Comprehensive evaluation, multidisciplinary care, individualized treatment, and ongoing follow-up are all key to the management of pediatric thyroid nodules and differentiated thyroid carcinoma (DTC), according to the first European guidelines for this rare disease.
The guidelines were recently published in the European Thyroid Journal.
Lead author Chantal A. Lebbink told this news organization one of the key takeaways for clinicians is that management of pediatric thyroid nodules and DTC is «challenging and cannot be captured in a one-size-fits-all model.”
She also underlined the need for a “multidisciplinary approach in pediatric thyroid cancer expertise centers.”
Above all, Ms. Lebbink, who is a PhD student in the department of pediatric endocrinology, Wilhelmina Children’s Hospital, Utrecht, the Netherlands, said that pediatric DTC “is not adult DTC in a small person; it has different genetics and a different clinical behavior.”
The authors noted that DTC may be a rare disease, but its worldwide incidence is rising. It has several histologic subtypes, although the “vast majority” of cases are papillary thyroid carcinoma.
Crucially, there are “important differences” between adult and pediatric DTC in terms of their clinical, molecular, and pathologic characteristics, with pediatric patients commonly presenting with more advanced disease with greater lymph node involvement, distant metastases, and multifocal disease.
“However, despite the aggressive presentation, the overall survival rates are excellent,” Ms. Lebbink said.
There are also differences in genetic alterations between adult and pediatric patients. RET-PTC and NTRK fusions are more common in pediatric patients, while mutations in BRAF V600E and RAS point mutations are less frequent.
First European guidelines on thyroid cancer, thyroid nodules in children
Despite these differences, and the existence of U.S. guidelines, until now there have been no European recommendations on the management of pediatric thyroid nodules and DTC.
The European Thyroid Association therefore convened a panel of experts in pediatric and adult endocrinology, pathology, endocrine surgery, nuclear medicine, clinical genetics, and oncology, and tasked them with looking at diagnostics and staging, treatment, and follow-up.
The 2015 American Thyroid Association pediatric guideline was used as framework for the European guideline, with the expert panel identifying areas of discordance and outstanding clinical questions (Thyroid. 2015 Jul;25[7]:716-59).
To answer these questions, they searched PubMed and identified 3,251 studies, of which 45 studies met the inclusion criteria. From this they developed a comprehensive set of recommendations. These include that a child with suspected or proven cancer be referred to an experienced multidisciplinary team and their likely benefit from higher- versus lower-intensity treatment be established.
In addition, children should undergo a preoperative evaluation, with neck palpation, comprehensive neck ultrasonography, and laboratory work-up as a minimum, with further testing suggested in case of a family history or extensive disease.
Total thyroidectomy is the recommended treatment, although the authors call for further studies to assess the impact of limited surgery, and they suggest that prophylactic central lymph node dissection be reserved for advanced cases.
Crucially, all children “should be operated on by high-volume pediatric thyroid cancer surgeons with experience in pediatric thyroid cancer and who are embedded in a center with expertise in the management of DTC,” they wrote.
RAI therapy recommended for all children, in contrast to ATA guidelines
Radioactive iodine (I-131) therapy is recommended for all children following total thyroidectomy, with treatment following an individual patient-based approach.
This differs slightly from the ATA guidelines, which recommend against radioactive iodine (RAI) therapy for children with low-risk differentiated thyroid cancer that is mostly confined to the thyroid (N0 or minimal N1a disease). A study presented at the recent 2022 annual meeting of the ATA found that such children who were spared RAI showed no increases in risk of remission compared with those who did receive it.
The ETA guidelines then go on to recommend that children should be followed up with thyroid-stimulating hormone monitoring and suppression to low-normal levels, as well as serum thyroglobulin measurement and neck ultrasound, although other imaging modalities are not recommended.
In children with persistent or recurrent cervical disease, “surgery or I-131 therapy are indicated depending on the size, tumor load, and degree of progression,” and the authors said that cases of radioactive refractory disease should be “thoroughly investigated.”
Patients should also be counseled on the risk of the late effects of treatment for DTC and undergo monitoring, with follow-up continued for at least 10 years. Any subsequent follow-up should be “the result of shared decision-making between the physician and the patient.”
Evidence for molecular testing is scarce
Ms. Lebbink said that developing the guidelines nevertheless revealed a series of gaps in current knowledge, notably that the evidence for molecular testing “and the clinical implications in the preoperative stage are scarce.”
Specifically, the “positive and negative predictive value of molecular testing in fine needle biopsy specimen for the presence of DTC in a thyroid nodule must be further investigated.»
She also said that there has been a shift towards less aggressive treatment, due to a reluctance to performed prophylactic central neck dissection, and to offer I-131 therapy after surgery.
“However, before less aggressive treatment could be recommended,” Ms. Lebbink said, “it first must be investigated if there are differences in outcomes,” such as recurrence rates, disease-free survival rates, and survival rates between patients who do and do not receive the treatments.
No funding was declared. One author has reported relationships with Sanofi, AstraZeneca, Bayer, and GE. No other relevant financial relationships were reported.
A version of this article first appeared on Medscape.com.