2017 Section 7 Green Book

Risk of second primary malignancy

in differentiated thyroid carcinoma

treated with radioactive iodine therapy

Brian Hung-Hin Lang, MS, FRACS,

Irene Oi Ling Wong, PhD,

Kai Pun Wong, MBBS, MRCS,

Benjamin J. Cowling, PhD,

and

Koon-Yat Wan, MBBS, FRCR,

Hong Kong, China

Background.

Differentiated thyroid cancer survivors are at increased risk of nonsynchronous second

primary malignancy, but the cause remains unclear. This study aimed to evaluate the association

between radioiodine therapy and risk of nonsynchronous second primary malignancy and to examine

whether the risk of nonsynchronous second primary malignancy in differentiated thyroid cancer

survivors treated with radioiodine therapy is increased relative to the general population.

Methods.

Among 895 radiation-na

€

ıve patients with differentiated thyroid cancer, 643 (71.8%) received

1 course of radioiodine therapy (radioiodine therapy–positive group) and 252 (28.2%) received no

radioiodine therapy (radioiodine therapy–negative group). After a median follow-up of 93.5 months

(range, 23.4–570.8), 64 (7.2%) patients developed

1 nonsynchronous second primary malignancy.

Potential risk factors for nonsynchronous second primary malignancy were entered into a multivariable

regression model and cancer incidence in the radioiodine therapy–positive and –negative groups were

compared to that of the general population by estimating the standardized incidence ratios.

Results.

The 20-year cumulative nonsynchronous second primary malignancy risk in radioiodine

therapy–positive group was significantly higher than radioiodine therapy–negative group (13.5% vs

3.1%;

= .015). Cumulative radioiodine therapy activity of 3.0 to 8.9 GBq (relative risk, 2.77; 95%

CI, 1.079–7.154;

= .034) was the only independent risk factor for nonsynchronous second primary

malignancy after adjusting for age, sex, period of differentiated thyroid cancer diagnosis, and stage of

differentiated thyroid cancer. For females, the standardized incidence ratio in the radioiodine therapy–

positive group was 1.54 (95% CI, 1.11–2.08) and in the radioiodine therapy–negative group it was

0.92 (95% CI, 0.37–1.90).

Conclusion.

Differentiated thyroid cancer female survivors treated by radioiodine therapy appeared to be

at elevated risk of nonsynchronous second primary malignancy when compared to the general population

and this risk was not apparent in those not previously treated by radioiodine therapy. (Surgery

2012;151:844-50.)

From the Department of Surgery,

the School of Public Health,

and the Department of Clinical Oncology,

The

University of Hong Kong, Hong Kong, China

IFFERENTIATED THYROID CARCINOMA

(DTC) accounts

for more than 90% of all follicular cell–derived thy-

roid malignancies and is the most common primary

endocrine-related malignancy. In our locality, its

age-adjusted incidence has doubled over the last

25 years, and a similar trend has been observed else-

where.

Despite this, the disease-specific mortality

remains low, with an overall 10-year disease-specific

survival above 90%.

However, because this cancer

affects mostly relatively young patients, the lifetime

risk of developing nonsynchronous second primary

malignancy (NSPM) poses a real concern.

In agree-

ment with other studies, our previous analysis found

that DTC survivors were at greater NSPM risk than

that of the general population (relative risk [RR],

1.39; 95% confidence interval [CI], 1.09–1.73).

4-7

In addition, those survivors who eventually devel-

oped NSPM had a significantly poorer overall

survival than those who did not.

While the occur-

rence of NSPM appeared to adversely affect the sur-

vival of DTC survivors,

the likely causes for the

increased risk of NSPM in DTC survivors remain

uncertain. Possibilities include the exposure to ion-

izing radiation from radioiodine therapy (RAI) or

external local radiotherapy (ERT), common envi-

ronmental or dietary factors, genetic predisposition,

Accepted for publication December 22, 2011.

Reprint requests: Brian Hung-Hin Lang, MS, FRACS, Division of

Endocrine Surgery, Department of Surgery, Queen Mary Hospi-

tal, 102 Pokfulam Road, Hong Kong SAR, China. E-mail:

blang@hkucc.hku.hk .

0039-6060/$ - see front matter

Crown Copyright

2012 Published by Mosby, Inc. All rights

reserved.

doi

: 10.1016/j.surg.2011.12.019

SURGERY

Reprinted by permission of Surgery. 2012; 151(6):844-850.