of 143 (29.6%) that have been examined. FNAC was conducted in one person with a negative result: No cancer case has been diagnosed from the third round as of now. 

Confusing issues
Conducted every 2 years up to age 20, the TUE transitions at age 25 to milestone screenings to be conducted every 5 years. Some residents are beginning to participate in the age 25 milestone screening, and if they have never participated in the TUE, their milestone screening results will be added to the second round screening results. Thus the number of the second round screening participants is expected to increase even though the screening period technically ended in March 2016. 

However, the third round screening survey population excludes the age 25 milestone screening participants: their results will be tallied up separately.

Also in some cases, confirmatory examinations from the second and third rounds might be simultaneously ongoing, or there could be significant delays in conducting confirmatory examinations due to logistical issues such as the lack of manpower. A two-year screening period originally designed for subsequent rounds of the Full-Scale Screening is essentially spread over a longer time period, overlapping with the next round of screening. A precise interpretation of results from each round of screening might be nearly impossible.

A newly diagnosed case in the second round
In the second round, only 1 case was newly diagnosed by FNAC with suspicion of cancer. It is a female from Koriyama-City who was 17 years old at the time of the March 2011 disaster. Her first round screening result was A1.

Prior diagnostic status of the cases newly diagnosed with cancer in the second round
Of 69 total cases suspected or confirmed with cancer in the second round, 32 were A1, 31 were A2, and 5 were B in the first round. One remaining case never underwent the first round screening (no information such as age, sex or place or residence, is available regarding this case).

Thirty-two cases that were A1 in the first round, by definition, had no ultrasound findings of cysts or nodules, whereas 7 of 31 cases that were previously diagnosed as A2 had nodules with the remaining 24 being cysts. All 5 cases that were previously diagnosed as B were nodules, and at least 2 of them had undergone the confirmatory examination in the first round. 

This means 56 (32 "A1" and 24 "A2 cysts")of 69 cases had no nodules detected by ultrasound in the first round which could have developed into cancer. This is 81% of the second round cases suspected or confirmed with cancer. It has been speculated by some that these 56 cases were new onset since the first round, suggesting the cancer began to form in 2 to 3 years after the first round screening, conflicting with the common notion that thyroid cancer in general is slow growing. 

Akira Ohtsuru, the head of the TUE, explained that even though some of the small nodules are very easy to detect by ultrasound, exceptions arise when 1) the border of the lesion is ambiguous, 2) the density of the lesion is so low that it blends into the normal tissue, or 3) the lesion resembles the normal tissue. Thus, it is not because the nodules newly formed since the first round screening, but because the nodules were simply not detected even though they were there, that cases which previously had no nodules are now being diagnosed with cancer. Ohtsuru said that when such previously undetected nodules become relatively large enough to become detectable by ultrasound, they might look as if they suddenly appeared. Ohtsuru added that nodules that have already been detected by ultrasound do not to appear to grow very rapidly in general.

This is a better, more legitimate explanation than the previous ones he offered that stated the nodules were present in the first round albeit invisible. However, 56 out of 69 cases seem like a lot to be explained by this.

An issue of the female to male ratio
The female to male ratio of cancer cases warrants a special attention. For thyroid cancer, the female to male ratio is nearly 1:1 in the very young, but it is known to increase with age and decrease with radiation exposure. (See below Slide 2 in this post for more information). In the second round, the female to male ratio has been ranging from 1.19:1 to 1.44:1 overall, but the FY2015 municipalities have consistently shown a higher number of males than females with the most recent female to male ratio of 0.7:1.

What Ohtsuru said about the the female to male ratio boils down to the following: 
The female to male ratio for thyroid cancer is influenced by the reason for diagnosis and the age. When the confirmatory examination of the second round screening is completed, the data will be analyzed by adjusting for age and participation rates by sex. The female to male ratio in Japan's cancer registry data, including all ages, is around 3:1, but it used to be bigger at 4:1 or 6:1 in the 1980's and earlier. In Fukushima, the TUE was conducted in asymptomatic youth around puberty--a different condition than the cancer registry. Yet even in the cancer registry, the female to male ratio tends to be close to 1:1 up to the puberty. Autopsy data of occult thyroid cancer in individuals who died of causes other than thyroid cancer show the female to male ratio of 1:1 or smaller (more males) in adults. This fact indicates that thyroid cancer screening would yield the female to male ratio close to 1:1 even in adults. Thus, it is scientifically expected that thyroid cancer screening in general leads to a smaller female to male ratio.
He is claiming that thyroid cancer diagnosed by cancer screening before becoming symptomatic--as opposed to symptomatic thyroid cancer diagnosed clinically--is expected to show the female to male ratio near 1:1 or smaller, i.e., as many males are diagnosed as females, or more males are diagnosed than females. 

