There are many guidelines and recommendations suggesting ablation/therapy in Differentiated Thyroid Carcinoma. This presentation will be focused on the details of these recommendations and guidelines. Furthermore, it will be discussed the use of recombinant human thyrotropin (rhTSH) prior to radioactive iodine remnant ablation for patients with differentiated thyroid cancer.

1. Radioiodine dosage and modality
John T. Koutsikos, MD, PhD
Nuclear Medicine Physician

2. Conflict of Interest
NOTHING TO DECLARE

3. Introduction
Radioiodine has been used in the management
of patients with well-differentiated thyroid
cancer since the 1940s.
Saul Hertz

4. Introduction
 Iodine (I-131) causes acute thyroid-cell death
by emission of short path-length (1 to 2 mm)
beta rays.
 I-131 must be taken up by thyroid tissue to be
effective.
 As a result, it is of no value in patients whose
thyroid cancers do not concentrate iodine, i.e.
patients with medullary cancer, lymphoma, or
anaplastic cancer.

5. General treatment recommendations
 The treatment of choice for patients diagnosed
with thyroid cancer is surgery, when possible.
 Usually, surgery is followed by treatment with
radioiodine and thyroxine therapy.
 Generally, radiation therapy and chemotherapy
do not have a prominent role in the treatment of
thyroid cancer.

6. Goals of initial therapy of DTC
The basic goals of initial therapy for patients with
DTC are to:
 improve overall and disease-specific survival,
 reduce the risk of persistent/recurrent disease and
associated morbidity,
 permit accurate disease staging and risk
stratification, while
 minimizing treatment-related morbidity and unnecessary
therapy.

7. Staging and Treatment of DTC
 The recommended treatment depends on the stage of
differentiated thyroid cancer and the risk of
recurrence.
 This risk varies from very low to high.
 The treatment may differ from the general statements,
for reasons related to patients’ individual
circumstances.

8. Systems of staging / risk evaluation
 They are similar to one another but not identical,
indicating our lack of precise long-term outcome
data for all the variables
 They remain valuable for prognostic purposes
and in considering therapeutic options.
 Using several prognostic fractors such as age,
grade, tumor size, metastasis, etc.

9. GUIDELINES

11. Goals of radioiodine administration

12. 2015 ATA guidelines
Post-Surgical RAI Indicated?

13. 2015 ATA guidelines
Post-Surgical RAI Indicated?

14. Post-Surgical RAI Indicated?

15. 2012
SNMMI
guidelines

16. Selection of Activity

17. 2012 SNMMI guidelines

18. 2012 SNMMI guidelines
 Ablation of thyroid bed remnants
 30-100 mCi
 Treatment of DTC in the cervical or
mediastinal lymph nodes
– 150-200 mCi
 Treatment of distant metastases
– 200 mCi or more

19. Limited Use Selected Use Definite Use
ATA low-risk ATA low-
intermediate risk
ATA high-risk
<45 yrs
<2 cm
≥45 yrs
≥2cm
Gross invasion
Residual disease
No LN or
invasion
Positive LN LN invasion
Distant mets
No RAI
(or 30mCi?)
rhTSH RAI
(30-50 mCi)
Wthdr RAI
(dosimetry?)
Remnant
Ablation
Adjuvant
Therapy
Therapy
2015 ATA guidelines

20. ESTIMABL (Fr) and HiLo (UK) studies
N Engl J Med, May 2012
Both randomised studies have shown
effective remnant ablation using lower RAI
dose (30 mCi)

21. Low vs High RAI dose for remnant
ablation: a Meta-Analysis
Cheng W et al, JCEM 98:1353, 2013
9% lower successful ablation rate was identified in low
doses than in high doses, though not reaching any
significance (RR, 0.91; 95% CI, 0.79–1.04; P = 0.15).

22. Clin Nucl Med. 2015 Oct;40(10):774-9.
The rate of complete ablation of high activities was
statistically significant higher than that of low
activities (RR, 0.89; 95% CI, 0.81–0.97; P = 0.008)

23. J Clin Endocrinol Metab 99: 4487– 4496, 2014
 1298 DTC patients were included (698 low risk,
434 high risk M0, and 136 M1)
 grouped according to ablation activity
– I ≤ 54 mCi
– II 54 – 81 mCi
– III > 81 mCi
 subdivided by age ( <45 y and >45 y at diagnosis)

24.  There were no long-term (10-15 year) overall survival
or disease-specific survival differences in younger
patients (<45 yo) who received lower administered
activities of 131I (≤54 mCi) compared with those
receiving higher administered activities
 The older patients (> 45 yo), however, who received
lower administered activities of 131I (≤54 mCi) did
have a lower disease-specific survival compared with
those receiving higher administered activities.

