1. The utility of “blind” 131I treatments for differentiated thyroid cancer:
an educational exhibit.
Elboga U1, Orquiza M2, Van Nostrand D2, Celen YZ1, Aktolun C3, Chao M4, Guan H5
1Department of Nuclear Medicine, Gaziantep University School of Medicine, Gaziantep, Turkey
2Division of Nuclear Medicine, Department of Medicine, MedStar Washington Hospital Center, Washington, D.C.
3Department of Radiology, Stanford University, Stanford, CA
4Department of Nuclear Medicine, Affiliated XinHua Hospital of Medical School Shanghai Jiaotong University, Shanghai, P.R. China
5Department of Endocrinology, The First Hospital of China Medical University, Shenyang, Liaoning, P.R. China
Abstract
Conclusion
Learning Objectives:
The objectives of this educational exhibit are to
review the literature regarding the utility of 131I
“blind” therapy, which is the 131I treatment of
patients with negative whole body scans (WBS)
and positive thyroglobulin (Tg) blood levels for
1. Assessing Tg rate of change,
2. Classifying the change using a modified
RECIST Criteria 1.1
3. Comparing outcome measures of the treated
and untreated groups
Summary: 131I is an important treatment modality
for patients with differentiated thyroid cancer
(DTC), and 131I has been documented as having
utility for remnant ablation, adjuvant treatment and
treatment of locoregional and distant metastases
of DTC. However, a problematic and controversial
area is the management and treatment of patients
with DTC who have negative radioiodine whole
body scans (WBC-) and positive thyroglobulin
blood levels (Tg+). Multiple articles have been
published regarding different approaches to the
management of such patients including he
spectrum from continued monitoring of the
patient’s Tg level to an extensive search for the
source of the elevated Tg level. Even after an
extensive search, the source of the elevated Tg is
frequently not identified, and the managing
physician or team of physicians must decide
whether or not to administer 131I despite not
knowing whether or not the patient will have any
131I uptake on the post-therapy scan and/or a
clinical response from the 131I therapy, a so called
“blind” therapy. As a result of the above, the
objective of this educational exhibit is to present a
review of the literature regarding the utility of
“blind” 131I therapy in the management of patients
with DTC who have a positive Tg level and
negative radioiodine whole body scan.
Literature Review
Journal searches were performed using
PubMed, Medline, and Google Scholar with the
key phrases: “blind” therapy, thyroid
cancer, whole body scan negative, and
thyroglobulin positive.
A total of nine articles [1-9] were identified
including an excellent review by Chao et al. [10].
From the nine articles a total 62 patients were
reported who had pre and post-therapy Tg
levels with no Tg antibodies and received a
“blind” therapeutic dose of 131I and a total of 112
patients with pre- and post-therapy Tg levels
with no Tg antibodies and no “blind” therapeutic
dose of 131I. Not all articles reported their
demographics, but the available demographics
are shown in Table 1.
changes in Tg blood levels. These changes were
categorized as complete response, partial
response, stable disease, or progressive disease by an
adaptation of a modified anatomical RECIST criteria 1.1
to a clinical laboratory test, which were:
•Complete response (CR): undetectable Tg
(1<ng/ml) on suppression,
•Partial response (PR): a decrease of >30% relative
to the pre-therapy Tg blood level,
•Stable response (SR): <20% increase and <30%
decrease relative to the pre-therapy Tg blood level,
•Progressive disease (PD): >20% increase relative
to the pre-therapy Tg blood level.
Treated
(N=62)
Untreated
(N=112)
Complete response (CR) 2/62 (3.2%)
50/112(44.6%)
(see footnote)
Partial response (PR) 37/62 (59.7%) 6/112(5.4%)
Stable disease (SD) 15/62 (24.2%) 30/112(26.8%)
Progressive disease
(PD)
8/62(12.9%) 26/112(23.2%)
Table 2
Comparison Between Treated and Untreated*
Graph 1
Comparison Between Treated and Untreated
Treated
(N=62)
Untreated
(N=112)
Gender (M/F)* 11/19 29/31
Age range (yrs) 22-69 25-62
Cancer type*
Papillary
Hürthle
Follicular
Tall Cell
39
3
2
2
60
0
0
0
“Blind” therapeutic dose
range (GBq)
2.8-11 0
Post therapy follow up
time
7 mos-6 yrs 1-4 yrs
Discussion
Table 1
Demographics*
References
*Available data
2/62
37/62
15/62
8/62
50/112
6/112
30/112
26/112
0%
10%
20%
30%
40%
50%
60%
CR PR SD PD
Treated
Untreated
1. De Keizer B, Koppeschaar HP, Zelissen PM, et al. Efficacy of high
therapeutic doses of iodine-131 in patients with differentiated thyroid cancer
and detectable serum thyroglobulin. Eur J Nucl Med 2001;28:198-202.
