Frequent adverse events after treatment for childhood-onset differentiated thyroid carcinoma: a single institute experience

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Abstract

Since the mortality rate for childhood differentiated thyroid carcinoma is nearly zero, the focus must be to minimise morbidity following treatment. Our aim was to analyse early and late adverse events. Twenty-five of 26 children treated between 1962 and 2002 were evaluated. Median follow-up was 14.2 years (range 0.9–39.4 years). All underwent total thyroidectomy, 15 (60%) with lymph node dissection and 15 (60%) with adjuvant radio-iodide therapy. Mortality was zero. Seven developed recurrent disease, two developed a third recurrence. Twenty-one (84%) had ⩾1 adverse event. Eight had permanent hypoparathyroidism (PH), six permanent recurrent nerve paralysis (PRNP) and two Horner's syndrome. Risk factors for PH and PRNP were total thyroidectomy with lymph node dissection (RR: 6.45, P=0.015) and recurrent nerve tumour encasement (RR: 8.00, P=0.001), respectively. Other adverse events were fatigue (n=5), scar problems (n=4) and chronic myeloid leukaemia (n=1). These results emphasise the need to improve treatment strategies.

Introduction

Thyroid carcinoma during childhood has an incidence of 0.2–3 per 100 000 [1] and comprises approximately 1.5% of all paediatric tumours [2], [3]. In the Netherlands, 103 children (70 girls) were diagnosed with differentiated thyroid carcinoma under the age of 19 years in the period 1989–1997 (incidence 0.4 per 100 000 for boys and 1.0 per 100 000 for girls) [4].

Thyroid tumours in children are often diagnosed in a more advanced stage than in adults; in 71–90% of children metastases in the cervical lymph nodes are found at diagnosis, and distant metastases (mainly in the lungs) are described in 10–21% of the patients [5]. Nevertheless, childhood-onset differentiated thyroid cancer generally has an excellent survival rate [2]. Therefore, at present, the goal of treatment must be to achieve the highest therapeutic efficacy with the lowest morbidity. Hence, awareness of the occurrence of adverse events in this group of children followed up into adulthood is of substantial importance. Knowledge gained this way may lead to changes in treatment strategies aimed to improve the quality of life of these survivors by reducing the number of adverse events.

Risk factors to develop differentiated thyroid carcinoma are female gender and age between 7 and 12 years [6]. In addition, elevated plasma thyroid stimulating hormone (TSH) concentration, Hashimoto's disease, exposure to radiation, and mutations in the RET-oncogene [7], [8], [9], [10], [11] have been suggested. Of these, only exposure to radiation and mutations in the RET-oncogene have been proven to cause childhood thyroid carcinoma. Examples of radiation-induced thyroid cancer are patients who previously received mantle field irradiation [12]. In the Ukraine-region, following the Chernobyl nuclear disaster, an increased incidence of thyroid cancer, mainly of the papillary type, was found in children exposed to radio-iodide [13]. It has been shown that thyroid tissue in children is more sensitive to radiation than in adults [8].

The currently recommended diagnostic test when confronted with a thyroid nodule is ultrasonography combined with fine needle aspiration cytology (FNAC) to differentiate between benign or malignant [14]. As lymph node involvement is present in 71–90% of cases [5], lymph node biopsy is a diagnostic option. Histological classification of thyroid carcinoma can be difficult and inter-observer disagreement has been reported in the range of 7–27% [15]. For staging, radio-iodide is used to detect metastases.

