After less-than-total thyroidectomy for thyroid cancer, I-131 is commonly used to ablate the remnant, as distinct from treatment of metastases. This PowerPoint discusses the rationale for ablation and the evidence in the medical literature regarding this, with clinical examples.

1. 33 y.o. woman with multifocal (largest 2.2 cm)
papillary carcinoma, follicular variant. Tg 1.6.
Rx 155 mCi. Uptake 1.5%.
Pre- and post-therapy scans.

2. 16 months later, Thyrogen-stimulated scan was negative with Tg <0.5.

5. When is ablate not ablate?
“Thyroid ablation refers to the use of radioiodine
to destroy the remaining normal thyroid tissue
after less-than-total thyroidectomy (intended or
otherwise) [as distinct from therapy].”
Sweeney DC et al cited in ref. 3, Woodrum et al
(2005)

6. 43 y.o. man with papillary carcinoma,
multifocal, extension to skeletal muscle and
metastasis to multiple lymph nodes. TSH 58.
Tg 22.4. Uptake 15%. 24- and 48-hour I-123
scans.

7. One year later, no detectable lesions, Tg <0.5.

8. Q. When is ablate not ablate?
A. When the initial treatment attacks cancer.
♦ Assertion: The initial I-131 dose in thyroid
cancer, often called an ablative dose, may in
fact be given in the presence of cancer and
likely treats the cancer. After all, if we are
treating because the cancer might recur, there
is surely a finite chance of cancer cells being
present at the time of the first treatment, even
when not visible on the scan.

9. CPT code book, 2003:
79030 Radiopharmaceutical ablation of gland
for thyroid carcinoma.
79035 Radiopharmaceutical therapy for
metastases of thyroid carcinoma.
2006:
Only 79005: Radiopharmaceutical therapy,
by oral administration. Others were deleted.
Some authors use “ablate” in quotes.

10. Objectives:
1. Review the rationale for initial post-surgical
I-131 treatment for differentiated thyroid
cancer (DTC)
2. Review the various initial presentations on
radioiodine imaging after surgery for DTC
3. Review considerations in choosing the dose
for initial post-surgical I-131 treatment in DTC

11. Bibliography:
1. Sisson JC. Applying the radioactive eraser: I-131 to ablate normal thyroid
tissue in patients from whom thyroid cancer has been resected (editorial).
J Nucl Med. 1983;24:743-745.
2. Mazzaferri EL. Thyroid remnant 131I ablation for papillary and follicular
thyroid carcinoma. Thyroid. 1997;7:265-271.
3, Woodrum DT, Gauger PG. Role of 131I in the treatment of well
differentiated thyroid cancer. J Surg Oncol. 2005:89:114-121.
4. Doi SAR, Woodhouse NJY. Ablation of the thyroid remnant and 131I
dose in differentiated thyroid cancer. Clin Endocrinol. 2000;52:764-773.
5. National Comprehensive Cancer Network Thyroid Carcinoma Panel
Members. NCCN Clinical Practice Guidelines in Oncology.
Thyroid Carcinoma.
6. The American Thyroid Association Guidelines Taskforce. Management
guidelines for patients with thyroid nodules and differentiated thyroid
cancer. Thyroid. 2006;16:109-142.
http://www.ncc.org/professionals/physician gls/PDF/thyroid.pdf 2006

12. Rationale for initial therapy, adapted from
Ref. 5, NCCN Guidelines (2006)
1. There is evidence that outcomes are
better.
2. Attack metastases that are visible on
the initial scan.
3. Ablate normal tissue destined to become
malignant,
4. Attack residual malignancy
a. microscopic in remnant
b. remote from remnant, e.g. tiny foci
c. outside remnant and obscured by
uptake in remnant

13. Rationale for initial therapy, cont.
5. Demonstration of unsuspected malignancy on
post-therapy scan (10-26%), which alters disease
stage and affects patient management.
6. Simplified patient follow-up, because elimination
of “thyroid bed” uptake eliminates mis-
interpretation of it as disease.
7. Remnant ablation eliminates normal tissue as a
source of Tg production, which facilitates
identification of patients who are free of disease
and promotes early identification of those with
residual cancer.
8. Elimination of normal tissue may eliminate the
nidus for continued confounding anti-Tg
antibody production.