2. Pineda JD, Lee T, Ain K, et al. Iodine-131 therapy for thyroid cancer
patients with elevated thyroglobulin and negative diagnostic scan. J Clin
Endocrinol Metab 1995;80:1488-1492.
3. Pacini F, Lippi F, Formica N, et al. Therapeautic doses of iodine-131 reveal
undiagnosed metastases in thyroid cancer patients with detectable serum
thyroglobulin levels. J Nucl Med 1987;28:1888-1891.
4. Kabasakal L, Selcuk NA, Shafipour H, et al. Treatment of iodine-negative
thyroglobulin-positive thyroid cancer: differences in outcome in patients with
macrometastases and patients with micrometastases. Eur J Nucl Med Mol Imag
2004;31:1500-1504.
5. Pachucki J, Burmeister LA. Evaluation and treatment of persistent
thyroglobulinemia in patients with well-differentiated thyroid cancer. Eur J
Endocrinol 1997;137:254-261.
6. Koh JM, Kim ES, Ryu JS, et al. Effects of therapeutic doses of 131I in thyroid
papillary carcinoma patients with elevated thyroglobulin level and negative 131I
whole-body scan: comparative study. Clin Endocrinol 2003;58:421-427.
7. Pacini L, Agate R, Elisei M. Outcome of differentiated thyroid cancer with
detectable serum Tg and negative 131I whole body scan: comparison of patients
treated with high 131I activities versus untreated patients. J Clin Endocrinol
Metab 2001;86:4092-4097.
8. Tian R, Pan M, Kuang A. Evaluation of 131I therapy for differentiated thyroid
carcinoma patients with elevated Tg and negative 131I whole body scan. Chin J
Nucl Med 2003;23:27-28.
9. Alzahrani AS, Mohamed G, Al Shammary A, Aldasouqi S, Abdal Salam
S, Shoukri M. Long-term course and predictive factors of elevated serum
thyroglobulin and negative diagnostic radioiodine whole body scan in
differentiated thyroid cancer. J Endocrinol Invest 2005;28:540-546.
10. Chao M. Management of differentiated thyroid cancer with rising
thyroglobulin and negative diagnostic radioiodine whole body scan. Clin Oncol
2010;22:438-447.
11. Wells KJ, Moreau S, Shin YR, Van Nostrand D, Burman KD, Wartofsky L.
Positive (+) post-treatment (tx) scans after the radioiodine (RAI) tx of patients
who have well-differentiated thyroid cancer (WDTC), positive serum thyroglobulin
levels (TG+), and negative diagnostic (dx) RAI whole body scans (WBS-):
predictive values and frequency. J Nucl Med 2008;49(Suppl):238P.
In order to evaluate whether or not
patient outcomes were affected by “blind” 131I
therapies, articles initially proposed that these
therapies may have had an effect on the
patient’s outcome because as many as 64% of
patients who were treated with a “blind” 131I
therapy had a positive post-therapy radioiodine
scans [11]. However, although positive post-
therapy scans raise the possibility that a
significant radiation absorbed dose may have
been delivered to the DTC metastases, it does
not necessarily equate with a positive
outcome.
Subsequently and as noted in this
review, articles have evaluated the response of
Tg blood levels after a “blind” 131I therapy.
Although some practitioners' may use the
reported data to either support or argue
against the utility of “blind” 131I treatments, we
submitted that there are too many limitations in
these studies to make any conclusions or
recommendations. First, the complete
response rate in those patients who were
untreated included patients with decreasing
thyroglobulin blood levels. We would submit
that most physicians would not treat a patient
with decreasing Tg, and these patients should
not be included in a control group. Inclusion of
patients with stable Tg is more
problematic, but again we would submit that
many physicians would not necessarily treat
stable and mild elevations of Tg. The key
group is those patients with rising Tg blood
levels, and two additional factors are the rate
of rise and the absolute rise. These studies did
not adequately evaluate those additional
factors. . Additional limitations include low
numbers of patients, the use of a blood marker
(e.g. Tg) as the only parameter for
outcomes, no standard regarding the
significance of a change in Tg, and finally, no
meaningful data available regarding changes
Based on the present publications, we
do not believe that the controversy of the utility
of “blind” 131I therapies has been resolved.
To assess the outcomes of 131I “blind”
therapies, we recommend more
comprehensive studies, which should
preferably be prospective and involve at least
(1) selected absolute levels of Tg, (2) selected
rising levels of Tg per unit time period, and (3)
selected absolute increased levels of Tg per
time period, and (4) measurable lesions on
imaging studies.
* In most of the untreated patients, the trend of Tg levels
were not report and may have been rising, stable or
decreasing.
For those patients who had “blind” 131I
therapies performed, we tabulated the mean
(X), standard deviation (SD), and the range
(min/max) of the individual’s absolute changes in
Tg as well as the X, SD, and range of the percent
(%)
The data for the treated and untreated using the
modified RECIST criteria are presented in Table 2 and
Graph 1.
imaging studies such as ultrasound, computer
tomography, and/or magnetic resonance imaging.