Online Supplementary Material for:

Determining Patient Preferences for Indeterminate Thyroid Nodules: Observation, Surgery, or Genetic Tests

Daniel Joonil Lee, BHSc1, Jason J. Xu, MD2, Dale H. Brown, MD2, Ralph W. Gilbert, MD2, Patrick J. Gullane, MB2, Jonathan C. Irish, MD, MSc2, Lorne E. Rotstein, MD3, David P. Goldstein, MD, MSc2, John R. de Almeida, MD, MSc2

1 Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

2 Department of Otolaryngology – Head and Neck Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada

3Department of Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada

*Send correspondence to John R. de Almeida, MD, MSc, Princess Margaret Hospital–University Health Network, 610 University Avenue, 3-955, Toronto, ON, Canada, M5G 2C4. e-mail:

Patient Survey Questionnaire

1)You have a thyroid nodule and undergo a fine needle aspiration biopsy. Your test result statesthere is 100%chance that you have thyroid cancer. The treatment is surgical removal, but there are risks. Assumingthat surgery will definitely cure your cancer, would you….

A) Elect to have repeated ultrasound and needle biopsy, as necessary, in 6 months

B) Have surgery to remove the tumor

* “as necessary” means that there is a size increase in ultrasound imaging.

2)You have a thyroid nodule and undergo a fine needle aspiration biopsy. However, the test result is not certainif you have cancer or not. Your treatment options are a) repeated ultrasound and needle biopsy in 6 months, but it is ineffective in treating cancer and there is a risk of tumor progression or b) surgical removal, but there are risks, such as permanent hoarse voice, bleeding, and low thyroid hormone level, which requires medications.

At what risk of malignancy will you elect to proceed with surgery?

0% / 25% / 50% / 75% / 100%
Chance of cancer based on biopsy

The bar represents the chance of cancer based on biopsy. You will be given a scenario and be asked at what point (risk of cancer) you would switch from option a) repeated imaging and biopsy in 6 months to b) surgical removal.

This point is your threshold. Below your threshold, you would have repeat ultrasound and biopsy in 6 months. Above the threshold, you would proceed with surgical removal.Here’s an example:

Example:

0% / 25% / 50% / 75% / 100%
Chance of cancer based on biopsy

In this example, my threshold is 65%. In other words, between 0% and 65% chance of cancer, I would choose to have repeatultrasound and needle biopsy, as necessary, every 6 months for chances of cancer. Above 65% chance of cancer, I will proceed with surgery. Alternatively, if you do not want to have surgery at all, you can simply check the box given in each scenario.

i)If surgery will definitely cure your cancer if you have one (100% 10-year survival after surgery), at which point will you elect to proceed with surgery (mark on the linebelow or check the box)?

0% / 25% / 50% / 75% / 100%
Chance of cancer based on biopsy

ii)Assume that if you do have cancer, it is a non-aggressive tumor with a very high cure rate with surgery (99% 10-year survival after surgery). At which point will you elect to proceed with surgery (mark on the line below or check the box)?

0% / 25% / 50% / 75% / 100%
Chance of cancer based on biopsy

iii)Assume that if you do have cancer, it is a relatively non-aggressive tumor with a high cure ratewith surgery (85% 10-year survival after surgery). At which point will you elect to proceed with surgery (mark on the line below or check the box)?

0% / 25% / 50% / 75% / 100%
Chance of cancer based on biopsy

iv)Assume that if you do have cancer, it is a somewhat aggressive tumor with a modest cure rate with surgery (75% 10-year survival after surgery). At which point will you elect to proceed with surgery (mark on the line below or check the box)?

0% / 25% / 50% / 75% / 100%
Chance of cancer based on biopsy

v)Assume that if you do have cancer, it is an extremely aggressive tumor with a low cure rate with surgery or without surgery (14% 10-year survival after surgery). At which point will you elect to proceed with surgery (mark on the line below or check the box)?

0% / 25% / 50% / 75% / 100%
Chance of cancer based on biopsy

3)You have a thyroid nodule and undergo a fine needle aspiration biopsy, but the test result is not certain if you have cancer or not. There is now a testin addition to the biopsy that can tell you with 100% certainty whether you have cancer or not. You can choose to repeat biopsy and imaging in 6 months, proceed directly to surgery or obtain this additional test.

i)If this additional test is free, at which point will you elect to proceed witha) repeat ultrasound and needle biopsy, as necessary, in 6 months b) surgery and c) the additionaltest?(Put √ on only one option per row)

Properties of Additional Test / Options
Your chance of having cancer based on needle biopsy test / % of detecting cancer / % of excluding cancer correctly / A
Repeat ultrasound and biopsy in 6 months / B
Go to surgery / C
Do additional FREE test and have surgery if +, and no surgery if -
1 / 1% / 100% / 100%
2 / 10% / 100% / 100%
3 / 25% / 100% / 100%
4 / 67.5% / 100% / 100%
5 / 98% / 100% / 100%

ii)If this additional test costs $850, will you elect to proceed with a) repeat ultrasound and needle biopsy, as necessary, in 6 months b) surgery c) the additional test? (Put √ on only one option per row)