To say the least, calling extrapolation from autopsy data to screening "scientific" seems a bit of a stretch. Furthermore, Ohtsuru's claim does not add up scientifically. South Korea, where active screening increased the incidence of thyroid cancer, did not observe a smaller female to male ratio as shown in the table of thyroid cancer incidence by sex and age group compiled from Ahn et al. (2016). It is obvious the female incidence is much higher than the male incidence without actually calculating the ratio.

Thyroid cancer incidence by sex and age group per 100,000 
in the 16 administrative regions in Korea
 Compiled from Supplementary Tables 2 & 3 in Ahn et al. (2016) Thyroid Cancer Screening in South Korea Increases Detection of Papillary Cancers with No Impact on Other Subtypes or Thyroid Cancer Mortality (link)

Furthermore, Ohtsuru's claim that the female to male ratio tends to be close to 1:1 up to the puberty in the cancer registry is not corroborated by the actual data. The table below was compiled from the National estimates of cancer incidence based on cancer registries. The number of thyroid cancer cases for each sex was listed side-by-side for each year and age group. Then a total from 2000 to 2012 was tallied for each sex and age group to obtain the female to male ratio, because the number of cases varies from year to year. Even without knowing exactly which age range Ohtsuru meant by "up to the puberty," it is clear that the female to male ratio is not at all close to 1:1.


The number of thyroid cancer cases by sex and age group from 2000 to 2012
Compiled from the National estimates of cancer incidence based on cancer registries in Japan (link)

According to this study, the female to male ratio peaks at puberty and declines with age, as excerpted below:
The increased F:M ratio in thyroid cancer incidence does not remain static with age. Female predominance peaks at puberty. [...] This pattern occurs as the thyroid cancer incidence begins to increase at an earlier age in females than in males, leading to a rise in the F:M ratio. The ratio starts to decline as the male incidence rate begins to increase and, concurrently, the rate of increase in female incidence rate slows down. The steady decrease in F:M ratio with age continues, and the peak male rate does not occur until between 65 and 69 years of age, compared with the earlier peak female rate between 45 and 49 years of age, just before the mean age of menopause at 50 years.

An issue of the participation rate
The primary examination participation rate of 70.9% in the second round screening is lower than 81.7% in the first round. Most notable is the participation rate of the oldest age group: 52.7% for ages 16-18 (age at exposure) in the first round plummeted to 25.7% for ages 18-22 (age at examination) in the second round. It is 6.6% for ages 18-24 (age at examination) for the ongoing third round so far.

Younger age groups in school have maintained pretty high participation rates thanks to the school-based screening. The older age group often leave the prefecture for college or jobs, and it becomes increasingly difficult to get them to participate, especially with their interests fading in their busy lives.

The status of the new third-party committee
The "international, third-party, neutral, scientific, up-to-date and evidence-based" expert committee proposed by Chairman Hokuto Hoshi at the last committee meeting is being discussed at the prefectural level in consultation with the central government. The prefectural official admitted that the plan was to establish an independent entity that will offer, from a neutral standpoint, the latest knowledge of thyroid cancer needed by the Oversight Committee.

A committee member Tamami Umeda from Ministry of the Environment elaborated on her vision of the third-party committee as an entity to review and organize the latest clinical and epidemiological knowledge and studies. It would be separate from the Thyroid Examination Evaluation Subcommittee that is intended to evaluate and analyze the status of the TUE, including the evaluation of radiation effects. (Note: In reality, the Thyroid Examination Evaluation Subcommittee has been far from being effective in analyzing the TUE data due to lack of information released by Fukushima Medical University on the premise of protecting personal clinical data).

Explaining that international organizations frequently separate a scientific review process from discussions relating to policy making in order to maintain neutrality, Umeda said she thought a similar process might be useful for the Fukushima Health Management Survey. This comment drew questions from committee members as well as the press about the status of the Oversight Committee itself: Is it a policy-making body? Is it not scientific enough?