The cornerstone of treatment for thyroid carcinoma at all ages is surgery, with or without adjuvant radio-iodide ablation. In cases of a unilateral tumour without lymph node involvement there is, worldwide, no consensus whether a hemi- or a total thyroidectomy should be preferred [16], [17]. At all other tumour stages, total thyroidectomy is indicated. In case of total thyroidectomy, radio-iodide is considered for adjuvant therapy for several reasons [14]. First, to detect and destroy occult microscopic local remnants and distant metastases (if these accumulate radio-iodide). Second, to destroy all remaining normal thyroid remnants, in order to increase both specificity of measurements of plasma thyroglobulin (TG) and its sensitivity during follow-up. Third, to permit post-ablative radio-iodide total body scanning for persistent or recurrent carcinoma. Whether radio-iodide could also be effective in an earlier stage of the treatment, for example administered preceding the surgical intervention, has never been investigated. There is no place for chemotherapy. Thyroxine supplementation is given to correct the inevitable hypothyroidism and to diminish proliferation of remnant thyroid (cancer) cells by suppressing pituitary TSH secretion.

The goal of this study was to obtain insight in early and late adverse events due to paediatric differentiated thyroid cancer, in relation to the therapeutic strategies used, in a cohort of consecutive paediatric patients in one academic medical centre.

Section snippets

Patients and methods

All consecutive patients treated for (assumed) paediatric papillary or follicular thyroid carcinoma in the Emma Children's Hospital of the Academic Medical Center (EKZ-AMC), in the period 1962–2002, were evaluated for complications and late adverse events caused by the tumour and the treatment given.

Data were collected from office notes, surgical reports and pathology reports of the departments of paediatric oncology, paediatric endocrinology, and paediatric surgery and from patient charts and

Patients

Between 1962 and 2002, 26 patients (20 girls, 77%), with a mean age of 12.5 years (range 5–19 years) were treated for (assumed) differentiated thyroid carcinoma in the EKZ/AMC. Of them, 20 (77%) were initially diagnosed with papillary carcinoma (including one follicular variant), five (19%) with follicular carcinoma and one with a dyshormonogenetic goiter with multiple follicular adenoma.

Data inclusion closed in August 2002. The median follow-up time was 14.2 years (range 0.9–39.4 years).

Discussion

A perfect treatment for malignant thyroid disease would be the complete removal of all malignant tissue, without any adverse events. As the mortality of patients, diagnosed with childhood-onset differentiated thyroid carcinoma, has become very low [18], increasing efforts should be directed to minimise or even prevent morbidity due to the disease and its treatment.

Our study substantiates the observation that thyroid tumours in the younger age group are found in a more advanced stage at

Acknowledgements

We acknowledge Prof. Dr. B.L.F. van Eck of the department of nuclear medicine of the AMC for her critical reading of the manuscript. We also thank Dr. J.G.M. Tinnemans, endocrine surgeon of the department of surgery of the AMC for sharing his expertise in endocrine surgery.

References (39)

  • M.P La Quaglia et al.

    Differentiated and medullary thyroid cancer in childhood and adolescence

    Semin. Pediatr. Surg.

    (1997)
  • Coebergh JWW, van Dijkck JAAM, Janssen-Heijnen MLG, Visser O. Childhood Cancer in the Netherlands 1989–1997,...
  • R Feinmesser et al.

    Carcinoma of the thyroid in children – a review

    J. Pediatr. Endocrinol. Metab.

    (1997)
  • S Franceschi et al.

    The epidemiology of thyroid carcinoma

    Crit. Rev. Oncog.

    (1993)
  • E Ron et al.

    Thyroid cancer after exposure to external radiation: a pooled analysis of seven studies

    Radiat. Res.

    (1995)
  • A Wirtschafter et al.

    Expression of the RET/PTC fusion gene as a marker for papillary carcinoma in Hashimoto's thyroiditis

    Laryngoscope

    (1997)
  • M.J Schlumberger

    Papillary and follicular thyroid carcinoma

    N. Engl. J. Med.

    (1998)
  • E Saxen et al.

    Observer variation in histologic classification of thyroid cancer

    Acta Pathol. Microbiol. Scand. [A]

    (1978)
  • W Hung et al.

    Current controversies in the management of pediatric patients with well-differentiated nonmedullary thyroid cancer: a review

    Thyroid

    (2002)
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