2017 Section 7 Green Book

for the association between DTC and breast cancer

included the presence of sodium iodide symporters

in mammary tissue leading to cumulative doses of

131

, the female dominance in DTC survivors, ge-

netic predisposition, and surveillance bias.

10,19

Nevertheless, when all types/sites of NSPM were

considered, our data are consistent with the hy-

pothesis that RAI therapy increased the overall risk

of developing NSPM in DTC survivors. In the

multivariable analysis, after adjusting for other

possible factors linked to the risk of NSPM, a

cumulative RAI activity of 3–8.9 GBq was found to

be an independent factor for the development of

NSPM in DTC survivors, and the relative increased

risk was approximately 2–3 times higher than

survivors who received no RAI. However, because

the RR was not significant in the group who had

cumulative RAI activity

9.0, the present study was

not able to establish a dose–effect relationship

between cumulative RAI activity and risk of NSPM.

This might have been because only 29 patients had

cumulative RAI activity

9.0 GBq, and our study

was therefore underpowered to identify an effect.

Another explanation might have been related to

the disease threshold phenomenon, where the risk

of RAI activity

9.0 GBq far exceeded the dose

threshold and so imparted the same risk as RAI

activity of 3.0–8.9 GBq. To further confirm that

RAI therapy was the factor responsible for the

increased risk of NSPM and not factors that influ-

enced the decision to prescribe RAI therapy in the

first place, the present analysis compared factors

that might have influenced the decision to pre-

scribe RAI (such as the stage of DTC, period of

DTC diagnosis, and age of DTC), and these

significant factors were entered into the multivar-

iable analysis together with other well-reported risk

factors, such as sex.

17,20

Although the male sex was

not an independent factor for NSPM, 2 previous

studies found that male survivors were at increased

risk of NSPM.

17,20

Therefore, male DTC survivors

treated with RAI might be at even greater risk of

NSPM. Nevertheless, our SIR analysis in NSPM

did not support this finding with the males in

the RAI

group having a slightly lower SIR value

than females in the RAI

group after adjusting

for age (1.41 vs 1.54). However, there appeared

to be a strong association between breast cancer

and DTC; the higher risk of NSPM observed in

RAI

female patients might have been a result of

this association.

4-6

Unlike other studies, our data

showed that the risk of NSPM in the RAI group

was similar to that of the general popula-

tion.

6,8,11,17

Perhaps this further strengthened the

association between RAI therapy and risk of

NSPM in DTC survivors. However, because

30%

of DTC patients received no RAI, our study might

have been underpowered in this aspect.

One of the strengths of the present study was

the complete patient follow-up status and data

collection, and this was not possible without the

establishment of the territory-wide CMS in 1995.

Unlike previous larger-scale analyses, all patients in

the present study were managed under a standard-

ized treatment protocol, and the histology of DTC

was confirmed by the same group of pathologists at

our institution. Given the completeness of the clin-

ical data, the chance of NSPM misclassification

would have been minimal, and our SIR results

were already adjusted for both patient age and

sex. However, similar to previous single-center

analysis, the total number of NSPMs remained rel-

atively small, which limited the power of our study

to identify smaller effects. Also, the present analysis

was potentially subject to a degree of institution

and referral biases, because our center is an aca-

demic tertiary care institute to which more com-

plex cases are often referred from other

hospitals. Because there were a number of signifi-

cant differences in baseline clinical and demo-

graphics between RAI

and RAI groups, they

might not have been fully adjusted by the multivar-

iate analysis. A future multicenter study involving

other institutions in our territory would be desir-

able to further confirm our findings. Although

none of the 64 patients with NSPM had known

Table IV.

Observed and expected number of cases

and standardized incidence ratio with the corre-

sponding 95% CIs of nonsynchronous second pri-

mary malignancy for those who did and did not

receive radioiodine in males, females, and both

sexes

Observed

no. of

NSPMs

Expected

number of

NSPMs

Standardized

incidence

ratio

95% CI

RAI

group

Males

9.90

1.41 0.77–2.37

Females

27.28

1.54 1.11–2.08

Both

sexes

37.18

1.51 1.14–1.96

RAI group

Male

1.88

0.53 0.01–2.96

Female

7.59

0.92 0.37–1.90

Both

sexes

9.47

0.84 0.36–1.66

*Expected numbers of NSPM were based on population incidence of all

sites in 2008 after adjusting for age.

, Confidence interval;

NSPM

, nonsynchronous second primary malig-

nancy;

RAI

, radioactive iodine (I

131

Surgery

Volume 151, Number 6

Lang