14. 44 y.o. woman, previous history of irradiation, with “multicentric
papillary carcinoma exhibiting follicular differentiation”, multiple
positive regional lymph nodes and infiltration of perinodal tissue.
Rx 194 mCi. Most lesions disappeared, but she required subsequent
treatment.

15. E.H. 44 y.o. M s/p thyrx, multifocal diffuse
sclerosing variant of pap. adenoca with active
vascular and lymphatic permeation, intraglandular
metastasis, and +LN’s. Tg 160. Rx 202 mCi.
Post –Rx 6 d.

16. 53 y.o. man, well differentiated papillary ca,
encapsulated follicular variant, ~5 cm. Relatively
low thyroid bed activity; abnormal focus upper
midline ant. thorax. Tg = 0.8. Rx 202 mCi. Pre-
and post-Rx scans.

17. This was 10.3 weeks after CT with contrast.
Urinary iodine was 346µg/24 h (<400 considered
important, under 50 desirable). 8 months later,
scan negative, Tg <0.5, urinary iodine 86 µg/24 h.

18. 54 y.o. man, S/P total laryngectomy (squamous cell ca), total thyroidectomy
and lymph node dissection. Papillary ca multifocal (largest 2.1 cm), focal
angiolymphatic invasion, positive LN’s. Tg <0.5. No therapy given.
24-hour urinary iodine: specimen lost.

19. 45 y.o. man with single 2.1 x 2.0 cm papillary ca. Scanned and treated
(100 mCi) with Thyrogen stimulation. Tg not known before treatment.

20. 40 y.o. woman with papillary carcinoma with follicular elements and positive
LN’s, whose TSH didn’t rise. Reported to have had thyroidectomy elsewhere.
Treated with I-131, 78 mCi, to ablate normal tissue.

21. 35 y.o. woman with papillary ca with follicular
elements, with direct extension into adjacent
soft tissue and not amenable to total removal, and 1 pos. LN, prior pos. lung
biopsy. Scan (I-131, 3.9 mCi): activity in neck and lungs. Neck uptake 26%.
Borderline hyperthyroid: TSH low! Repeated for dosimetry 2 months later; TSH
elevated (thought 2˚ to 4 mCi I-131 dose!). Rx 250 mCi. Needed subsequent
treatments.

22. A young woman scanned 5 years after initial treatment.

23. Same patient scanned after therapeutic dose.

24. When TSH doesn’t go up (after withdrawal)
♦ Too much normal tissue
♦ Functioning tumor (euthyroid or
hyperthyroid)
♦ Patient kept taking hormone
♦ Sluggish pituitary
When there is no tissue seen on scan
♦ Really total thyroidectomy
♦ Iodine load

25. Ref. 1. Sisson (1983).
Applying the Radioactive Eraser: I-131 to Ablate…:
“Although continued depiction of thyroid cancer is
ominous, it does not necessarily follow that a blank
scintigram is ideal. The menace of residual portions
of normal thyroid glands has not been established,
and their elimination must be controversial…30 mCi…
succeeded in 81% of the patients…But complete…
ablation of all normal tissue is not required to achieve
…high [TSH]…If the remnant…is already small,…
benefits from its removal are not readily perceived…
To ablate or not to ablate is a question that will haut
us for some time to come.”

26. Inference:
Some may not need ablation, and incomplete
ablation (e.g. with a low dose) may be
tolerable in others. Tg not discussed in this
editorial.

27. Ref. 2. Mazzaferri (1997).
1004 patients with DTC followed for median
14.7 years or more. Tumor recurrence was
about 3-fold lower (p<0.001) and fewer patients
developed distant metastases (p<0.002) after
ablation than thyroid hormone alone or no
therapy. There were fewer cancer deaths after
ablation ((p<0.001); this difference occurred
only in patients ≥ 40 y.o. These effects are not
apparent in patients with isolated tumors
< 1.5 cm that are not metastatic to regional
lymph nodes or invading the thyroid capsule.

