Paediatric Oncology


Of note is the fact that the increased risk of secondary cancers was demonstrated in patients treated with high radioiodine activity. At up to 7.4GBq, no increase in secondary cancers was observed.49


This


could suggest that the risk of secondary malignancies is highest in advanced disease (e.g. distant metastases) as these are the only cases where high radioiodine activities are used. However, this group of patients benefited the most from radioiodine therapy. Additionally, in a recent study of chromosome damage in children and adolescents treated with ablative activities (1.1–4.4GBq) of radioiodine it was demonstrated that in peripheral T lymphocytes, early genome toxicity (expressed as a stable level of micronuclei formation) was not induced.51


Although the above-cited data are reassuring, the recent study by Hay and colleagues13


in which increased mortality rate from


secondary malignancies among paediatric DTC patients was demonstrated is alarming. Of the 15 patients who died from secondary malignancies, 11 (73%) had received post-operative therapeutic irradiation. All of the deaths occurred 30–50 years after initial diagnosis of DTC. However, if one looks closely at the results, only four cases were diagnosed after surgery and adjuvant radioiodine treatment. In seven cases, the patients were treated before 1950 and there was history of radium-seed or X-ray therapy. Among the patients who died from secondary malignancies and were treated after 1950, only four had received radioactive iodine (two with activity ≤7.4GBq) and three were treated with surgery alone. The difference in mortality from secondary malignancies between these two groups is statistically insignificant (χ2 test p=0.2. Data extracted from original manuscript: radioiodine group 4/63 events; surgery group 3/125 events). Based on these results, one cannot unequivocally say that radioiodine treatment increases the risk of secondary malignancies, but the general risk of radiation-induced cancer must be considered in this group of patients.


Fertility Disorders


To date, no study has found a statistically significant association between 131I exposure and unfavourable pregnancy outcome or increased infertility in women and in men. Nevertheless, transient gonadal effects of radioiodine therapy – i.e. oligospermia, increased follicle-stimulating hormone (FSH) levels, etc. – have been reported.52 All of these observations are derived from studies on adults of childbearing potential where the dose after an estimated 3.7GBq radiation to the testis was 0.09cGy.


Long-term adverse events were recently evaluated in adults who had thyroid cancer diagnosed


1.


Bernstein L Gurney JG, Carcinomas and other malignant epithelial neoplasms, SEER Paediatric Monograph, 2009:139– 48. Available at: seer.cancer.gov/publications/childhood/ carcinomas.pdf (accessed 8 June 2010).


2.


Steliarova-Foucher E, Stiller CA, Pukkala E, et al., Thyroid cancer incidence and survival among European children and adolescents (1978–1997): report from the Automated Childhood Cancer Information System project, Eur J Cancer,


2006;42(13):2150–69. 3.


Hung W, Sarlis NJ, Current controversies in the management of paediatric patients with well- differentiated nonmedullary thyroid cancer: a review, Thyroid, 2002;12(8):683–702.


4.


Parisi MT, Mankoff D, Differentiated paediatric thyroid cancer: correlates with adult disease, controversies in treatment, Semin Nucl Med, 2007;37(5):340–56.


5.


could have been found. Semen specimens were not evaluated, so conclusions about the functional consequences of increased FSH level cannot be made. Nevertheless, if a boy is post-puberty and there are no psychological contraindications, semen collection and banking should be considered before referral for 131I treatment.


Conclusions


Treating children with DTC is a challenge, given that children frequently present with advanced disease yet very rarely die from it. All of the available data on radioactive iodine in the management of paediatric DTC are retrospective and are usually based on a small number of patients. The two largest studies – one from the US13 the other from Europe16


and – have found contradictory results on


recurrence free-survival. One can only speculate about the reasons for such results. In the US study, disease was less advanced at diagnosis, as only 6% of patients suffered from distant metastases at this time (which is much less than in other studies). Patient follow-up was based on physician examinations or on correspondence from patients and relatives, so some of the unfavourable events could have been missed. Of note is the fact that in the study by Hay and colleagues there was a tendency towards better recurrence-free survival in regional lymph nodes.


Based on the results of these two studies, it is hard to unequivocally recommend whether radioactive iodine should be used or not in the post-operative management of childhood DTC. However, the authors believe that, currently, when most children present with advanced disease radioiodine should be used to decrease the risk of disease recurrence. When referring children and adolescents for radioiodine therapy one should remember the possible side effects of radiation. However, there is no clear evidence that radioiodine can actually induce secondary neoplasms. n


Daria Handkiewicz-Junak is an Assistant Professor at the Comprehensive Cancer Center, Maria Sklodowska-Curie Memorial Institute Branch, in Gliwice, where she is also Head of the Nuclear Medicine Unit in the Department of Nuclear Medicine and Endocrine Oncology. Her previous positions include Consultant in Radiation Oncology and Consultant in Nuclear Medicine. Dr Handkiewicz-Junak has a special interest in endocrine malignancies, with emphasis on nuclear medicine applications in diagnosis


and treatment. She is a member of numerous medical societies and, since March 2008, has been a member of the therapy committee of the European Association of Nuclear Medicine (EANM).


Aleksandra Kropinska is a Doctor in the Department of Nuclear Medicine and Endocrine Oncology at the Comprehensive Cancer Center, Maria Sklodowska-Curie Memorial Institute Branch, in Gliwice. She completed her medical education at Silesian University in 2004 and since then has been actively involved in endocrine cancer research. Her particular interest is thyroid cancer and her recent research has focused on the side effects of paediatric differentiated thyroid cancer treatment.


Thompson GB, Hay ID, Current strategies for surgical management and adjuvant treatment of childhood papillary thyroid carcinoma, World J Surg, 2004;28(12): 1187–98.


6. 7.


Seidlin SM, Marinelli LD, Oshry E, Radioactive iodine therapy, effect of functioning metastases of adenocarcinoma of the thyroid, JAMA, 1946;12:838. Schlumberger M, De VF, Travagli JP, et al., Differentiated


68


EUROPEAN ONCOLOGY


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