It would make more sense to invite experts to join the Thyroid Examination Evaluation Subcommittee to incorporate knowledge gained from the latest research on thyroid cancer. Why it has to be an "international" committee is unclear other than to say that it was recommended by the Organizing Committee of 5th International Expert Symposium in Fukushima on Radiation and Health, including Shunichi Yamashita. A former chair to the Oversight Committee, Yamashita resigned from the position in March 2013 amid controversies surrounding "secret meetings." Although no longer involved with the Oversight Committee, he has maintained ties with the Survey as Founding Senior Director of the Radiation Medical Science Center for the Fukushima Health Management Survey, the Office of International Cooperation for the Survey.

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Below is the summary of the basic information from each round of screening.

First Round Screening (October 2011 - April 2015)
(This is the final results as of March 31, 2016. It is unchanged from the September 2016 report).

Total number targeted: 367,672
Number of participants in primary examination: 300,476
Number with confirmed results: 300,476
  • A1   154,607 (51.5%) (no nodules or cysts found)
  • A2   143,575 (47.8%) (nodules ≦ 5.0 mm or cysts ≦ 20.0 mm)
  • B        2,293   (0.8%) (nodules ≧ 5.1 mm or cysts ≧ 20.1 mm)
  • C               1   (0.0%) (requiring immediate secondary examination)
(Note: Cysts with solid components are treated as nodules).

Number eligible for confirmatory (secondary) examination: 2,294
Number of participants in confirmatory (secondary) examination: 2,128
Number with confirmed results : 2,086
Number of fine-needle aspiration cytology (FNAC): 545
Number suspicious or confirmed of malignancy: 116 (including one case of benign nodules)

Number with confirmed tissue diagnosis after surgery: 102
  • 1 benign nodule
  • 100 papillary thyroid cancer
  • 1 poorly differentiated cancer
Second Round Screening (April 2014 - March 2016) (see report here)

Total number targeted: 381,282
Number of participants in primary examination: 270,489
Number with confirmed results: 270,468
  • A1   108,688 (40.2%) (no nodules or cysts found)
  • A2   159,554 (59.0%) (nodules ≦ 5.0 mm or cysts ≦ 20.0 mm)
  • B        2,226   (0.8%) (nodules ≧ 5.1 mm or cysts ≧ 20.1 mm)
  • C              0   (0.0%) (requiring immediate secondary examination)
(Note: Cysts with solid components are treated as nodules).

Number of residents requiring confirmatory (secondary) examination: 2,226
Number of participants in confirmatory examination: 1,770
Number with confirmed results: 1,681
Number of FNAB: 195
Number of cases with malignancy or suspicion of malignancy: 69
Number with confirmed tissue diagnosis after surgery: 44
  • 43 papillary thyroid cancer
  • 1 "other thyroid cancer"
Third Round Screening (May 2016 - March 2018) (see report here)

Total number targeted: 336,623
Number of participants in primary examination: 87,217
Number with confirmed results: 71,983
  • A1   25,182 (35.4%) (no nodules or cysts found)
  • A2   45,418 (63.9%) (nodules ≦ 5.0 mm or cysts ≦ 20.0 mm)
  • B          483  (0.7%) (nodules ≧ 5.1 mm or cysts ≧ 20.1 mm)
  • C             0   (0.0%) (requiring immediate secondary examination)
(Note: Cysts with solid components are treated as nodules).

Number of residents requiring confirmatory (secondary) examination: 483
Number of participants in confirmatory examination: 143
Number with confirmed results: 64
Number of FNAB: 1
Number of cases with malignancy or suspicion of malignancy: 0
Number with confirmed tissue diagnosis after surgery: 0


Second Round Screening


Table 6. Cytology results (including information from Appendix 6: Number of surgeries among cases with malignancy or suspicion of malignancy) as of December 31, 2016



Table 6. Cytology results for FY 2014-2015 
(including information from Appendix 6: Surgical cases of suspicious or malignant cases) 
(Data as of December 31, 2016)

Age distribution of 69 cases confirmed or suspected of thyroid cancer in the second round screening (as of December 31, 2016)
Age at the time of the March 11, 2011 nuclear accident

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