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

doi:10.1016/j.surg.2011.12.019

Surgery

Volume 151, Issue 6, June 2012, Pages 844-850

https://doi.org/10.1016/j.surg.2011.12.019 Get rights and content

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-naïve 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.

Section snippets

Patients

Between 1971 and 2009, 1,122 patients with DTC were managed at our institution. Of these, 98 (8.7%) had clinically occult microcarcinoma, 41 (3.7%) had a documented history of radiotherapy or radiation exposure before the diagnosis of DTC, and 88 (7.8%) received ERT as adjuvant treatment for DTC. For the purpose of the present study, they were excluded, and therefore a total of 895 radiation-naïve patients were eligible for analysis. All eligible patients had at least 1 year of follow-up. There

Results

Table I shows the baseline patient characteristics. Six hundred ninety-five (77.7%) patients had papillary thyroid carcinoma and 200 (22.3%) had follicular thyroid carcinoma. The majority were female (80.6%) and ethnic Chinese (94.1%). The median age of DTC diagnosis was 44.0 years (range, 7.1–90.6), and the median follow-up period was 93.5 months (range, 23.1–570.8). Seven hundred sixty-three (85.3%) patients underwent bilateral thyroid resection, and of these, 643 (84.3%) patients received at

Discussion

Previous studies found that the overall lifetime risk of developing NSPM was higher in DTC survivors 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 evaluating whether RAI therapy was a potential risk factor for NSPM in a cohort of radiation-naïve DTC survivors.4, 15 Other proposed risk factors included exposure of ionizing radiation during DTC treatment, common environmental and dietary factors,

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Genetic damage associated to131I therapy and secondary cancer risk
2022, Nuclear Medicine and Molecular Imaging: Volume 1-4
Radioactive ¹³¹Iodine (I) is absorbed via the gastrointestinal tract and circulates in the blood, whereby, in addition to the damage to thyroid cells through the specific incorporation, the remainder of the body is also exposed to radiation. Some research groups were able to demonstrate the processes of apoptosis and necrosis of thyrocytes exposed to ¹³¹I. In addition, genetic damage to other somatic cells, e.g., chromosomal damage in peripheral lymphocytes can be detected after radioactive iodine (RAI) therapy. Chromosomal alteration is considered a predictor of future cancer risk and generally increases the risk of developing primary or secondary malignancies.
There are factors that suggest causality between RAI therapy and the occurrence of second primary malignancies (SPM). This association would be biologically plausible and coherent. Most studies also find a higher risk in the groups with the highest cumulative ¹³¹I activity compared with the groups with lower cumulative activity.
But there are factors that call the interconnection into question. First, the time course of second primary malignancies is not consistent with causality. SPM are observed after thyroid cancer diagnosis and RAI treatment, but an increased risk of thyroid cancer is also observed after other cancers. This may suggest a common etiology rather than carcinogenic effect of DTC treatment. Moreover, the magnitude of the effect was often small, and even the most comprehensive and recent meta-analysis found no effect in an unadjusted analysis and a small effect in an adjusted analysis.
The available evidence suggests a potential risk of SPM from RAI treatment. Nevertheless, the absolute excess risk, whether caused by RAI treatment or not, appears to be small, and further research is needed to verify whether RAI treatment is responsible for the excess risk.
Hepatotoxicity of iodine-131 ablation for post-surgical differentiated thyroid cancer patients with hepatitis B virus infection
2021, Clinics and Research in Hepatology and Gastroenterology
Radioiodine (Iodine-131, ¹³¹I) ablation is a standard treatment for differentiated thyroid cancer (DTC) after thyroidectomy. Hepatotoxicity is a rare side effect of ¹³¹I, and little information is available on the hepatotoxicity of ¹³¹I ablation for post-surgical DTC patients with hepatitis B virus (HBV) infection.
We performed a retrospective study of 94 post-surgical DTC patients between November 2012 and August 2015 in our hospital. All the patients had been screened for HBV infection and divided into HBV group and non-HBV group. Clinical data were compared between the two groups.
14 patients with HBV infection and 80 patients without HBV infection were analyzed. The baseline characteristics of the two groups had no statistical differences. Incidence of hepatotoxicity was higher in HBV group than in non-HBV group and HBV infection was confirmed as a risk factor of hepatotoxicity by univariate and multivariate regression analysis.
Post-surgical DTC patients with HBV infection were prone to hepatotoxicity by ¹³¹I ablation treatment. Physicians should pay more attention to the liver function of patients at risk.
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Citation Excerpt :
The cumulative incidence of SPM is higher in patients treated with RAI than those who are not.30,31 RAI tends to accumulate in the salivary glands and stomach because these tissues have a high number of sodium-iodide symporters (transmembrane surface protein controlling transport of sodium and iodine ions into the cell), leading to an increased risk for cancer in both sites.31,32 Patients treated with RAI are also at an elevated risk for leukemia; the incidence of leukemia correlates with a higher dose of RAI.32
Advances in early detection and treatment of cancer have resulted in a growing population of cancer survivors across the United States. Cancer survivors may be at increased risk for the development of a second primary malignancy as a result of environmental factors, genetic predisposition, or as a late effect of the cancer treatment they received. This review examines the risk for second primary malignancy and necessary screening in the six cancers with the highest 5-year survival rates, including: breast cancer, Hodgkin's lymphoma, melanoma, prostate, testicular, and thyroid cancer.
Conservative thyroidectomy for papillary thyroid microcarcinoma
2019, American Journal of Otolaryngology - Head and Neck Medicine and Surgery
According to American Thyroid Association (ATA) guideline, thyroid lobectomy is recommended for the management of papillary thyroid microcarcinomas (PTMC) with a diameter lesser than 1 cm. However, this procedure is associated with a risk of potential complications such as vocal cord palsy. Thus, we considered the applicability of conservative thyroidectomy, involving partial removal of the thyroid cancer lesion, not the entire ipsilateral thyroid lobe.
A retrospective analysis of all PTMC patients who underwent conservative thyroidectomy at Konkuk University Hospital between August 2008 and February 2014 was performed. Oncologic results of these patients along with the incidence of postoperative complications were evaluated. Seventy-nine patients who underwent conservative thyroidectomy for the treatment of PTMC were enrolled in the present study.
Four of the 79 patients (5.0%) showed recurrence, 2 local (2.5%) and 2 regional (2.5%), respectively. All of these patients consequently underwent surgery alone and were salvaged. Temporary postoperative complications such as vocal cord palsy and hypocalcemia developed in 1 and 1 case, respectively, but completely recovered over time.
Conservative thyroidectomy is an oncologically and functionally safe procedure for surgical treatment of PTMC and can be considered as an alternative to thyroid lobectomy for the surgical management of PTMC.
Diagnostic Performance of [18F]TFB PET/CT Compared with Therapeutic Activity [131I]Iodine SPECT/CT and [18F]FDG PET/CT in Recurrent Differentiated Thyroid Carcinoma
2024, Journal of Nuclear Medicine
The effect of radioiodine therapy on blood cell count in patients with differentiated thyroid cancer
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Surgery

