Second primary cancer prevalence in differentiated thyroid cancer patients and correlation with thyroid primary tumor stage: A population-based cohort study in Iran

Document Type : Original Article

Authors

1 Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2 Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

3 Department of Nuclear Medicine, Rasoul Akarm Hospital, Iran University of Medical Sciences, Tehran, Iran

4 Oncologic Surgery Department, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Introduction: Thyroid cancer is the most common endocrine malignancy. This often involves the middle-aged and active population, typically younger compared to those with other types of cancers. Some people with thyroid cancer may develop secondary malignancy. The reason for this is not well understood. This study was designed to evaluate the prevalence of second primary cancers in patients with differentiated thyroid cancer and its probable relationship with the severity of treatment and staging of the primary tumor.
Methods: Among 2638 patients who underwent thyroidectomy between 1996 and 2018, we checked cases who suffered from non-thyroidal second primary cancers before, during, or after the diagnosis of thyroid cancer. Forty-nine patients met the criteria and were included in the study. The information was gathered from the medical records and supplemented by direct communication with the patients. The Data was then analyzed using appropriate statistical test with   SPSS version 22, considering a P-value of 0.05 was considered as significant.
Results: Out of the 2638 checked records reviewed, 49 patients (1.85%) were found to have second primary cancers with 75.5% being female. One patient had two concurrent second primary cancers, while the remaining 48 patients had a single second primary cancer. Most of the thyroid cancers were papillary (89.8%, 44 cases), with the others remaining cases being follicular type. Stage 2, according to the 8th AJCC staging system, was the most common (50%), followed by stage 1 (36.8%) among the primary staging categories. Breast cancer was the most prevalent (17 cases), followed by hematologic malignancies (8 cases) and GI tract cancers (8 cases). 
Conclusion: The findings revealed a significant increase in the number of breast cancers in patients with the differentiated thyroid cancer (DTC), which was not observed for other malignancies.

