115 / 220
and sex, the incidence or risk of developing NSPM
in RAI
+
group was significantly higher, but in the
RAI group, the incidence or risk appeared not sig-
nificantly different to the general population. In
the RAI
+
group, for both sexes, the SIR was 1.51
(95% CI, 1.14–1.96). For males in the RAI
+
group,
the SIR was 1.41 (95% CI, 0.77–2.37), and for fe-
males the SIR was 1.54 (95% CI, 1.11–2.02). In con-
trast, for males in the RAI group, the SIR was 0.53
(95% CI, 0.01–2.96), and for females the SIR was
0.92 (95% CI, 0.37–1.90).
DISCUSSION
Previous studies found that the overall lifetime
risk of developing NSPM was higher in DTC survi-
vors by up to 30% to 40% more than that of the
general population.
4,14
The present study, unlike
our previous studies, was aimed at specifically evalu-
ating whether RAI therapy was a potential risk factor
for NSPM in a cohort of radiation-na
€
ıve DTC survi-
vors.
4,15
Other proposed risk factors included expo-
sure of ionizing radiation during DTC treatment,
common environmental and dietary factors, ge-
netic predisposition, and surveillance bias.
5,8
How-
ever, ionizing radiation exposure from treatment
of DTC remains one of the most likely culprits for
NSPM because RAI therapy is commonly admin-
istered in DTC either in the setting of thyroid rem-
nant ablation after total or near-total thyroidectomy
or in the setting of recurrence or metastasis.
5,6,16,17
As a result, more selective use of RAI therapy in
DTC, particularly for low-risk tumors, has been in-
creasingly advocated.
18
Although I
131
is preferen-
tially taken up by the normal and malignant
thyroid follicular cells, particularly under the hypo-
thyroid state, it is also taken up and accumulated
into the stomach, salivary glands, colon, and blad-
ders; these sites are often exposed to prolonged ra-
diation. Interestingly, these sites were reported to
the common sites for NSPM in DTC survivors.
5,15
In the present study, because only 2 female patients
belonging to the RAI
+
group developed stomach
and bladder cancers during the study period (data
not shown), respectively, it was difficult to know
whether these tumors were actually related to RAI
therapy or occurred by chance. Calculating the
SIR value for these 2 primary tumors was also not
possible. Nevertheless, similar to previous studies,
we did find that breast cancer was one of the most
common NSPMs in DTC survivors. In addition,
the relative frequency of the 3 most common
NSPMs (ie, breast, colon, and lung) observed in
the present study appeared similar to the frequency
observed in other population studies.
5,6
Their fre-
quencies ranged between 0.1% and 0.2% per
1 person-year of observation.
6
Possible explanations
Figure.
The cumulative risk curves of developing non-
synchronous second primary malignancy (NSPM) after
the diagnosis of differentiated thyroid carcinoma
(DTC) in those who received radioiodine therapy
(RAI
+
group) and those who received no radioiodine
therapy (RAI group).
Table III.
Cox proportional hazards analysis of
factors for the development of nonsynchronous
second primary malignancy in differentiated thy-
roid carcinoma
Covariates
Relative risk
95% CI
P
value
Age of DTC by groups, y
<
30
Reference
30–49
1.468
0.690–3.121
.319
$
50
1.704
0.910–5.085
.263
Sex
Female
Reference
Male
1.299
0.695–2.430
.413
Period of DTC diagnosis
Before 1980 Reference
1980–1999 1.676
0.840–3.346
.143
After 2000 1.717
0.601–4.910
.313
Cumulative RAI activity, GBq
None
Reference
3–8.9
2.777
1.079–7.145
.034
>
9.0
3.149
0.645–12.816 .131
Stage of DTC by TNM
I
Reference
II
1.678
0.764–3.627
.162
III
1.513
0.681–3.364
.309
IV
1.760
0.781–3.969
.173
CI
, Confidence interval;
DTC
, differentiated thyroid carcinoma;
NSPM
,
nonsynchronous second primary malignancy;
RAI
, radioactive iodine
(I
131
);
TNM
, American Joint Cancer Committee/Union Internationale
Contre le Cancer tumor-nodes-metastasis staging system, 6th edition.
Surgery
June 2012
Lang
et
al
95