Background

Methods

Results

Conclusion

Section snippets

Patients

Results

Discussion

References (23)

Moral hazard or realised access to care? Empirical observation in Hong Kong

Health Policy

Radiotherapy for primary thyroid cancer as a risk factor for second primary cancers

Cancer Lett

CHEK2 is a multiorgan cancer susceptibility gene

Am J Hum Genet

Prognostic factors in papillary and follicular thyroid carcinoma: implications for cancer staging

Ann Surg Oncol

Long-term outcome in 215 children and adolescents with papillary thyroid cancer treated during 1940 through 2008

World J Surg

Impact of second primary malignancy on outcomes of differentiated thyroid carcinoma

Surgery

Second primary malignancies in thyroid cancer patients

Br J Cancer

The risk of second primary malignancies up to three decades after the treatment of differentiated thyroid cancer

J Clin Endocrinol Metab

Second primary cancers in thyroid cancer patients: a multinational record linkage study

J Clin Endocrinol Metab

Risk of second primary cancer following differentiated thyroid cancer

Eur J Nucl Med Mol Imaging

Cited by (67)

Genetic damage associated to<sup>131</sup>I therapy and secondary cancer risk

Hepatotoxicity of iodine-131 ablation for post-surgical differentiated thyroid cancer patients with hepatitis B virus infection

Second Primary Malignancies in Cancer Survivors

Conservative thyroidectomy for papillary thyroid microcarcinoma

Diagnostic Performance of [<sup>18</sup>F]TFB PET/CT Compared with Therapeutic Activity [<sup>131</sup>I]Iodine SPECT/CT and [<sup>18</sup>F]FDG PET/CT in Recurrent Differentiated Thyroid Carcinoma

The effect of radioiodine therapy on blood cell count in patients with differentiated thyroid cancer

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

Background

Methods

Results

Conclusion

Section snippets

Patients

Results

Discussion

Health Policy

Cancer Lett

Am J Hum Genet

Prognostic factors in papillary and follicular thyroid carcinoma: implications for cancer staging

Ann Surg Oncol

Long-term outcome in 215 children and adolescents with papillary thyroid cancer treated during 1940 through 2008

World J Surg

Impact of second primary malignancy on outcomes of differentiated thyroid carcinoma

Surgery

Second primary malignancies in thyroid cancer patients

Br J Cancer

The risk of second primary malignancies up to three decades after the treatment of differentiated thyroid cancer

J Clin Endocrinol Metab

Second primary cancers in thyroid cancer patients: a multinational record linkage study

J Clin Endocrinol Metab

Risk of second primary cancer following differentiated thyroid cancer

Eur J Nucl Med Mol Imaging

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