Properties of Additional Test / Options
Your chance of having cancer based on needle biopsy test / % of detecting cancer / % of excluding cancer correctly / A
Repeat ultrasound and biopsy in 6 months / B
Go to surgery / C
Do additional $850test and have surgery if +, and no surgery if -
1 / 1% / 100% / 100%
2 / 10% / 100% / 100%
3 / 25% / 100% / 100%
4 / 67.5% / 100% / 100%
5 / 98% / 100% / 100%

iii)If this additional test costs $3500, will you elect to proceed with a) repeat ultrasound and needle biopsy, as necessary, in 6 months b) surgery c) the additional test? (Put √ on only one option per row)

Properties of Additional Test / Options
Your chance of having cancer based on needle biopsy test / % of detecting cancer / % of excluding cancer correctly / A
Repeat ultrasound and biopsy in 6 months / B
Go to surgery / C
Do additional $3500 test and have surgery if +, and no surgery if -
1 / 1% / 100% / 100%
2 / 10% / 100% / 100%
3 / 25% / 100% / 100%
4 / 67.5% / 100% / 100%
5 / 98% / 100% / 100%

If you answered ii or iii (with cost) differently from i (without cost), at what cost would you answer them the same?

4)You have a thyroid nodule and undergo a fine needle aspiration biopsy, but the test result is not certain if you have cancer or not. There are two tests in addition to the biopsy, butneither test is perfect.

  • Test 1 rarely misdiagnoses those who have disease and therefore, if negative, you are unlikely to have a cancer (i.e. negativeresult: you would not need surgery, positive result: uncertain if surgery is beneficial).
  • Test 2 rarely gives positive results in healthy patients and therefore, if positive, you are likely to have cancer (i.e. positiveresult: you need surgery, negativeresult: uncertain if tumor is benign).

If the additional tests were free, indicate in these following scenarios what you would like to do (Put √ on only one option per row).

Test 1 / Test 2 / Options
% of having cancer based on needle biopsy test / % of detecting cancer / % of excluding cancer correctly / % of detecting cancer / % of excluding cancer correctly / A
Repeat ultrasound and biopsy in 6 months / B
Go to surgery / Additional Tests
C
Test 1 ($0) / D
Test 2 ($0) / E
Both ($0)
1 / 1% / 100% / 70% / - / -
2 / 10% / 90% / 53% / 63% / 99%
3 / 25% / 90% / 49% / 57% / 97%
4 / 67.5% / 94% / 52% / 68% / 96%
5 / 98% / 100% / - / - / -

If you did not choose option (c), (d) or (e) for any of the above, explain why?

5)Please assume that both tests are the same as previously described, but now there is a cost for both tests. Test 1 costs $3500 and the second test costs $850.

  • Test 1 rarely misdiagnoses those who have disease and therefore, if negative, you are unlikely to have a cancer (i.e. negative result: you would not need surgery, positive result: uncertain if surgery is beneficial).
  • Test 2 rarely gives positive results in healthy patients and therefore, if positive, you are likely to have cancer (i.e. positive result: you need surgery, negative result: uncertain if tumor is benign).

Indicate in these following scenarios what you would like to do (Put √ on only one option per row).

Test 1 / Test 2 / Options
% of having cancer based on needle biopsy test / % of detecting cancer / % of excluding cancer correctly / % of detecting cancer / % of excluding cancer correctly / A
Repeat ultrasound and biopsy in 6 months / B
Go to surgery / Additional Tests
C
Test 1 ($3500) / D
Test 2 ($850) / E
Both ($4350)
1 / 1% / 100% / 70% / - / -
2 / 10% / 90% / 53% / 63% / 99%
3 / 25% / 90% / 49% / 57% / 97%
4 / 67.5% / 94% / 52% / 68% / 96%
5 / 98% / 100% / - / - / -

If you did not choose option (c), (d) or (e) for any of the above, explain why?

If you answered this question (#5) differently from the previous question (#4), at what cost would you answer them the same?

Benefits and risk information for patients

Observation / Hemi-thyroidectomy / Total/completion thyroidectomy
Benefits / Avoid risks of surgery / Treatment of cancer / Treatment of cancer
Risks / Risk of missed cancer/growth of tumor
  • Invasion of local structures (e.g. trachea, esophagus)
  • Potential Spread to lymph nodes and other parts of the body
Anxiety of not knowing what the nodule is exactly
Extra tests (ultrasounds, biopsies) every 6 months – 1 year to monitor the nodule / Neck Scar (4-6 cm)
Risk of permanent hoarse voice (1%)
Risk of hypocalcemia (1%)
Risk of hypothyroidism requiring a medication daily (22%)
Risk of bleeding (0.4%)
Risk of death (0.2%)
Two weeks recovery and missed work / Neck Scar (4-6 cm)
Risk of permanent hoarse voice (2%)
Risk of hypocalcemia (1%)
Risk of hypothyroidism requiring a medication daily (100%)
Risk of bleeding (0.4%)
Risk of death (0.2%)
Two weeks recovery and missed work

Cancer characteristics

Non-aggressive /
  • Slow growth
  • Low risk of death
  • Low risk of metastasis (spreading)
  • Low risk of invading local structures (e.g. trachea, esophagus)

Aggressive /
  • Rapid growth
  • High risk of death
  • High risk of metastasis (spreading)
  • High risk of invading local structures (e.g. trachea, esophagus)