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  1. Seib CD, Sosa JA. Evolving understanding of the epidemiology of thyroid cancer. Endocrinol Metab Clin North Am. 2019 Mar;48(1):23-35. 
  2. Kong N, Xu Q, Zhang Z, Cui A, Tan S, Bai N. Age Influences the prognosis of anaplastic thyroid cancer patients. Front Endocrinol (Lausanne). 2021 Jul 27;12:704596.
  3. Rahbari R, Zhang L, Kebebew E. Thyroid cancer gender disparity. Future Oncology. 2010;6(11):1771-9.
  4. Karimi N, Faradmal J, Zakavi SR, Roshanaei G, Naderi A. Assessment of risk factors on the relapse and death in patients with thyroid cancer in Khorasan Razavi province, during 2005-2015. J Inflamm Dis. 2019;23(2):128-39.
  5. Williams D. Radiation carcinogenesis: lessons from Chernobyl. Oncogene. 2008 Dec;27 Suppl 2:S9-18.
  6. Schlumberger M, Leboulleux S. Current practice in patients with differentiated thyroid cancer. Nat Rev Endocrinol. 2021 Mar;17(3):176-88. 
  7. Lee SL. Complications of radioactive iodine treatment of thyroid carcinoma. J Natl Compr Canc Netw. 2010 Nov;8(11):1277-86. 
  8. Sandeep TC, Strachan MW, Reynolds RM, Brewster DH, Scélo G, Pukkala E, Hemminki K, Anderson A, Tracey E, Friis S, McBride ML. Second primary cancers in thyroid cancer patients: a multinational record linkage study. J Clin Endocrinol Metab. 2006 May 1;91(5):1819-25.
  9. McDonald AM, Lindeman B, Bahl D. Radioactive iodine: recognizing the need for risk-benefit balance. J Clin Oncol. 2022 May 1;40(13):1396-9. 
  10. Samhouri L, Kriz J, Elsayad K, Channaoui M, Pascher A, Riemann B, Wiewrodt R, Haverkamp U, Scobioala S, Eich HT. The Role of radiotherapy for patients with thyroid cancer in the modern era. Anticancer Res. 2020 Jun;40(6):3379-86.
  11. Izkhakov E, Barchana M, Liphshitz I, Silverman BG, Stern N, Keinan-Boker L. Trends of second primary malignancy in patients with thyroid cancer: a population-based cohort study in israel. Thyroid. 2017 Jun;27(6):793-801. 
  12. Gandolfi G, Sancisi V, Piana S, Ciarrocchi A. Time to re-consider the meaning of BRAF V600E mutation in papillary thyroid carcinoma. Int J Cancer. 2015 Sep 1;137(5):1001-11.
  13. Gilani SM, Abi-Raad R, Garritano J, Cai G, Prasad ML, Adeniran AJ. RAS mutation and associated risk of malignancy in the thyroid gland: An FNA study with cytology-histology correlation. Cancer Cytopathol. 2022 Apr;130(4):284-93.
  14. Wirth LJ, Sherman E, Robinson B, Solomon B, Kang H, Lorch J, Worden F, Brose M, Patel J, Leboulleux S, Godbert Y, Barlesi F, Morris JC, Owonikoko TK, Tan DSW, Gautschi O, Weiss J, de la Fouchardière C, Burkard ME, Laskin J, Taylor MH, Kroiss M, Medioni J, Goldman JW, Bauer TM, Levy B, Zhu VW, Lakhani N, Moreno V, Ebata K, Nguyen M, Heirich D, Zhu EY, Huang X, Yang L, Kherani J, Rothenberg SM, Drilon A, Subbiah V, Shah MH, Cabanillas ME. Efficacy of Selpercatinib in RET-altered thyroid cancers. N Engl J Med. 2020 Aug 27;383(9):825-35. 
  15. Berthe E, Henry-Amar M, Michels JJ, Rame JP, Berthet P, Babin E, Icard P, Samama G, Galateau-Sallé F, Mahoudeau J, Bardet S. Risk of second primary cancer following differentiated thyroid cancer. Eur J Nucl Med Mol Imaging. 2004 May;31(5):685-91. 
  16. Piciu D, Pestean C, Barbus E, Larg MI, Piciu A. Second malignancies in patients with differentiated thyroid carcinoma treated with low and medium activities of radioactive I-131. Clujul Med. 2016;89(3):384-9.
  17. Rubino C, de Vathaire F, Dottorini ME, Hall P, Schvartz C, Couette JE, Dondon MG, Abbas MT, Langlois C, Schlumberger M. Second primary malignancies in thyroid cancer patients. Br J Cancer. 2003 Nov 3;89(9):1638-44. 
  18. Fallahi B, Adabi K, Majidi M, Fard-Esfahani A, Heshmat R, Larijani B, Haghpanah V. Incidence of second primary malignancies during a long-term surveillance of patients with differentiated thyroid carcinoma in relation to radioiodine treatment. Clin Nucl Med. 2011 Apr;36(4):277-82. 
  19. Cappagli V, Caldarella A, Manneschi G, Piaggi P, Bottici V, Agate L, Molinaro E, Bianchi F, Elisei R. Nonthyroidal second primary malignancies in differentiated thyroid cancer patients: Is the incidence increased comparing to the general population and could it be a radioiodine therapy consequence?. Int J Cancer. 2020 Nov 15;147(10):2838-46.
  20. Tan H, Wang S, Huang F, Tong Z. Association between breast cancer and thyroid cancer risk: a two-sample Mendelian randomization study. Front Endocrinol (Lausanne). 2023 May 23;14:1138149. 
  21. Wang H, Li S, Shi J, Feng C, Wang Y, Zhang F. Unbalanced bidirectional causal association between thyroid cancer and ER-positive breast cancer: should we recommend screening for thyroid cancer in breast cancer patients? BMC Genomics. 2023 Dec 11;24(1):762.