2017 Section 7 Green Book

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

Risk of second primary malignancy in differentiated thyroid carcinoma treated with radioactive iodine therapy

Brian Hung-Hin Lang, MS, FRACS, a Irene Oi Ling Wong, PhD, b Kai Pun Wong, MBBS, MRCS, a Benjamin J. Cowling, PhD, b and Koon-Yat Wan, MBBS, FRCR, c 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%; P = .015). Cumulative radioiodine therapy activity of 3.0 to 8.9 GBq (relative risk, 2.77; 95% CI, 1.079–7.154; P = .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, a the School of Public Health, b and the Department of Clinical Oncology, c The University of Hong Kong, Hong Kong, China

survival above 90%. 2 However, because this cancer affects mostly relatively young patients, the lifetime risk of developing nonsynchronous second primary malignancy (NSPM) poses a real concern. 3 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. 4 While the occur- rence of NSPM appeared to adversely affect the sur- vival of DTC survivors, 4 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,

D 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. 1 Despite this, the disease-specific mortality remains low, with an overall 10-year disease-specific 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

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