25. DTC-specific survival in low-risk patients Recurrence-free survival in high-risk
patients without distant metastases
DTC-specific survival in high-risk
pts without distant metastases
older patients
> 45 yo

26. Fallahi B. et al.
Low versus high radioiodine dose in postoperative
ablation of residual thyroid tissue in patients with
differentiated thyroid carcinoma: a large randomized
clinical trial.
 In the low-dose group, more patients needed
a second dose of I-131, resulting in a higher
cumulative activity (median, 4810 vs. 3700
MBq, P<0.0001).
 The higher dose of I-131 (3700 MBq)
resulted in successful ablation more often
than the low dose (1110 MBq).
Nucl Med Commun. 2012 Mar;33(3):275-82.

27. Can we rely on guidelines
very much?

29. Radioactive iodine uptake
measurements

30. Neither the ATA or ETA guidelines
recommend this test
Radioactive iodine uptake
measurements
“…, depending on the radioiodine uptake
measurement and amount of residual
functioning tissue present”

31. Case 1
 Female, 20 y.o.
 June 2014 total thyroidectomy (general surgeon)
 Histology: papillary carcinoma
– 0.9 cm l.l. (diffuse sclerosing) and
– 0.5 cm r.l.
– 2 ln’s not metastatic

32. Case 1
 I-131?
 YES
 What dose?
 > 100 mCi

33. Case 1
 U/S: no findings (no residual thyroid tissue, no ln’s)
 TSH 127.8 μIU/ml
 Tg 19.2 ng/ml
 Anti-Tg: (-)ve
 Uptake measurement
 Yes?
 No?

34. Uptake measurement (60 μCi I-131)
Thyroid Uptake = 14,3 %

35. Next what?
 Surgery ?
 Low Dose I-131 ?
 30 mCi I-131

36. Post ablation WBS

37. Follow-up
 June 2015
 TSH 0.2 μIU/ml
 Tg < 0.1 ng/ml
 Anti-Tg: (-)ve
 U/S: (-)ve
 WBS (5 mCi I-131) with rh-TSH

38. WBS (5 mCi I-131)
Tg = 0.2 ng/ml

39. Guidelines usually are formulated by physicians
from international centers of excellence, and may
not be fully applicable elsewhere

40. U/S
Surgeon
Endocrinologist

41. Frangos S, Iakovou IP, et. al
Eur J Nucl Med Mol Imaging. 2015 Dec;42(13):2045-55
“… putatively “low-risk” DTC patients frequently
had higher-risk features, or characteristics
confounding risk stratification. This finding
suggests that outside international centres of
excellence, limitations in surgical experience
and in histopathology reporting may cast
important doubt on such patients’ “low-risk”
classification.”

42. Can we rely on guidelines
very much?

44. Part II - Modality
 Molecular Marker Status
 Low-iodine diet
 Hormone withdrawl
 rh-TSH

45. What is the role of molecular marker status
in therapeutic RAI decision-making?
 Has yet to be established.
 Can’t be recommended at this time.
 The ESTIMABL2 study will analyze the
relevance of BRAF status on outcome.

46. Of the 97 T1aN0M0
pts who received post-op
RAI, the rate of biochemical
persistence of disease
(defined by a stimulated
thyroglobulin of >1 ng/mL),
was 13% in the 39 BRAF
positive patients and 1.7% in
the BRAF negative patients.
To distinguish those
pts who require less or more
aggressive treatments.
J Clin Endocrinol Metab. 2012; 97:4390- 4398

47. Low-iodine diet
The purpose of a low-iodine diet is to
deplete the body of its stores of iodine, to
help increase the effectiveness of the
radioactive iodine

48. Is a low-iodine diet necessary
before remnant ablation?

49. Dietary Sources of Significant
Amounts of Iodine

50. Pharmaceuticals Blocking
Radioiodine Uptake

52. To withdraw or not to withdraw
[To rhTSH or not to rhTSH]

53. ESTIMABL (Fr) and HiLo (UK) studies
N Engl J Med, May 2012
Both studies have shown equal results either
using withdrawal or rhTSH stimulation of RAI
uptake
As a result of these studies the use of rhTSH
was expanded for the RAI range 30-100 mCi
in Europe (Dec 2012)

54. Recurrence rate in the same subgroups

61. Take home message

62. 70 years Nuc Med & DTC