28. Years After Initial Therapy
Cumulative
Deaths
(%)
0 5 10 15 20 25 30 35
16
14
12
10
8
6
4
2
0
No medical therapy
Thyroid hormone only
P<0.001
P<0.05
131 l Remnant ablation
Cancer death rate after thyroid remnant ablation, thyroid hormone therapy alone,
or no postoperative medical therapy.

29. Comments on “ablation” benefit
♦ No mention of patients whose initial scans
showed metastases. Where do they fit into
the picture?
♦ Ref. 5, NCCN Guidelines: “…Long-term
evaluation of recurrence risk after adjuvant
radioiodine may be confounded by the…
possibility that patients who receive
adjuvant
therapy may be more likely to undergo more
intensive follow-up testing”

30. Comments on “ablation” benefit (cont.)
♦ Ref. 6, ATA Guidelines (2006):
“[Some] studies show no…benefit of [ablation],
at least among the majority of patients with
papillary…carcinoma…Lower risk patients
do not show evidence for benefit…No
prospective studies have been performed…”

31. Ref. 3, Woodrum et al (2005):
♦ “The future of [DTC] treatment will like
involve
an approach where patients are selected for
postoperative radioiodine therapy based
on individual risk assessment…”
♦ This is a good recent review in which Sisson
is thanked for his critical review of the text,
22 years after ref. 1.

32. Ref. 4, Doi et al (2000):
Meta-analysis. High dose was more efficient
than low dose for remnant ablation, and a
higher proportion of those with a near-total
resection than with a less complete resection
achieved ablation.

33. Ref. 5, NCCN Guidelines (2006):
“[Some] experts advocate that the whole-body
[radioiodine] diagnostic scan may alter therapy, for
example: (1) when unsuspected metastases are
identified, or (2) when an unexpectedly large remnant
is identified that requires additional surgery or a
reduction in radioiodine dosage…123I does not carry a
risk of stunning…Empiric administration of radioiodine
without a diagnostic scan is not routinely
recommended
by the panel.”
Comment: Lack of uptake may trigger suspicion of an
iodine load.

34. Considerations in I-131 dose choice:
Risk factors include gender, age, size and multifocality
of tumor, aggressive histology, molecular markers,
elevated thyroglobulin, nodal metastases,
extrathyroidal
or vascular invasion
Examples:
♦ Low risk patient, e.g. 35-y.o. woman with single 1.5 cm
lesion of papillary cancer, no evidence of spread, no
radiation history, Tg <0.5
Low dose or no Rx
♦ High risk patient: e.g. 60-y.o. man with multifocal
papillary carcinoma, largest 2.0 cm, one positive LN,
Tg = 20 (even though only remnants on scan)
High dose

35. Considerations in I-131 dose choice (cont.):
• I-131 has risks
• Tg may be falsely elevated for several weeks by
injury from surgery.

36. Suggested guidelines for dose decisions:
1. Metastases evident on diagnostic scan
High dose, 150-200 mCi, consider
dosimetry
2. Other high risk
High dose, 150-200 mCi
3. Low risk, definite low-grade thyroid remnant
uptake, low Tg
Low dose, 30-100 mCi—or no Rx
4. Low risk, low risk, remnant or Tg may interfere
with detection
Low dose, 30-100 mCi

37. Suggested guidelines for dose decisions (cont.):
5. Scan negative, Tg low
No Rx. Consider urine iodide
6. Scan negative, Tg elevated
Consider Rx. Consider urine iodide
7. Only remnants visible, very high Tg
Rx (conventional wisdom), but this could
already be a herald of non- iodine-avid
lesions

38. Pet peeves
♦ “Ablation” is misleading.
♦ “Ablation” to the point of seeing zero activity
is probably a pointless fetish.
♦ Ref. 4, Doi et al (200): “Residual thyroid may
compete with recurrent or metastatic thyroid
cancer for radioiodine uptake.” Tissue in the
neck will not inhibit detection of a metastasis
in the femur, so long as the TSH is elevated.

39. "Why did the ibis cross the road?"